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Conserved domains on  [gi|2039782227|emb|CAG5861777|]
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unnamed protein product [Menidia menidia]

Protein Classification

FERM, ARHGEF and pleckstrin domain-containing protein( domain architecture ID 12200574)

FERM, ARHGEF and pleckstrin domain-containing protein (either FARP1 or FARP2) functions as guanine nucleotide exchange factor for RAC1

Gene Ontology:  GO:0005085|GO:0008092|GO:0030036

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
FERM_C_FARP1-like cd13193
FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related ...
 227-347 1.86e-69

FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FRMD7(FERM domain containing 7). FARP1 and FARP2 are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. These members are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. Other members in this family do not contain the DH domains such as the Human FERM domain containing protein 7 and Caenorhabditis elegans CFRM3, both of which have unknown functions. They contain an N-terminal FERM domain, a PH domain, followed by a FA (FERM adjacent) domain. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


:

Pssm-ID: 270014  Cd Length: 122  Bit Score: 228.38  E-value: 1.86e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  227 EIARKLEMYGIRFHPAADREGTKINLAVAHMGLQVFQGNIRINTFNWSKIRKLSFKRKRFLIKLHPEVHGPHQDTLEFMM 306
Cdd:cd13193      1 ETARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIKLHPEAYGSYKDTVEFSF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2039782227  307 ASRDQCKIFWKICVEYHSFFRLFDQPQPKS-KAILFTRGSSF 347
Cdd:cd13193     81 ESRNECKSFWKKCIEHHAFFRCSEVPKPPSpKLRLFSRGSSF 122
PH2_FARP1-like cd13235
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 1222-1319 1.98e-67

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 2; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270055  Cd Length: 98  Bit Score: 221.42  E-value: 1.98e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1222 VENQLSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKLQFKSHVYFFR 1301
Cdd:cd13235      1 VENQMSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKSHQDEFPLASLPLLGYSVGLPSEADNIDKDYVFKLQFKSHVYFFR 80

                           90
                   ....*....|....*...
gi 2039782227 1302 AESEYTFERWMEVIKSAA 1319
Cdd:cd13235     81 AESEYTFERWMEVIRSAT 98
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 1036-1151 2.45e-60

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 269928  Cd Length: 109  Bit Score: 201.77  E-value: 2.45e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1036 LTAPGREFIREGCLYKLTKKGLQQRMFFLFSDMLLYTSKGVTATNQFKVHGQLPLHGMIlivldapVEESENEWSVPHCF 1115
Cdd:cd01220      1 LVQPGREFIREGCLQKLSKKGLQQRMFFLFSDVLLYTSRSPTPSLQFKVHGQLPLRGLM-------VEESEPEWGVAHCF 73

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2039782227 1116 TIYSAQRTIVVAASSKVEMGKWIEDLNMAIDMAKKS 1151
Cdd:cd01220     74 TIYGGNRALTVAASSEEEKERWLEDLQRAIDAAKKS 109
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 52-240 1.85e-53

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


:

Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 185.58  E-value: 1.85e-53
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227    52 IRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMN-WVWLEPTKPVAKQVRRPANTLFRLSVKFF 130
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDlRHWLDPAKTLLDQDVKSEPLTLYFRVKFY 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   131 PPDPGQLQEEYTRY-LFSLQMKRDLMEGRLICTENTGALLASHLVQSEIGDYD--DIADREFLRVNKLLPYQ-------D 200
Cdd:smart00295   82 PPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDeeLHDLRGELSLKRFLPKQlldsrklK 161

                           170       180       190       200
                    ....*....|....*....|....*....|....*....|
gi 2039782227   201 KVQERIMEFHRRHLGQTPAESDFQILEIARKLEMYGIRFH 240
Cdd:smart00295  162 EWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 824-1011 9.84e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


:

Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 174.41  E-value: 9.84e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  824 YFIAKEILTTERTYLKDLEVITVWFRSAVIKENA-MPEGLMTLLFSNIDPIYEFHRGFLKELDQRLALWEGrsnahvkgD 902
Cdd:cd00160      2 QEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDK--------S 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  903 YQRIGDVMLKNMCALKEFTSYLQKHDEVLTELEKASKRLKKLETVYKEFELQkVCYLPLNTFLLKPIQRLMHYKLILERL 982
Cdd:cd00160     74 GPRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE-CGRLKLESLLLKPVQRLTKYPLLLKEL 152

                          170       180
                   ....*....|....*....|....*....
gi 2039782227  983 CKHYSPGHRDYYDCKEALKEVADIATQLQ 1011
Cdd:cd00160    153 LKHTPDGHEDREDLKKALEAIKEVASQVN 181
FA pfam08736
FERM adjacent (FA); This region is found adjacent to Band 4.1 / FERM domains (pfam00373) in a ...
 340-381 1.09e-14

FERM adjacent (FA); This region is found adjacent to Band 4.1 / FERM domains (pfam00373) in a subset of FERM containing protein. The region has been hypothesized to play a role in regulatory adaptation, based on similarity to other protein kinase substrates.


:

Pssm-ID: 462582  Cd Length: 44  Bit Score: 69.11  E-value: 1.09e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2039782227  340 LFTRGSSFRYSGRTQKQLVDYVRENGSKRTPYQRRNSKIRMS 381
Cdd:pfam08736    2 FFSLGSKFRYSGRTQKQTVEDSSEILRPQPEFERSPSKRYPS 43
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 423-489 1.59e-04

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 46.47  E-value: 1.59e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2039782227  423 PQTKLPSQPQPLSTLSPAPPKQQQLHSPLQTTRPPSPPKEDLIKAPSPPHYSFQGAPSNQAAGHCSP 489
Cdd:PHA03247  2889 PAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEP 2955
 
Name Accession Description Interval E-value
FERM_C_FARP1-like cd13193
FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related ...
 227-347 1.86e-69

FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FRMD7(FERM domain containing 7). FARP1 and FARP2 are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. These members are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. Other members in this family do not contain the DH domains such as the Human FERM domain containing protein 7 and Caenorhabditis elegans CFRM3, both of which have unknown functions. They contain an N-terminal FERM domain, a PH domain, followed by a FA (FERM adjacent) domain. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270014  Cd Length: 122  Bit Score: 228.38  E-value: 1.86e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  227 EIARKLEMYGIRFHPAADREGTKINLAVAHMGLQVFQGNIRINTFNWSKIRKLSFKRKRFLIKLHPEVHGPHQDTLEFMM 306
Cdd:cd13193      1 ETARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIKLHPEAYGSYKDTVEFSF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2039782227  307 ASRDQCKIFWKICVEYHSFFRLFDQPQPKS-KAILFTRGSSF 347
Cdd:cd13193     81 ESRNECKSFWKKCIEHHAFFRCSEVPKPPSpKLRLFSRGSSF 122
PH2_FARP1-like cd13235
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 1222-1319 1.98e-67

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 2; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270055  Cd Length: 98  Bit Score: 221.42  E-value: 1.98e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1222 VENQLSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKLQFKSHVYFFR 1301
Cdd:cd13235      1 VENQMSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKSHQDEFPLASLPLLGYSVGLPSEADNIDKDYVFKLQFKSHVYFFR 80

                           90
                   ....*....|....*...
gi 2039782227 1302 AESEYTFERWMEVIKSAA 1319
Cdd:cd13235     81 AESEYTFERWMEVIRSAT 98
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 1036-1151 2.45e-60

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269928  Cd Length: 109  Bit Score: 201.77  E-value: 2.45e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1036 LTAPGREFIREGCLYKLTKKGLQQRMFFLFSDMLLYTSKGVTATNQFKVHGQLPLHGMIlivldapVEESENEWSVPHCF 1115
Cdd:cd01220      1 LVQPGREFIREGCLQKLSKKGLQQRMFFLFSDVLLYTSRSPTPSLQFKVHGQLPLRGLM-------VEESEPEWGVAHCF 73

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2039782227 1116 TIYSAQRTIVVAASSKVEMGKWIEDLNMAIDMAKKS 1151
Cdd:cd01220     74 TIYGGNRALTVAASSEEEKERWLEDLQRAIDAAKKS 109
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 52-240 1.85e-53

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 185.58  E-value: 1.85e-53
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227    52 IRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMN-WVWLEPTKPVAKQVRRPANTLFRLSVKFF 130
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDlRHWLDPAKTLLDQDVKSEPLTLYFRVKFY 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   131 PPDPGQLQEEYTRY-LFSLQMKRDLMEGRLICTENTGALLASHLVQSEIGDYD--DIADREFLRVNKLLPYQ-------D 200
Cdd:smart00295   82 PPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDeeLHDLRGELSLKRFLPKQlldsrklK 161

                           170       180       190       200
                    ....*....|....*....|....*....|....*....|
gi 2039782227   201 KVQERIMEFHRRHLGQTPAESDFQILEIARKLEMYGIRFH 240
Cdd:smart00295  162 EWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 824-1011 9.84e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 174.41  E-value: 9.84e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  824 YFIAKEILTTERTYLKDLEVITVWFRSAVIKENA-MPEGLMTLLFSNIDPIYEFHRGFLKELDQRLALWEGrsnahvkgD 902
Cdd:cd00160      2 QEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDK--------S 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  903 YQRIGDVMLKNMCALKEFTSYLQKHDEVLTELEKASKRLKKLETVYKEFELQkVCYLPLNTFLLKPIQRLMHYKLILERL 982
Cdd:cd00160     74 GPRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE-CGRLKLESLLLKPVQRLTKYPLLLKEL 152

                          170       180
                   ....*....|....*....|....*....
gi 2039782227  983 CKHYSPGHRDYYDCKEALKEVADIATQLQ 1011
Cdd:cd00160    153 LKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 826-1011 3.54e-46

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 164.01  E-value: 3.54e-46
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   826 IAKEILTTERTYLKDLEVITVWFRSAVIKEN-AMPEGLMTLLFSNIDPIYEFHRGFLKELDQRLALWEGrsnahvkgDYQ 904
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDD--------SVE 72

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   905 RIGDVMLKNMCALKEFTSYLQKHDEVLTELEKASKRlKKLETVYKEFELQKVCY-LPLNTFLLKPIQRLMHYKLILERLC 983
Cdd:smart00325   73 RIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKN-PRFQKFLKEIESSPQCRrLTLESLLLKPVQRLTKYPLLLKELL 151

                           170       180
                    ....*....|....*....|....*...
gi 2039782227   984 KHYSPGHRDYYDCKEALKEVADIATQLQ 1011
Cdd:smart00325  152 KHTPEDHEDREDLKKALKAIKELANQVN 179
FERM_F1_FARP2 cd17190
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF ...
 50-134 2.64e-45

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF and pleckstrin domain-containing protein 2 (FARP2) and similar proteins; FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FARP2 contains a FERM domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340710  Cd Length: 85  Bit Score: 158.03  E-value: 2.64e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKF 129
Cdd:cd17190      1 LQLRVKLLDNTTEPLEIEPKADGQALLSQVFKRLNLVESDYFGLEFQNSQSNWIWLEPMKLIVKQVRRPKNTKLRLAVKF 80


                   ....*
gi 2039782227  130 FPPDP 134
Cdd:cd17190     81 FPPDP 85
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 826-1010 8.06e-44

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 157.08  E-value: 8.06e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  826 IAKEILTTERTYLKDLEVITVWFRSAVIKENAMPEGLMTLLFSNIDPIYEFHRGFLkeLDQRLALWEgrsnahvkgDYQR 905
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLKEWI---------SIQR 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  906 IGDVMLKNMCALKEFTSYLQKHDEVLTELEKASKRLKKLETVYKEFELQKVCY-LPLNTFLLKPIQRLMHYKLILERLCK 984
Cdd:pfam00621   70 IGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRgLDLNSFLIKPVQRIPRYPLLLKELLK 149

                          170       180
                   ....*....|....*....|....*.
gi 2039782227  985 HYSPGHRDYYDCKEALKEVADIATQL 1010
Cdd:pfam00621  150 HTPPDHPDYEDLKKALEAIKEVAKQI 175
FERM_C pfam09380
FERM C-terminal PH-like domain;
244-328 1.17e-30

FERM C-terminal PH-like domain;


Pssm-ID: 462779 [Multi-domain]  Cd Length: 85  Bit Score: 115.81  E-value: 1.17e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  244 DREGTKINLAVAHMGLQVFQGNIRI-NTFNWSKIRKLSFKRKRFLIKLHpevHGPHQDTLEFMMASRDQCKIFWKICVEY 322
Cdd:pfam09380    1 DKEGTDLWLGVSAKGILVYEDNNKIlNLFPWREIRKISFKRKKFLIKLR---DKSSEETLGFYTESSRACKYLWKLCVEQ 77


                   ....*.
gi 2039782227  323 HSFFRL 328
Cdd:pfam09380   78 HTFFRL 83
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 132-240 1.29e-22

FERM central domain; This domain is the central structural domain of the FERM domain.


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 94.26  E-value: 1.29e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  132 PDPGQLQEEYTRYLFSLQMKRDLMEGRLICTENTGALLASHLVQSEIGDYDD-IADREFLRVNKLLPYQ-------DKVQ 203
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPsSHTSEYLSLESFLPKQllrkmksKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 2039782227  204 ERIMEFHRRHLGQTPAESDFQILEIARKLEMYGIRFH 240
Cdd:pfam00373   81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1226-1320 1.09e-17

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 79.51  E-value: 1.09e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  1226 LSGYLLRKFKNSN-GWQKLWVVFTNFCLFFYKTHQ---DDFPLASLPLLGYTVSTPEESDSIHKEYVFKLQFKS-HVYFF 1300
Cdd:smart00233    3 KEGWLYKKSGGGKkSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDrKTLLL 82

                            90       100
                    ....*....|....*....|
gi 2039782227  1301 RAESEYTFERWMEVIKSAAS 1320
Cdd:smart00233   83 QAESEEEREKWVEALRKAIA 102
FA pfam08736
FERM adjacent (FA); This region is found adjacent to Band 4.1 / FERM domains (pfam00373) in a ...
 340-381 1.09e-14

FERM adjacent (FA); This region is found adjacent to Band 4.1 / FERM domains (pfam00373) in a subset of FERM containing protein. The region has been hypothesized to play a role in regulatory adaptation, based on similarity to other protein kinase substrates.


Pssm-ID: 462582  Cd Length: 44  Bit Score: 69.11  E-value: 1.09e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2039782227  340 LFTRGSSFRYSGRTQKQLVDYVRENGSKRTPYQRRNSKIRMS 381
Cdd:pfam08736    2 FFSLGSKFRYSGRTQKQTVEDSSEILRPQPEFERSPSKRYPS 43
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1227-1320 1.30e-14

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 71.05  E-value: 1.30e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKFK-NSNGWQKLWVVFTNFCLFFYK---THQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKL----QFKSHVY 1298
Cdd:pfam00169    4 EGWLLKKGGgKKKSWKKRYFVLFDGSLLYYKddkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELrtgeRTGKRTY 83

                           90       100
                   ....*....|....*....|..
gi 2039782227 1299 FFRAESEYTFERWMEVIKSAAS 1320
Cdd:pfam00169   84 LLQAESEEERKDWIKAIQSAIR 105
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1043-1146 2.09e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 70.27  E-value: 2.09e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  1043 FIREGCLYKLT---KKGLQQRMFFLFSDMLLYTSKGvTATNQFKVHGQLPLHGMILIVLDAPVEESEnewsvPHCFTIYS 1119
Cdd:smart00233    1 VIKEGWLYKKSgggKKSWKKRYFVLFNSTLLYYKSK-KDKKSYKPKGSIDLSGCTVREAPDPDSSKK-----PHCFEIKT 74

                            90       100
                    ....*....|....*....|....*...
gi 2039782227  1120 AQR-TIVVAASSKVEMGKWIEDLNMAID 1146
Cdd:smart00233   75 SDRkTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1044-1145 2.29e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 53.34  E-value: 2.29e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1044 IREGCLYKLT---KKGLQQRMFFLFSDMLLYTSKGVTATNQFKVhGQLPLHGmiLIVLDAPVEESENEwsvPHCFTIYSA 1120
Cdd:pfam00169    2 VKEGWLLKKGggkKKSWKKRYFVLFDGSLLYYKDDKSGKSKEPK-GSISLSG--CEVVEVVASDSPKR---KFCFELRTG 75

                           90       100
                   ....*....|....*....|....*....
gi 2039782227 1121 Q----RTIVVAASSKVEMGKWIEDLNMAI 1145
Cdd:pfam00169   76 ErtgkRTYLLQAESEEERKDWIKAIQSAI 104
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 814-1010 1.47e-04

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 46.42  E-value: 1.47e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  814 RRKRYPtdkayfIAKEILTTERTYLKDLEVITVWFRSAVIKENAMPEG----LMTLLFSNIDPIYEFHRGFLKELDQRLA 889
Cdd:COG5422    482 EIKRQE------AIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENarrnFIKHVFANINEIYAVNSKLLKALTNRQC 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  890 LwegrsnahvKGDYQRIGDVMLKNMCALKEFTSYL--QKHDEVLTELEKASKR--LKKLETVYKEFELQKvcyLPLNTFL 965
Cdd:COG5422    556 L---------SPIVNGIADIFLDYVPKFEPFIKYGasQPYAKYEFEREKSVNPnfARFDHEVERLDESRK---LELDGYL 623

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 2039782227  966 LKPIQRLMHYKLILERLCKHYSPGHRDYYDCKEALKEVADIATQL 1010
Cdd:COG5422    624 TKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRL 668
PHA03247 PHA03247
large tegument protein UL36; Provisional
 423-489 1.59e-04

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 46.47  E-value: 1.59e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2039782227  423 PQTKLPSQPQPLSTLSPAPPKQQQLHSPLQTTRPPSPPKEDLIKAPSPPHYSFQGAPSNQAAGHCSP 489
Cdd:PHA03247  2889 PAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEP 2955
DUF4657 pfam15552
Domain of unknown function (DUF4657); This family of proteins is found in eukaryotes. Proteins ...
 445-497 1.75e-04

Domain of unknown function (DUF4657); This family of proteins is found in eukaryotes. Proteins in this family are typically between 305 and 370 amino acids in length.


Pssm-ID: 464762  Cd Length: 301  Bit Score: 45.22  E-value: 1.75e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2039782227  445 QQLHSPLQTTRPPSPP-KEDLIKAPSPPHYSfqgAPSNQAAGHCSPLFVCVESG 497
Cdd:pfam15552  143 QQLYLQLQTQRPPGDPeEEESALAPSPPPSH---APGNEVQGPWELLSQTEETG 193
Amelogenin smart00818
Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem ...
 415-479 2.07e-04

Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem to regulate formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organisation and mineralisation of developing enamel. The extracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins. Circular dichroism studies of porcine amelogenin have shown that the protein consists of 3 discrete folding units: the N-terminal region appears to contain beta-strand structures, while the C-terminal region displays characteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain a repetitive beta-turn segment and a "beta-spiral" between Gln112 and Leu138, which sequester a (Pro, Leu, Gln) rich region. The beta-spiral offers a probable site for interactions with Ca2+ ions. Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplastic amelogenesis imperfecta, a disease characterised by defective enamel. A 9bp deletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disrupting the 16-residue (Met1-Ala16) amelogenin signal peptide.


Pssm-ID: 197891 [Multi-domain]  Cd Length: 165  Bit Score: 43.24  E-value: 2.07e-04
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2039782227   415 PAHMTSILPQTKLPSQPQPLSTLSPAPPKQQQlhSPLQTTRPPSPPKedlikaPSPPHYSFQGAP 479
Cdd:smart00818   86 QHHQPNLPQPAQQPFQPQPLQPPQPQQPMQPQ--PPVHPIPPLPPQP------PLPPMFPMQPLP 142
 
Name Accession Description Interval E-value
FERM_C_FARP1-like cd13193
FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related ...
 227-347 1.86e-69

FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FRMD7(FERM domain containing 7). FARP1 and FARP2 are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. These members are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. Other members in this family do not contain the DH domains such as the Human FERM domain containing protein 7 and Caenorhabditis elegans CFRM3, both of which have unknown functions. They contain an N-terminal FERM domain, a PH domain, followed by a FA (FERM adjacent) domain. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270014  Cd Length: 122  Bit Score: 228.38  E-value: 1.86e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  227 EIARKLEMYGIRFHPAADREGTKINLAVAHMGLQVFQGNIRINTFNWSKIRKLSFKRKRFLIKLHPEVHGPHQDTLEFMM 306
Cdd:cd13193      1 ETARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIKLHPEAYGSYKDTVEFSF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2039782227  307 ASRDQCKIFWKICVEYHSFFRLFDQPQPKS-KAILFTRGSSF 347
Cdd:cd13193     81 ESRNECKSFWKKCIEHHAFFRCSEVPKPPSpKLRLFSRGSSF 122
PH2_FARP1-like cd13235
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 1222-1319 1.98e-67

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 2; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270055  Cd Length: 98  Bit Score: 221.42  E-value: 1.98e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1222 VENQLSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKLQFKSHVYFFR 1301
Cdd:cd13235      1 VENQMSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKSHQDEFPLASLPLLGYSVGLPSEADNIDKDYVFKLQFKSHVYFFR 80

                           90
                   ....*....|....*...
gi 2039782227 1302 AESEYTFERWMEVIKSAA 1319
Cdd:cd13235     81 AESEYTFERWMEVIRSAT 98
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 1036-1151 2.45e-60

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269928  Cd Length: 109  Bit Score: 201.77  E-value: 2.45e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1036 LTAPGREFIREGCLYKLTKKGLQQRMFFLFSDMLLYTSKGVTATNQFKVHGQLPLHGMIlivldapVEESENEWSVPHCF 1115
Cdd:cd01220      1 LVQPGREFIREGCLQKLSKKGLQQRMFFLFSDVLLYTSRSPTPSLQFKVHGQLPLRGLM-------VEESEPEWGVAHCF 73

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2039782227 1116 TIYSAQRTIVVAASSKVEMGKWIEDLNMAIDMAKKS 1151
Cdd:cd01220     74 TIYGGNRALTVAASSEEEKERWLEDLQRAIDAAKKS 109
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 52-240 1.85e-53

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 185.58  E-value: 1.85e-53
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227    52 IRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMN-WVWLEPTKPVAKQVRRPANTLFRLSVKFF 130
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDlRHWLDPAKTLLDQDVKSEPLTLYFRVKFY 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   131 PPDPGQLQEEYTRY-LFSLQMKRDLMEGRLICTENTGALLASHLVQSEIGDYD--DIADREFLRVNKLLPYQ-------D 200
Cdd:smart00295   82 PPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDeeLHDLRGELSLKRFLPKQlldsrklK 161

                           170       180       190       200
                    ....*....|....*....|....*....|....*....|
gi 2039782227   201 KVQERIMEFHRRHLGQTPAESDFQILEIARKLEMYGIRFH 240
Cdd:smart00295  162 EWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 824-1011 9.84e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 174.41  E-value: 9.84e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  824 YFIAKEILTTERTYLKDLEVITVWFRSAVIKENA-MPEGLMTLLFSNIDPIYEFHRGFLKELDQRLALWEGrsnahvkgD 902
Cdd:cd00160      2 QEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDK--------S 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  903 YQRIGDVMLKNMCALKEFTSYLQKHDEVLTELEKASKRLKKLETVYKEFELQkVCYLPLNTFLLKPIQRLMHYKLILERL 982
Cdd:cd00160     74 GPRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE-CGRLKLESLLLKPVQRLTKYPLLLKEL 152

                          170       180
                   ....*....|....*....|....*....
gi 2039782227  983 CKHYSPGHRDYYDCKEALKEVADIATQLQ 1011
Cdd:cd00160    153 LKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 826-1011 3.54e-46

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 164.01  E-value: 3.54e-46
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   826 IAKEILTTERTYLKDLEVITVWFRSAVIKEN-AMPEGLMTLLFSNIDPIYEFHRGFLKELDQRLALWEGrsnahvkgDYQ 904
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDD--------SVE 72

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   905 RIGDVMLKNMCALKEFTSYLQKHDEVLTELEKASKRlKKLETVYKEFELQKVCY-LPLNTFLLKPIQRLMHYKLILERLC 983
Cdd:smart00325   73 RIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKN-PRFQKFLKEIESSPQCRrLTLESLLLKPVQRLTKYPLLLKELL 151

                           170       180
                    ....*....|....*....|....*...
gi 2039782227   984 KHYSPGHRDYYDCKEALKEVADIATQLQ 1011
Cdd:smart00325  152 KHTPEDHEDREDLKKALKAIKELANQVN 179
FERM_F1_FARP2 cd17190
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF ...
 50-134 2.64e-45

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF and pleckstrin domain-containing protein 2 (FARP2) and similar proteins; FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FARP2 contains a FERM domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340710  Cd Length: 85  Bit Score: 158.03  E-value: 2.64e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKF 129
Cdd:cd17190      1 LQLRVKLLDNTTEPLEIEPKADGQALLSQVFKRLNLVESDYFGLEFQNSQSNWIWLEPMKLIVKQVRRPKNTKLRLAVKF 80


                   ....*
gi 2039782227  130 FPPDP 134
Cdd:cd17190     81 FPPDP 85
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 826-1010 8.06e-44

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 157.08  E-value: 8.06e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  826 IAKEILTTERTYLKDLEVITVWFRSAVIKENAMPEGLMTLLFSNIDPIYEFHRGFLkeLDQRLALWEgrsnahvkgDYQR 905
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLKEWI---------SIQR 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  906 IGDVMLKNMCALKEFTSYLQKHDEVLTELEKASKRLKKLETVYKEFELQKVCY-LPLNTFLLKPIQRLMHYKLILERLCK 984
Cdd:pfam00621   70 IGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRgLDLNSFLIKPVQRIPRYPLLLKELLK 149

                          170       180
                   ....*....|....*....|....*.
gi 2039782227  985 HYSPGHRDYYDCKEALKEVADIATQL 1010
Cdd:pfam00621  150 HTPPDHPDYEDLKKALEAIKEVAKQI 175
FERM_F1_FARP1_like cd17098
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, RhoGEF and ...
 50-134 1.33e-34

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, RhoGEF and pleckstrin domain-containing protein 1 (FARP1) and similar proteins; This family includes the F1 sub-domain of FERM, RhoGEF and pleckstrin domain-containing proteins FARP1, FARP2, and FERM domain-containing protein 7 (FRMD7). FARP1, also termed chondrocyte-derived ezrin-like protein (CDEP), or pleckstrin homology (PH) domain-containing family C member 2 (PLEKHC2), is a neuronal activator of the RhoA GTPase. It promotes outgrowth of developing motor neuron dendrites. It also regulates excitatory synapse formation and morphology, as well as activates the GTPase Rac1 to promote F-actin assembly. FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. All family members contain a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340618  Cd Length: 85  Bit Score: 127.33  E-value: 1.33e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKF 129
Cdd:cd17098      1 LHVKVQMLDDTVHIFQVQQKALGEVLFDQVCKHLNLLESDYFGLEFTDPEGNKCWLDPEKPILRQVKRPKDVVFKFVVKF 80


                   ....*
gi 2039782227  130 FPPDP 134
Cdd:cd17098     81 YTPDP 85
FERM_C_PTPN4_PTPN3_like cd13189
FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 3 and 4 (PTPN4 and ...
 234-328 2.60e-31

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 3 and 4 (PTPN4 and PTPN3); PTPN4 (also called PTPMEG, protein tyrosine phosphatase, megakaryocyte) is a cytoplasmic protein-tyrosine phosphatase (PTP) thought to play a role in cerebellar function. PTPMEG-knockout mice have impaired memory formation and cerebellar long-term depression. PTPN3/PTPH1 is a membrane-associated PTP that is implicated in regulating tyrosine phosphorylation of growth factor receptors, p97 VCP (valosin-containing protein, or Cdc48 in Saccharomyces cerevisiae), and HBV (Hepatitis B Virus) gene expression; it is mutated in a subset of colon cancers. PTPMEG and PTPN3/PTPH1 contains a N-terminal FERM domain, a middle PDZ domain, and a C-terminal phosphatase domain. PTP1/Tyrosine-protein phosphatase 1 from nematodes and a FERM_C repeat 1 from Tetraodon nigroviridis are also included in this cd. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270010  Cd Length: 95  Bit Score: 118.18  E-value: 2.60e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  234 MYGIRFHPAADREGTKINLAVAHMGLQVFQGNIRINTFNWSKIRKLSFKRKRFLIKLHPEVHGPHQDTLEFMMASRDQCK 313
Cdd:cd13189      1 LYGVELHSARDSNNLELQIGVSSAGILVFQNGIRINTFPWSKIVKISFKRKQFFIQLRREPNESRDTILGFNMLSYRACK 80

                           90
                   ....*....|....*
gi 2039782227  314 IFWKICVEYHSFFRL 328
Cdd:cd13189     81 NLWKSCVEHHTFFRL 95
FERM_C pfam09380
FERM C-terminal PH-like domain;
244-328 1.17e-30

FERM C-terminal PH-like domain;


Pssm-ID: 462779 [Multi-domain]  Cd Length: 85  Bit Score: 115.81  E-value: 1.17e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  244 DREGTKINLAVAHMGLQVFQGNIRI-NTFNWSKIRKLSFKRKRFLIKLHpevHGPHQDTLEFMMASRDQCKIFWKICVEY 322
Cdd:pfam09380    1 DKEGTDLWLGVSAKGILVYEDNNKIlNLFPWREIRKISFKRKKFLIKLR---DKSSEETLGFYTESSRACKYLWKLCVEQ 77


                   ....*.
gi 2039782227  323 HSFFRL 328
Cdd:pfam09380   78 HTFFRL 83
FERM_C_4_1_family cd13184
FERM domain C-lobe of Protein 4.1 family; The protein 4.1 family includes four well-defined ...
 235-328 3.51e-27

FERM domain C-lobe of Protein 4.1 family; The protein 4.1 family includes four well-defined members: erythroid protein 4.1 (4.1R), the best known and characterized member, 4.1G (general), 4.1N (neuronal), and 4.1 B (brain). The less well understood 4.1O/FRMD3 is not a true member of this family and is not included in this hierarchy. Besides three highly conserved domains, FERM, SAB (spectrin and actin binding domain) and CTD (C-terminal domain), the proteins from this family contain several unique domains: U1, U2 and U3. FERM domains like other members of the FERM domain superfamily have a cloverleaf architecture with three distinct lobes: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The brain is a particularly rich source of protein 4.1 isoforms. The various 4.1R, 4.1G, 4.1N, and 4.1B mRNAs are all expressed in distinct patterns within the brain. It is likely that 4.1 proteins play important functional roles in the brain including motor coordination and spatial learning, postmitotic differentiation, and synaptic architecture and function. In addition they are found in nonerythroid, nonneuronal cells where they may play a general structural role in nuclear architecture and/or may interact with splicing factors. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270005  Cd Length: 94  Bit Score: 106.25  E-value: 3.51e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  235 YGIRFHPAADREGTKINLAVAHMGLQVFQGNIRINTFNWSKIRKLSFKRKRFLIKLHPEVHGPHQDTLEFMMASRDQCKI 314
Cdd:cd13184      1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEQYETTIGFKLPNHRAAKR 80

                           90
                   ....*....|....
gi 2039782227  315 FWKICVEYHSFFRL 328
Cdd:cd13184     81 LWKVCVEHHTFFRL 94
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
 1030-1161 1.14e-25

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 103.12  E-value: 1.14e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1030 LIGIENLTAPGREFIREGCLYKLTKKGLQQRMFFLFSDMLLYTSKgVTATNQFKVHGQLPLHGMilivldaPVEESENEw 1109
Cdd:cd13389      1 LLGQYNIVKPGRKLIKEGELMKVSRKEMQPRYFFLFNDCLLYTTP-VQSSGMLKLNNELPLSGM-------KVKLPEDE- 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2039782227 1110 SVPHCFTIYSAQRTIVVAASSKVEMGKWIEDLNMAIDMAKKSQekSSFLLDR 1161
Cdd:cd13389     72 EYSNEFQIISTKRSFTLIASSEEERDEWVKALSRAIEEHTKKQ--RTFAENV 121
FERM_F1_FRMD7 cd17188
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM ...
 50-134 2.08e-24

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 7 (FRMD7); FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. It interacts with the Rho GTPase regulator, RhoGDIalpha, and activates the Rho subfamily member Rac1, which regulates reorganization of actin filaments and controls neuronal outgrowth. Mutations in the FRMD7 gene are responsible for the X-linked idiopathic congenital nystagmus (ICN), a disease which affects ocular motor control. FRMD7 contains a FERM domain, and a pleckstrin homology (PH) domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340708  Cd Length: 86  Bit Score: 98.34  E-value: 2.08e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKF 129
Cdd:cd17188      2 LHLKVQFLDDSQKVFVVDQKSTGKDLFNMSCSHLNLVEKEYFGLEFRNHAGNNVWLELLKPITKQIKNPKELIFKFTVKF 81


                   ....*
gi 2039782227  130 FPPDP 134
Cdd:cd17188     82 FPVDP 86
FERM_F1_FARP1 cd17189
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF ...
 50-133 1.25e-23

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF and pleckstrin domain-containing protein 1 (FARP1); FARP1, also termed chondrocyte-derived ezrin-like protein (CDEP), or pleckstrin homology (PH) domain-containing family C member 2 (PLEKHC2), is a neuronal activator of the RhoA GTPase. It promotes outgrowth of developing motor neuron dendrites. It also regulates excitatory synapse formation and morphology, as well as activates the GTPase Rac1 to promote F-actin assembly. As a novel downstream signaling partner of Rif, FARP1 is involved in the regulation of semaphorin signaling in neurons. FARP1 contains a FERM domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340709  Cd Length: 85  Bit Score: 96.03  E-value: 1.25e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKF 129
Cdd:cd17189      1 VPIKVQMLDDTQEVFEVPQRAPGKVLLDAVCSHLNLVEGDYFGLEFQDHRKVMVWLDLLKPIVKQIRRPKHVVLRFVVKF 80


                   ....
gi 2039782227  130 FPPD 133
Cdd:cd17189     81 FPPD 84
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 132-240 1.29e-22

FERM central domain; This domain is the central structural domain of the FERM domain.


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 94.26  E-value: 1.29e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  132 PDPGQLQEEYTRYLFSLQMKRDLMEGRLICTENTGALLASHLVQSEIGDYDD-IADREFLRVNKLLPYQ-------DKVQ 203
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPsSHTSEYLSLESFLPKQllrkmksKELE 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 2039782227  204 ERIMEFHRRHLGQTPAESDFQILEIARKLEMYGIRFH 240
Cdd:pfam00373   81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
FERM_B-lobe cd14473
FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C ...
 142-232 2.02e-22

FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 271216  Cd Length: 99  Bit Score: 93.08  E-value: 2.02e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  142 TRYLFSLQMKRDLMEGRLICTENTGALLASHLVQSEIGDYD-DIADREFLRVNKLLPYQ-------DKVQERIMEFHRRH 213
Cdd:cd14473      1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDpSEHKPKYLSLKRFLPKQllkqrkpEEWEKRIVELHKKL 80

                           90
                   ....*....|....*....
gi 2039782227  214 LGQTPAESDFQILEIARKL 232
Cdd:cd14473     81 RGLSPAEAKLKYLKIARKL 99
FERM_F0_F1 cd01765
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain and F1 sub-domain, found ...
 50-129 9.57e-20

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain and F1 sub-domain, found in FERM (Four.1/Ezrin/Radixin/Moesin) family proteins; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain is present at the N-terminus of a large and diverse group of proteins that mediate linkage of the cytoskeleton to the plasma membrane. FERM-containing proteins are ubiquitous components of the cytocortex and are involved in cell transport, cell structure and signaling functions. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N), which is structurally similar to ubiquitin.


Pssm-ID: 340464  Cd Length: 80  Bit Score: 84.56  E-value: 9.57e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKF 129
Cdd:cd01765      1 ISCRVRLLDGTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNDGQKHWLDLDKKISKQLKRSGPYQFYFRVKF 80
FERM_C_FRMD3_FRMD5 cd13192
FERM domain C-lobe of FERM domain-containing protein 3 and 5 (FRMD3 and 5); FRMD3 (also called ...
 219-327 5.56e-19

FERM domain C-lobe of FERM domain-containing protein 3 and 5 (FRMD3 and 5); FRMD3 (also called Band 4.1-like protein 4O/4.1O though it is not a true member of that family) is a novel putative tumor suppressor gene that is implicated in the origin and progression of lung cancer. In humans there are 5 isoforms that are produced by alternative splicing. Less is known about FRMD5, though there are 2 isoforms of the human protein are produced by alternative splicing. Both FRMD3 and FRMD5 contain a N-terminal FERM domain, followed by a FERM adjacent (FA) domain, and 4.1 protein C-terminal domain (CTD). The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270013  Cd Length: 105  Bit Score: 83.60  E-value: 5.56e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  219 AESDFqiLEIARKLEMYGIRFHPAADREGTKINLAVAHMGLQVFQGNIRINTFNWSKIRKLSFKRKRFLIKLHpeVHGPH 298
Cdd:cd13192      1 AEDNF--LRKAATLETYGVDPHPVKDHRGNQLYLGFTHTGIVTFQGGKRVHHFRWNDITKFNYEGKMFILHVM--QKEEK 76

                           90       100
                   ....*....|....*....|....*....
gi 2039782227  299 QDTLEFMMASRDQCKIFWKICVEYHSFFR 327
Cdd:cd13192     77 KHTLGFKCPTPAACKHLWKCAVEQQAFYT 105
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 1226-1319 2.45e-18

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 81.55  E-value: 2.45e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1226 LSGYLLRK----FKNsngWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKL-QFKSHVYFF 1300
Cdd:cd13248      9 MSGWLHKQggsgLKN---WRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKAeHANMRTYYF 85

                           90
                   ....*....|....*....
gi 2039782227 1301 RAESEYTFERWMEVIKSAA 1319
Cdd:cd13248     86 AADTAEEMEQWMNAMSLAA 104
PH1_FGD6 cd15793
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin ...
 1030-1150 2.75e-18

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275436  Cd Length: 123  Bit Score: 82.00  E-value: 2.75e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1030 LIGIENLTAPGREFIREGCLYKLTKKGLQQRMFFLFSDMLLYTSKgvTATNQFKVHGQLPLHGMiliVLDAPVEES-ENE 1108
Cdd:cd15793      1 LNGHHEIVQPGRVFLKEGTLMKLSRKVMQPRMFFLFNDALLYTTP--VQSGMYKLNNMLSLAGM---KVSKPSQEAyQNE 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2039782227 1109 wsvphcFTIYSAQRTIVVAASSKVEMGKWIEDLNMAID-MAKK 1150
Cdd:cd15793     76 ------LNIESVERSFILSASSATERDEWLEAISRAIEeYAKK 112
FERM_F1_EPB41L5_like cd17108
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte ...
 50-130 3.78e-18

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like 5 (EPB41L5) and similar proteins; This family includes FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like proteins, EPB41L5 and EPB41L4B. EPB41L5 is a mesenchymal-specific protein that is an integral component of the ARF6-based pathway. EPB41L4B is a positive regulator of keratinocyte adhesion and motility, suggesting a role in wound healing. It also promotes cancer metastasis in melanoma, prostate cancer and breast cancer. Both EPB41L5 and EPB41L4B contain a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340628  Cd Length: 81  Bit Score: 80.09  E-value: 3.78e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVR-RPANTlFRLSVK 128
Cdd:cd17108      1 IQCKVILLDGTDLSIELPKKAKGQELYEQVFYHLDLIEKDYFGLQFMDAAQVQHWLDPTKKIKKQVKiGPPYT-LRFRVK 79


                   ..
gi 2039782227  129 FF 130
Cdd:cd17108     80 FY 81
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1226-1320 1.09e-17

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 79.51  E-value: 1.09e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  1226 LSGYLLRKFKNSN-GWQKLWVVFTNFCLFFYKTHQ---DDFPLASLPLLGYTVSTPEESDSIHKEYVFKLQFKS-HVYFF 1300
Cdd:smart00233    3 KEGWLYKKSGGGKkSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDrKTLLL 82

                            90       100
                    ....*....|....*....|
gi 2039782227  1301 RAESEYTFERWMEVIKSAAS 1320
Cdd:smart00233   83 QAESEEEREKWVEALRKAIA 102
FERM_C-lobe cd00836
FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N ...
 236-327 1.79e-17

FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 275389  Cd Length: 93  Bit Score: 78.57  E-value: 1.79e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  236 GIRFHPAADRE--GTKINLAVAHMGLQVFQGN--IRINTFNWSKIRKLSFKR-KRFLIKLHPEvhgPHQDTLEFMMASRd 310
Cdd:cd00836      1 GVEFFPVKDKSkkGSPIILGVNPEGISVYDELtgQPLVLFPWPNIKKISFSGaKKFTIVVADE---DKQSKLLFQTPSR- 76

                           90
                   ....*....|....*..
gi 2039782227  311 QCKIFWKICVEYHSFFR 327
Cdd:cd00836     77 QAKEIWKLIVGYHRFLL 93
FERM_F1_PTPN3_like cd17100
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein ...
 50-130 4.79e-17

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 3 (PTPN3) and similar proteins; This family includes two tyrosine-protein phosphatase non-receptors, PTPN3 and PTPN4, both of which belong to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a conserved N-terminal FERM domain, a PDZ domain, and a C-terminal PTP catalytic domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340620  Cd Length: 86  Bit Score: 77.35  E-value: 4.79e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQM---NWVWLEPTKPVAKQVRRPANTLFRLS 126
Cdd:cd17100      2 VRCIVHFLDDTEQTFEVEKRDKGQVLLDKVFNHLELVEKDYFGLQFSDDSPatdSMRWLDPLKPIRKQIKGGPPYYLNFR 81


                   ....
gi 2039782227  127 VKFF 130
Cdd:cd17100     82 VKFY 85
FERM_N pfam09379
FERM N-terminal domain; This domain is the N-terminal ubiquitin-like structural domain of the ...
 57-116 7.06e-17

FERM N-terminal domain; This domain is the N-terminal ubiquitin-like structural domain of the FERM domain.


Pssm-ID: 430570  Cd Length: 63  Bit Score: 76.09  E-value: 7.06e-17
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   57 LDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVR 116
Cdd:pfam09379    4 LDGTVLEFDVQPKATGQVLLDQVCNHLNLKEKDYFGLQFLDDNGEHRWLDLSKRLSKQAP 63
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
 1226-1315 1.84e-16

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin homology (PH) domain, C-terminus; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270057  Cd Length: 91  Bit Score: 75.91  E-value: 1.84e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1226 LSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKLQFKSHVYF-FRAES 1304
Cdd:cd13237      1 MSGYLQRRKKSKKSWKRLWFVLKDKVLYTYKASEDVVALESVPLLGFTVVTIDESFEEDESLVFQLLHKGQLPIiFRADD 80

                           90
                   ....*....|.
gi 2039782227 1305 EYTFERWMEVI 1315
Cdd:cd13237     81 AETAQRWIEAL 91
FERM_C_NBL4_NBL5 cd13186
FERM domain C-lobe of Novel band 4.1-like protein 4 and 5 (NBL4 and 5); NBL4 (also called ...
 236-327 9.82e-16

FERM domain C-lobe of Novel band 4.1-like protein 4 and 5 (NBL4 and 5); NBL4 (also called Erythrocyte protein band 4.1-like 4; Epb4 1l4) plays a role the beta-catenin/Tcf signaling pathway and is thought to be involved in establishing the cell polarity or proliferation. NBL4 may be also involved in adhesion, in cell motility and/or in cell-to-cell communication. No role for NBL5 has been proposed to date. Both NBL4 and NBL5 contain a N-terminal FERM domain which has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe is a member of the PH superfamily. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270007  Cd Length: 92  Bit Score: 73.86  E-value: 9.82e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  236 GIRFHPAADREGTKINLAVAHMGLQVFQGNIRINTFNWSKIRKLSFKRKRFLIKLHPEVHGPHQDTLEFMMASRDQCKIF 315
Cdd:cd13186      1 GVDLHPVKGEDGNEYFLGLTPTGILVFENKTKIGLFFWPRITKLDFKGKKLKLVVKEKDDQEQEHTFVFRLPNKKACKHL 80

                           90
                   ....*....|..
gi 2039782227  316 WKICVEYHSFFR 327
Cdd:cd13186     81 WKCAVEHHAFFR 92
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
 1036-1142 1.03e-15

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 74.60  E-value: 1.03e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1036 LTAPGREFIREGCLYKLTKKGLQQRMFFLFSDMLLYTSkGVTATNQFKVHGQLPLHGMILivldAPVEESENEwsvPHCF 1115
Cdd:cd01218     23 LVKPGRVLVGEGVLTKVCRKKPKPRQFFLFNDILVYGS-IVINKKKYNKQRIIPLEDVKI----EDLEDTGEL---KNGW 94

                           90       100
                   ....*....|....*....|....*..
gi 2039782227 1116 TIYSAQRTIVVAASSKVEMGKWIEDLN 1142
Cdd:cd01218     95 QIISPKKSFVVYAATATEKSEWMDHIN 121
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
 1216-1319 1.22e-15

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270056  Cd Length: 105  Bit Score: 73.92  E-value: 1.22e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1216 SDHSLavenqLSGYLlRKFKNSNGWQKLWVVFTN---FCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKLQ 1292
Cdd:cd13236      5 PENSL-----LCGFL-QYSEKGKTWQKVWCVIPRtepLVLYLYGAPQDVRAQRTIPLPGCEVTVPPPEERLDGRHVFKLS 78

                           90       100
                   ....*....|....*....|....*..
gi 2039782227 1293 FKSHVYFFRAESEYTFERWMEVIKSAA 1319
Cdd:cd13236     79 QSKQSHYFSAESEELQQRWLEALSRAA 105
FERM_F1_EPB41L cd17106
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte ...
 51-133 2.09e-15

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like proteins; The family includes erythrocyte membrane protein band 4.1-like proteins EPB41L1/4.1N, EPB41L2/4.1G, and EPB41L3/4.1B. They belong to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L1 is a cytoskeleton-associated protein that may serve as a tumor suppressor in solid tumors. EPB41L2 is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L3 also acts as a tumor suppressor implicated in a variety of meningiomas and carcinomas. Members in this family contain a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340626  Cd Length: 84  Bit Score: 72.47  E-value: 2.09e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   51 QIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRpANTLFRLSVKFF 130
Cdd:cd17106      3 QCKVLLLDGTEYTCEVEKRAKGQVLFDKVCEHLNLLEKDYFGLTYRDAQDQKNWLDPAKEIKKQIRS-GPWLFSFNVKFY 81


                   ...
gi 2039782227  131 PPD 133
Cdd:cd17106     82 PPD 84
FERM_F1_EPB41L3 cd17203
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte ...
 50-133 2.60e-15

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 3 (EPB41L3) and similar proteins; EPB41L3, also termed 4.1B, or differentially expressed in adenocarcinoma of the lung protein 1 (DAL-1), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L3 is a tumor suppressor that has been implicated in a variety of meningiomas and carcinomas. EPB41L3 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340723  Cd Length: 84  Bit Score: 72.28  E-value: 2.60e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTlFRLSVKF 129
Cdd:cd17203      2 MQCKVTLLDGSEYTCEVEKRSKGQVLFDKVCEHLNLLEKDYFGLTYRDSENQKNWLDPAKEIKKQIRSGAWQ-FSFNVKF 80


                   ....
gi 2039782227  130 FPPD 133
Cdd:cd17203     81 YPPD 84
FERM_F1_EPB41L2 cd17202
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte ...
 50-133 3.09e-15

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 2 (EPB41L2) and similar proteins; EPB41L2, also termed generally expressed protein 4.1 (4.1G), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L2 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340722  Cd Length: 84  Bit Score: 71.93  E-value: 3.09e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRpANTLFRLSVKF 129
Cdd:cd17202      2 VLCKVTLLDGTEYSCDLEKRAKGQVLFDKVCEHLNLLEKDYFGLLYQVSANQKNWLDSTKEIKRQIRR-LPWLFTFNVKF 80


                   ....
gi 2039782227  130 FPPD 133
Cdd:cd17202     81 YPPD 84
FERM_F1_EPB41 cd17105
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte ...
 50-133 5.25e-15

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1 (EPB41) and similar proteins; EPB41, also termed protein 4.1 (P4.1), or 4.1R, or Band 4.1, or EPB4.1, belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41 is a widely expressed cytoskeletal phosphoprotein that stabilizes the spectrin-actin cytoskeleton and anchors the cytoskeleton to the cell membrane. EPB41 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340625  Cd Length: 83  Bit Score: 71.38  E-value: 5.25e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRR-PANtlFRLSVK 128
Cdd:cd17105      1 MHCKVSLLDDTVYECEVEKHAKGQDLFKKVCEHLNLLEEDYFGLAIWDSPTSKTWLDPAKEIKKQVHGgPWE--FTFNVK 78


                   ....*
gi 2039782227  129 FFPPD 133
Cdd:cd17105     79 FYPPD 83
FA pfam08736
FERM adjacent (FA); This region is found adjacent to Band 4.1 / FERM domains (pfam00373) in a ...
 340-381 1.09e-14

FERM adjacent (FA); This region is found adjacent to Band 4.1 / FERM domains (pfam00373) in a subset of FERM containing protein. The region has been hypothesized to play a role in regulatory adaptation, based on similarity to other protein kinase substrates.


Pssm-ID: 462582  Cd Length: 44  Bit Score: 69.11  E-value: 1.09e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2039782227  340 LFTRGSSFRYSGRTQKQLVDYVRENGSKRTPYQRRNSKIRMS 381
Cdd:pfam08736    2 FFSLGSKFRYSGRTQKQTVEDSSEILRPQPEFERSPSKRYPS 43
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1227-1320 1.30e-14

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 71.05  E-value: 1.30e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKFK-NSNGWQKLWVVFTNFCLFFYK---THQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKL----QFKSHVY 1298
Cdd:pfam00169    4 EGWLLKKGGgKKKSWKKRYFVLFDGSLLYYKddkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELrtgeRTGKRTY 83

                           90       100
                   ....*....|....*....|..
gi 2039782227 1299 FFRAESEYTFERWMEVIKSAAS 1320
Cdd:pfam00169   84 LLQAESEEERKDWIKAIQSAIR 105
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1043-1146 2.09e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 70.27  E-value: 2.09e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  1043 FIREGCLYKLT---KKGLQQRMFFLFSDMLLYTSKGvTATNQFKVHGQLPLHGMILIVLDAPVEESEnewsvPHCFTIYS 1119
Cdd:smart00233    1 VIKEGWLYKKSgggKKSWKKRYFVLFNSTLLYYKSK-KDKKSYKPKGSIDLSGCTVREAPDPDSSKK-----PHCFEIKT 74

                            90       100
                    ....*....|....*....|....*...
gi 2039782227  1120 AQR-TIVVAASSKVEMGKWIEDLNMAID 1146
Cdd:smart00233   75 SDRkTLLLQAESEEEREKWVEALRKAIA 102
FERM_F1_EPB41L1 cd17201
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte ...
 53-133 1.72e-13

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 1 (EPB41L1) and similar proteins; EPB41L1, also termed neuronal protein 4.1 (4.1N), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. It is a cytoskeleton-associated protein that may serve as a tumor suppressor in solid tumors. It suppresses hypoxia-induced epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) cells. The down-regulation of EPB41L1 expression is a critical step for non-small cell lung cancer (NSCLC) development. Moreover, EPB41L1 functions as a linker protein between inositol 1,4,5-trisphosphate receptor type1 (IP3R1) and actin filaments in neurons. EPB41L1 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340721  Cd Length: 84  Bit Score: 67.22  E-value: 1.72e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   53 RVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTlFRLSVKFFPP 132
Cdd:cd17201      5 KVTLLDGSEYECEVEKHARGQVLFDTVCEHLNLLEKDYFGLTFCDTESQKNWLDPSKEIKKQIRSGPWH-FAFTVKFYPP 83


                   .
gi 2039782227  133 D 133
Cdd:cd17201     84 D 84
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 1226-1315 1.03e-12

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 65.26  E-value: 1.03e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1226 LSGYLLRK-FKNSNGWQKLWVVFTNFCLFFYKTHQDD--FPLASLPLLGytVSTPEESDSIHKEYVFKLQFKSH-VYFFR 1301
Cdd:cd00821      1 KEGYLLKRgGGGLKSWKKRWFVLFEGVLLYYKSKKDSsyKPKGSIPLSG--ILEVEEVSPKERPHCFELVTPDGrTYYLQ 78

                           90
                   ....*....|....
gi 2039782227 1302 AESEYTFERWMEVI 1315
Cdd:cd00821     79 ADSEEERQEWLKAL 92
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
 1045-1139 6.33e-12

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275410  Cd Length: 92  Bit Score: 62.89  E-value: 6.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1045 REGCLYKLTKKG--LQQRMFFLFSDMLLYTSKGVTATNQ-FKVHGQLPLHGMilivldaPVEESENEwSVPHCFTIYSAQ 1121
Cdd:cd13328      1 KEGQILKLSAKNgtPQPRYLFLFNDMLLYCVPKLSLVGQkFSVRNRLDVAGM-------KVREPVNE-NYPHTFKISGKE 72

                           90
                   ....*....|....*...
gi 2039782227 1122 RTIVVAASSKVEMGKWIE 1139
Cdd:cd13328     73 RSLELQASSAEEKDEWIQ 90
FERM_F1_PTPN4 cd17194
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein ...
 57-130 9.71e-11

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 4 (PTPN4); PTPN4, also termed protein-tyrosine phosphatase MEG1 (MEG) or PTPase-MEG1, belongs to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a conserved N-terminal FERM domain, a PDZ domain, and a C-terminal PTP catalytic domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PTPN4 protects cells against apoptosis. It associates with the mitogen-activated protein kinase p38gamma (also known as MAPK12) to form a PTPN4-p38gamma complex that promotes cellular signaling, preventing cell death induction. It also inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRIF-related adaptor molecule (TRAM, also known as TICAM2), resulting in the disturbance of TRAM-TRIF interaction. Moreover, PTPN4 negatively regulates cell proliferation and motility through dephosphorylation of CrkI.


Pssm-ID: 340714  Cd Length: 84  Bit Score: 59.16  E-value: 9.71e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2039782227   57 LDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQM-NWVWLEPTKPVAKQVRR--PANTLFRlsVKFF 130
Cdd:cd17194      9 LDNTVQAFKVNKHDQGQVLLDLVFKHLDLTERDYFGLQLADDSTdNPRWLDPNKPIRKQLKRgsPHNLNFR--VKFF 83
FERM_F1_FRMD3 cd17102
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM ...
 57-130 1.47e-10

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 3 (FRMD3) and similar proteins; FRMD3, also termed band 4.1-like protein 4O, or ovary type protein 4.1 (4.1O), belongs to the 4.1 protein superfamily, which share the highly conserved membrane-association FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). FRMD3 is involved in maintaining cell shape and integrity. It also functions as a tumour suppressor in non-small cell lung carcinoma (NSCLC). Some single nucleotide polymorphisms (SNPs) located in FRMD3 have been associated with diabetic kidney disease (DKD) in different ethnicities.


Pssm-ID: 340622  Cd Length: 82  Bit Score: 58.79  E-value: 1.47e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2039782227   57 LDDSQEFFDI-DPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKFF 130
Cdd:cd17102      8 LDDSEVICCEfKKDTKGQFLLDYVCNYLNLLEKDYFGLRYVDTEKQRHWLDPNKSIYKQLKGVPPYVLCFRVKFY 82
PH1_FGD5 cd15792
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin ...
 1032-1157 4.15e-10

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275435  Cd Length: 123  Bit Score: 58.70  E-value: 4.15e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1032 GIENLTAPGREFIREGCLYKLTKKGLQQRMFFLFSDMLLYTSKgvTATNQFKVHGQLPLHGMiliVLDAPVEEsenewSV 1111
Cdd:cd15792      3 GQRDLLQPGREFVKEGTLMKVSGKNRHPRHLFLMNDVLLYTYP--QKDGKYRLKNTLAVSGM---KVSRPVIE-----KA 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2039782227 1112 PHCFTIYSAQRTIVVAASSKVEMGKWIEDLNMAIDMAKKSQEKSSF 1157
Cdd:cd15792     73 QNVLKIEVSEVCLTLSASSCSERDEWYSCLSRTIPDDYKAQNASSS 118
FERM_F1_MYLIP cd17104
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in E3 ...
 65-130 4.27e-10

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in E3 ubiquitin-protein ligase MYLIP and similar proteins; MYLIP, also termed inducible degrader of the LDL-receptor (Idol), or myosin regulatory light chain interacting protein (MIR), is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Its activity depends on E2 ubiquitin-conjugating enzymes of the UBE2D family, including UBE2D1, UBE2D2, UBE2D3, and UBE2D4. MYLIP stimulates clathrin-independent endocytosis and acts as a sterol-dependent inhibitor of cellular cholesterol uptake by binding directly to the cytoplasmic tail of the LDLR and promoting its ubiquitination via the UBE2D1/E1 complex. The ubiquitinated LDLR then enters the multivesicular body (MVB) protein-sorting pathway and is shuttled to the lysosome for degradation. Moreover, MYLIP has been identified as a novel ERM-like protein that affects cytoskeleton interactions regulating cell motility, such as neurite outgrowth. The ERM proteins includes ezrin, radixin, and moesin, which are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. MYLIP contains a FERM-domain and a C-terminal C3HC4-type RING-HC finger. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340624  Cd Length: 81  Bit Score: 57.28  E-value: 4.27e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2039782227   65 DIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKFF 130
Cdd:cd17104     16 EVDPKANGQECLDKVCQKLGIIEKDYFGLQYTGPKGERLWLNLRNRISRQLPGPPPYRLRLRVKFF 81
FERM_F1_EPB41L5 cd17205
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte ...
 50-130 4.44e-10

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like 5 (EPB41L5); EPB41L5 is a mesenchymal-specific protein that is an integral component of the ARF6-based pathway. It is normally induced during epithelial-mesenchymal transition (EMT) by an EMT-related transcriptional factor, ZEB1, which drives ARF6-based invasion, metastasis and drug resistance. EPB41L5 also binds to paxillin to enhance integrin/paxillin association, and thus promotes focal adhesion dynamics. Moreover, EPB41L5 acts as a substrate for the E3 ubiquitin ligase Mind bomb 1 (Mib1), which is essential for activation of Notch signaling. EPB41L5 is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It contains a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340725  Cd Length: 86  Bit Score: 57.36  E-value: 4.44e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTLFRLSVKF 129
Cdd:cd17205      3 ITCRVSLLDGTDVSVDLPKKAKGQELFEQIMYHLDLIEKDYFGLRFMDSAQVAHWLDVTKSIKKQVKIGPPYCLHLRVKF 82


                   .
gi 2039782227  130 F 130
Cdd:cd17205     83 Y 83
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 1045-1141 6.20e-10

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 57.17  E-value: 6.20e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1045 REGCLYKLT---KKGLQQRMFFLFSDMLLYTSKGVTATNQFKvhgqlplhGMILIVLDAPVEESENEwSVPHCFTIYSA- 1120
Cdd:cd00821      1 KEGYLLKRGgggLKSWKKRWFVLFEGVLLYYKSKKDSSYKPK--------GSIPLSGILEVEEVSPK-ERPHCFELVTPd 71

                           90       100
                   ....*....|....*....|.
gi 2039782227 1121 QRTIVVAASSKVEMGKWIEDL 1141
Cdd:cd00821     72 GRTYYLQADSEEERQEWLKAL 92
PH2_FGD4_insect-like cd13238
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...
 1226-1312 8.91e-10

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) domain, C-terminus, in insect and related arthropods; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. This cd contains insects, crustaceans, and chelicerates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270058  Cd Length: 97  Bit Score: 56.89  E-value: 8.91e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1226 LSGYLLRKFKNSNGWQKLWVVF-TNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSI------HKEYVFKLQFKSHVY 1298
Cdd:cd13238      1 LSGYLKLKTNGRKTWSRRWFALqPDFVLYSYKSQEDKLPLTATPVPGFLVTLLEKGSAVdplndpKRPRTFKMFHVKKSY 80

                           90
                   ....*....|....
gi 2039782227 1299 FFRAESEYTFERWM 1312
Cdd:cd13238     81 YFQANDGDEQKKWV 94
FERM_F1_EPB41L4A cd17107
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band ...
 48-133 1.97e-09

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band 4.1-like protein 4A (EPB41L4A) and similar proteins; EPB41L4A, also termed protein NBL4, is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It contains a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). EPB41L4A is an important component of the beta-catenin/Tcf pathway. It may be related to determination of cell polarity or proliferation.


Pssm-ID: 340627  Cd Length: 91  Bit Score: 55.81  E-value: 1.97e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   48 RGIQIRVYGLDDSQEFFDIDPKAL----GQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRR--PANT 121
Cdd:cd17107      1 EEFYCEIVLLDESELILTIQQDGIksskGSVVLDVVFQHLNLLETDYFGLRYIDRQHQTHWLDPAKTLSEQLKLigPPYT 80

                           90
                   ....*....|..
gi 2039782227  122 LFrLSVKFFPPD 133
Cdd:cd17107     81 LY-FGVKFYAED 91
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 1226-1322 3.17e-09

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 55.71  E-value: 3.17e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1226 LSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDsiHKEYVFKLQFKSHVYFFRAESE 1305
Cdd:cd13298      8 KSGYLLKRSRKTKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVAPLKDK--KRKNVFGIYTPSKNLHFRATSE 85

                           90
                   ....*....|....*..
gi 2039782227 1306 YTFERWMEVIKSAASTT 1322
Cdd:cd13298     86 KDANEWVEALREEFRLD 102
PH1_FGD2 cd13386
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin ...
 1043-1153 3.63e-09

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275421  Cd Length: 108  Bit Score: 55.69  E-value: 3.63e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1043 FIREGCLYKLT--KKGLQQRMFFLFSDMLLY-TSKGVTATNQFKVHgqlplhgMILIVLDAPVEESeNEWSVPHCFTIYS 1119
Cdd:cd13386      1 LLKEGPVLKISfrNNNPKERYLFLFNNMLLYcVPKVIQVGAKFQVH-------MRIDVDGMKVREL-NDAEFPHSFLVSG 72

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2039782227 1120 AQRTIVVAASSKVEMGKWIEDLNMAIDMAKKSQE 1153
Cdd:cd13386     73 KQRTLELQARSQEEMEAWIQAFQEAIDQNEKRTE 106
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 1226-1315 4.21e-09

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from insects, spiders, mollusks, and nematodes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270135  Cd Length: 91  Bit Score: 54.66  E-value: 4.21e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1226 LSGYLLRKFKNSNG---WQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSihKEYVFKLQFKSHVYFFRA 1302
Cdd:cd13326      1 YQGWLYQRRRKGKGggkWAKRWFVLKGSNLYGFRSQESTKADCVIFLPGFTVSPAPEVKS--RKYAFKVYHTGTVFYFAA 78

                           90
                   ....*....|...
gi 2039782227 1303 ESEYTFERWMEVI 1315
Cdd:cd13326     79 ESQEDMKKWLDLL 91
FERM_F1_PTPN3 cd17193
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein ...
 54-130 4.75e-09

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 3 (PTPN3); PTPN3, also termed protein-tyrosine phosphatase H1 (PTP-H1), belongs to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a conserved N-terminal FERM domain, a PDZ domain, and a C-terminal PTP catalytic domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PTPN3 associates with the mitogen-activated protein kinase p38gamma (also known as MAPK12) to form a PTPN3-p38gamma complex that promotes Ras-induced oncogenesis. It may also act as a tumor suppressor in lung cancer through its modulation of epidermal growth factor receptor (EGFR) signaling. Moreover, PTPN3 shows sensitizing effect to anti-estrogens. It dephosphorylates the tyrosine kinase EGFR, disrupts its interaction with the nuclear estrogen receptor, and increases breast cancer sensitivity to small molecule tyrosine kinase inhibitors (TKIs). It also cooperates with vitamin D receptor to stimulate breast cancer growth through their mutual stabilization.


Pssm-ID: 340713  Cd Length: 84  Bit Score: 54.47  E-value: 4.75e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   54 VYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNW-VWLEPTKPVAKQVR--RPANTLFRlsVKFF 130
Cdd:cd17193      6 VHFLDGSVQSFKVNKQDTGQVLLDMAYNHLGLTEREYFGLQHNEDSVDSpRWLEPSKPIRKQLKggFPCSLHFR--VRFF 83
FERM_F1_EPB41L4B cd17204
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band ...
 50-130 8.09e-09

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band 4.1-like protein 4B (EPB41L4B); EPB41L4B, also termed FERM-containing protein CG1, or expressed in high metastatic cells (Ehm2), or Lulu2, is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It contains a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). EPB41L4B is a positive regulator of keratinocyte adhesion and motility, suggesting a role in wound healing. It also promotes cancer metastasis in melanoma, prostate cancer and breast cancer.


Pssm-ID: 340724  Cd Length: 84  Bit Score: 53.67  E-value: 8.09e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRR-PANTLFrLSVK 128
Cdd:cd17204      1 LTCRVLLLDGTDVSVELPKHAKGQDLFDQIVYHLDLVETDYFGLQFMDAAQVAHWLDHTKPIKKQIKIgPPYTLH-FRIK 79


                   ..
gi 2039782227  129 FF 130
Cdd:cd17204     80 YY 81
FERM_F1_PTPN14_like cd17099
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein ...
 52-130 8.71e-09

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptors PTPN14, PTPN21, and similar proteins; This family includes tyrosine-protein phosphatase non-receptors PTPN14 and PTPN21, both of which are protein-tyrosine phosphatase (PTP). They belong to the FERM family of PTPs characterized by a conserved N-terminal FERM domain and a C-terminal PTP catalytic domain with an intervening sequence containing an acidic region and a putative SH3 domain-binding sequence. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PTPN14 plays a role in the nucleus during cell proliferation. PTPN21 interacts with a Tec tyrosine kinase family member, the epithelial and endothelial tyrosine kinase (Etk, also known as Bmx), modulates Stat3 activation, and plays a role in the regulation of cell growth and differentiation.


Pssm-ID: 340619  Cd Length: 85  Bit Score: 53.77  E-value: 8.71e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   52 IRVYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANT-LFRLSVKFF 130
Cdd:cd17099      6 VRIQLLDNTVLECTLSPESTGQDCLEYVAQRLELREIEYFGLRYVNKKGQLRWVDLEKPLKKQLDKHAHEpLLYFGVMFY 85
FERM_C_ERM cd13194
FERM domain C-lobe/F3 of the ERM family; The ERM family includes ezrin, radixin, moesin and ...
 234-326 2.19e-08

FERM domain C-lobe/F3 of the ERM family; The ERM family includes ezrin, radixin, moesin and merlin. They are composed of a N-terminal FERM (ERM) domain (also called N-ERMAD (N-terminal ERM association domain)), a coiled coil region (CRR), and a C-terminal domain CERMAD (C-terminal ERM association domain) which has an F-actin-binding site (ABD). Two actin-binding sites have been identified in the middle and N-terminal domains. Merlin is structurally similar to the ERM proteins, but instead of an actin-binding domain (ABD), it contains a C-terminal domain (CTD), just like the proteins from the 4.1 family. Activated ezrin, radixin and moesin are thought to be involved in the linking of actin filaments to CD43, CD44, ICAM1-3 cell adhesion molecules, various membrane channels and receptors, such as the Na+/H+ exchanger-3 (NHE3), cystic fibrosis transmembrane conductance regulator (CFTR), and the beta2-adrenergic receptor. The ERM proteins exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain of ERM is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270015  Cd Length: 97  Bit Score: 53.05  E-value: 2.19e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  234 MYGIRFHPAADREGTKINLAVAHMGLQVFQGNIRIN---TFNWSKIRKLSFKRKRFLIKlhpeVHGPHQDTLEFMMASRD 310
Cdd:cd13194      1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTpkiGFPWSEIRNISFNDKKFVIK----PIDKKAPDFVFYSPRLR 76

                           90
                   ....*....|....*.
gi 2039782227  311 QCKIFWKICVEYHSFF 326
Cdd:cd13194     77 INKRILDLCMGNHELY 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1044-1145 2.29e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 53.34  E-value: 2.29e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1044 IREGCLYKLT---KKGLQQRMFFLFSDMLLYTSKGVTATNQFKVhGQLPLHGmiLIVLDAPVEESENEwsvPHCFTIYSA 1120
Cdd:pfam00169    2 VKEGWLLKKGggkKKSWKKRYFVLFDGSLLYYKDDKSGKSKEPK-GSISLSG--CEVVEVVASDSPKR---KFCFELRTG 75

                           90       100
                   ....*....|....*....|....*....
gi 2039782227 1121 Q----RTIVVAASSKVEMGKWIEDLNMAI 1145
Cdd:pfam00169   76 ErtgkRTYLLQAESEEERKDWIKAIQSAI 104
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
 1227-1316 4.26e-08

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 52.79  E-value: 4.26e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRK---FKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSIHKeYVFKL---QFKSHVYFF 1300
Cdd:cd13308     12 SGTLTKKggsQKTLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNRRAAEERTSKLK-FVFKIihlSPDHRTWYF 90

                           90
                   ....*....|....*.
gi 2039782227 1301 RAESEYTFERWMEVIK 1316
Cdd:cd13308     91 AAKSEDEMSEWMEYIR 106
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
 1017-1139 4.97e-08

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269931  Cd Length: 138  Bit Score: 53.03  E-value: 4.97e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1017 LENFQKLTELQRDLIG--IENLTAPGREFIREGCLYKLTKKGLQQRMFFLFSDMLLYTSKGVTATNQFKVHGQLPLHGMI 1094
Cdd:cd01224      1 MENLEKLAAWQSTVEGweGEDLSDRSSELIHSGELTKISAGRAQERTFFLFDHQLVYCKKDLLRRKNYIYKGRIDTDNME 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2039782227 1095 LIVLDAPvEESENEWSVPHCFTIYSAQR--TIVVAASSKVEMGKWIE 1139
Cdd:cd01224     81 IEDLPDG-KDDESGVTVKNAWKIYNASKnkWYVLCAKSAEEKQRWLE 126
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 1228-1318 6.38e-08

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270113  Cd Length: 108  Bit Score: 51.99  E-value: 6.38e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1228 GYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEEsDSIHKEYVFKLQF-KSHVYFFRAESEY 1306
Cdd:cd13301      7 GYLVKKGHVVNNWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTITSPCL-EYGKRPLVFKLTTaKGQEHFFQACSRE 85

                           90
                   ....*....|..
gi 2039782227 1307 TFERWMEVIKSA 1318
Cdd:cd13301     86 ERDAWAKDITKA 97
PH1_FDG4 cd15791
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin ...
 1043-1141 8.46e-08

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275434  Cd Length: 94  Bit Score: 51.15  E-value: 8.46e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1043 FIREGCLYKLTKKGL--QQRMFFLFSDMLLY-TSKGVTATNQFKVHGQLPLHGMilivldaPVEESENEwSVPHCFTIYS 1119
Cdd:cd15791      1 LIKEGQILKLAARNTsaQERYLFLFNNMLLYcVPKFSLVGSKYTVRTRIGIDGM-------KVVETQNE-DYPHTFQVSG 72

                           90       100
                   ....*....|....*....|..
gi 2039782227 1120 AQRTIVVAASSKVEMGKWIEDL 1141
Cdd:cd15791     73 KERTLELQASSEQDKEEWIKAL 94
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
 1044-1141 9.77e-08

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275423  Cd Length: 94  Bit Score: 51.17  E-value: 9.77e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1044 IREGCLYKLTKKG--LQQRMFFLFSDMLLYTS-KGVTATNQFKVHGQLPLHGMIlivldapVEESENEwSVPHCFTIYSA 1120
Cdd:cd13388      2 IKEGKILKISARNgdTQERYLFLFNDMLLYCSpRLRLIGQKYKVRARFDVDGMQ-------VLEGDNL-ETPHTFYVRGK 73

                           90       100
                   ....*....|....*....|.
gi 2039782227 1121 QRTIVVAASSKVEMGKWIEDL 1141
Cdd:cd13388     74 QRSLELQASTQEEKAEWVDAI 94
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 1227-1320 1.63e-07

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 50.37  E-value: 1.63e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLR---KFKNsngWQKLWVVFTNFCLFFYKtHQDDF---PLASLPLLGYTVSTPEESDSihkeyVFKLQFKSHVYFF 1300
Cdd:cd13282      2 AGYLTKlggKVKT---WKRRWFVLKNGELFYYK-SPNDVirkPQGQIALDGSCEIARAEGAQ-----TFEIVTEKRTYYL 72

                           90       100
                   ....*....|....*....|
gi 2039782227 1301 RAESEYTFERWMEVIKSAAS 1320
Cdd:cd13282     73 TADSENDLDEWIRVIQNVLR 92
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 1227-1317 2.55e-07

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 50.02  E-value: 2.55e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLgyTVSTPEESDSIHKEYVFKLQFKSHVYFFRAESEY 1306
Cdd:cd10573      6 EGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDTKPIRVLDLR--ECSSVQRDYSQGKVNCFCLVFPERTFYMYANTEE 83

                           90
                   ....*....|.
gi 2039782227 1307 TFERWMEVIKS 1317
Cdd:cd10573     84 EADEWVKLLKW 94
FERM_F1_ERM_like cd17097
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family ...
 59-131 3.09e-07

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins; The ezrin-radixin-moesin (ERM) family includes a group of closely related cytoskeletal proteins that play an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. They exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Merlin, which is highly related to the members of the ezrin, radixin, and moesin (ERM) protein family that are directly attached to and functionally linked with NHE1, is included in this family.


Pssm-ID: 340617  Cd Length: 83  Bit Score: 49.20  E-value: 3.09e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2039782227   59 DSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTL-FRLSVKFFP 131
Cdd:cd17097      9 DAELEFSIKPKAKGRELFDLVCRTIGLRETWYFGLQYENKKGRVAWLKPDKKVLTQDVSKNNTLkFFFLVKFYP 82
FERM_F1_Moesin cd17237
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in moesin and ...
 50-131 4.35e-07

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in moesin and similar proteins; Moesin, also termed membrane-organizing extension spike protein, is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. The C-terminal domain can fold back to bind to the FERM domain forming an autoinhibited conformation. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Moesin is involved in mitotic spindle function through stabilizing cell shape and microtubules at the cell cortex. It is required for the formation of F-actin networks that mediate endosome biogenesis or maturation and transport through the degradative pathway.


Pssm-ID: 340757  Cd Length: 84  Bit Score: 48.97  E-value: 4.35e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFfDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPV-AKQVRRPANTLFRLSVK 128
Cdd:cd17237      2 ISVRVTTMDAELEF-AIQPNTTGKQLFDQVVKTIGLREVWFFGLQYQDTKGFSTWLKLNKKVtAQDVRKESPLLFKFRAK 80


                   ...
gi 2039782227  129 FFP 131
Cdd:cd17237     81 FYP 83
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 1228-1318 8.30e-07

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 49.16  E-value: 8.30e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1228 GYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDsihkEYVFKLQF---KSHVYFFRAES 1304
Cdd:cd13288     12 GYLWKKGERNTSYQKRWFVLKGNLLFYFEKKGDREPLGVIVLEGCTVELAEDAE----PYAFAIRFdgpGARSYVLAAEN 87

                           90
                   ....*....|....
gi 2039782227 1305 EYTFERWMEVIKSA 1318
Cdd:cd13288     88 QEDMESWMKALSRA 101
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
 1228-1317 2.22e-06

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270111  Cd Length: 102  Bit Score: 47.62  E-value: 2.22e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1228 GYLLR-KFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLlgYTVSTPEESDSIHKEYVFKLQF----KShvYFFRA 1302
Cdd:cd13299     10 GYLQVlKKKGVNQWKKYWLVLRNRSLSFYKDQSEYSPVKIIPI--DDIIDVVELDPLSKSKKWCLQIitpeKR--IRFCA 85

                           90
                   ....*....|....*
gi 2039782227 1303 ESEYTFERWMEVIKS 1317
Cdd:cd13299     86 DDEESLIKWLGALKS 100
PH1_FGD3 cd13387
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin ...
 1043-1153 2.65e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275422  Cd Length: 108  Bit Score: 47.27  E-value: 2.65e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1043 FIREGCLYKLTKKG--LQQRMFFLFSDMLLYTSKGVTATNQ-FKVHGQLPLHGMilivldaPVEESENEwSVPHCFTIYS 1119
Cdd:cd13387      1 LIKEGHIQKLSAKNgtAQDRYLYLFNSMVLYCVPKLRLMGQkFSVREKIDIAGM-------QVQEIVKQ-NVPHTFTITG 72

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2039782227 1120 AQRTIVVAASSKVEMGKWIEDLNMAIDMAKKSQE 1153
Cdd:cd13387     73 KKRSLELQARTEEEKKEWIQVIQATIEKHKQNSE 106
FERM_F1_Ezrin cd17239
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Ezrin and ...
 50-131 3.06e-06

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Ezrin and similar proteins; Ezrin, also termed cytovillin, or villin-2, or p81, is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. The C-terminal domain can fold back to bind to the FERM domain forming an autoinhibited conformation. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Ezrin is a tyrosine kinase substrate that functions as a cross-linker between actin cytoskeleton and plasma membrane. It has been implicated in the regulation of the proliferation, apoptosis, adhesion, invasion, metastasis and angiogenesis of cancer cells.


Pssm-ID: 340759  Cd Length: 85  Bit Score: 46.52  E-value: 3.06e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFfDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTL-FRLSVK 128
Cdd:cd17239      3 INVRVTTMDAELEF-AIQPNTTGKQLFDQVVKTIGLREVWYFGLQYVDNKGFPTWLKLDKKVSAQEVRKENPLqFKFRAK 81


                   ...
gi 2039782227  129 FFP 131
Cdd:cd17239     82 FYP 84
PH_IQSEC cd13318
IQ motif and SEC7 domain-containing protein family Pleckstrin homology domain; The IQSEC (also ...
 1051-1145 3.19e-06

IQ motif and SEC7 domain-containing protein family Pleckstrin homology domain; The IQSEC (also called BRAG/Brefeldin A-resistant Arf-gunanine nucleotide exchange factor) family are a subset of Arf GEFs that have been shown to activate Arf6, which acts in the endocytic pathway to control the trafficking of a subset of cargo proteins including integrins and have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina. The family consists of 3 members: IQSEC1 (also called BRAG2/GEP100), IQSEC2 (also called BRAG1), and IQSEC3 (also called SynArfGEF, BRAG3, or KIAA1110). IQSEC1 interacts with clathrin and modulates cell adhesion by regulating integrin surface expression and in addition to Arf6, it also activates the class II Arfs, Arf4 and Arf5. Mutations in IQSEC2 cause non-syndromic X-linked intellectual disability as well as reduced activation of Arf substrates (Arf1, Arf6). IQSEC3 regulates Arf6 at inhibitory synapses and associates with the dystrophin-associated glycoprotein complex and S-SCAM. These members contains a IQ domain that may bind calmodulin, a PH domain that is thought to mediate membrane localization by binding of phosphoinositides, and a SEC7 domain that can promote GEF activity on ARF. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270128  Cd Length: 128  Bit Score: 47.69  E-value: 3.19e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1051 KLTKKGLQQRMFFLFSDMLLYTS----KGVTATNQFKVHgqLPLHGMilivldaPVEESENEWsVPHCFTIYSAQRTIVV 1126
Cdd:cd13318     19 KREKPGLHQREVFLFNDLLVVTKifskKKSSVTYSFRQS--FSLLGM-------QVLLFETSH-YPFGIRLTSPLDNKVL 88

                           90       100
                   ....*....|....*....|..
gi 2039782227 1127 A---ASSKVEMGKWIEDLNMAI 1145
Cdd:cd13318     89 ItfnARNESDRKKFVEDLRESI 110
PH_alsin cd13269
Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual ...
 1034-1148 5.05e-06

Alsin Pleckstrin homology (PH) domain; The ALS2 gene encodes alsin, a GEF, that has dual specificity for Rac1 and Rab5 GTPases. Alsin mutations in the form of truncated proteins are responsible for motor function disorders including juvenile-onset amyotrophic lateral sclerosis, familial juvenile primary lateral sclerosis, and infantile-onset ascending hereditary spastic paralysis. The alsin protein is widely expressed in the developing CNS including neurons of the cerebral cortex, brain stem, spinal cord, and cerebellum. Alsin contains a regulator of chromosome condensation 1 (RCC1) domain, a Rho guanine nucleotide exchanging factor (RhoGEF) domain, a PH domain, a Membrane Occupation and Recognition Nexus (MORN), a vacuolar protein sorting 9 (Vps9) domain, and a Dbl homology (DH) domain. Alsin interacts with Rab5 through its Vps9 domain and through this interaction modulates early endosome fusion and trafficking. The GEF activity of alsin towards Rab5 is regulated by Rac1 function. The GEF activity of alsin for Rac1 occurs via its DH domain and this interaction plays a role in promoting spinal motor neuron survival via multiple Rac-dependent signaling pathways. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241423  Cd Length: 106  Bit Score: 46.62  E-value: 5.05e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1034 ENLTAPGREFIREGCLYKLTKKG---LQQRMFFLFSDMLLYTskgvtatnQFKVHGQLPLhgmiLIVLDAPVEESEnewS 1110
Cdd:cd13269      1 DSLRSPDRRLIRESSTRPLTLQNagrFSSHWFILFNDALVHA--------QFSTHHIFPL----ATLWVEPIPDED---S 65

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2039782227 1111 VPHCFTIYSAQRTIVVAASSKVEMGKWIEDLNMAIDMA 1148
Cdd:cd13269     66 GQNALKITTPEESFTLVASTPQEKAEWLRAINQAIDQA 103
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
 1227-1323 7.50e-06

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270181  Cd Length: 106  Bit Score: 46.10  E-value: 7.50e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKFKN----SNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTpeeSDSIHKEYVFKLQFK-----SHV 1297
Cdd:cd13381      4 AGYLEKRRKDhsffGFEWQKRWCALSNSVFYYYGSDKDKQQKGEFAIDGYDVKM---NNTLRKDAKKDCCFEicapdKRV 80

                           90       100
                   ....*....|....*....|....*.
gi 2039782227 1298 YFFRAESEYTFERWMEVIKSAASTTG 1323
Cdd:cd13381     81 YQFTAASPKEAEEWVQQIKFILQDLG 106
FERM_F1_Radixin cd17238
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in radixin and ...
 50-131 8.17e-06

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in radixin and similar proteins; Radixin is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. The C-terminal domain can fold back to bind to the FERM domain forming an autoinhibited conformation. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Radixin plays important roles in cell polarity, cell motility, invasion and tumor progression. It mediates the binding of F-actin to the plasma membrane after a conformational activation through Akt2-dependent phosphorylation at Thr564. It is also involved in reversal learning and short-term memory by regulating synaptic GABAA receptor density.


Pssm-ID: 340758 [Multi-domain]  Cd Length: 83  Bit Score: 45.50  E-value: 8.17e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFfDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQVRRPANTL-FRLSVK 128
Cdd:cd17238      1 INVRVTTMDAELEF-AIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTQQDVKKENPLqFKFRAK 79


                   ...
gi 2039782227  129 FFP 131
Cdd:cd17238     80 FFP 82
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 1228-1320 1.43e-05

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269962  Cd Length: 114  Bit Score: 45.48  E-value: 1.43e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1228 GYLLRKFKN----SNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESdsiHKEYVFKL---QFKShvYFF 1300
Cdd:cd01260     17 GWLWKKKEAksffGQKWKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIERASEC---KKKYAFKAchpKIKT--FYF 91

                           90       100
                   ....*....|....*....|
gi 2039782227 1301 RAESEYTFERWMEVIKSAAS 1320
Cdd:cd01260     92 AAENLDDMNKWLSKLNMAIN 111
FERM_C_PTPN14_PTPN21 cd13188
FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 14 and 21 (PTPN14 and ...
 235-328 1.55e-05

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 14 and 21 (PTPN14 and 21); This CD contains PTP members: pez/PTPN14 and PTPN21. A number of mutations in Pez have been shown to be associated with breast and colorectal cancer. The PTPN protein family belong to larger family of PTPs. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. The members are composed of a N-terminal FERM domain and a C-terminal PTP catalytic domain. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270009  Cd Length: 91  Bit Score: 44.59  E-value: 1.55e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  235 YGIRFHPAADREGTKINLAVAHMGLQVFQGNIRIN-TFNWSKIRKLSFKRKRFLIKLHPEvhgphQDTLEFMMASRDQCK 313
Cdd:cd13188      1 YGEESFPAKDEQGNEVLIGASLEGIFVKHDNGRPPvFFRWEDIKNVINHKRTFSIECQNS-----EETVQFQFEDAETAK 75

                           90
                   ....*....|....*
gi 2039782227  314 IFWKICVEYHSFFRL 328
Cdd:cd13188     76 YVWKLCVLQHKFYRQ 90
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 1225-1318 3.18e-05

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269966  Cd Length: 102  Bit Score: 44.24  E-value: 3.18e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1225 QLSGYLLRKFKNS---NGWQKLWVVF---TNFcLFFYKTHQDDFPLASLPLLGYTVSTPEESdsihKEYVFKLQFKSHVY 1298
Cdd:cd01265      1 RLCGYLNKLETRGlglKGWKRRWFVLdesKCQ-LYYYRSPQDATPLGSIDLSGAAFSYDPEA----EPGQFEIHTPGRVH 75

                           90       100
                   ....*....|....*....|
gi 2039782227 1299 FFRAESEYTFERWMEVIKSA 1318
Cdd:cd01265     76 ILKASTRQAMLYWLQALQSK 95
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
 1223-1318 4.10e-05

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270081  Cd Length: 136  Bit Score: 44.72  E-value: 4.10e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1223 ENQLSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYT---VSTPEES----DSIHKEYVFKLQFK- 1294
Cdd:cd13261      4 DGTKRGYLSKKTSDSGKWHERWFALYQNLLFYFENESSSRPSGLYLLEGCYcerLPTPKGAlkgkDHLEKQHYFTISFRh 83

                           90       100
                   ....*....|....*....|....*.
gi 2039782227 1295 --SHVYFFRAESEYTFERWMEVIKSA 1318
Cdd:cd13261     84 enQRQYELRAETESDCDEWVEAIKQA 109
FERM_F1_ERM cd17187
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family ...
 50-131 5.12e-05

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins, Ezrin, Radixin, and Moesin; The ezrin-radixin-moesin (ERM) family includes a group of closely related cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. They exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340707 [Multi-domain]  Cd Length: 83  Bit Score: 42.84  E-value: 5.12e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   50 IQIRVYGLDDSQEFfDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQ-VRRPANTLFRLSVK 128
Cdd:cd17187      1 VNVRVTTMDAELEF-AIQPNTTGKQLFDQVVKTIGLREIWFFGLQYVDSKGYSTWLKLNKKVLSQdVKKENPLQFKFRAK 79


                   ...
gi 2039782227  129 FFP 131
Cdd:cd17187     80 FYP 82
PH1_FGD1 cd01219
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin ...
 1043-1153 5.95e-05

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275392  Cd Length: 108  Bit Score: 43.47  E-value: 5.95e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1043 FIREGCLYKLTKKG--LQQRMFFLFSDMLLYTSKGVTATNQ-FKVHGQLPLHGMILivldapvEESENEwSVPHCFTIYS 1119
Cdd:cd01219      1 LIKEGHILKLSAKNgtTQDRYLILFNDRLLYCVPKLRLIGQkFSVRARIDVEGMEL-------KESSSL-NLPRTFLVSG 72

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2039782227 1120 AQRTIVVAASSKVEMGKWIEDLNMAIDMAKKSQE 1153
Cdd:cd01219     73 KQRSLELQARTEEEKKDWIQAIQATIQRHEQTLE 106
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 1226-1320 1.27e-04

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 42.37  E-value: 1.27e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1226 LSGYLLRK--FKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEesdsihKEYVFKLQFKSHVYFFRAE 1303
Cdd:cd13253      2 KSGYLDKQggQGNNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAV------GDNKFELVTTNRTFVFRAE 75

                           90
                   ....*....|....*..
gi 2039782227 1304 SEYTFERWMEVIKSAAS 1320
Cdd:cd13253     76 SDDERNLWCSTLQAAIS 92
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 814-1010 1.47e-04

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 46.42  E-value: 1.47e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  814 RRKRYPtdkayfIAKEILTTERTYLKDLEVITVWFRSAVIKENAMPEG----LMTLLFSNIDPIYEFHRGFLKELDQRLA 889
Cdd:COG5422    482 EIKRQE------AIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENarrnFIKHVFANINEIYAVNSKLLKALTNRQC 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  890 LwegrsnahvKGDYQRIGDVMLKNMCALKEFTSYL--QKHDEVLTELEKASKR--LKKLETVYKEFELQKvcyLPLNTFL 965
Cdd:COG5422    556 L---------SPIVNGIADIFLDYVPKFEPFIKYGasQPYAKYEFEREKSVNPnfARFDHEVERLDESRK---LELDGYL 623

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 2039782227  966 LKPIQRLMHYKLILERLCKHYSPGHRDYYDCKEALKEVADIATQL 1010
Cdd:COG5422    624 TKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRL 668
PHA03247 PHA03247
large tegument protein UL36; Provisional
 423-489 1.59e-04

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 46.47  E-value: 1.59e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2039782227  423 PQTKLPSQPQPLSTLSPAPPKQQQLHSPLQTTRPPSPPKEDLIKAPSPPHYSFQGAPSNQAAGHCSP 489
Cdd:PHA03247  2889 PAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEP 2955
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
 1227-1319 1.74e-04

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 42.37  E-value: 1.74e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRK---FKNsngWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTV----STPEESDsihkEYVFKL-----QFK 1294
Cdd:cd13263      6 SGWLKKQgsiVKN---WQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVkevpFNPEEPG----KFLFEIipgggGDR 78

                           90       100
                   ....*....|....*....|....*....
gi 2039782227 1295 SHV----YFFRAESEYTFERWMEVIKSAA 1319
Cdd:cd13263     79 MTSnhdsYLLMANSQAEMEEWVKVIRRVI 107
DUF4657 pfam15552
Domain of unknown function (DUF4657); This family of proteins is found in eukaryotes. Proteins ...
 445-497 1.75e-04

Domain of unknown function (DUF4657); This family of proteins is found in eukaryotes. Proteins in this family are typically between 305 and 370 amino acids in length.


Pssm-ID: 464762  Cd Length: 301  Bit Score: 45.22  E-value: 1.75e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2039782227  445 QQLHSPLQTTRPPSPP-KEDLIKAPSPPHYSfqgAPSNQAAGHCSPLFVCVESG 497
Cdd:pfam15552  143 QQLYLQLQTQRPPGDPeEEESALAPSPPPSH---APGNEVQGPWELLSQTEETG 193
Amelogenin smart00818
Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem ...
 415-479 2.07e-04

Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem to regulate formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organisation and mineralisation of developing enamel. The extracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins. Circular dichroism studies of porcine amelogenin have shown that the protein consists of 3 discrete folding units: the N-terminal region appears to contain beta-strand structures, while the C-terminal region displays characteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain a repetitive beta-turn segment and a "beta-spiral" between Gln112 and Leu138, which sequester a (Pro, Leu, Gln) rich region. The beta-spiral offers a probable site for interactions with Ca2+ ions. Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplastic amelogenesis imperfecta, a disease characterised by defective enamel. A 9bp deletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disrupting the 16-residue (Met1-Ala16) amelogenin signal peptide.


Pssm-ID: 197891 [Multi-domain]  Cd Length: 165  Bit Score: 43.24  E-value: 2.07e-04
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2039782227   415 PAHMTSILPQTKLPSQPQPLSTLSPAPPKQQQlhSPLQTTRPPSPPKedlikaPSPPHYSFQGAP 479
Cdd:smart00818   86 QHHQPNLPQPAQQPFQPQPLQPPQPQQPMQPQ--PPVHPIPPLPPQP------PLPPMFPMQPLP 142
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
 1225-1322 2.31e-04

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270099  Cd Length: 139  Bit Score: 42.70  E-value: 2.31e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1225 QLSGYLLRKFKN--SNGWQK-LWVVFTNFCLFFYKTHQDDF---------PLASLPLLGYTVSTPEESDsihKEYVFKL- 1291
Cdd:cd13281     13 QLHGILWKKPFGhqSAKWSKrFFIIKEGFLLYYSESEKKDFektrhfnihPKGVIPLGGCSIEAVEDPG---KPYAISIs 89

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2039782227 1292 --QFKSHVyFFRAESEYTFERWMEVIKSAASTT 1322
Cdd:cd13281     90 hsDFKGNI-ILAADSEFEQEKWLDMLRESGKIT 121
IQ_SEC7_PH pfam16453
PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.
 1050-1145 3.40e-04

PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.


Pssm-ID: 465120  Cd Length: 127  Bit Score: 41.88  E-value: 3.40e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1050 YKLTKKGLQQRMFFLFSDMLLYT----SKGVTATNQFKVHgqLPLHGMilivldaPVEESENEWsVPHCFTIYSA---QR 1122
Cdd:pfam16453   23 NKKQKLGLHQREVFLFNDLLVVTkifsKKKSSVTYSFRQS--FGLLGM-------QVSLFENSY-YPHGIRLTSRvdsKV 92

                           90       100
                   ....*....|....*....|...
gi 2039782227 1123 TIVVAASSKVEMGKWIEDLNMAI 1145
Cdd:pfam16453   93 LITFNARNEHDRKKFVEDLRESI 115
FERM_C_PTPH13 cd13187
FERM domain C-lobe of Protein tyrosine phosphatase non-receptor 13 (PTPH13); There are many ...
 236-325 3.67e-04

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor 13 (PTPH13); There are many functions of PTPN13 (also called PTPL1, PTP-BAS, hPTP1E, FAP1, or PTPL1). Mice lacking PTPN13 activity have abnormal regulation of signal transducer and activator of transcription signaling in their T cells, mild impairment of motor nerve repair, and a significant reduction in the growth of retinal glia cultures. It also plays a role in adipocyte differentiation. PTPN13 contains a kinase non-catalytic C-lobe domain (KIND), a FERM domain with two potential phosphatidylinositol 4,5-biphosphate [PtdIns(4,5)P2]-binding motifs, 5 PDZ domains, and a carboxy-terminal catalytic domain. There is an nteraction between the FERM domain of PTPL1 and PtdIns(4,5)P2 which is thought to regulate the membrane localization of PTPN13. PDZ are protein/protein interaction domains so there is the potential for numerous partners that can actively participate in the regulation of its phosphatase activity or can permit direct or indirect recruitment of tyrosine phosphorylated PTPL1 substrates. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270008  Cd Length: 103  Bit Score: 41.15  E-value: 3.67e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  236 GIRFHPAAD---REGTKINLAVAHMGLQVF--QGNIRINT--FNWSKIRKLSFKRKRFLIKlhPEVHGPHQDTleFMMAS 308
Cdd:cd13187      1 GVHFHRVYRekkSSTLSLWLGICSRGIIIYeeKNGARTPVlrFPWRETQKISFDKKKFTIE--SRGGSGIKHT--FYTDS 76

                           90
                   ....*....|....*..
gi 2039782227  309 RDQCKIFWKICVEYHSF 325
Cdd:cd13187     77 YKKSQYLLQLCSAQHKF 93
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 1227-1318 4.07e-04

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 41.24  E-value: 4.07e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLlgYTVSTPEESDSIHKEYVFKLQFKSHVYFFRAESEY 1306
Cdd:cd13255      9 AGYLEKKGERRKTWKKRWFVLRPTKLAYYKNDKEYRLLRLIDL--TDIHTCTEVQLKKHDNTFGIVTPARTFYVQADSKA 86

                           90
                   ....*....|..
gi 2039782227 1307 TFERWMEVIKSA 1318
Cdd:cd13255     87 EMESWISAINLA 98
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 1227-1320 4.39e-04

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269954  Cd Length: 119  Bit Score: 41.53  E-value: 4.39e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVstpEESDSIHKEYVFKL-------QFKS---- 1295
Cdd:cd01252      6 EGWLLKLGGRVKSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSV---REVEDKKKPFCFELyspsngqVIKAcktd 82

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2039782227 1296 ---------H-VYFFRAESEYTFERWMEVIKSAAS 1320
Cdd:cd01252     83 sdgkvvegnHtVYRISAASEEERDEWIKSIKASIS 117
PH_Cla4_Ste20 cd13279
Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), ...
 1240-1315 4.74e-04

Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), Cla4 and Ste20. The yeast Ste20 protein kinase is involved in pheromone response, though the function of Ste20 mammalian homologs is unknown. Cla4 is involved in budding and cytokinesis and interacts with Cdc42, a GTPase required for polarized cell growth as is Pak. Cla4 and Ste20 kinases share a function in localizing cell growth with respect to the septin ring. They both contain a PH domain, a Cdc42/Rac interactive binding (CRIB) domain, and a C-terminal Protein Kinase catalytic (PKc) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270097  Cd Length: 92  Bit Score: 40.69  E-value: 4.74e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2039782227 1240 WQKLWVVFTNFCLFFYKTHQDDFPLASLPLlgYTVSTPEESDSihKEYVFKLQFKSH--VYFFRAESEYTFERWMEVI 1315
Cdd:cd13279     19 WSKRYLVLREQSLDFYKNESSSSASLSIPL--KDISNVSRTDL--KPYCFEIVRKSStkSIYISVKSDDELYDWMDDI 92
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 415-502 4.82e-04

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 44.76  E-value: 4.82e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  415 PAHMTSILPQTKLPSQPQPLSTLSPAPPK---QQ--QLHSPlqttRPPSP--PKEDLIKAPSPPHYSFQGAPSNQAAGHC 487
Cdd:pfam03154  200 TPSAPSVPPQGSPATSQPPNQTQSTAAPHtliQQtpTLHPQ----RLPSPhpPLQPMTQPPPPSQVSPQPLPQPSLHGQM 275

                           90
                   ....*....|....*
gi 2039782227  488 SPLFVCVESGISKLQ 502
Cdd:pfam03154  276 PPMPHSLQTGPSHMQ 290
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
 1226-1323 5.34e-04

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called Collagen type IV alpha-3-binding protein/hCERT; START domain-containing protein 11/StARD11; StAR-related lipid transfer protein 11) is a kinase that phosphorylates an N-terminal region of the alpha 3 chain of type IV collagen, which is commonly known as the goodpasture antigen. Its splice variant the ceramide transporter (CERT) mediates the cytosolic transport of ceramide. There have been additional splice variants identified, but all of them function as ceramide transport proteins. GPBP and CERT both contain an N-terminal PH domain, followed by a serine rich domain, and a C-terminal START domain. However, GPBP has an additional serine rich domain just upstream of its START domain. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270100 [Multi-domain]  Cd Length: 100  Bit Score: 40.73  E-value: 5.34e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1226 LSGYLlRKFKNS-NGWQKLWVVFTNFCLFFYKTHQD-DFPL-ASLPLLGYTVsTPEESDsihkEYVFKLQFKSHVYFFRA 1302
Cdd:cd13283      1 LRGVL-SKWTNYiHGWQDRYFVLKDGTLSYYKSESEkEYGCrGSISLSKAVI-KPHEFD----ECRFDVSVNDSVWYLRA 74

                           90       100
                   ....*....|....*....|.
gi 2039782227 1303 ESEYTFERWMEVIKSAASTTG 1323
Cdd:cd13283     75 ESPEERQRWIDALESHKAASG 95
FERM_C_FRMD1_FRMD6 cd13185
FERM domain C-lobe of FERM domain containing 1 and 6 proteins; FRMD6 (also called willin and ...
 252-288 6.05e-04

FERM domain C-lobe of FERM domain containing 1 and 6 proteins; FRMD6 (also called willin and hEx/human expanded) is localized throughout the cytoplasm or along the plasma membrane. The Drosophilla protein Ex is a regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in organ size control and is tumor suppression by restricting proliferation and promoting apoptosis. Surprisingly, hEx is thought to function independently of the Hippo pathway. Instead it is hypothesized that hEx inhibits progression through the S phase of the cell cycle by upregulating p21(Cip1) and downregulating Cyclin A. It is also implicated in the progression of Alzheimer disease. Not much is known about FRMD1 to date. Both FRMD1 and FRMD6 contains a single FERM domain which has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe is a member of the PH superfamily. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270006  Cd Length: 107  Bit Score: 40.75  E-value: 6.05e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2039782227  252 LAVAHMGLQVFQG----NIRINTFNWSKIRKLSFKRKRFLI 288
Cdd:cd13185     23 LGITAKGIQIYQEsdgeQQLLRTFPWSNIGKLSFDRKKFEI 63
PH_Slm1 cd13311
Slm1 Pleckstrin homology (PH) domain; Slm1 is a component of the target of rapamycin complex 2 ...
 1227-1320 9.21e-04

Slm1 Pleckstrin homology (PH) domain; Slm1 is a component of the target of rapamycin complex 2 (TORC2) signaling pathway. It plays a role in the regulation of actin organization and is a target of sphingolipid signaling during the heat shock response. Slm1 contains a single PH domain that binds PtdIns(4,5)P2, PtdIns(4)P, and dihydrosphingosine 1-phosphate (DHS-1P). Slm1 possesses two binding sites for anionic lipids. The non-canonical binding site of the PH domain of Slm1 is used for ligand binding, and it is proposed that beta-spectrin, Tiam1 and ArhGAP9 also have this type of phosphoinositide binding site. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270121  Cd Length: 110  Bit Score: 40.40  E-value: 9.21e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKFKNSNGWQKLWVVFT-NFCLFFYKThQDDF----PLASLPLLGYTVSTPEESDSihKEYVFKLQFK------- 1294
Cdd:cd13311      6 SGILERKSKFLKSYSKGYYVLTpAGYLHEFKS-SDRKkdpaPEMSLYLPECKIGAPSNKGS--KSHKFILKGKdvgsgkf 82

                           90       100
                   ....*....|....*....|....*...
gi 2039782227 1295 --SHVYFFRAESEYTFERWMEVIKSAAS 1320
Cdd:cd13311     83 hrGHEWVFKAESHEEMMAWWEDIKELTK 110
FERM_F1_FRMD4 cd17103
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM ...
 54-130 1.16e-03

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing proteins FRMD4A, FRMD4B, and similar proteins; This family includes FERM domain-containing proteins FRMD4A and FRMD4B, both of which contain a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). FRMD4A is a cytohesin adaptor involved in cell structure, transport and signaling. It promotes the growth of cancer cells in tongue, head and neck squamous cell carcinomas. FRMD4B, also termed GRP1-binding protein GRSP1, interacts with the coil-coil domain of ARF exchange factor GRP1 to form the Grsp1-Grp1 complex that co-localizes with cortical actin rich regions in response to stimulation of CHO-T cells with insulin or epidermal growth factor (EGF).


Pssm-ID: 340623  Cd Length: 91  Bit Score: 39.57  E-value: 1.16e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   54 VYGLDDSQEFFDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQV--RRPANTLFRL--SVKF 129
Cdd:cd17103      7 VVLLDDRRLEILVQPKLLAGDLLDLVASHFNLKEKEYFGLAYEDETGHYNWLQLDKRVLDHEfpKKWSSGPLVLhfAVKF 86


                   .
gi 2039782227  130 F 130
Cdd:cd17103     87 Y 87
PH1_AFAP cd13306
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are ...
 1228-1320 1.35e-03

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are 3 members of the AFAP family of adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. AFAP1 is a cSrc binding partner and actin cross-linking protein. AFAP1L1 is thought to play a similar role to AFAP1 in terms of being an actin cross-linking protein, but it preferentially binds to cortactin and not cSrc, thereby playing a role in invadosome formation. AFAP1L2 is a cSrc binding protein, but does not bind to actin filaments. AFAP1L2 acts as an intermediary between the RET/PTC kinase and PI-3kinase pathway in the thyroid. The AFAPs share a similar structure of a SH3 binding motif, 3 SH2 binding motifs, 2 PH domains, a coiled-coil region corresponding to the AFAP1 leucine zipper, and an actin binding domain. The amino terminal PH1 domain of AFAP1 has been known to function in intra-molecular regulation of AFAP1. In addition, the PH1 domain is a binding partner for PKCa and phospholipids. This cd is the first PH domain of AFAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270116  Cd Length: 107  Bit Score: 39.77  E-value: 1.35e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1228 GYLLRKfKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVsTPEESDSIHKEYVFKL-QFKSHVYFFRAESEY 1306
Cdd:cd13306     16 AFLLRK-KRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSV-IYVPKDGRRKKHELKFtPPGAEALVLAVQSKE 93

                           90
                   ....*....|....
gi 2039782227 1307 TFERWMEVIKSAAS 1320
Cdd:cd13306     94 QAEQWLKVIREVSS 107
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
 1227-1318 1.47e-03

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 39.65  E-value: 1.47e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKfknSNG-----WQKLWVVFTNFclFFYKTHQDDF-PLASLPLLGYTVSTPEEsdsihKEYVFKLQFKSHVYFF 1300
Cdd:cd13251     13 SGYLLKK---SEGkirkvWQKRRCSIKDG--FLTISHADENkPPAKLNLLTCQVKLVPE-----DKKCFDLISHNRTYHF 82

                           90
                   ....*....|....*...
gi 2039782227 1301 RAESEYTFERWMEVIKSA 1318
Cdd:cd13251     83 QAEDENDANAWMSVLKNS 100
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 1223-1316 1.62e-03

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 39.53  E-value: 1.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1223 ENQLSGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDD-FPLASLPLlGYTVSTPEESDSIHKEYVFKLQFKSHVYFFR 1301
Cdd:cd13215     20 AVIKSGYLSKRSKRTLRYTRYWFVLKGDTLSWYNSSTDLyFPAGTIDL-RYATSIELSKSNGEATTSFKIVTNSRTYKFK 98

                           90
                   ....*....|....*
gi 2039782227 1302 AESEYTFERWMEVIK 1316
Cdd:cd13215     99 ADSETSADEWVKALK 113
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 1220-1322 1.68e-03

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2.Neither of these fall in the PHn domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269937  Cd Length: 127  Bit Score: 39.75  E-value: 1.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1220 LAVENQLsgyLLRKFK-----NSNGWQKLWVVFTNFCLFFYKTH------QDDFPLASLPLLGYTV-STPEESDsihKEY 1287
Cdd:cd01230      9 LSVKNFL---VHKKNKkvelaTRRKWKKYWVCLKGCTLLFYECDersgidENSEPKHALFVEGSIVqAVPEHPK---KDF 82

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2039782227 1288 VFKLQFK-SHVYFFRAESEYTFERWMEVIKSAASTT 1322
Cdd:cd01230     83 VFCLSNSfGDAYLFQATSQTELENWVTAIHSACASA 118
FERM_F1_Merlin cd17186
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in merlin and ...
 52-131 1.92e-03

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in merlin and similar proteins; Merlin, also termed moesin-ezrin-radixin-like protein, or neurofibromin-2 (NF2), or Schwannomerlin, or Schwannomin, is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif, merlin however lacks the typical actin-binding motif in the C-tail. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Merlin plays vital roles in controlling proper development of organ sizes by specifically binding to a large number of target proteins localized both in cytoplasm and nuclei. Merlin may function as a tumor suppressor that functions upstream of the core Hippo pathway kinases Lats1/2 (Wts in Drosophila) and Mst1/2 (Hpo in Drosophila), as well as the nuclear E3 ubiquitin ligase DDB1-and-Cullin 4-associated Factor 1 (DCAF1)-associated cullin 4-Roc1 ligase, CRL4(DCAF1). Merlin may also has a tumor suppressor function in melanoma cells, the inhibition of the proto-oncogenic Na(+)/H(+) exchanger isoform 1 (NHE1) activity.


Pssm-ID: 340706  Cd Length: 85  Bit Score: 38.52  E-value: 1.92e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227   52 IRVYGLDDSQEFfDIDPKALGQVLLSEVFHRGNIIESDYFGLEFQNMQMNWVWLEPTKPVAKQ-VRRPANTLFRLSVKFF 130
Cdd:cd17186      5 VRIVTMDAEMEF-NCEMKWKGKDLFDLVCRTIGLRETWYFGLQYTDSKGTVAWLKMDKKVLDQdVPKEEPVTFHFLAKFY 83


                   .
gi 2039782227  131 P 131
Cdd:cd17186     84 P 84
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 1045-1148 1.93e-03

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 39.12  E-value: 1.93e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1045 REGCLYKLTKKGL---QQRMFFLFSDMLLYTSKGVTatNQFKVHgqlplhgmiliVLD------APVEESEnewsVPHCF 1115
Cdd:cd13250      1 KEGYLFKRSSNAFktwKRRWFSLQNGQLYYQKRDKK--DEPTVM-----------VEDlrlctvKPTEDSD----RRFCF 63

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2039782227 1116 TIYSAQRTIVVAASSKVEMGKWIEDLNMAIDMA 1148
Cdd:cd13250     64 EVISPTKSYMLQAESEEDRQAWIQAIQSAIASA 96
PH_BCR-related cd01228
Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the ...
 1041-1112 2.40e-03

Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. ABR, a related smaller protein, is structurally similar to BCR, but lacks the N-terminal kinase domain and has GAP activity for both Rac and Cdc42. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269935  Cd Length: 166  Bit Score: 40.41  E-value: 2.40e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2039782227 1041 REFIREGCLYKLTKKGLQQRMFFLFSDMLL---YTSKGVTATNQFKVHGQLPLHGMILIvldaPVEESENEWSVP 1112
Cdd:cd01228      1 RQLVKDGFLVELSEGSRKLRHLFLFTDVLLcakLKSAGRGFQGQYECKWYIPLRDLSLH----PKDESEASPIVP 71
FERM_C_FRMD4A_FRMD4B cd13191
FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B); FRMD4A is part ...
 236-337 3.15e-03

FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B); FRMD4A is part of the Par-3/FRMD4A/cytohesin-1 complex that activates Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodeling and epithelial polarization. The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables. When primordial AJs are formed, Par-3 recruits scaffolding protein FRMD4A which connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1. FRMD4B (also called GRP1-binding protein, GRSP1) is a novel member of GRP1 signaling complexes that are recruited to plasma membrane ruffles in response to insulin receptor signaling. The GRSP1/FRMD4B protein contains a FERM protein domain as well as two coiled coil domains and may function as a scaffolding protein. GRP1 and GRSP1 interact through the coiled coil domains in the two proteins. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270012  Cd Length: 113  Bit Score: 38.87  E-value: 3.15e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227  236 GIRFHPAADREGTKINLAVAHMGLQVFQGNIRIN---TFNWSKIRKLSFKRKRFLIklhpEVHGPHQDtlEFMMASRDQ- 311
Cdd:cd13191      1 GVHYYEVKDKNGIPWWLGVSYKGIGQYDLQDKVKprkFFQWKQLENLYFRDRKFSI----EVRDPRRN--SHRSRRTFQs 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2039782227  312 ---------------CKIFWKICVEYHSFFRlfDQPQPKSK 337
Cdd:cd13191     75 ssvsvhvwygqtpalCKTIWSMAIAQHQFYL--DRKQSKKK 113
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 1240-1318 5.64e-03

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 37.68  E-value: 5.64e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1240 WQKLWVVFTNFCLFFYKT---HQDDFPLASLPLLG-YTVSTPEesDSIHKEYVFKLQFKSHVYFFRAESEYTFERWMEVI 1315
Cdd:cd13276     15 WRRRWFVLKQGKLFWFKEpdvTPYSKPRGVIDLSKcLTVKSAE--DATNKENAFELSTPEETFYFIADNEKEKEEWIGAI 92


                   ...
gi 2039782227 1316 KSA 1318
Cdd:cd13276     93 GRA 95
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
 1227-1318 6.92e-03

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270126  Cd Length: 97  Bit Score: 37.35  E-value: 6.92e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2039782227 1227 SGYLLRKFKNSNGWQKLWVVFTNFCLFFYKTHQDDFPLASLPLLGYTVSTPEESDSIHKEYVFKL----QFKSHvyFFRA 1302
Cdd:cd13316      3 SGWMKKRGERYGTWKTRYFVLKGTRLYYLKSENDDKEKGLIDLTGHRVVPDDSNSPFRGSYGFKLvppaVPKVH--YFAV 80

                           90
                   ....*....|....*.
gi 2039782227 1303 ESEYTFERWMEVIKSA 1318
Cdd:cd13316     81 DEKEELREWMKALMKA 96
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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