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Conserved domains on  [gi|1188456521|ref|NP_001337995|]
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actin filament-associated protein 1-like 2 isoform 6 [Homo sapiens]

Protein Classification

AFAP1 family PH domain-containing protein( domain architecture ID 10193118)

AFAP1 family Pleckstrin homology (PH) domain-containing protein similar to mammalian actin filament-associated protein 1 (AFAP1) that can cross-link actin filaments into both network and bundle structures

CATH:  2.30.29.30
Gene Ontology:  GO:0005515
PubMed:  15493994|22728242
SCOP:  3000134

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH1_AFAP cd13306
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are ...
193-299 1.37e-61

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: 201.94  E-value: 1.37e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 193 SPEAGIELMRDARICAFLWRKKWLGQWAKQLCVIKDNRLLCYKSSKDHSPQLDVNLLGSSVIHKEKQVRKKEHKLKITPM 272
Cdd:cd13306     1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80
                          90       100
                  ....*....|....*....|....*..
gi 1188456521 273 NADVIVLGLQSKDQAEQWLRVIQEVSG 299
Cdd:cd13306    81 GAEALVLAVQSKEQAEQWLKVIREVSS 107
PH2_AFAP cd13307
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; There are ...
381-481 6.11e-59

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; 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. This cd is the second 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: 270117  Cd Length: 101  Bit Score: 194.52  E-value: 6.11e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 381 SLETSSYLNVLVNSQWKSRWCSVRDNHLHFYQDRNRSKVAQQPLSLVGCEVVPDPSPDHLYSFRILHKGEELAKLEAKSS 460
Cdd:cd13307     1 GVPTCGYLNVLVNQQWRSRWCCVKDGQLHFYQDRNKTKSPQQSLPLHGCEVVPGPDPKHPYSFRILRNGEEVAALEASSS 80
                          90       100
                  ....*....|....*....|.
gi 1188456521 461 EEMGHWLGLLLSESGSKTDPE 481
Cdd:cd13307    81 EDMGRWLGVLLAETGSATDPE 101
PRK03918 super family cl35229
DNA double-strand break repair ATPase Rad50;
627-693 2.26e-03

DNA double-strand break repair ATPase Rad50;


The actual alignment was detected with superfamily member PRK03918:

Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 41.59  E-value: 2.26e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1188456521 627 IRGHLAQLRKEKRELKETLLKCTDKEV-LASLEQKLKEIDEECRGEESRRVDLELSIMEVKDNLKKAE 693
Cdd:PRK03918  219 LREELEKLEKEVKELEELKEEIEELEKeLESLEGSKRKLEEKIRELEERIEELKKEIEELEEKVKELK 286
 
Name Accession Description Interval E-value
PH1_AFAP cd13306
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are ...
193-299 1.37e-61

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: 201.94  E-value: 1.37e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 193 SPEAGIELMRDARICAFLWRKKWLGQWAKQLCVIKDNRLLCYKSSKDHSPQLDVNLLGSSVIHKEKQVRKKEHKLKITPM 272
Cdd:cd13306     1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80
                          90       100
                  ....*....|....*....|....*..
gi 1188456521 273 NADVIVLGLQSKDQAEQWLRVIQEVSG 299
Cdd:cd13306    81 GAEALVLAVQSKEQAEQWLKVIREVSS 107
PH2_AFAP cd13307
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; There are ...
381-481 6.11e-59

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; 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. This cd is the second 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: 270117  Cd Length: 101  Bit Score: 194.52  E-value: 6.11e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 381 SLETSSYLNVLVNSQWKSRWCSVRDNHLHFYQDRNRSKVAQQPLSLVGCEVVPDPSPDHLYSFRILHKGEELAKLEAKSS 460
Cdd:cd13307     1 GVPTCGYLNVLVNQQWRSRWCCVKDGQLHFYQDRNKTKSPQQSLPLHGCEVVPGPDPKHPYSFRILRNGEEVAALEASSS 80
                          90       100
                  ....*....|....*....|.
gi 1188456521 461 EEMGHWLGLLLSESGSKTDPE 481
Cdd:cd13307    81 EDMGRWLGVLLAETGSATDPE 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
393-467 2.03e-10

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: 58.33  E-value: 2.03e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521  393 NSQWKSRWCSVRDNHLHFYQDR--NRSKVAQQPLSLVGCEVVPDPSPDHL---YSFRILHKGEELAKLEAKSSEEMGHWL 467
Cdd:smart00233  15 KKSWKKRYFVLFNSTLLYYKSKkdKKSYKPKGSIDLSGCTVREAPDPDSSkkpHCFEIKTSDRKTLLLQAESEEEREKWV 94
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
209-298 4.14e-08

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: 51.78  E-value: 4.14e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521  209 FLWRKKW--LGQWAKQLCVIKDNRLLCYKSSK---DHSPQLDVNLLGSSVIH-KEKQVRKKEHKLKITPMNADVIVLGLQ 282
Cdd:smart00233   6 WLYKKSGggKKSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREaPDPDSSKKPHCFEIKTSDRKTLLLQAE 85
                           90
                   ....*....|....*.
gi 1188456521  283 SKDQAEQWLRVIQEVS 298
Cdd:smart00233  86 SEEEREKWVEALRKAI 101
PH pfam00169
PH domain; PH stands for pleckstrin homology.
394-467 7.34e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 48.33  E-value: 7.34e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 394 SQWKSRWCSVRDNHLHFYQDR--NRSKVAQQPLSLVGCEVV---PDPSPDHLYSFRILH---KGEELAKLEAKSSEEMGH 465
Cdd:pfam00169  16 KSWKKRYFVLFDGSLLYYKDDksGKSKEPKGSISLSGCEVVevvASDSPKRKFCFELRTgerTGKRTYLLQAESEEERKD 95

                  ..
gi 1188456521 466 WL 467
Cdd:pfam00169  96 WI 97
PH pfam00169
PH domain; PH stands for pleckstrin homology.
199-298 7.15e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 45.25  E-value: 7.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 199 ELMRDARICAFLWRKKWlgqwakqlCVIKDNRLLCYKSS---KDHSPQLDVNLLGSSVIHKEKQVR-KKEHKLKI---TP 271
Cdd:pfam00169   6 WLLKKGGGKKKSWKKRY--------FVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSpKRKFCFELrtgER 77
                          90       100
                  ....*....|....*....|....*..
gi 1188456521 272 MNADVIVLGLQSKDQAEQWLRVIQEVS 298
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIKAIQSAI 104
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
627-693 2.26e-03

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 41.59  E-value: 2.26e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1188456521 627 IRGHLAQLRKEKRELKETLLKCTDKEV-LASLEQKLKEIDEECRGEESRRVDLELSIMEVKDNLKKAE 693
Cdd:PRK03918  219 LREELEKLEKEVKELEELKEEIEELEKeLESLEGSKRKLEEKIRELEERIEELKKEIEELEEKVKELK 286
 
Name Accession Description Interval E-value
PH1_AFAP cd13306
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are ...
193-299 1.37e-61

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: 201.94  E-value: 1.37e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 193 SPEAGIELMRDARICAFLWRKKWLGQWAKQLCVIKDNRLLCYKSSKDHSPQLDVNLLGSSVIHKEKQVRKKEHKLKITPM 272
Cdd:cd13306     1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80
                          90       100
                  ....*....|....*....|....*..
gi 1188456521 273 NADVIVLGLQSKDQAEQWLRVIQEVSG 299
Cdd:cd13306    81 GAEALVLAVQSKEQAEQWLKVIREVSS 107
PH2_AFAP cd13307
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; There are ...
381-481 6.11e-59

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; 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. This cd is the second 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: 270117  Cd Length: 101  Bit Score: 194.52  E-value: 6.11e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 381 SLETSSYLNVLVNSQWKSRWCSVRDNHLHFYQDRNRSKVAQQPLSLVGCEVVPDPSPDHLYSFRILHKGEELAKLEAKSS 460
Cdd:cd13307     1 GVPTCGYLNVLVNQQWRSRWCCVKDGQLHFYQDRNKTKSPQQSLPLHGCEVVPGPDPKHPYSFRILRNGEEVAALEASSS 80
                          90       100
                  ....*....|....*....|.
gi 1188456521 461 EEMGHWLGLLLSESGSKTDPE 481
Cdd:cd13307    81 EDMGRWLGVLLAETGSATDPE 101
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
393-470 1.44e-11

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: 61.02  E-value: 1.44e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 393 NSQWKSRWCSVRDNHLHFYQDRN-RSKVAQQPLSLVG-CEVVPDPSPDHLYSFRILHKGEELAKLEAKSSEEMGHWLGLL 470
Cdd:cd00821    13 LKSWKKRWFVLFEGVLLYYKSKKdSSYKPKGSIPLSGiLEVEEVSPKERPHCFELVTPDGRTYYLQADSEEERQEWLKAL 92
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
393-467 2.03e-10

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: 58.33  E-value: 2.03e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521  393 NSQWKSRWCSVRDNHLHFYQDR--NRSKVAQQPLSLVGCEVVPDPSPDHL---YSFRILHKGEELAKLEAKSSEEMGHWL 467
Cdd:smart00233  15 KKSWKKRYFVLFNSTLLYYKSKkdKKSYKPKGSIDLSGCTVREAPDPDSSkkpHCFEIKTSDRKTLLLQAESEEEREKWV 94
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
209-298 4.14e-08

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: 51.78  E-value: 4.14e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521  209 FLWRKKW--LGQWAKQLCVIKDNRLLCYKSSK---DHSPQLDVNLLGSSVIH-KEKQVRKKEHKLKITPMNADVIVLGLQ 282
Cdd:smart00233   6 WLYKKSGggKKSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREaPDPDSSKKPHCFEIKTSDRKTLLLQAE 85
                           90
                   ....*....|....*.
gi 1188456521  283 SKDQAEQWLRVIQEVS 298
Cdd:smart00233  86 SEEEREKWVEALRKAI 101
PH pfam00169
PH domain; PH stands for pleckstrin homology.
394-467 7.34e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 48.33  E-value: 7.34e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 394 SQWKSRWCSVRDNHLHFYQDR--NRSKVAQQPLSLVGCEVV---PDPSPDHLYSFRILH---KGEELAKLEAKSSEEMGH 465
Cdd:pfam00169  16 KSWKKRYFVLFDGSLLYYKDDksGKSKEPKGSISLSGCEVVevvASDSPKRKFCFELRTgerTGKRTYLLQAESEEERKD 95

                  ..
gi 1188456521 466 WL 467
Cdd:pfam00169  96 WI 97
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
199-299 3.52e-06

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: 46.63  E-value: 3.52e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 199 ELMRDARICAFLWRK----KWLGQWAKQLCVIKDNRLLCYKSSKDHSPQLDVNLLGSSVIHKEKQVRKKEHKLKITPMNA 274
Cdd:cd13308     4 TLPRDVIHSGTLTKKggsqKTLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNRRAAEERTSKLKFVFKIIHLSP 83
                          90       100
                  ....*....|....*....|....*..
gi 1188456521 275 DVIVLGLQSKDQAEQ--WLRVIQEVSG 299
Cdd:cd13308    84 DHRTWYFAAKSEDEMseWMEYIRREID 110
PH_fermitin cd01237
Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin ...
396-467 4.67e-06

Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin inside-out signalling. The recruitment of Fermitin proteins and Talin to the membrane mediates the terminal event of integrin signalling, via interaction with integrin beta subunits. Fermatin has FERM domain interrupted with a pleckstrin homology (PH) domain. Fermitin family homologs (Fermt1, 2, and 3, also known as Kindlins) are each encoded by a different gene. In mammalian studies, Fermt1 is generally expressed in epithelial cells, Fermt2 is expressed inmuscle tissues, and Fermt3 is expressed in hematopoietic lineages. Specifically Fermt2 is expressed in smooth and striated muscle tissues in mice and in the somites (a trunk muscle precursor) and neural crest in Xenopus embryos. As such it has been proposed that Fermt2 plays a role in cardiomyocyte and neural crest differentiation. Expression of mammalian Fermt3 is associated with hematopoietic lineages: the anterior ventral blood islands, vitelline veins, and early myeloid cells. In Xenopus embryos this expression, also include the notochord and cement gland. 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: 269943  Cd Length: 125  Bit Score: 46.62  E-value: 4.67e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1188456521 396 WKSRWCSVRDNHLHFYQDRNRSK-VAQQPLSLVGCEVVPDPSpdhlysfriLHKGEELAKLEAKSSEEM-GHWL 467
Cdd:cd01237    20 YKRYWFVFKDTHLSYYKSKEESNgAPIQQINLKGCEVTPDVN---------VSQQKFCIKLLVPSPEGMsEVWL 84
PH pfam00169
PH domain; PH stands for pleckstrin homology.
199-298 7.15e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 45.25  E-value: 7.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 199 ELMRDARICAFLWRKKWlgqwakqlCVIKDNRLLCYKSS---KDHSPQLDVNLLGSSVIHKEKQVR-KKEHKLKI---TP 271
Cdd:pfam00169   6 WLLKKGGGKKKSWKKRY--------FVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSpKRKFCFELrtgER 77
                          90       100
                  ....*....|....*....|....*..
gi 1188456521 272 MNADVIVLGLQSKDQAEQWLRVIQEVS 298
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIKAIQSAI 104
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
210-294 2.15e-05

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: 43.69  E-value: 2.15e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 210 LWRKKWLGQWAKQLCVIKDNRLLCYKSSKDHSPQLD--VNLLGSSVIhKEKQVRKKEHKLKITPMNADVIVLGLQSKDQA 287
Cdd:cd00821     7 KRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKgsIPLSGILEV-EEVSPKERPHCFELVTPDGRTYYLQADSEEER 85

                  ....*..
gi 1188456521 288 EQWLRVI 294
Cdd:cd00821    86 QEWLKAL 92
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
393-470 9.55e-05

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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: 270078  Cd Length: 123  Bit Score: 42.70  E-value: 9.55e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 393 NSQWKSRWCSVRDNHLhFYQDRNRSKVAQQPLSLV---GCEVVPDPSPDHLYSFRILHKGEELAK--LEAKSSEEMGHWL 467
Cdd:cd13258    33 SEVFKERWFKLKGNLL-FYFRTNEFGDCSEPIGAIvleNCRVQMEEITEKPFAFSIVFNDEPEKKyiFSCRSEEQCEQWI 111

                  ...
gi 1188456521 468 GLL 470
Cdd:cd13258   112 EAL 114
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
378-467 2.40e-04

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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: 269975  Cd Length: 106  Bit Score: 41.06  E-value: 2.40e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 378 VERSLETSSYLNVLVNSQWKSRWCSVRDNHLHFYQDRNRSKVAQ-----QPLSLVG--CEVVPDpspdhlY-----SFRI 445
Cdd:cd10571     5 LERKHEWESGGKKASNRSWKNVYTVLRGQELSFYKDQKAAKSGItyaaePPLNLYNavCEVASD------YtkkkhVFRL 78
                          90       100
                  ....*....|....*....|...
gi 1188456521 446 -LHKGEELAkLEAKSSEEMGHWL 467
Cdd:cd10571    79 kLSDGAEFL-FQAKDEEEMNQWV 100
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
394-481 2.57e-04

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: 41.07  E-value: 2.57e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 394 SQWKSRWCSVRDNHLHFYQDRNRSK-VAQQPLS-LVGCEVVPDPSPDH---LYS-FRILHkgeelakLEAKSSEEMGHWL 467
Cdd:cd13298    20 KNWKKRWVVLRPCQLSYYKDEKEYKlRRVINLSeLLAVAPLKDKKRKNvfgIYTpSKNLH-------FRATSEKDANEWV 92
                          90
                  ....*....|....
gi 1188456521 468 GLLLSESGSKTDPE 481
Cdd:cd13298    93 EALREEFRLDDEEE 106
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
395-467 4.84e-04

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: 39.95  E-value: 4.84e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1188456521 395 QWKSRWCSVRDNHLHFYQDRNrSKVAQQPLSLVGCEVVPDPSPDHL---YSFRILHKGEELAKLEAKSSEEMGHWL 467
Cdd:cd13248    23 NWRKRWFVLKDNCLYYYKDPE-EEKALGSILLPSYTISPAPPSDEIsrkFAFKAEHANMRTYYFAADTAEEMEQWM 97
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
396-470 8.19e-04

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: 39.23  E-value: 8.19e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1188456521 396 WKSRWCSVRDNHLHFYQDRNrSKVAQQPLSLVGC-EVVPDPSPDHLYSFRILHKGEELAkLEAKSSEEMGHWLGLL 470
Cdd:cd10573    19 WKTRWFVLRRNELKYFKTRG-DTKPIRVLDLRECsSVQRDYSQGKVNCFCLVFPERTFY-MYANTEEEADEWVKLL 92
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
396-492 9.98e-04

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. 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: 241529  Cd Length: 116  Bit Score: 39.54  E-value: 9.98e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 396 WKSRWCSVRDNHLHFYQDRNRSKvAQQPLSLVGCEV---VPDPSPDHLYSFRILHKGEelaklEAKSSEEMGHWLGLLLS 472
Cdd:cd13378    19 WQQRWFVLRGDQLFYYKDEEETK-PQGCISLQGSQVnelPPNPEEPGKHLFEILPGGA-----GDREKVPMNHEAFLLMA 92
                          90       100
                  ....*....|....*....|
gi 1188456521 473 ESGSKTDpeeftyDYVDADR 492
Cdd:cd13378    93 NSQSDME------DWVKAIR 106
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
210-298 1.18e-03

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: 39.18  E-value: 1.18e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 210 LWRKKWlgqwakqlCVIKDNRLLCYKSSKDHSPQLDVNLLGSSV--IHKEKQVRKKeHKLKITPMNADVIVLGLQSKDQA 287
Cdd:cd13248    23 NWRKRW--------FVLKDNCLYYYKDPEEEKALGSILLPSYTIspAPPSDEISRK-FAFKAEHANMRTYYFAADTAEEM 93
                          90
                  ....*....|.
gi 1188456521 288 EQWLRVIQEVS 298
Cdd:cd13248    94 EQWMNAMSLAA 104
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
627-693 2.26e-03

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 41.59  E-value: 2.26e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1188456521 627 IRGHLAQLRKEKRELKETLLKCTDKEV-LASLEQKLKEIDEECRGEESRRVDLELSIMEVKDNLKKAE 693
Cdd:PRK03918  219 LREELEKLEKEVKELEELKEEIEELEKeLESLEGSKRKLEEKIRELEERIEELKKEIEELEEKVKELK 286
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
393-470 3.87e-03

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: 37.32  E-value: 3.87e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 393 NSQWKSRWCSVRDNHLHFYQDRNRSKvAQQPLSLVGCEVVPDP---SPDhlYSFRILHKGEELAkLEAKSSEEMGHWLGL 469
Cdd:cd13326    15 GGKWAKRWFVLKGSNLYGFRSQESTK-ADCVIFLPGFTVSPAPevkSRK--YAFKVYHTGTVFY-FAAESQEDMKKWLDL 90

                  .
gi 1188456521 470 L 470
Cdd:cd13326    91 L 91
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
211-305 4.35e-03

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: 37.75  E-value: 4.35e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1188456521 211 WRKKWLG---QWAKQLCVIKDNRLLCYKSSKDHSPQLDVNLLGSSVihKEKQVRKKE---HKLKITP--------MNADV 276
Cdd:cd13263     8 WLKKQGSivkNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKV--KEVPFNPEEpgkFLFEIIPggggdrmtSNHDS 85
                          90       100
                  ....*....|....*....|....*....
gi 1188456521 277 IVLGLQSKDQAEQWLRVIQEVSGLPSEGA 305
Cdd:cd13263    86 YLLMANSQAEMEEWVKVIRRVIGSPFGGG 114
 
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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