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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 142 SEEASMDLVKDAKICAFLLRKKRFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCSITYIPRDSKKKKHELKITQQ 221
Cdd:cd13306    1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80

                         90       100
                 ....*....|....*....|....*..
gi 672076537 222 GTDPLVLAVQSKEQAEQWLKVIKEAYS 248
Cdd:cd13306   81 GAEALVLAVQSKEQAEQWLKVIREVSS 107

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 641 EQYKYGKNRVEADAKRLQSKEEELLKRKEALRNRLAQLRKERKDLRAAI-----EVNAGRKTQVALEDKLKRLEEECKQR 715
Cdd:COG1196  270 EELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLeeleeELAELEEELEELEEELEELEEELEEA 349

                         90       100
                 ....*....|....*....|...
gi 672076537 716 EAERVSLELELTEVKESLKKALA 738
Cdd:COG1196  350 EEELEEAEAELAEAEEALLEAEA 372

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 142 SEEASMDLVKDAKICAFLLRKKRFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCSITYIPRDSKKKKHELKITQQ 221
Cdd:cd13306    1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80

                         90       100
                 ....*....|....*....|....*..
gi 672076537 222 GTDPLVLAVQSKEQAEQWLKVIKEAYS 248
Cdd:cd13306   81 GAEALVLAVQSKEQAEQWLKVIREVSS 107

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537   158 FLLRKK--RFGQWTKLLCVIKDTKLLCYKSSKDQQ---PQMELPLQGCSITYIP-RDSKKKKHELKITQQGTDPLVLAVQ 231
Cdd:smart00233   6 WLYKKSggGKKSWKKRYFVLFNSTLLYYKSKKDKKsykPKGSIDLSGCTVREAPdPDSSKKPHCFEIKTSDRKTLLLQAE 85

                           90
                   ....*....|....*
gi 672076537   232 SKEQAEQWLKVIKEA 246
Cdd:smart00233  86 SEEEREKWVEALRKA 100

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537  154 KICAFLLRKK--RFGQWTKLLCVIKDTKLLCYKSS---KDQQPQMELPLQGCSITYIPR-DSKKKKHELKI---TQQGTD 224
Cdd:pfam00169   2 VKEGWLLKKGggKKKSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVAsDSPKRKFCFELrtgERTGKR 81

                          90       100
                  ....*....|....*....|..
gi 672076537  225 PLVLAVQSKEQAEQWLKVIKEA 246
Cdd:pfam00169  82 TYLLQAESEEERKDWIKAIQSA 103

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 641 EQYKYGKNRVEADAKRLQSKEEELLKRKEALRNRLAQLRKERKDLRAAI-----EVNAGRKTQVALEDKLKRLEEECKQR 715
Cdd:COG1196  270 EELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLeeleeELAELEEELEELEEELEELEEELEEA 349

                         90       100
                 ....*....|....*....|...
gi 672076537 716 EAERVSLELELTEVKESLKKALA 738
Cdd:COG1196  350 EEELEEAEAELAEAEEALLEAEA 372

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537  655 KRLQSKEEELLKRKEALRN--------------------RLAQLRKERKDLRAAIEVNAGR--KTQVALEDKL------- 705
Cdd:pfam20492  13 ERLKQYEEETKKAQEELEEseetaeeleeerrqaeeeaeRLEQKRQEAEEEKERLEESAEMeaEEKEQLEAELaeaqeei 92

                          90       100
                  ....*....|....*....|....*...
gi 672076537  706 KRLEEECKQREAERVSLELELTEVKESL 733
Cdd:pfam20492  93 ARLEEEVERKEEEARRLQEELEEAREEE 120

phosphodiesterase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 641 EQYKYGKNRVEADAKR----LQSKEEELLKRKEALRNRLAQLRKERKDLraaievNAGRKTQVALEDKLKRLEEECKQRE 716
Cdd:PRK12704  64 EEIHKLRNEFEKELRErrneLQKLEKRLLQKEENLDRKLELLEKREEEL------EKKEKELEQKQQELEKKEEELEELI 137

                         90       100
                 ....*....|....*....|...
gi 672076537 717 AERVsLELE----LT--EVKESL 733
Cdd:PRK12704 138 EEQL-QELErisgLTaeEAKEIL 159

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 142 SEEASMDLVKDAKICAFLLRKKRFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCSITYIPRDSKKKKHELKITQQ 221
Cdd:cd13306    1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80

                         90       100
                 ....*....|....*....|....*..
gi 672076537 222 GTDPLVLAVQSKEQAEQWLKVIKEAYS 248
Cdd:cd13306   81 GAEALVLAVQSKEQAEQWLKVIREVSS 107

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537   158 FLLRKK--RFGQWTKLLCVIKDTKLLCYKSSKDQQ---PQMELPLQGCSITYIP-RDSKKKKHELKITQQGTDPLVLAVQ 231
Cdd:smart00233   6 WLYKKSggGKKSWKKRYFVLFNSTLLYYKSKKDKKsykPKGSIDLSGCTVREAPdPDSSKKPHCFEIKTSDRKTLLLQAE 85

                           90
                   ....*....|....*
gi 672076537   232 SKEQAEQWLKVIKEA 246
Cdd:smart00233  86 SEEEREKWVEALRKA 100

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 352 CGYLNVLSN---SRWRERWCRVKDSKLILHKDRAD-LKTHIVSIPLRG-CEVIPGLDSKHPLTFRLLRNGQEVAVLEASS 426
Cdd:cd00821    2 EGYLLKRGGgglKSWKKRWFVLFEGVLLYYKSKKDsSYKPKGSIPLSGiLEVEEVSPKERPHCFELVTPDGRTYYLQADS 81

                         90
                 ....*....|.
gi 672076537 427 SEDMGRWIGIL 437
Cdd:cd00821   82 EEERQEWLKAL 92

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 166 GQWTKLLCVIKDTKLLCYKS-SKDQQPQMELPLQGCSItyIPRDSKKKKHELKITQQGTDPLVLAVQSKEQAEQWLKV-I 243
Cdd:cd13307   14 QQWRSRWCCVKDGQLHFYQDrNKTKSPQQSLPLHGCEV--VPGPDPKHPYSFRILRNGEEVAALEASSSEDMGRWLGVlL 91

                         90
                 ....*....|....
gi 672076537 244 KEAYSGCsgpvDPE 257
Cdd:cd13307   92 AETGSAT----DPE 101

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 155 ICAFLLRKKRFGQWTKLLCVIKDTKLLC---YKSSKDQQPQMELPLQGCSITYIPRDSK-KKKHELKITQQGTdPLVLAV 230
Cdd:cd13236   10 LCGFLQYSEKGKTWQKVWCVIPRTEPLVlylYGAPQDVRAQRTIPLPGCEVTVPPPEERlDGRHVFKLSQSKQ-SHYFSA 88

                         90
                 ....*....|....*.
gi 672076537 231 QSKEQAEQWLKVIKEA 246
Cdd:cd13236   89 ESEELQQRWLEALSRA 104

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 167 QWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCSIT-YIPRDSKKKKHELKITQQGTDPLVLAVQSKEQAEQWLKVIKE 245
Cdd:cd13248   23 NWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISpAPPSDEISRKFAFKAEHANMRTYYFAADTAEEMEQWMNAMSL 102

                 .
gi 672076537 246 A 246
Cdd:cd13248  103 A 103

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 641 EQYKYGKNRVEADAKRLQSKEEELLKRKEALRNRLAQLRKERKDLRAAI-----EVNAGRKTQVALEDKLKRLEEECKQR 715
Cdd:COG1196  270 EELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLeeleeELAELEEELEELEEELEELEEELEEA 349

                         90       100
                 ....*....|....*....|...
gi 672076537 716 EAERVSLELELTEVKESLKKALA 738
Cdd:COG1196  350 EEELEEAEAELAEAEEALLEAEA 372

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 146 SMDLVKDAKiCAFLLRKKRFGQ----WTKLLCVIKDTKLLCYKSSK----------DQQPQMELPLQGCSITyiPRDSKK 211
Cdd:cd13281    5 DLDITTKVQ-LHGILWKKPFGHqsakWSKRFFIIKEGFLLYYSESEkkdfektrhfNIHPKGVIPLGGCSIE--AVEDPG 81

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 672076537 212 KKHELKIT-QQGTDPLVLAVQSKEQAEQWLKVIKEA 246
Cdd:cd13281   82 KPYAISIShSDFKGNIILAADSEFEQEKWLDMLRES 117

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 168 WTKLLCVIKDTKLLCYKSSKDQQPQMElPLQGCSIT------YIPRDSKKKKHELKITQQGTDP---LVLAVQSKEQAEQ 238
Cdd:cd13249   20 WTRLYCVLKGGNLLCYYSPEEIEAKVE-PLLTIPINketrirAVEKDSKGRASSLSIINPYSGEevtHVLSADSREELQK 98

                 ..
gi 672076537 239 WL 240
Cdd:cd13249   99 WM 100

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 652 ADAKRLQSKEEELLKRKEALRNRLAQLRKERKDLRAAIE-----VNAGRKTQVALEDKLKRLEEECKQREAERVSLELEL 726
Cdd:COG4942   20 DAAAEAEAELEQLQQEIAELEKELAALKKEEKALLKQLAalerrIAALARRIRALEQELAALEAELAELEKEIAELRAEL 99

                         90
                 ....*....|..
gi 672076537 727 TEVKESLKKALA 738
Cdd:COG4942  100 EAQKEELAELLR 111

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537   623 QQKKVESAGGVKRTASNAEQYKYGKNRVEADAKRLQSKEEELLKRKEALRNRLAQLRKERKDLRAAIEVNagRKTQVALE 702
Cdd:TIGR02168  329 ESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQIASL--NNEIERLE 406

                           90       100
                   ....*....|....*....|....*...
gi 672076537   703 DKLKRLEEECKQREAERVSLELELTEVK 730
Cdd:TIGR02168  407 ARLERLEDRRERLQQEIEELLKKLEEAE 434

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 158 FLLRKKRFGQ-WTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCSITYIPRDSKKKKHELKITQQGTDPLVLAVQSKEQA 236
Cdd:cd13301    8 YLVKKGHVVNnWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTITSPCLEYGKRPLVFKLTTAKGQEHFFQACSREER 87

                         90
                 ....*....|....*.
gi 672076537 237 EQWLKVIKEAYSGCSG 252
Cdd:cd13301   88 DAWAKDITKAITCLEG 103

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 636 TASNAEQYKYGKNRVEADAKRLQSKEEELL---KRKEALRNRLAQLRKERKDLRAAievnagrktqvaLEDKLKRLEEEC 712
Cdd:COG1579   84 NVRNNKEYEALQKEIESLKRRISDLEDEILelmERIEELEEELAELEAELAELEAE------------LEEKKAELDEEL 151

                         90       100
                 ....*....|....*....|....*
gi 672076537 713 KQREAERVSLELELTEVKESLKKAL 737
Cdd:COG1579  152 AELEAELEELEAEREELAAKIPPEL 176

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 650 VEADAKRLQSKEEELLKRKEALRNRLAQLR--KERKDLRAAIEVNAGRKTQvaLEDKLKRLEEECKQREAERVSLELELT 727
Cdd:COG1579   57 LEKEIKRLELEIEEVEARIKKYEEQLGNVRnnKEYEALQKEIESLKRRISD--LEDEILELMERIEELEEELAELEAELA 134

                         90
                 ....*....|.
gi 672076537 728 EVKESLKKALA 738
Cdd:COG1579  135 ELEAELEEKKA 145

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 651 EADAKRLQSKEEELLKRKEALRNRLAQLRKERKDLRAAIEVNAGRKTQvaLEDKLKRLEEECKQREAERVSLELELTEVK 730
Cdd:COG1196  266 EAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRE--LEERLEELEEELAELEEELEELEEELEELE 343

                 ....*...
gi 672076537 731 ESLKKALA 738
Cdd:COG1196  344 EELEEAEE 351

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537  655 KRLQSKEEELLKRKEALRN--------------------RLAQLRKERKDLRAAIEVNAGR--KTQVALEDKL------- 705
Cdd:pfam20492  13 ERLKQYEEETKKAQEELEEseetaeeleeerrqaeeeaeRLEQKRQEAEEEKERLEESAEMeaEEKEQLEAELaeaqeei 92

                          90       100
                  ....*....|....*....|....*...
gi 672076537  706 KRLEEECKQREAERVSLELELTEVKESL 733
Cdd:pfam20492  93 ARLEEEVERKEEEARRLQEELEEAREEE 120

phosphodiesterase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 641 EQYKYGKNRVEADAKR----LQSKEEELLKRKEALRNRLAQLRKERKDLraaievNAGRKTQVALEDKLKRLEEECKQRE 716
Cdd:PRK12704  64 EEIHKLRNEFEKELRErrneLQKLEKRLLQKEENLDRKLELLEKREEEL------EKKEKELEQKQQELEKKEEELEELI 137

                         90       100
                 ....*....|....*....|...
gi 672076537 717 AERVsLELE----LT--EVKESL 733
Cdd:PRK12704 138 EEQL-QELErisgLTaeEAKEIL 159

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 651 EADAKRLQSKEEELLKRKEALRNRLAQLRKERKDLRAAIEVNAGRKTQVALEDKLKRLEEECKQREAERVSLELELTEVK 730
Cdd:COG4717  424 ALDEEELEEELEELEEELEELEEELEELREELAELEAELEQLEEDGELAELLQELEELKAELRELAEEWAALKLALELLE 503

                 ....*.
gi 672076537 731 ESLKKA 736
Cdd:COG4717  504 EAREEY 509

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 158 FLLRK-----------KRfgQWTKLLCVIKDTKLLCYKSSKDQQPQM----ELP--LQGCSITyIPRDSKKKKHELKI-T 219
Cdd:cd10571    4 FLERKhewesggkkasNR--SWKNVYTVLRGQELSFYKDQKAAKSGItyaaEPPlnLYNAVCE-VASDYTKKKHVFRLkL 80

                         90       100
                 ....*....|....*....|....*..
gi 672076537 220 QQGTDPLVLAvQSKEQAEQWLKVIKEA 246
Cdd:cd10571   81 SDGAEFLFQA-KDEEEMNQWVKKISFA 106

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 624 QKKVESAGGVKRTASNAEQYKYGKNRVEADAKRLQSKEE------ELLKRKEALRNRLAQLRKERKDL------------ 685
Cdd:COG4717  115 REELEKLEKLLQLLPLYQELEALEAELAELPERLEELEErleelrELEEELEELEAELAELQEELEELleqlslateeel 194

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 672076537 686 -RAAIEVNAGRKTQVALEDKLKRLEEECKQREAERVSLE--LELTEVKESLKKALAGGVTLGLAI 747
Cdd:COG4717  195 qDLAEELEELQQRLAELEEELEEAQEELEELEEELEQLEneLEAAALEERLKEARLLLLIAAALL 259

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537   633 VKRTASNAEQYKYGKNRVEADAKRLQSKEEELLKRKEA----LRNRLAQLRKERKDLRAAIEVNAGRKTQ-----VALED 703
Cdd:TIGR02168  703 LRKELEELEEELEQLRKELEELSRQISALRKDLARLEAeveqLEERIAQLSKELTELEAEIEELEERLEEaeeelAEAEA 782

                           90       100       110
                   ....*....|....*....|....*....|.
gi 672076537   704 KLKRLEEECKQREAERVSLELELTEVKESLK 734
Cdd:TIGR02168  783 EIEELEAQIEQLKEELKALREALDELRAELT 813

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 634 KRTASNAEQYKygknrveadakRLQSKEEELlkRKEALRNRLAQLRKERKDLRAAIEvnagrktqvALEDKLKRLEEECK 713
Cdd:COG1196  206 ERQAEKAERYR-----------ELKEELKEL--EAELLLLKLRELEAELEELEAELE---------ELEAELEELEAELA 263

                         90       100
                 ....*....|....*....|....*
gi 672076537 714 QREAERVSLELELTEVKESLKKALA 738
Cdd:COG1196  264 ELEAELEELRLELEELELELEEAQA 288

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672076537 155 ICAFLLRK-KRFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCSITYI-PRDSKKKKHELKItQQGTDPLVLAVQS 232
Cdd:cd13235    5 MSGYLLRKfKNSNGWQKLWVVFTNFCLFFYKSHQDEFPLASLPLLGYSVGLPsEADNIDKDYVFKL-QFKSHVYFFRAES 83