Ca2+-dependent activator protein (also called CAPS) Pleckstrin homology (PH) domain; CADPS/CAPS consists of two members, CAPS1 which regulates catecholamine release from neuroendocrine cells and CAPS2 which is involved in the release of two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) from cerebellar granule cells. CADPS plays an important role in vesicle exocytosis in neurons and endocrine cells where it functions to prime the exocytic machinery for Ca2+-triggered fusion. Priming involves the assembly of trans SNARE complexes. The initial interaction of vesicles with target membranes is mediated by diverse stage-specific tethering factors or multi-subunit tethering complexes. CADPS and Munc13 proteins are proposed to be the functional homologs of the stage-specific tethering factors that prime membrane fusion. Interestingly, regions in the C-terminal half of CADPS are similar to the C-terminal region of Munc13-1 that was reported to bind syntaxin-1. CADPS has independent interactions with each of the SNARE proteins (Q-SNARE and R-SNARE) required for vesicle fusion. CADPS interacts with Q-SNARE proteins syntaxin-1 (H3 SNARE) and SNAP-25 (SN1) and might promote Q-SNARE heterodimer formation. Through its N-terminal R-SNARE VAMP-2 interactions, CADPS bound to heterodimeric Q-SNARE complexes could be involved in catalyzing the zippering of VAMP-2 into recipient complexes. It also contains a central PH domain that binds to phosphoinositide 4,5 bisphosphate containing liposomes. Membrane association may also be mediated by binding to phosphatidlyserine via general electrostatic interactions. 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 2508874476  480 RMDKPQNMKHSGYLWAFGKNVWKRWKKRFFVLVQVSQYTFAMCSYREKKSEPQELLQLDGYTVDYTDPQP--GLDGGRAF 557
Cdd:cd01234      1 RMDKPQNMKHCGYLYALGKSVWKKWKKRYFVLVQVSQYTFAMCSYREKKSEPQEMMQLDGYTVDYTDPQPdlGLEGGRFF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2508874476  558 FNAVKEGDTVIFASDDEQDRILWVQAMYRATGQSHKPVPPTQ 599
Cdd:cd01234     81 FNAVKEGDSVIFASDDENDRQLWVQALYRATGQSHKPVPPTQ 122

Ca2+-dependent activator protein (also called CAPS) Pleckstrin homology (PH) domain; CADPS/CAPS consists of two members, CAPS1 which regulates catecholamine release from neuroendocrine cells and CAPS2 which is involved in the release of two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) from cerebellar granule cells. CADPS plays an important role in vesicle exocytosis in neurons and endocrine cells where it functions to prime the exocytic machinery for Ca2+-triggered fusion. Priming involves the assembly of trans SNARE complexes. The initial interaction of vesicles with target membranes is mediated by diverse stage-specific tethering factors or multi-subunit tethering complexes. CADPS and Munc13 proteins are proposed to be the functional homologs of the stage-specific tethering factors that prime membrane fusion. Interestingly, regions in the C-terminal half of CADPS are similar to the C-terminal region of Munc13-1 that was reported to bind syntaxin-1. CADPS has independent interactions with each of the SNARE proteins (Q-SNARE and R-SNARE) required for vesicle fusion. CADPS interacts with Q-SNARE proteins syntaxin-1 (H3 SNARE) and SNAP-25 (SN1) and might promote Q-SNARE heterodimer formation. Through its N-terminal R-SNARE VAMP-2 interactions, CADPS bound to heterodimeric Q-SNARE complexes could be involved in catalyzing the zippering of VAMP-2 into recipient complexes. It also contains a central PH domain that binds to phosphoinositide 4,5 bisphosphate containing liposomes. Membrane association may also be mediated by binding to phosphatidlyserine via general electrostatic interactions. 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 2508874476  480 RMDKPQNMKHSGYLWAFGKNVWKRWKKRFFVLVQVSQYTFAMCSYREKKSEPQELLQLDGYTVDYTDPQP--GLDGGRAF 557
Cdd:cd01234      1 RMDKPQNMKHCGYLYALGKSVWKKWKKRYFVLVQVSQYTFAMCSYREKKSEPQEMMQLDGYTVDYTDPQPdlGLEGGRFF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2508874476  558 FNAVKEGDTVIFASDDEQDRILWVQAMYRATGQSHKPVPPTQ 599
Cdd:cd01234     81 FNAVKEGDSVIFASDDENDRQLWVQALYRATGQSHKPVPPTQ 122

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2508874476  488 KHSGYLWAFGKNVWKRWKKRFFVLVQVSQYTFAmCSYREKKSEPQELLQLDGYTVDYTDPQPglDGGRAF-----FNAVK 562
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYK-DDKSGKSKEPKGSISLSGCEVVEVVASD--SPKRKFcfelrTGERT 78

                           90       100
                   ....*....|....*....|....*
gi 2508874476  563 EGDTVIFASDDEQDRILWVQAMYRA 587
Cdd:pfam00169   79 GKRTYLLQAESEEERKDWIKAIQSA 103

Ca2+-dependent activator protein (also called CAPS) Pleckstrin homology (PH) domain; CADPS/CAPS consists of two members, CAPS1 which regulates catecholamine release from neuroendocrine cells and CAPS2 which is involved in the release of two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) from cerebellar granule cells. CADPS plays an important role in vesicle exocytosis in neurons and endocrine cells where it functions to prime the exocytic machinery for Ca2+-triggered fusion. Priming involves the assembly of trans SNARE complexes. The initial interaction of vesicles with target membranes is mediated by diverse stage-specific tethering factors or multi-subunit tethering complexes. CADPS and Munc13 proteins are proposed to be the functional homologs of the stage-specific tethering factors that prime membrane fusion. Interestingly, regions in the C-terminal half of CADPS are similar to the C-terminal region of Munc13-1 that was reported to bind syntaxin-1. CADPS has independent interactions with each of the SNARE proteins (Q-SNARE and R-SNARE) required for vesicle fusion. CADPS interacts with Q-SNARE proteins syntaxin-1 (H3 SNARE) and SNAP-25 (SN1) and might promote Q-SNARE heterodimer formation. Through its N-terminal R-SNARE VAMP-2 interactions, CADPS bound to heterodimeric Q-SNARE complexes could be involved in catalyzing the zippering of VAMP-2 into recipient complexes. It also contains a central PH domain that binds to phosphoinositide 4,5 bisphosphate containing liposomes. Membrane association may also be mediated by binding to phosphatidlyserine via general electrostatic interactions. 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 2508874476  480 RMDKPQNMKHSGYLWAFGKNVWKRWKKRFFVLVQVSQYTFAMCSYREKKSEPQELLQLDGYTVDYTDPQP--GLDGGRAF 557
Cdd:cd01234      1 RMDKPQNMKHCGYLYALGKSVWKKWKKRYFVLVQVSQYTFAMCSYREKKSEPQEMMQLDGYTVDYTDPQPdlGLEGGRFF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2508874476  558 FNAVKEGDTVIFASDDEQDRILWVQAMYRATGQSHKPVPPTQ 599
Cdd:cd01234     81 FNAVKEGDSVIFASDDENDRQLWVQALYRATGQSHKPVPPTQ 122

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 2508874476  490 SGYLWAFGKNVWKRWKKRFFVLVQvsqytfaMCSYREKKSEPQELL---QLDGYTVdyTDPQPGLDGGRAF-FNAVKEG- 564
Cdd:cd13248     10 SGWLHKQGGSGLKNWRKRWFVLKD-------NCLYYYKDPEEEKALgsiLLPSYTI--SPAPPSDEISRKFaFKAEHANm 80

                           90       100
                   ....*....|....*....|...
gi 2508874476  565 DTVIFASDDEQDRILWVQAMYRA 587
Cdd:cd13248     81 RTYYFAADTAEEMEQWMNAMSLA 103

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 2508874476  489 HSGYLWAFGKNVWKRWKKRFFVLvqvSQYTFAMCSYR-EKKSEPQELLQLDGyTVDYTDPQPGlDGGRAFFNAVKEGDTV 567
Cdd:cd00821      1 KEGYLLKRGGGGLKSWKKRWFVL---FEGVLLYYKSKkDSSYKPKGSIPLSG-ILEVEEVSPK-ERPHCFELVTPDGRTY 75

                           90
                   ....*....|....*..
gi 2508874476  568 IFASDDEQDRILWVQAM 584
Cdd:cd00821     76 YLQADSEEERQEWLKAL 92

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2508874476  485 QNMKHSGYLWAFGKNVwKRWKKRFFVLVQVSQYTFAmcsyREKKSEPQELLQLDGYTVDYTDPQPGlDGGRAFFNAVKEG 564
Cdd:cd13263      1 ERPIKSGWLKKQGSIV-KNWQQRWFVLRGDQLYYYK----DEDDTKPQGTIPLPGNKVKEVPFNPE-EPGKFLFEIIPGG 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2508874476  565 ---------DTVIFASDDEQDRILWVQAMYRATG 589
Cdd:cd13263     75 ggdrmtsnhDSYLLMANSQAEMEEWVKVIRRVIG 108

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2508874476  489 HSGYLWAFGKNvWKRWKKRFFVLVQVSQYTFamcsYREKKSEPQELLQLDGYTVdYTDPQPGLDGGRAFFNAV--KEGDT 566
Cdd:cd13316      2 HSGWMKKRGER-YGTWKTRYFVLKGTRLYYL----KSENDDKEKGLIDLTGHRV-VPDDSNSPFRGSYGFKLVppAVPKV 75

                           90       100
                   ....*....|....*....|..
gi 2508874476  567 VIFASDDEQDRILWVQAMYRAT 588
Cdd:cd13316     76 HYFAVDEKEELREWMKALMKAT 97