Engulfment and cell motility protein 1 pleckstrin homology (PH) domain; DOCK2 (Dedicator of cytokinesis 2), a hematopoietic cell-specific, atypical GEF, controls lymphocyte migration through Rac activation. A DOCK2-ELMO1 complex s necessary for DOCK2-mediated Rac signaling. DOCK2 contains a SH3 domain at its N-terminus, followed by a lipid binding DHR1 domain, and a Rac-binding DHR2 domain at its C-terminus. ELMO1, a mammalian homolog of C. elegans CED-12, contains the N-terminal RhoG-binding region, the ELMO domain, the PH domain, and the C-terminal sequence with three PxxP motifs. The C-terminal region of ELMO1, including the Pro-rich sequence, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle along with the PH domain of ELMO1. Autoinhibition of ELMO1 and DOCK2 is accomplished by the interactions of the EID and EAD domains and SH3 and DHR2 domains, respectively. The interaction of DOCK2 and ELMO1 mutually relieve their autoinhibition and results in the activation of Rac1. The PH domain of ELMO1 does not bind phosphoinositides due to the absence of key binding residues. It more closely resembles the FERM domain rather than other PH domains. 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 1907135249 522 ELIKQQRLNRLCEGSSFRKIGNRRRQERFWHCRLALNHKVLHYGDLDDNPQGEvTFESLQEKIPVADIKAIVTGKDCPHM 601
Cdd:cd13359     1 ELIKQQRLNFLVEGTLFPKYNARGRKDKFWYCRLSPNHKVLHYGDCEESAQPA-PLEELPEKLPVADIKALVTGKDCPHM 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907135249 602 KEKSAlkqNKEVLELAFSILYDPDETLNFIAPNKYEYCIWIDGLSALLGK 651
Cdd:cd13359    80 KELKK---NKSVASLAFSILYDSDESLDFVAPNETVFDIWTDGLNALLGK 126

ELMO/CED-12 family; This family represents a conserved domain which is found in a number of eukaryotic proteins including CED-12, ELMO I and ELMO II. ELMO1 is a component of signalling pathways that regulate phagocytosis and cell migration and is the mammalian orthologue of the C. elegans gene, ced-12. CED-12 is required for the engulfment of dying cells and cell migration. In mammalian cells, ELMO1 interacts with Dock180 as part of the CrkII/Dock180/Rac pathway responsible for phagocytosis and cell migration. ELMO1 is ubiquitously expressed, although its expression is highest in the spleen, an organ rich in immune cells. ELMO1 has a PH domain and a polyproline sequence motif at its C terminus which are not present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907135249 278 NLLEERMMTKMDPNDQAQRDIIFELRRIAFDAESDPSNVPgsgtekrkamytKDYKMLGFTNHiNPALDFTqtPPGMLAL 357
Cdd:pfam04727   1 NLLRKRRKTPFDSENPEHERLLKELWKALFPDEPLESRIS------------EKWKRLGFQGE-DPATDFR--GMGLLGL 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907135249 358 DNMLYLAKVHQDTYIRIVLENSSREDkhECPFGRSAIELTKMLCEILQVGELPNEGRNDYhpMFFTHDRAFEELFGICIQ 437
Cdd:pfam04727  66 ENLLYFARNHPDSFQKILLEQSHRPQ--RYPFAVASINLTSLLYELLKIGKLDPEENKSY--LFFPLLLAFEELYCAAFQ 141

                         170       180
                  ....*....|....*....|
gi 1907135249 438 LLNKTWKEMRATAEDFNKVM 457
Cdd:pfam04727 142 LFDRTWKEMGATIMDFNKVL 161

Engulfment and cell motility protein 1 pleckstrin homology (PH) domain; DOCK2 (Dedicator of cytokinesis 2), a hematopoietic cell-specific, atypical GEF, controls lymphocyte migration through Rac activation. A DOCK2-ELMO1 complex s necessary for DOCK2-mediated Rac signaling. DOCK2 contains a SH3 domain at its N-terminus, followed by a lipid binding DHR1 domain, and a Rac-binding DHR2 domain at its C-terminus. ELMO1, a mammalian homolog of C. elegans CED-12, contains the N-terminal RhoG-binding region, the ELMO domain, the PH domain, and the C-terminal sequence with three PxxP motifs. The C-terminal region of ELMO1, including the Pro-rich sequence, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle along with the PH domain of ELMO1. Autoinhibition of ELMO1 and DOCK2 is accomplished by the interactions of the EID and EAD domains and SH3 and DHR2 domains, respectively. The interaction of DOCK2 and ELMO1 mutually relieve their autoinhibition and results in the activation of Rac1. The PH domain of ELMO1 does not bind phosphoinositides due to the absence of key binding residues. It more closely resembles the FERM domain rather than other PH domains. 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 1907135249 522 ELIKQQRLNRLCEGSSFRKIGNRRRQERFWHCRLALNHKVLHYGDLDDNPQGEvTFESLQEKIPVADIKAIVTGKDCPHM 601
Cdd:cd13359     1 ELIKQQRLNFLVEGTLFPKYNARGRKDKFWYCRLSPNHKVLHYGDCEESAQPA-PLEELPEKLPVADIKALVTGKDCPHM 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907135249 602 KEKSAlkqNKEVLELAFSILYDPDETLNFIAPNKYEYCIWIDGLSALLGK 651
Cdd:cd13359    80 KELKK---NKSVASLAFSILYDSDESLDFVAPNETVFDIWTDGLNALLGK 126

ELMO/CED-12 family; This family represents a conserved domain which is found in a number of eukaryotic proteins including CED-12, ELMO I and ELMO II. ELMO1 is a component of signalling pathways that regulate phagocytosis and cell migration and is the mammalian orthologue of the C. elegans gene, ced-12. CED-12 is required for the engulfment of dying cells and cell migration. In mammalian cells, ELMO1 interacts with Dock180 as part of the CrkII/Dock180/Rac pathway responsible for phagocytosis and cell migration. ELMO1 is ubiquitously expressed, although its expression is highest in the spleen, an organ rich in immune cells. ELMO1 has a PH domain and a polyproline sequence motif at its C terminus which are not present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907135249 278 NLLEERMMTKMDPNDQAQRDIIFELRRIAFDAESDPSNVPgsgtekrkamytKDYKMLGFTNHiNPALDFTqtPPGMLAL 357
Cdd:pfam04727   1 NLLRKRRKTPFDSENPEHERLLKELWKALFPDEPLESRIS------------EKWKRLGFQGE-DPATDFR--GMGLLGL 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907135249 358 DNMLYLAKVHQDTYIRIVLENSSREDkhECPFGRSAIELTKMLCEILQVGELPNEGRNDYhpMFFTHDRAFEELFGICIQ 437
Cdd:pfam04727  66 ENLLYFARNHPDSFQKILLEQSHRPQ--RYPFAVASINLTSLLYELLKIGKLDPEENKSY--LFFPLLLAFEELYCAAFQ 141

                         170       180
                  ....*....|....*....|
gi 1907135249 438 LLNKTWKEMRATAEDFNKVM 457
Cdd:pfam04727 142 LFDRTWKEMGATIMDFNKVL 161

Engulfment and cell motility protein 1 pleckstrin homology (PH) domain; DOCK2 (Dedicator of cytokinesis 2), a hematopoietic cell-specific, atypical GEF, controls lymphocyte migration through Rac activation. A DOCK2-ELMO1 complex s necessary for DOCK2-mediated Rac signaling. DOCK2 contains a SH3 domain at its N-terminus, followed by a lipid binding DHR1 domain, and a Rac-binding DHR2 domain at its C-terminus. ELMO1, a mammalian homolog of C. elegans CED-12, contains the N-terminal RhoG-binding region, the ELMO domain, the PH domain, and the C-terminal sequence with three PxxP motifs. The C-terminal region of ELMO1, including the Pro-rich sequence, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle along with the PH domain of ELMO1. Autoinhibition of ELMO1 and DOCK2 is accomplished by the interactions of the EID and EAD domains and SH3 and DHR2 domains, respectively. The interaction of DOCK2 and ELMO1 mutually relieve their autoinhibition and results in the activation of Rac1. The PH domain of ELMO1 does not bind phosphoinositides due to the absence of key binding residues. It more closely resembles the FERM domain rather than other PH domains. 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 1907135249 522 ELIKQQRLNRLCEGSSFRKIGNRRRQERFWHCRLALNHKVLHYGDLDDNPQGEvTFESLQEKIPVADIKAIVTGKDCPHM 601
Cdd:cd13359     1 ELIKQQRLNFLVEGTLFPKYNARGRKDKFWYCRLSPNHKVLHYGDCEESAQPA-PLEELPEKLPVADIKALVTGKDCPHM 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907135249 602 KEKSAlkqNKEVLELAFSILYDPDETLNFIAPNKYEYCIWIDGLSALLGK 651
Cdd:cd13359    80 KELKK---NKSVASLAFSILYDSDESLDFVAPNETVFDIWTDGLNALLGK 126

ELMO/CED-12 family; This family represents a conserved domain which is found in a number of eukaryotic proteins including CED-12, ELMO I and ELMO II. ELMO1 is a component of signalling pathways that regulate phagocytosis and cell migration and is the mammalian orthologue of the C. elegans gene, ced-12. CED-12 is required for the engulfment of dying cells and cell migration. In mammalian cells, ELMO1 interacts with Dock180 as part of the CrkII/Dock180/Rac pathway responsible for phagocytosis and cell migration. ELMO1 is ubiquitously expressed, although its expression is highest in the spleen, an organ rich in immune cells. ELMO1 has a PH domain and a polyproline sequence motif at its C terminus which are not present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907135249 278 NLLEERMMTKMDPNDQAQRDIIFELRRIAFDAESDPSNVPgsgtekrkamytKDYKMLGFTNHiNPALDFTqtPPGMLAL 357
Cdd:pfam04727   1 NLLRKRRKTPFDSENPEHERLLKELWKALFPDEPLESRIS------------EKWKRLGFQGE-DPATDFR--GMGLLGL 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907135249 358 DNMLYLAKVHQDTYIRIVLENSSREDkhECPFGRSAIELTKMLCEILQVGELPNEGRNDYhpMFFTHDRAFEELFGICIQ 437
Cdd:pfam04727  66 ENLLYFARNHPDSFQKILLEQSHRPQ--RYPFAVASINLTSLLYELLKIGKLDPEENKSY--LFFPLLLAFEELYCAAFQ 141

                         170       180
                  ....*....|....*....|
gi 1907135249 438 LLNKTWKEMRATAEDFNKVM 457
Cdd:pfam04727 142 LFDRTWKEMGATIMDFNKVL 161

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The C-terminal region of ELMO1, the PH domain and Pro-rich sequences, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle allowing for DOCK mediated Rac1 activation. ELMO1, a mammalian homolog of C. elegans CED-12, contains an N-terminal RhoG-binding region, a ELMO domain, a PH domain, and a C-terminal sequence with three PxxP motifs. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). All PLCs, except for PLCzeta, have a PH domain which is for most part N-terminally located, though lipid binding specificity is not conserved between them. In addition PLC gamma contains a split PH domain within its catalytic domain that is separated by 2 SH2 domains and a single SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907135249 532 LCEGSSFRKIGNRRRQeRFWHCRLALNHKVLHYGDLDDnpqgevtfESLQEKIPVADIKAIVTGKDCPHMKEKSalKQNK 611
Cdd:cd01248     1 LQQGTLLLKYREGSKP-KERTFYLDPDGTRITWESSKK--------KSEKKSIDISDIKEIRPGKDTDGFKRKK--KSNK 69

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907135249 612 EVLELAFSILY-DPDETLNFIAPNKYEYCIWIDGLSALL 649
Cdd:cd01248    70 PKEERCFSIIYgSNNKTLDLVAPSEDEANLWVEGLRALL 108

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). 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.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. 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 kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907135249 583 KIPVADIKAIVTGKDCPHMKEKSALKQNKEvlELAFSILY-DPDETLNFIAPNKYEYCIWIDGLSALL 649
Cdd:cd13364    43 KIPISSIREVREGKTTDIFRSCDISGDFPE--ECCFSIIYgEEYETLDLVASSPDEANIWITGLRYLM 108