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Conserved domains on  [gi|530371989|ref|XP_005264972|]
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dedicator of cytokinesis protein 3 isoform X2 [Homo sapiens]

Protein Classification

SH3 domain-containing protein( domain architecture ID 10879023)

Src Homology 3 (SH3) domain-containing protein plays versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1235-1626 0e+00

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock3, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


:

Pssm-ID: 212577  Cd Length: 392  Bit Score: 813.47  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQTEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 1314
Cdd:cd11704     1 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQSEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1315 RELACQYESLYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 1394
Cdd:cd11704    81 RELAFQYESLYDYQSLSWIRKMEAAYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1395 PQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDVLQMDRVPDRVKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 1474
Cdd:cd11704   161 PQAIAMQHPNHPDDGILQCDAQYLQIYAVTPIPDNMDVLQMDRVPDRIKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1475 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHKQVHGNINLLSMCLNGVIDAAVNG 1554
Cdd:cd11704   241 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQHKQLHGNINLLSMCLNGVIDAAVNG 320

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530371989 1555 GIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11704   321 GIARYQEAFFDKDYISKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
DOCK_N pfam16172
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 73-412 1.25e-129

DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) proteins, between the variant SH3 domain (pfam07653) and the C2 domain (pfam14429).


:

Pssm-ID: 465040  Cd Length: 317  Bit Score: 409.21  E-value: 1.25e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989    73 GQYETVVPLEDSIVTEVTATLQEWASLWKQLYVKHKVDLFYKLRHVMNELIDLRRQLLSGHLTQDQVREVKRHITVRLDW 152
Cdd:pfam16172    1 IGDETPTSAEEPLVDEIASCLREWHSTLHELLLSRQYQLFDKLSQLIYELDLARRQLLHGVLTADELKELREKTVWDLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   153 GNEHLGLDLVPRKDFE--VVDSDQISVSDLYKMHLSSrqsvqqSTSQVdtmRPRHGETCRMPVPHHFFLSLKSFTYNTIG 230
Cdd:pfam16172   81 GNKLLGLDVIVRDPTGrgRLLTDDDSVVELYKLQSEM------SLLDE---PPTPQVEPDATSLHHLLVDVKNFVGSSIG 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   231 EDTDVFFSLYDMREGKQISERFLVRLNKNGGPRNPEKIERMCALFTDLSSKDMKR-DLYIVAHVIRIgrmllndskkgpp 309
Cdd:pfam16172  152 EDAELFFSLYDKKELKFLSENFVVRLPSNGMPKSLAQSLNLRTLFTDLSSSDLARsKLYLVCKVIRN------------- 218

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   310 hlhYRRPYGCAVLSILDVLQSLTEVKEEKDFVLKVYTCNNESEWSQIHENIIRKSSAKYSAPSASHGLIISLQLLRGDME 389
Cdd:pfam16172  219 ---VRRPFGVAVLDLTDILKGLKQSDEEVEHVVPIWSPNNESDFDELHRDIIKSITGKYEKSPRAERLWVSLKLFHGDAE 295

                          330       340
                   ....*....|....*....|...
gi 530371989   390 QIRRENPMIFnRGLAITRKLGFP 412
Cdd:pfam16172  296 QLRKENPTLL-HNVAITRKLGFP 317
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 420-609 1.31e-125

C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 classes of Dock family proteins. The members here include: Dock3/MOCA (modifier of cell adhesion) and Dock4. Most of these members have been shown to be GEFs specific for Rac, although Dock4 has also been shown to interact indirectly with the Ras family GTPase Rap1, probably through Rap regulatory proteins. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-B members contain a SH3 domain upstream of the C2 domain and a proline-rich region downstream. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


:

Pssm-ID: 176077  Cd Length: 189  Bit Score: 392.13  E-value: 1.31e-125
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  420 IRNDLYLTLEKGDFERGGKSVQKNIEVTMYVLYADGEILKDCISLGSGEPNRSSYHSFVLYHSNSPRWGEIIKLPIPIDR 499
Cdd:cd08695     1 VRNDLYLTLERGEFEKGGKSTAKNIEVTMVVLDADGQVLKDCISLGSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPIDK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  500 FRGSHLRFEFRHCSTKDKGEKKLFGFAFSTLMRDDGTTLSDDIHELYVYKCDENSTFNNHALYLGLPCCKEDYNGCPNIP 579
Cdd:cd08695    81 FRGSHLRFEFRHCSTKDKGEKKLFGFSFVPLMREDGTTLPDGSHELYVYKCDENATFLDPALYLGLPCSKEDFQGCPNSP 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 530371989  580 SSLiFQRSTKESFFISTQLSSTKLTQNVDL 609
Cdd:cd08695   161 SPL-FSRSSKESFWIRTLLCSTKLTQNVDL 189
SH3_DOCK3_B cd12048
Src Homology 3 domain of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of ...
 10-65 4.32e-35

Src Homology 3 domain of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), and presenilin binding protein (PBP), is a class B DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; Dock3 is a specific GEFs for Rac. The SH3 domain of Dock3 binds to DHR-2 in an autoinhibitory manner; binding of the scaffold protein Elmo to the SH3 domain of Dock3 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212981  Cd Length: 56  Bit Score: 128.09  E-value: 4.32e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEGWYRGVSTKKPNVKGIFPANYIHLK 65
Cdd:cd12048     1 YGVVICSFRGSVPQGLVLELGETVQILEKCEGWYRGVSIKKPNVKGIFPANYIHLK 56
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 1751-2046 1.48e-03

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.77  E-value: 1.48e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1751 APSQMITSAPSSARDKYRHAREMMlllPTYRDRPSSAMYPAAILEN-----GQPPNFQRALFQQVVGACKPCSDPNLSVA 1825
Cdd:PHA03247 2655 DPAPGRVSRPRRARRLGRAAQASS---PPQRPRRRAARPTVGSLTSladppPPPPTPEPAPHALVSATPLPPGPAAARQA 2731

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1826 EKAVPAAPSSWSLDSGAqeAQPFLSAHMGRILAPPVPPRSLlhghyslhfdAFHHPLGDTPPALP----ARTLRKSPLHP 1901
Cdd:PHA03247 2732 SPALPAAPAPPAVPAGP--ATPGGPARPARPPTTAGPPAPA----------PPAAPAAGPPRRLTrpavASLSESRESLP 2799

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1902 IPASPTSPQSGLDGSNSTLSGSASSGVSSLSESNFGHSSEAPPRTDTMDSMPSQAWNA-DEDLE---PPYLPVHYSLSES 1977
Cdd:PHA03247 2800 SPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVApGGDVRrrpPSRSPAAKPAAPA 2879

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530371989 1978 AVLDSIKAQPCRSHSAPGCVIPQDPMDPPALPPKPYHPRLPALEhdEGVLLREETERPRGLhRKAPLPP 2046
Cdd:PHA03247 2880 RPPVRRLARPAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQP--PPPPQPQPPPPPPPR-PQPPLAP 2945
 
Name Accession Description Interval E-value
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1235-1626 0e+00

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock3, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212577  Cd Length: 392  Bit Score: 813.47  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQTEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 1314
Cdd:cd11704     1 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQSEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1315 RELACQYESLYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 1394
Cdd:cd11704    81 RELAFQYESLYDYQSLSWIRKMEAAYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1395 PQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDVLQMDRVPDRVKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 1474
Cdd:cd11704   161 PQAIAMQHPNHPDDGILQCDAQYLQIYAVTPIPDNMDVLQMDRVPDRIKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1475 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHKQVHGNINLLSMCLNGVIDAAVNG 1554
Cdd:cd11704   241 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQHKQLHGNINLLSMCLNGVIDAAVNG 320

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530371989 1555 GIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11704   321 GIARYQEAFFDKDYISKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
DOCK_N pfam16172
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 73-412 1.25e-129

DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) proteins, between the variant SH3 domain (pfam07653) and the C2 domain (pfam14429).


Pssm-ID: 465040  Cd Length: 317  Bit Score: 409.21  E-value: 1.25e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989    73 GQYETVVPLEDSIVTEVTATLQEWASLWKQLYVKHKVDLFYKLRHVMNELIDLRRQLLSGHLTQDQVREVKRHITVRLDW 152
Cdd:pfam16172    1 IGDETPTSAEEPLVDEIASCLREWHSTLHELLLSRQYQLFDKLSQLIYELDLARRQLLHGVLTADELKELREKTVWDLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   153 GNEHLGLDLVPRKDFE--VVDSDQISVSDLYKMHLSSrqsvqqSTSQVdtmRPRHGETCRMPVPHHFFLSLKSFTYNTIG 230
Cdd:pfam16172   81 GNKLLGLDVIVRDPTGrgRLLTDDDSVVELYKLQSEM------SLLDE---PPTPQVEPDATSLHHLLVDVKNFVGSSIG 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   231 EDTDVFFSLYDMREGKQISERFLVRLNKNGGPRNPEKIERMCALFTDLSSKDMKR-DLYIVAHVIRIgrmllndskkgpp 309
Cdd:pfam16172  152 EDAELFFSLYDKKELKFLSENFVVRLPSNGMPKSLAQSLNLRTLFTDLSSSDLARsKLYLVCKVIRN------------- 218

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   310 hlhYRRPYGCAVLSILDVLQSLTEVKEEKDFVLKVYTCNNESEWSQIHENIIRKSSAKYSAPSASHGLIISLQLLRGDME 389
Cdd:pfam16172  219 ---VRRPFGVAVLDLTDILKGLKQSDEEVEHVVPIWSPNNESDFDELHRDIIKSITGKYEKSPRAERLWVSLKLFHGDAE 295

                          330       340
                   ....*....|....*....|...
gi 530371989   390 QIRRENPMIFnRGLAITRKLGFP 412
Cdd:pfam16172  296 QLRKENPTLL-HNVAITRKLGFP 317
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 420-609 1.31e-125

C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 classes of Dock family proteins. The members here include: Dock3/MOCA (modifier of cell adhesion) and Dock4. Most of these members have been shown to be GEFs specific for Rac, although Dock4 has also been shown to interact indirectly with the Ras family GTPase Rap1, probably through Rap regulatory proteins. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-B members contain a SH3 domain upstream of the C2 domain and a proline-rich region downstream. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176077  Cd Length: 189  Bit Score: 392.13  E-value: 1.31e-125
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  420 IRNDLYLTLEKGDFERGGKSVQKNIEVTMYVLYADGEILKDCISLGSGEPNRSSYHSFVLYHSNSPRWGEIIKLPIPIDR 499
Cdd:cd08695     1 VRNDLYLTLERGEFEKGGKSTAKNIEVTMVVLDADGQVLKDCISLGSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPIDK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  500 FRGSHLRFEFRHCSTKDKGEKKLFGFAFSTLMRDDGTTLSDDIHELYVYKCDENSTFNNHALYLGLPCCKEDYNGCPNIP 579
Cdd:cd08695    81 FRGSHLRFEFRHCSTKDKGEKKLFGFSFVPLMREDGTTLPDGSHELYVYKCDENATFLDPALYLGLPCSKEDFQGCPNSP 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 530371989  580 SSLiFQRSTKESFFISTQLSSTKLTQNVDL 609
Cdd:cd08695   161 SPL-FSRSSKESFWIRTLLCSTKLTQNVDL 189
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 417-608 5.10e-68

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 227.48  E-value: 5.10e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   417 PGDIRNDLYLTLEKGDFERGGKSVQKNIEVTMYVLYADGEILKDCISLGSGEPNRSSYHSFVLYHSNSPRWGEIIKLPIP 496
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSARNIEVTVEVRDSDGEPLPNCIYGGSGGPFVTEFKSTVYYHNKSPTWYEEIKIALP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   497 IDRFRGSHLRFEFRHCSTKDKGEK--KLFGFAFSTLMRDDGTTLSDDIHELYVYKCDENStfnnhALYLGLPCCKEDYNG 574
Cdd:pfam14429   81 AELTPKHHLLFTFYHVSCDEKKDKveKPFGYAFLPLLDDDGAFLRDGEHTLPVYKYDELP-----PGYLSLPWSSGGEKE 155

                          170       180       190
                   ....*....|....*....|....*....|....
gi 530371989   575 CPNIPSSlifqRSTKESFFISTQLSSTKLTQNVD 608
Cdd:pfam14429  156 SSALPGL----KGGKDLFKVRTRLCSTKYTQDEH 185
SH3_DOCK3_B cd12048
Src Homology 3 domain of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of ...
 10-65 4.32e-35

Src Homology 3 domain of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), and presenilin binding protein (PBP), is a class B DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; Dock3 is a specific GEFs for Rac. The SH3 domain of Dock3 binds to DHR-2 in an autoinhibitory manner; binding of the scaffold protein Elmo to the SH3 domain of Dock3 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212981  Cd Length: 56  Bit Score: 128.09  E-value: 4.32e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEGWYRGVSTKKPNVKGIFPANYIHLK 65
Cdd:cd12048     1 YGVVICSFRGSVPQGLVLELGETVQILEKCEGWYRGVSIKKPNVKGIFPANYIHLK 56
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1527-1628 1.10e-29

DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe C which form an antiparallel four alpha-helical bundle and contains a loop known as the nucleotide sensor characterized by a conserved valine residue essential for catalytic activity.


Pssm-ID: 466570 [Multi-domain]  Cd Length: 103  Bit Score: 114.61  E-value: 1.10e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  1527 QYQHKQVHGNINLLSMCLNGVIDAAVNGGIARYQEAFFDKDYINKHPgdAEKITQLKELMQEQVHVLGVGLAVHEKFVHP 1606
Cdd:pfam20421    3 EAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYP--AEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|..
gi 530371989  1607 EMRPLHKKLIDQFQMMRASLYH 1628
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEP 102
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 7-62 1.61e-07

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 49.84  E-value: 1.61e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 530371989      7 EEKYGVVICSFRGSVPQGLVLEIGETVQILEKCE-GWYRGvsTKKPNVKGIFPANYI 62
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDdGWWKG--RLGRGKEGLFPSNYV 55
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
 10-62 1.31e-05

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 44.12  E-value: 1.31e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 530371989    10 YGVVICSFRGSVPQGLVLEIGETVQILEK-CEGWYRGVSTKKpnvKGIFPANYI 62
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKdNDGWWEGETGGR---VGLVPSTAV 51
PHA03247 PHA03247
large tegument protein UL36; Provisional
 1751-2046 1.48e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.77  E-value: 1.48e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1751 APSQMITSAPSSARDKYRHAREMMlllPTYRDRPSSAMYPAAILEN-----GQPPNFQRALFQQVVGACKPCSDPNLSVA 1825
Cdd:PHA03247 2655 DPAPGRVSRPRRARRLGRAAQASS---PPQRPRRRAARPTVGSLTSladppPPPPTPEPAPHALVSATPLPPGPAAARQA 2731

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1826 EKAVPAAPSSWSLDSGAqeAQPFLSAHMGRILAPPVPPRSLlhghyslhfdAFHHPLGDTPPALP----ARTLRKSPLHP 1901
Cdd:PHA03247 2732 SPALPAAPAPPAVPAGP--ATPGGPARPARPPTTAGPPAPA----------PPAAPAAGPPRRLTrpavASLSESRESLP 2799

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1902 IPASPTSPQSGLDGSNSTLSGSASSGVSSLSESNFGHSSEAPPRTDTMDSMPSQAWNA-DEDLE---PPYLPVHYSLSES 1977
Cdd:PHA03247 2800 SPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVApGGDVRrrpPSRSPAAKPAAPA 2879

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530371989 1978 AVLDSIKAQPCRSHSAPGCVIPQDPMDPPALPPKPYHPRLPALEhdEGVLLREETERPRGLhRKAPLPP 2046
Cdd:PHA03247 2880 RPPVRRLARPAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQP--PPPPQPQPPPPPPPR-PQPPLAP 2945
 
Name Accession Description Interval E-value
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1235-1626 0e+00

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock3, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212577  Cd Length: 392  Bit Score: 813.47  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQTEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 1314
Cdd:cd11704     1 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQSEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1315 RELACQYESLYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 1394
Cdd:cd11704    81 RELAFQYESLYDYQSLSWIRKMEAAYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1395 PQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDVLQMDRVPDRVKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 1474
Cdd:cd11704   161 PQAIAMQHPNHPDDGILQCDAQYLQIYAVTPIPDNMDVLQMDRVPDRIKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1475 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHKQVHGNINLLSMCLNGVIDAAVNG 1554
Cdd:cd11704   241 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQHKQLHGNINLLSMCLNGVIDAAVNG 320

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530371989 1555 GIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11704   321 GIARYQEAFFDKDYISKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1235-1626 0e+00

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. Dock3 is a specific GEF for Rac and it regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class B DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212569  Cd Length: 391  Bit Score: 758.13  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQTEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 1314
Cdd:cd11696     1 EMYLRYIYKLHDLHLQAENYTEAAFTLLLYAELLSWSSDPLPADLHHPSQPEWQRKEALYLKILQYFDRGKCWEKGIPLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1315 RELACQYESLYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 1394
Cdd:cd11696    81 RELAELYESLYDYAKLSHILRMEASFYDNILTQLRPEPEYFRVGFYGKGFPLFLRNKQFVYRGLDYERIGAFTQRLQSEF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1395 PQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDVLQMDRVPDRVKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 1474
Cdd:cd11696   161 PQAHILTKNTPPDDAILQADGQYIQICNVKPVPERRPVLQMVGVPDKVRSFYRVNDVRKFQYDRPIHKGPIDKDNEFKSL 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1475 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHkQVHGNINLLSMCLNGVIDAAVNG 1554
Cdd:cd11696   241 WIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQA-DPTRNINPFSMRLQGVIDAAVNG 319

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530371989 1555 GIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11696   320 GIAKYQEAFFTPEFILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVERFTQMKQSL 391
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1235-1626 0e+00

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock4, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212578  Cd Length: 391  Bit Score: 618.58  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQTEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 1314
Cdd:cd11705     1 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLSYPMQTEWQRKEYLHLTIIQNFDRGKCWENGIILC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1315 RELACQYESLYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 1394
Cdd:cd11705    81 RKLAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1395 PQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDVLQMDRVPDRVKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 1474
Cdd:cd11705   161 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRDGVPDNIKSFYKVNHIWRFRYDRPFHKGTKDKENEFKSL 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1475 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHKQVHgNINLLSMCLNGVIDAAVNG 1554
Cdd:cd11705   241 WVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQCQTRQMQ-NINPLTMCLNGVIDAAVNG 319

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530371989 1555 GIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11705   320 GVSRYQEAFFVKEYILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1235-1626 1.07e-157

Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins comprise a family of atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. They are also called the CZH (CED-5, Dock180, and MBC-zizimin homology) family, after the first family members identified. Dock180 was first isolated as a binding partner for the adaptor protein Crk. The Caenorhabditis elegans protein, Ced-5, is essential for cell migration and phagocytosis, while the Drosophila ortholog, Myoblast city (MBC), is necessary for myoblast fusion and dorsal closure. DOCKs are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1 (or Dock180), 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1, and DHR-2 (also called CZH2 or Docker). This alignment model represents the DHR-2 domain of DOCK proteins, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212566 [Multi-domain]  Cd Length: 392  Bit Score: 490.66  E-value: 1.07e-157
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDR----PLREFLHYPSQTEWQRKEGLCRKIIHYFNKGKSWEFG 1310
Cdd:cd11684     1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKalvpALAESLSFPEQTSFERKEALYKKAIDLFDKGKAWEFA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1311 IPLCRELACQYESLYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRM 1390
Cdd:cd11684    81 IALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEKDRLFPTYFRVGFYGKGFPESLRGKEFIYRGPEFERLGDFCERL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1391 LSEFPQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDvlQMDRVPDRVKSFYRVNNVRKFRYDRPFHKGPKDKENE 1470
Cdd:cd11684   161 KSLYPGAEIIQSSEEPDDEILDSEGQYIQITSVEPYFDDED--LVSRAAPGVRQFYRNNNINTFVYERPFTKGGKKSQNE 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1471 FKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHKQvHGNINLLSMCLNGVIDA 1550
Cdd:cd11684   239 ITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIEDIEKKTEELRSLINKYRSGD-SPNVNPLQMLLQGTVDA 317

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530371989 1551 AVNGGIARYQEAFFDKDYINKHPgDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11684   318 AVNGGPVAYAEAFLSEEYLSNYP-EAEKVKKLKEAFEEFLEILKRGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1235-1625 2.78e-154

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. Class A DOCKs are specific GEFs for Rac. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock2 plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class A DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212570  Cd Length: 400  Bit Score: 481.83  E-value: 2.78e-154
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFL----HYPSQTEWQRKEGLCRKIIHYFNKGKSWEFG 1310
Cdd:cd11697     1 EMYIRYLYKLCDLHLECDNYTEAAYTLQLHAELLKWSDEPLPTLLrsrrYPEAQTHRQLKEALYYDIIDYFDKGKMWECA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1311 IPLCRELACQYES-LYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQR 1389
Cdd:cd11697    81 ISLCKELAEQYENeTFDYLQLSELLKRMATFYDNIMKTLRPEPEYFRVGYYGQGFPSFLRNKVFIYRGKEYERLSDFSAR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1390 MLSEFPQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDVLQMDRVPDRVKSFYRVNNVRKFRYDRPFHKGPKDKEN 1469
Cdd:cd11697   161 LLNQFPNAELMNTLTPPGDEIKESPGQYLQINKVDPVMDERPRFKGKPVSDQILNYYKVNEVQRFTFSRPFRRGTKDPDN 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1470 EFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQH-KQVHgnINLLSMCLNGVI 1548
Cdd:cd11697   241 EFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIETMEDTNKKIRDLILQHQSdPTLP--INPLSMLLNGIV 318

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530371989 1549 DAAVNGGIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRAS 1625
Cdd:cd11697   319 DAAVMGGIANYEKAFFTEEYLDEHPEDQELIERLKDLIAEQIPLLEAGLKIHKQKAPESLRPLHERMEECFAKMKEH 395
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1216-1630 9.93e-139

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock2, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock2, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212579  Cd Length: 421  Bit Score: 439.42  E-value: 9.93e-139
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1216 KIGCTVNLMNFYKsEINKEEMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREF---LHYPS-QTEWQRKE 1291
Cdd:cd11706     1 RMSCTVNLLNFYK-DINREAMYIRYLYKLRDLHLDCENYTEAAYTLLLHTRLLKWSDEQCASQvmqTGQQHpQTQRQLKE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1292 GLCRKIIHYFNKGKSWEFGIPLCRELACQYES-LYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRN 1370
Cdd:cd11706    80 TLYETIIGYFDKGKMWEEAISLCKELAEQYEMeIFDYELLSQNLIQQAKFYESIMKILRPKPDYFAVGYYGQGFPSFLRN 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1371 KEYVCRGHDYERLEAFQQRMLSEFPQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDVLQMDRVPDRVKSFYRVNN 1450
Cdd:cd11706   160 KVFIYRGKEYERREDFQMQLMSQFPNAEKLNTTSAPGDDIKNSPGQYIQCFTVQPVLEEHPRLKNKPVPDQIINFYKSNY 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1451 VRKFRYDRPFHKGPKDKENEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQH 1530
Cdd:cd11706   240 VQRFHYSRPVRKGPVDPENEFASMWIERTTFVTAYKLPGILRWFEVTHMSQTTISPLENAIETMSTTNEKILMMINQYQS 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1531 KQVHgNINLLSMCLNGVIDAAVNGGIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRP 1610
Cdd:cd11706   320 DESL-PINPLSMLLNGIVDPAVMGGFAKYEKAFFTEEYVRDHPEDQDKLTRLKDLIAWQIPLLGAGIKIHGKRVTDDLRP 398

                         410       420
                  ....*....|....*....|
gi 530371989 1611 LHKKLIDQFQMMRASLYHEF 1630
Cdd:cd11706   399 FHERMEECFKQLKMKVEKEY 418
DOCK_N pfam16172
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 73-412 1.25e-129

DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) proteins, between the variant SH3 domain (pfam07653) and the C2 domain (pfam14429).


Pssm-ID: 465040  Cd Length: 317  Bit Score: 409.21  E-value: 1.25e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989    73 GQYETVVPLEDSIVTEVTATLQEWASLWKQLYVKHKVDLFYKLRHVMNELIDLRRQLLSGHLTQDQVREVKRHITVRLDW 152
Cdd:pfam16172    1 IGDETPTSAEEPLVDEIASCLREWHSTLHELLLSRQYQLFDKLSQLIYELDLARRQLLHGVLTADELKELREKTVWDLVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   153 GNEHLGLDLVPRKDFE--VVDSDQISVSDLYKMHLSSrqsvqqSTSQVdtmRPRHGETCRMPVPHHFFLSLKSFTYNTIG 230
Cdd:pfam16172   81 GNKLLGLDVIVRDPTGrgRLLTDDDSVVELYKLQSEM------SLLDE---PPTPQVEPDATSLHHLLVDVKNFVGSSIG 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   231 EDTDVFFSLYDMREGKQISERFLVRLNKNGGPRNPEKIERMCALFTDLSSKDMKR-DLYIVAHVIRIgrmllndskkgpp 309
Cdd:pfam16172  152 EDAELFFSLYDKKELKFLSENFVVRLPSNGMPKSLAQSLNLRTLFTDLSSSDLARsKLYLVCKVIRN------------- 218

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   310 hlhYRRPYGCAVLSILDVLQSLTEVKEEKDFVLKVYTCNNESEWSQIHENIIRKSSAKYSAPSASHGLIISLQLLRGDME 389
Cdd:pfam16172  219 ---VRRPFGVAVLDLTDILKGLKQSDEEVEHVVPIWSPNNESDFDELHRDIIKSITGKYEKSPRAERLWVSLKLFHGDAE 295

                          330       340
                   ....*....|....*....|...
gi 530371989   390 QIRRENPMIFnRGLAITRKLGFP 412
Cdd:pfam16172  296 QLRKENPTLL-HNVAITRKLGFP 317
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 420-609 1.31e-125

C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 classes of Dock family proteins. The members here include: Dock3/MOCA (modifier of cell adhesion) and Dock4. Most of these members have been shown to be GEFs specific for Rac, although Dock4 has also been shown to interact indirectly with the Ras family GTPase Rap1, probably through Rap regulatory proteins. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-B members contain a SH3 domain upstream of the C2 domain and a proline-rich region downstream. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176077  Cd Length: 189  Bit Score: 392.13  E-value: 1.31e-125
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  420 IRNDLYLTLEKGDFERGGKSVQKNIEVTMYVLYADGEILKDCISLGSGEPNRSSYHSFVLYHSNSPRWGEIIKLPIPIDR 499
Cdd:cd08695     1 VRNDLYLTLERGEFEKGGKSTAKNIEVTMVVLDADGQVLKDCISLGSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPIDK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  500 FRGSHLRFEFRHCSTKDKGEKKLFGFAFSTLMRDDGTTLSDDIHELYVYKCDENSTFNNHALYLGLPCCKEDYNGCPNIP 579
Cdd:cd08695    81 FRGSHLRFEFRHCSTKDKGEKKLFGFSFVPLMREDGTTLPDGSHELYVYKCDENATFLDPALYLGLPCSKEDFQGCPNSP 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 530371989  580 SSLiFQRSTKESFFISTQLSSTKLTQNVDL 609
Cdd:cd08695   161 SPL-FSRSSKESFWIRTLLCSTKLTQNVDL 189
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1235-1630 7.67e-124

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also called Dock180, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. In the nervous system, it mediates attractive responses to netrin-1 and thus, plays a role in axon outgrowth and pathfinding. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock1, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock1, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212580  Cd Length: 400  Bit Score: 396.33  E-value: 7.67e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLH----YPSQTEWQRKEGLCRKIIHYFNKGKSWEFG 1310
Cdd:cd11707     1 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEEACAAHLTqrdgYQATTQGQLKDQLYQEIIHYFDKGKMWEEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1311 IPLCRELACQYES-LYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQR 1389
Cdd:cd11707    81 IALGKELAEQYENeMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRNKMFIYRGKEYERREDFEAR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1390 MLSEFPQAVAMQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDVLQMDRVPDRVKSFYRVNNVRKFRYDRPFHKGPKDKEN 1469
Cdd:cd11707   161 LLTQFPNAEKMKTTSPPGDDIKNSSGQYIQCFTVKPLLELPPKFQNKPVSEQIVSFYRVNEVQRFQYSRPVRKGEKDPDN 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1470 EFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHKQvHGNINLLSMCLNGVID 1549
Cdd:cd11707   241 EFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNEKINNMVQQHLNDP-NLPINPLSMLLNGIVD 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1550 AAVNGGIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASLYHE 1629
Cdd:cd11707   320 PAVMGGFANYEKAFFTEKYMQEHPEDHEKIEKLKDLIAWQIPFLAEGIRIHGEKVTEALRPFHERMEACFRQLKEKVEKQ 399


                  .
gi 530371989 1630 F 1630
Cdd:cd11707   400 Y 400
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1235-1624 6.67e-120

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It functions upstream of Rac1 to regulate osteoclast function. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock5, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock5, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212581  Cd Length: 400  Bit Score: 385.07  E-value: 6.67e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1235 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFL----HYPSQTEWQRKEGLCRKIIHYFNKGKSWEFG 1310
Cdd:cd11708     1 DIYIRYLYKLRDLHLDCENYTEAAYTLLLHAELLQWSEKPCVPHLlqrdSYYVYTQQELKERLYQEIISFFDKGKMWEKA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1311 IPLCRELACQYES-LYDYQSLSWIRKMEASYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQR 1389
Cdd:cd11708    81 IELSKELADMYENqVFDYEGLGNLLKKQAQFYENIMKAMRPQPEYFAVGYYGQGFPSFLRNKIFIYRGKEYERLEDFSLK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1390 MLSEFPQAVAMQHPNHPDDAILQCDAQYLQIYAVTPI----PDYVDVLqmdrVPDRVKSFYRVNNVRKFRYDRPFHKGPK 1465
Cdd:cd11708   161 LLTQFPNAEKMTSTSPPGDEIKSSTKQYVQCFTVKPVmnlpSHYKDKP----VPEQILNYYRANEVQQFQYSRPFRKGEK 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1466 DKENEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHKQ---VHGninlLSM 1542
Cdd:cd11708   237 DPDNEFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLENAIETMELTNEKISNLVQQHAWDRslpVHP----LSM 312

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1543 CLNGVIDAAVNGGIARYQEAFFDKDYINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMM 1622
Cdd:cd11708   313 LLNGIVDPAVMGGFSNYEKAFFTEKYLQEHPEDQEKIELLKQLIALQMPLLAEGIRIHGEKLTEQLKPLHERLVSCFKDL 392


                  ..
gi 530371989 1623 RA 1624
Cdd:cd11708   393 RA 394
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 420-609 2.99e-68

C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 classes of Dock family proteins. The members here include: Dock180/Dock1, Dock2, and Dock5. Most of these members have been shown to be GEFs specific for Rac. Dock5 has not been well characterized to date, but most likely also is a GEF specific for Rac. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-A members contain a proline-rich region and a SH3 domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176076  Cd Length: 196  Bit Score: 228.44  E-value: 2.99e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  420 IRNDLYLTLEKGDFERGGKSVQKNIEVTMYVLYADGEILKDCISLGSGEPNRSSYHSFVLYHSNSPRWGEIIKLPIPIDR 499
Cdd:cd08694     1 VRNDLYLTLVQGDFDKGSKTSDKNVEVTVSVCNEDGKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  500 FRGSHLRFEFRHCST---KDKGEkKLFGFAFSTLMRDDGTTLSDDIHELYVYKCDENSTFNNHALYLGLPCCKEDYNG-- 574
Cdd:cd08694    81 FKSSHLRFTFKHRSSneaKDKSE-KPFALSFVKLMQENGTTLTDGEHDLIVYKVDAKKKLEDAKAYLSLPSTRAELEArk 159

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 530371989  575 --CPNIPSSLIFQRSTKESFFISTQLSSTKLTQNVDL 609
Cdd:cd08694   160 ssPSGSASNLGLSLSSKDSFQISTLVCSTKLTQNVDL 196
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 417-608 5.10e-68

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 227.48  E-value: 5.10e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   417 PGDIRNDLYLTLEKGDFERGGKSVQKNIEVTMYVLYADGEILKDCISLGSGEPNRSSYHSFVLYHSNSPRWGEIIKLPIP 496
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSARNIEVTVEVRDSDGEPLPNCIYGGSGGPFVTEFKSTVYYHNKSPTWYEEIKIALP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989   497 IDRFRGSHLRFEFRHCSTKDKGEK--KLFGFAFSTLMRDDGTTLSDDIHELYVYKCDENStfnnhALYLGLPCCKEDYNG 574
Cdd:pfam14429   81 AELTPKHHLLFTFYHVSCDEKKDKveKPFGYAFLPLLDDDGAFLRDGEHTLPVYKYDELP-----PGYLSLPWSSGGEKE 155

                          170       180       190
                   ....*....|....*....|....*....|....
gi 530371989   575 CPNIPSSlifqRSTKESFFISTQLSSTKLTQNVD 608
Cdd:pfam14429  156 SSALPGL----KGGKDLFKVRTRLCSTKYTQDEH 185
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 421-609 1.18e-52

C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was first identified as an 180kd proto-oncogene product c-Crk-interacting protein involved in actin cytoskeletal changes. It is now known that it has Rac-specific GEF activity, but lacks the conventional Dbl homology (DH) domain. There are 10 additional related proteins that can be divided into four classes based on sequence similarity and domain organization: Dock-A which includes Dock180/Dock1, Dock2, and Dock5; Dock-B which includes Dock3/MOCA (modifier of cell adhesion) and Dock4; Dock-C which includes Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3; and Dock-D, which includes Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Most of members of classes Dock-A and Dock-B are the GEFs specific for Rac. Those of Dock-D are Cdc42-specific GEFs while those of Dock-C are the GEFs for both. All Dock180-related proteins have two common homology domains: the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker). DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176061  Cd Length: 178  Bit Score: 183.30  E-value: 1.18e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  421 RNDLYLTLEKGDFERGgKSVQKNIEVTMYVLYADGEILKDCISL-GSGEPNRSSYHSfVLYHSNSPRWGEIIKLPIPIDR 499
Cdd:cd08679     2 RNDLYVYPQSGELSKA-KSKGRNIEITVEVRDDDGDIIEPCISApGSGSELRSEYTS-VVYYHKNPVFNDEIKIQLPADL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  500 FRGSHLRFEFRHCSTKDKG---EKKLFGFAFSTLMRDDGTTLSDDIHELYVYKCDENsTFNNHALYLGLPCCKEDyngcp 576
Cdd:cd08679    80 TPQHHLLFTFYHVSSKKKQgdkEETPFGYAFLPLMDKDGAFIKDGDHTLPVYKYDKR-PDVGPSGYLSLPSTLAN----- 153

                         170       180       190
                  ....*....|....*....|....*....|...
gi 530371989  577 nipsslifQRSTKESFFISTQLSSTKLTQNVDL 609
Cdd:cd08679   154 --------GKSSKDTFKIKTRLCSTILTQDKSL 178
SH3_DOCK3_B cd12048
Src Homology 3 domain of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of ...
 10-65 4.32e-35

Src Homology 3 domain of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), and presenilin binding protein (PBP), is a class B DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; Dock3 is a specific GEFs for Rac. The SH3 domain of Dock3 binds to DHR-2 in an autoinhibitory manner; binding of the scaffold protein Elmo to the SH3 domain of Dock3 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212981  Cd Length: 56  Bit Score: 128.09  E-value: 4.32e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEGWYRGVSTKKPNVKGIFPANYIHLK 65
Cdd:cd12048     1 YGVVICSFRGSVPQGLVLELGETVQILEKCEGWYRGVSIKKPNVKGIFPANYIHLK 56
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1527-1628 1.10e-29

DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe C which form an antiparallel four alpha-helical bundle and contains a loop known as the nucleotide sensor characterized by a conserved valine residue essential for catalytic activity.


Pssm-ID: 466570 [Multi-domain]  Cd Length: 103  Bit Score: 114.61  E-value: 1.10e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  1527 QYQHKQVHGNINLLSMCLNGVIDAAVNGGIARYQEAFFDKDYINKHPgdAEKITQLKELMQEQVHVLGVGLAVHEKFVHP 1606
Cdd:pfam20421    3 EAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYP--AEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|..
gi 530371989  1607 EMRPLHKKLIDQFQMMRASLYH 1628
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEP 102
SH3_DOCK_AB cd11872
Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are ...
 10-65 7.11e-27

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212805 [Multi-domain]  Cd Length: 56  Bit Score: 104.59  E-value: 7.11e-27
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEGWYRGVSTKKPNVKGIFPANYIHLK 65
Cdd:cd11872     1 YGVAIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGFSLRNKSLKGIFPKSYVHIK 56
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1321-1626 3.91e-26

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also called Zizimin1, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. It plays important roles in spine formation and dendritic growth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock9, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212571  Cd Length: 415  Bit Score: 113.59  E-value: 3.91e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1321 YESLYDYQSLSWIRKMEASYYDNIME----QQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEFPQ 1396
Cdd:cd11698   111 YEKRRDFERLAHLYDTLHRAYSKVTEvmhsGKRLLGTYFRVAFFGQGFFEDEDGKEYIYKEPKLTPLSEISQRLLKLYSD 190

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1397 AVAMQHPN--------HPDDaiLQCDAQYLQIYAVTPipdYVDVLQMDrvpDRVKSFYRVNNVRKFRYDRPFHKGPKdKE 1468
Cdd:cd11698   191 KFGSENVKmiqdsgkvNPKD--LDSKYAYIQVTHVTP---YFDEKELQ---ERKTDFERSHNIRRFMFEMPFTQSGK-RQ 261

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1469 NEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQYQHKQVHgninlLSMCLNGVI 1548
Cdd:cd11698   262 GGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKKVAELRQLCSSAEVDMIK-----LQLKLQGSV 336

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530371989 1549 DAAVNGGIARYQEAFFDKDYINKHPGDaeKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11698   337 SVQVNAGPLAYARAFLDDTNTKRYPDN--KVKLLKEVFRQFVEACGQALAVNERLIKEDQLEYQEEMKANYREMAKEL 412
SH3_DOCK4_B cd12049
Src Homology 3 domain of Class B Dedicator of Cytokinesis 4; Dock4 is a class B DOCK and is an ...
 10-65 8.10e-26

Src Homology 3 domain of Class B Dedicator of Cytokinesis 4; Dock4 is a class B DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. The SH3 domain of Dock4 binds to DHR-2 in an autoinhibitory manner; binding of the scaffold protein Elmo to the SH3 domain of Dock4 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212982  Cd Length: 56  Bit Score: 101.87  E-value: 8.10e-26
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEGWYRGVSTKKPNVKGIFPANYIHLK 65
Cdd:cd12049     1 YGVVVASFRGTVQHGLTLEIGDTVQILEKCEGWYRGFALKNPNVKGIFPQLYLHLK 56
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1244-1626 3.06e-25

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class D, also called the Zizimin subfamily, includes Dock9, 10 and 11. Class D Docks are specific GEFs for Cdc42. Dock9 plays important roles in spine formation and dendritic growth. Dock10 and Dock11 are preferentially expressed in lymphocytes. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class D DOCKs, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212567  Cd Length: 376  Bit Score: 110.12  E-value: 3.06e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1244 LCDMHLQAENYTEAAFTLL----LYCELLQWEDRpLREFLHYPSQTEWqrkeglcrKIIHYFNKGKSWEFGIPLcrelac 1319
Cdd:cd11694    10 MARIHEKNGNFSEAAMCYIhiaaLVAEYLKRKDL-LLELLEACVEGLW--------KAERYELLGELYKLIIPI------ 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1320 qYESLYDYQSLSWI-RKMEASYyDNIMEQQ----RLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 1394
Cdd:cd11694    75 -YEKRRDFEQLADCyRTLHRAY-EKVVEVMesgkRLLGTYYRVAFYGQAFFEEEDGKEYIYKEPKVTSLSEISERLLKLY 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1395 -----PQAVAM-QHPNHPDDAILQCDAQYLQIYAVTPipdYVDVLQMDrvpDRVKSFYRVNNVRKFRYDRPFHKGPK--- 1465
Cdd:cd11694   153 gdkfgSENVKLiQDSGKVNPKDLDPKYAYIQVTHVTP---YFDEKELE---DRKTEFERNHNIRRFVFETPFTLSGKarg 226

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1466 DKENEFKslwiERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISqyqhkQVHGNINLLSMCLN 1545
Cdd:cd11694   227 AVEEQWK----RRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSKVKELEELIS-----TEPVDMKKLQLRLQ 297

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1546 GVIDAAVNGGIARYQEAFFDKDYINKHPgdAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRAS 1625
Cdd:cd11694   298 GSVSVQVNAGPLAYARAFLEPTTVKNYP--DDQVEDLKDVFRDFIKACGQALELNERLIKEDQREYHEVLKENYRKMVKE 375


                  .
gi 530371989 1626 L 1626
Cdd:cd11694   376 L 376
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1292-1626 2.12e-23

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class C, also called the Zizimin-related (Zir) subfamily, includes Dock6, 7 and 8. Class C DOCKs have been shown to have GEF activity for both Rac and Cdc42. Dock6 regulates neurite outgrowth. Dock7 plays a critical roles in the early stages of axon formation, neuronal polarity, and myelination. Dock8 regulates T and B cell numbers and functions, and plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Class C Docks, which contains the catalytic GEF activity for Rac and Cdc42.


Pssm-ID: 212568  Cd Length: 368  Bit Score: 104.30  E-value: 2.12e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1292 GLCRKIIHYFNKGKSWEFGIPLCRELACQYESLYDYQSLSWIRKMEASYYDNIMEQQ---RLEPEFFRVGFYGRKFPFfL 1368
Cdd:cd11695    39 GLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQggkRMFGTYFRVGFYGSKFGD-L 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1369 RNKEYVCR----------GHdyeRLEAFQQRMLSEfPQAVAMQHPNHPDDAILQCDAQYLQIYAVTPipdYVDVLQMDrv 1438
Cdd:cd11695   118 DGKEFIYKepaitklpeiSH---RLETFYGERFGE-ERVEVIKDSNPVDTSKLDPDKAYIQITYVEP---YFDEYELK-- 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1439 pDRVKSFYRVNNVRKFRYDRPFHKGPK---DKENEFKslwiERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVE 1515
Cdd:cd11695   189 -ERTTYFERNYNLRRFMYATPFTPDGKahgELAEQYK----RKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQ 263

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1516 NKNQELRSLISQYQhkqvhGNINLLSMCLNGVIDAAVNGG---IAR--YQEAFFDKDYINKHPGDaekitqLKELMQEQV 1590
Cdd:cd11695   264 KKTRELAAATTQEP-----PDPKMLQMVLQGSIGTTVNQGpleVANvfLSDIPLDPKELDRHQNK------LRLCFKEFS 332

                         330       340       350
                  ....*....|....*....|....*....|....*.
gi 530371989 1591 HVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11695   333 KKCYDALEKNKELIGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1321-1626 7.12e-22

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also called Zizimin2 or activated Cdc42-associated GEF (ACG), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock11 is predominantly expressed in lymphocytes and is found in high levels in germinal center B lymphocytes after T cell dependent antigen immunization. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock11, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212573  Cd Length: 413  Bit Score: 100.84  E-value: 7.12e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1321 YESLYDYQSLSWIRKMEASYYDNIME----QQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEFPQ 1396
Cdd:cd11700   112 YEKRREFEKLTQLYRTLHGAYAKILEvmhtGKRLLGTFFRVAFYGQGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGE 191

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1397 AVA------MQHPNHPDDAILQCDAQYLQIYAVTPipdYVDVLQMdrvPDRVKSFYRVNNVRKFRYDRPFHKGPKdKENE 1470
Cdd:cd11700   192 KFGsenvkiIQDSNKVNQKDLDPKYAHIQVTYVKP---YFDDKEM---AERKTEFERNHNIQRFVFETPYTLSGK-KQGG 264

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1471 FKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRSLISQyqhkqvhGNINL--LSMCLNGVI 1548
Cdd:cd11700   265 VEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKDKTAELQKLCSN-------QDVDMiqLQLKLQGCV 337

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530371989 1549 DAAVNGGIARYQEAFFDKDYINKHPgdAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11700   338 SVQVNAGPLAYARAFLDDSQASKYP--NKKVKELKEMFRKFIQACSIALELNERLIKEDQVEYHEGLKSNFRDMVKEL 413
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1404-1486 3.13e-21

DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe B which adopts an unusual architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement. This lobe changes its position relative to lobe C and the bound GTPase, which suggests that lobe B distinguishes between the switch 1 conformations of Rac1 and Cdc42.


Pssm-ID: 466571 [Multi-domain]  Cd Length: 77  Bit Score: 89.20  E-value: 3.13e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  1404 NHPDDAILQCDAQYLQIYAVTPipdYVDVLQMdrvPDRVKSFYRVNNVRKFRYDRPFHKGPKdKENEFKSLWIERTTLTL 1483
Cdd:pfam20422    2 NPVDESILDPDKAYIQITSVEP---YFDDSEL---NDRVTYFERNNNVNRFVFETPFTKSGK-AQGEFEEQWKRRTILTT 74


                   ...
gi 530371989  1484 THS 1486
Cdd:pfam20422   75 EHS 77
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1292-1626 9.06e-21

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also called Zizimin-related 3 (Zir3), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. Dock8 is highly expressed in the immune system and it regulates T and B cell numbers and functions. It plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. Dock8 deficiency is a primary immune deficiency that results in extreme susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia. It was originally described as an autosomal recessive form of hyper IgE syndrome (AR-HIES). DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock8, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212574  Cd Length: 422  Bit Score: 97.41  E-value: 9.06e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1292 GLCRKIIHYFNKGKSWEFGIPLCRELACQYESLYDYQSLSWIRKMEASYYDNIME--QQRLEPEFFRVGFYGRKFPfFLR 1369
Cdd:cd11701    95 GLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINkgHKRMFGTYFRVGFYGSKFG-DLD 173

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1370 NKEYVCRGHDYERLEAFQQRMLSEFPQ-----AVAMQHPNHP-DDAILQCDAQYLQIYAVTPipdYVDVLQMDrvpDRVK 1443
Cdd:cd11701   174 EQEFIYKEPAITKLPEISHRLEGFYGQcfgddVVEVIKDSTPvDKSKLDPNKAYIQITFVEP---YFDDYEMK---DRVT 247

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1444 SFYRVNNVRKFRYDRPFHKGPKDKeNEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRS 1523
Cdd:cd11701   248 YFEKNFNLRRFMYTTPFTLDGRPR-GELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAE 326

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1524 LISQYQHKQVhgninLLSMCLNGVIDAAVNGGIARYQEAFFDKdyINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKF 1603
Cdd:cd11701   327 ATHQEPPDAK-----MLQMVLQGSVGATVNQGPLEVAQVFLAE--IPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRL 399

                         330       340
                  ....*....|....*....|...
gi 530371989 1604 VHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11701   400 ITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1292-1626 4.97e-19

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also called Zizimin-related 1 (Zir1), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. It is widely expressed and shows highest expression in the dorsal root ganglion and the brain. It regulates neurite outgrowth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock6, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212575  Cd Length: 423  Bit Score: 91.99  E-value: 4.97e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1292 GLCRKIIHYFNKGKSWEFGIPLCRELACQYESLYDYQSLSWIRKMEASYYDNIMEQ----QRLEPEFFRVGFYGRKFPFf 1367
Cdd:cd11702    94 GLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQssgwERMFGTYFRVGFYGCKFGD- 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1368 LRNKEYVCRGHDYERLEAFQQRmLSEF------PQAVAM-QHPNHPDDAILQCDAQYLQIYAVTPipdYVDVLQMDrvpD 1440
Cdd:cd11702   173 LDEQEFVYKEPSITKLAEISHR-LEEFyterfgDEVVEIiKDSNPVDKSKLDPNKAYIQITYVEP---FFDTYELK---D 245

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1441 RVKSFYRVNNVRKFRYDRPFHKGPKdKENEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQE 1520
Cdd:cd11702   246 RVTYFDKNYNLRTFLFCTPFTLDGR-AHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQKKTQE 324

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1521 LrslisQYQHKQVHGNINLLSMCLNGVIDAAVNGGIARYQEAFFDKdyINKHPGDAEKITQLKELMQEQVHVLGVGLAVH 1600
Cdd:cd11702   325 L-----AFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSE--IPEDPKLFRHHNKLRLCFKDFTKRCEDALRKN 397

                         330       340
                  ....*....|....*....|....*.
gi 530371989 1601 EKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11702   398 KALIGPDQKEYHRELERNYQRLREAL 423
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1293-1619 5.35e-19

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 92.42  E-value: 5.35e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1293 LCrkiIHYFNKGKSWEFGIPLCRELACQYESLYDYQSLSWIrkmeasYYD------NIME----QQRLEPEFFRVGFYGR 1362
Cdd:cd11699   120 LC---VDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSEL------YYDihrsylKVAEvvnsEKRLFGRYYRVAFYGQ 190

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1363 KFPFFLRNKEYVCRGHDYERLEAFQQRMLSEFPQAVA------MQHPNHPDDAILQCDAQYLQIYAVTPIPDYVDvlQMD 1436
Cdd:cd11699   191 GFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGadnvkiIQDSNKVNPKELDPKFAYIQVTYVTPYFDEKE--QED 268

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1437 RVPDrvksFYRVNNVRKFRYDRPFHKGPKdKENEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVEN 1516
Cdd:cd11699   269 RKTD----FEMHHNINRFVFETPFTLSGK-KHGGVEEQCKRRTILTTSHSFPYVKKRIQVVSQTSTELNPIEVAIDEMSK 343

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1517 KNQELRSLISQYQHKQVHgninlLSMCLNGVIDAAVNGGIARYQEAFFDKDYINKHPGDAEKItqLKELMQEQVHVLGVG 1596
Cdd:cd11699   344 KVSELNQLCTMEEVDMIR-----LQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFAEACGQA 416

                         330       340       350
                  ....*....|....*....|....*....|
gi 530371989 1597 LAVHEKFV-------HPEMRPLHKKLIDQF 1619
Cdd:cd11699   417 LDVNERLIkedqleyQEEMRSHYRDMLSEL 446
SH3_DOCK1_5_A cd12051
Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called ...
 10-65 5.45e-15

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212984 [Multi-domain]  Cd Length: 56  Bit Score: 71.00  E-value: 5.45e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEGWYRGVSTKKPNVKGIFPANYIHLK 65
Cdd:cd12051     1 YGVAIYNYDARGPDELSLQIGDTVHILETYEGWYRGYTLRKKSKKGIFPASYIHLK 56
SH3_DOCK2_A cd12050
Src Homology 3 domain of Class A Dedicator of Cytokinesis protein 2; Dock2 is a hematopoietic ...
 10-65 2.55e-14

Src Homology 3 domain of Class A Dedicator of Cytokinesis protein 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock2 binds to DHR-2 in an autoinhibitory manner; binding of the scaffold protein Elmo to the SH3 domain of Dock2 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212983  Cd Length: 56  Bit Score: 69.10  E-value: 2.55e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEGWYRGVSTKKPNVKGIFPANYIHLK 65
Cdd:cd12050     1 YGVAIYNFKGSGVPQLSLQIGDVVHIQETCEDWYKGYLVRHKDLQGIFPKSFIHIK 56
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1321-1626 2.79e-14

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also called Zizimin-related 2 (Zir2), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. It plays a critical role in the initial specification of axon formation in hippocampal neurons. It affects neuronal polarity by regulating microtubule dynamics. Dock7 also plays a role in controlling myelination by Schwann cells. It may also play important roles in the function and distribution of dermal and follicular melanocytes. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock7, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212576  Cd Length: 473  Bit Score: 77.81  E-value: 2.79e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1321 YESLYDYQSLSWIRKMEASYYDNIMEQ--QRLEPEFFRVGFYGRKFPFfLRNKEYVCR-------GHDYERLEAFQQRML 1391
Cdd:cd11703   162 HEANRDAKKLATIHGKLQEAFSKIVHQdgKRMFGTYFRVGFYGTKFGD-LDEQEFVYKepaitklAEISHRLEGFYGERF 240

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1392 SEfPQAVAMQHPNHPDDAILQCDAQYLQIYAVTPipdYVDVLQMDrvpDRVKSFYRVNNVRKFRYDRPFH---KGPKDKE 1468
Cdd:cd11703   241 GE-DVVEVIKDSNPVDKCKLDPNKAFIQITYVEP---YFDTYEMK---DRITYFDKNYNLRRFMYCTPFTldgRAHGELH 313

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1469 NEFKslwiERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELrslisQYQHKQVHGNINLLSMCLNGVI 1548
Cdd:cd11703   314 EQFK----RKTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQEL-----AFATHQDPADPKMLQMVLQGSV 384

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530371989 1549 DAAVNGGIARYQEAFFDKdyINKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRASL 1626
Cdd:cd11703   385 GTTVNQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEAL 460
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1222-1346 8.57e-13

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 68.09  E-value: 8.57e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  1222 NLMNFYKSEinkEEMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQwEDRPLREFLHYPSQT-------------EWQ 1288
Cdd:pfam06920    5 SLANSYKSS---PDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIA-EYLKLKGKIPNPLGAsafekispnilreESA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530371989  1289 RKE--GLC--------------RKIIHYFNKGKSWEFGIPLCRELACQYESLYDYQSLSWIRKMEASYYDNIME 1346
Cdd:pfam06920   81 LKDdsGVCdsphftedglvgllEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIVE 154
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 458-609 2.98e-08

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176079  Cd Length: 185  Bit Score: 55.79  E-value: 2.98e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  458 LKdCISLGSGEPNRSSYHSFVLYHSNSPRWGEIIKLPIPIDRFRGSHLRFEFRH--CSTKDKGEKK-----LFGFAFSTL 530
Cdd:cd08697    43 LK-CIYYGPGGGFTTSAYAAVLHHNQNPEFYDEIKIELPTQLHEKHHLLFTFYHvsCDINKKGKKKdgvetPVGYAWLPL 121

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530371989  531 MRDDGtTLSDDIHELYVYKCDENSTFNNHALYLGLPCCKEDYNGcpnipsslifqrstKESFFISTQLSSTKLTQNVDL 609
Cdd:cd08697   122 LKDKG-RLNSEEQTPPVANLLPNYPDGYLSIQPHGPEVKWVDGG--------------KPLFKVSTHLVSTVYTQDQHL 185
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 7-62 1.61e-07

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 49.84  E-value: 1.61e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 530371989      7 EEKYGVVICSFRGSVPQGLVLEIGETVQILEKCE-GWYRGvsTKKPNVKGIFPANYI 62
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDdGWWKG--RLGRGKEGLFPSNYV 55
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 10-61 2.27e-06

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 46.30  E-value: 2.27e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKC-EGWYRGVSTKkpNVKGIFPANY 61
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDdDGWWEGELNG--GREGLFPANY 51
SH3_Eve1_2 cd11815
Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
 10-62 8.07e-06

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212749 [Multi-domain]  Cd Length: 52  Bit Score: 44.86  E-value: 8.07e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEG-WYRGvstKKPNVKGIFPANYI 62
Cdd:cd11815     1 HAVVLHDFPAEHSDDLSLNSGEIVYLLEKIDTeWYRG---KCKNTTGIFPANHV 51
SH3_SH3RF2_3 cd11784
Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
 12-62 8.70e-06

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212718  Cd Length: 55  Bit Score: 44.77  E-value: 8.70e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530371989   12 VVICSFRGSVPQGLVLEIGETVQILEKC-EGWYRGVSTKKPNVkGIFPANYI 62
Cdd:cd11784     3 VALHSYSAHRPEELELQKGEGVRVLGKFqEGWLRGLSLVTGRV-GIFPSNYV 53
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
 10-62 1.31e-05

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 44.12  E-value: 1.31e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 530371989    10 YGVVICSFRGSVPQGLVLEIGETVQILEK-CEGWYRGVSTKKpnvKGIFPANYI 62
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKdNDGWWEGETGGR---VGLVPSTAV 51
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
 25-62 1.09e-04

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 41.55  E-value: 1.09e-04
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 530371989   25 LVLEIGETVQILEKCE-GWYRGvstKKPNVKGIFPANYI 62
Cdd:cd11874    16 LELKVGDTIEVLGEVEeGWWEG---KLNGKVGVFPSNFV 51
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
 12-62 2.00e-04

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 41.08  E-value: 2.00e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530371989   12 VVICSFRGSVPQGLVLEIGETVQILEK-CEGWYRgvsTKKPNVKGIFPANYI 62
Cdd:cd11856     3 VAIADYEAQGDDEISLQEGEVVEVLEKnDSGWWY---VRKGDKEGWVPASYL 51
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
 10-64 2.17e-04

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 40.87  E-value: 2.17e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 530371989   10 YGVVICSFRGSVPQGLVLEIGETVQILEKCEG---WYRGvstKKPNVKGIFPANYIHL 64
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSqndWWTG---RIGGREGIFPANYVEL 55
SH3_Sorbs_3 cd11780
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) ...
 25-62 2.82e-04

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212714 [Multi-domain]  Cd Length: 55  Bit Score: 40.36  E-value: 2.82e-04
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 530371989   25 LVLEIGETVQILEKC-EGWYRGVSTKKPNVkGIFPANYI 62
Cdd:cd11780    16 LELREGDIVYVMEKCdDGWFVGTSERTGLF-GTFPGNYV 53
SH3_SH3RF3_3 cd11925
Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
 25-62 5.33e-04

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212858  Cd Length: 57  Bit Score: 39.98  E-value: 5.33e-04
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 530371989   25 LVLEIGETVQILEKCE-GWYRGVSTKKpNVKGIFPANYI 62
Cdd:cd11925    17 LELRKGEMYRVIEKCQdGWFKGTSLRT-GVSGVFPGNYV 54
SH3_SH3RF_3 cd11783
Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and ...
 12-62 7.42e-04

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212717 [Multi-domain]  Cd Length: 55  Bit Score: 39.30  E-value: 7.42e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530371989   12 VVICSFRGSVPQGLVLEIGETVQILEKC-EGWYRGVSTKKpNVKGIFPANYI 62
Cdd:cd11783     3 VALYPYKPQKPDELELRKGEMYTVTEKCqDGWFKGTSLRT-GQSGVFPGNYV 53
PHA03247 PHA03247
large tegument protein UL36; Provisional
 1751-2046 1.48e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.77  E-value: 1.48e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1751 APSQMITSAPSSARDKYRHAREMMlllPTYRDRPSSAMYPAAILEN-----GQPPNFQRALFQQVVGACKPCSDPNLSVA 1825
Cdd:PHA03247 2655 DPAPGRVSRPRRARRLGRAAQASS---PPQRPRRRAARPTVGSLTSladppPPPPTPEPAPHALVSATPLPPGPAAARQA 2731

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1826 EKAVPAAPSSWSLDSGAqeAQPFLSAHMGRILAPPVPPRSLlhghyslhfdAFHHPLGDTPPALP----ARTLRKSPLHP 1901
Cdd:PHA03247 2732 SPALPAAPAPPAVPAGP--ATPGGPARPARPPTTAGPPAPA----------PPAAPAAGPPRRLTrpavASLSESRESLP 2799

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989 1902 IPASPTSPQSGLDGSNSTLSGSASSGVSSLSESNFGHSSEAPPRTDTMDSMPSQAWNA-DEDLE---PPYLPVHYSLSES 1977
Cdd:PHA03247 2800 SPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVApGGDVRrrpPSRSPAAKPAAPA 2879

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530371989 1978 AVLDSIKAQPCRSHSAPGCVIPQDPMDPPALPPKPYHPRLPALEhdEGVLLREETERPRGLhRKAPLPP 2046
Cdd:PHA03247 2880 RPPVRRLARPAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQP--PPPPQPQPPPPPPPR-PQPPLAP 2945
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 421-534 5.35e-03

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 classes of Dock family proteins. The members here include: Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3. Dock-C members are GEFs for both Rac and Cdc42. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-C members contain a functionally uncharacterized domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176078  Cd Length: 179  Bit Score: 40.03  E-value: 5.35e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530371989  421 RNDLYLTLEKGDF-ERGGKSvqKNIEVTMYVLYADGEILKDCISLGSGEPNRSSYHSF--VLYHSNSPRWGEIIKLPIPI 497
Cdd:cd08696     2 RNLLYVYPQSLNFsNRLGSA--RNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYtaVTYHNKSPDFYDEIKIKLPA 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 530371989  498 DRFRGSHLRFEFRH--CSTKDKGE--KKLFGFAFSTLMRDD 534
Cdd:cd08696    80 DLTDNHHLLFTFYHisCQKKQEGGsvETPIGYTWLPLLRNG 120
 
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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