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Conserved domains on  [gi|299473744|ref|NP_001177387|]
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dedicator of cytokinesis protein 8 isoform 2 [Homo sapiens]

Protein Classification

dedicator of cytokinesis protein 7( domain architecture ID 10570936)

dedicator of cytokinesis protein 7 functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1536-1957 0e+00

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: 924.44  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1536 ASPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDED 1615
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1616 GVCAGQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDHKRMFGTYF 1695
Cdd:cd11701    81 GVCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINKGHKRMFGTYF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1696 RVGFFGSKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDEY 1775
Cdd:cd11701   161 RVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDY 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1776 EMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKK 1855
Cdd:cd11701   241 EMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1856 TLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 1935
Cdd:cd11701   321 TRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 400

                         410       420
                  ....*....|....*....|..
gi 299473744 1936 TADQREYQQELKKNYNKLKENL 1957
Cdd:cd11701   401 TADQREYQQELKKNYNKLRENL 422
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 491-671 1.34e-109

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: 346.26  E-value: 1.34e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  491 YRNLLYVYPQRLNFVNKLASARNITIKIQFMCGEDASNAMPVIFGKSSGPEFLQEVYTAVTYHNKSPDFYEEVKIKLPAK 570
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  571 LTVNHHLLFTFYHISCQQKQ-GASVETLLGYSWLPILLNERLQTGSYCLPVALEKLPPNYSMHSAEkvpLQNPPIKWAEG 649
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPE---VKLPGTKWVDN 157

                         170       180
                  ....*....|....*....|..
gi 299473744  650 HKGVFNIEVQAVSSVHTQDNHL 671
Cdd:cd08696   158 HKGVFSVSVEAVSSVHTQDSYL 179
DOCK_C-D_N super family cl13339
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 1-98 3.11e-33

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


The actual alignment was detected with superfamily member pfam11878:

Pssm-ID: 463380  Cd Length: 112  Bit Score: 125.07  E-value: 3.11e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744     1 MTHLNSLDVQLAQELGDFTDDDLDVVFTPKECRTLQPSLPEEG-VELDPHVRDCVQTYIREWLIVNRKNQGSPEICGFKK 79
Cdd:pfam11878   14 SQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAeKEADPLVRECIKTYTSDWHVVNYKYEDYSGDFRQLP 93

                           90
                   ....*....|....*....
gi 299473744    80 TGSRKDFHKTLPKQTFESE 98
Cdd:pfam11878   94 KSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1536-1957 0e+00

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: 924.44  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1536 ASPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDED 1615
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1616 GVCAGQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDHKRMFGTYF 1695
Cdd:cd11701    81 GVCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINKGHKRMFGTYF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1696 RVGFFGSKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDEY 1775
Cdd:cd11701   161 RVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDY 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1776 EMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKK 1855
Cdd:cd11701   241 EMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1856 TLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 1935
Cdd:cd11701   321 TRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 400

                         410       420
                  ....*....|....*....|..
gi 299473744 1936 TADQREYQQELKKNYNKLKENL 1957
Cdd:cd11701   401 TADQREYQQELKKNYNKLRENL 422
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 491-671 1.34e-109

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: 346.26  E-value: 1.34e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  491 YRNLLYVYPQRLNFVNKLASARNITIKIQFMCGEDASNAMPVIFGKSSGPEFLQEVYTAVTYHNKSPDFYEEVKIKLPAK 570
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  571 LTVNHHLLFTFYHISCQQKQ-GASVETLLGYSWLPILLNERLQTGSYCLPVALEKLPPNYSMHSAEkvpLQNPPIKWAEG 649
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPE---VKLPGTKWVDN 157

                         170       180
                  ....*....|....*....|..
gi 299473744  650 HKGVFNIEVQAVSSVHTQDNHL 671
Cdd:cd08696   158 HKGVFSVSVEAVSSVHTQDSYL 179
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 488-670 2.61e-63

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: 214.00  E-value: 2.61e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744   488 HTVYRNLLYVYPQRLNFVN-KLASARNITIKIQFMCGEdaSNAMP-VIFGKSSGPeFLQEVYTAVTYHNKSPDFYEEVKI 565
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKqKKSSARNIEVTVEVRDSD--GEPLPnCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744   566 KLPAKLTVNHHLLFTFYHISCQQKQGaSVETLLGYSWLPILLNER--LQTGSYCLPVAL-EKLPPNY----SMHSAEKVP 638
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKKD-KVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKyDELPPGYlslpWSSGGEKES 156

                          170       180       190
                   ....*....|....*....|....*....|..
gi 299473744   639 LQNPPIKwaeGHKGVFNIEVQAVSSVHTQDNH 670
Cdd:pfam14429  157 SALPGLK---GGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1525-1683 1.39e-62

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: 210.61  E-value: 1.39e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  1525 DLMYRIAKSYQASPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLeDHSYLPVGSVSFQNISSNVL-EES 1603
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  1604 VVSEDTlspdedGVCAGQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIV 1683
Cdd:pfam06920   80 ALKDDS------GVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIV 153
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 1-98 3.11e-33

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 125.07  E-value: 3.11e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744     1 MTHLNSLDVQLAQELGDFTDDDLDVVFTPKECRTLQPSLPEEG-VELDPHVRDCVQTYIREWLIVNRKNQGSPEICGFKK 79
Cdd:pfam11878   14 SQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAeKEADPLVRECIKTYTSDWHVVNYKYEDYSGDFRQLP 93

                           90
                   ....*....|....*....
gi 299473744    80 TGSRKDFHKTLPKQTFESE 98
Cdd:pfam11878   94 KSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1536-1957 0e+00

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: 924.44  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1536 ASPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDED 1615
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1616 GVCAGQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDHKRMFGTYF 1695
Cdd:cd11701    81 GVCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINKGHKRMFGTYF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1696 RVGFFGSKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDEY 1775
Cdd:cd11701   161 RVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDY 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1776 EMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKK 1855
Cdd:cd11701   241 EMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1856 TLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 1935
Cdd:cd11701   321 TRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 400

                         410       420
                  ....*....|....*....|..
gi 299473744 1936 TADQREYQQELKKNYNKLKENL 1957
Cdd:cd11701   401 TADQREYQQELKKNYNKLRENL 422
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1537-1957 0e+00

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: 738.74  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1537 SPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDEDG 1616
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1617 VCAGQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDH--KRMFGTY 1694
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSgwERMFGTY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1695 FRVGFFGSKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDE 1774
Cdd:cd11702   161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1775 YEMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKK 1854
Cdd:cd11702   241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1855 KTLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRL 1934
Cdd:cd11702   321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                         410       420
                  ....*....|....*....|...
gi 299473744 1935 ITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11702   401 IGPDQKEYHRELERNYQRLREAL 423
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1498-1970 0e+00

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: 736.12  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1498 ELLCNLNSILYDTVKMREFQEDPEMLMDLMYRIAKSYQASPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLS 1577
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1578 MLEDHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDEDGVCAGQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIP 1657
Cdd:cd11703    81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1658 ILEAHREFRKLTLTHSKLQRAFDSIVNKDHKRMFGTYFRVGFFGSKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCF 1737
Cdd:cd11703   161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGKRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERF 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1738 GAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDEYEMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNT 1817
Cdd:cd11703   241 GEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKT 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1818 VLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKKTLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFL 1897
Cdd:cd11703   321 ILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFL 400

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 299473744 1898 AEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITADQREYQQELKKNYNKLKENLRPMIERKIPELYK 1970
Cdd:cd11703   401 SEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 473
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1537-1957 0e+00

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: 693.66  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1537 SPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALvaeylsmledhsylpvgsvsfqnissnvleesvvsedtlspdedg 1616
Cdd:cd11695     1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1617 vcagqyftesGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKD-HKRMFGTYF 1695
Cdd:cd11695    36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQgGKRMFGTYF 105

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1696 RVGFFGSKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDEY 1775
Cdd:cd11695   106 RVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEY 185

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1776 EMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKK 1855
Cdd:cd11695   186 ELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKK 265

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1856 TLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPK-LYRHHNKLRLCFKEFIMRCGEAVEKNKRL 1934
Cdd:cd11695   266 TRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKeLDRHQNKLRLCFKEFSKKCYDALEKNKEL 345

                         410       420
                  ....*....|....*....|...
gi 299473744 1935 ITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11695   346 IGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1539-1957 1.88e-130

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: 414.04  E-value: 1.88e-130
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1539 DLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMledhsylpvgsvsfqnissnvleesvvsEDTLspdedgvc 1618
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKR----------------------------KDLL-------- 44

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1619 agqyftesglVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDH--KRMFGTYFR 1696
Cdd:cd11694    45 ----------LELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMEsgKRLLGTYYR 114

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1697 VGFFG-SKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDEY 1775
Cdd:cd11694   115 VAFYGqAFFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEK 194

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1776 EMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKK 1855
Cdd:cd11694   195 ELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSK 274

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1856 TLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLaEIPADPKLYRHH-NKLRLCFKEFIMRCGEAVEKNKRL 1934
Cdd:cd11694   275 VKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFL-EPTTVKNYPDDQvEDLKDVFRDFIKACGQALELNERL 353

                         410       420
                  ....*....|....*....|...
gi 299473744 1935 ITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11694   354 IKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1538-1957 4.73e-117

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: 377.41  E-value: 4.73e-117
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1538 PDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLsmlEDHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDedgv 1617
Cdd:cd11700     1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFL---HRKKLFPSGCAAFKKITPNIDEEGAMKEDIGMMD---- 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1618 cagQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDH--KRMFGTYF 1695
Cdd:cd11700    74 ---VHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMHtgKRLLGTFF 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1696 RVGFFG-SKFGDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDE 1774
Cdd:cd11700   151 RVAFYGqGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYFDD 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1775 YEMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKK 1854
Cdd:cd11700   231 KEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKD 310

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1855 KTLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRL 1934
Cdd:cd11700   311 KTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKKVKELKEMFRKFIQACSIALELNERL 390

                         410       420
                  ....*....|....*....|...
gi 299473744 1935 ITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11700   391 IKEDQVEYHEGLKSNFRDMVKEL 413
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1539-1957 8.93e-112

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: 361.62  E-value: 8.93e-112
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1539 DLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLEDHSylpvgsvsfqnissnvleesvvSEDTLSPDEdgvc 1618
Cdd:cd11684     1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKALVPAL----------------------AESLSFPEQ---- 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1619 agqyFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDhkRMFGTYFRVG 1698
Cdd:cd11684    55 ----TSFERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEKD--RLFPTYFRVG 128

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1699 FFGSKF-GDLDEQEFVYKEPAITKLPEISHRLEAFYGQCfgaefvEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDEYEM 1777
Cdd:cd11684   129 FYGKGFpESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDEDL 202

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1778 K----DRVTYFEKNFNLRRFMYTTPFTLEGRPR-GELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDM 1852
Cdd:cd11684   203 VsraaPGVRQFYRNNNINTFVYERPFTKGGKKSqNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIEDI 282

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1853 KKKTLQLAVAINQ----EPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHH-NKLRLCFKEFIMRCGEA 1927
Cdd:cd11684   283 EKKTEELRSLINKyrsgDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEEYLSNYPEAEKvKKLKEAFEEFLEILKRG 362

                         410       420       430
                  ....*....|....*....|....*....|
gi 299473744 1928 VEKNKRLITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11684   363 LALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 491-671 1.34e-109

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: 346.26  E-value: 1.34e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  491 YRNLLYVYPQRLNFVNKLASARNITIKIQFMCGEDASNAMPVIFGKSSGPEFLQEVYTAVTYHNKSPDFYEEVKIKLPAK 570
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  571 LTVNHHLLFTFYHISCQQKQ-GASVETLLGYSWLPILLNERLQTGSYCLPVALEKLPPNYSMHSAEkvpLQNPPIKWAEG 649
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPE---VKLPGTKWVDN 157

                         170       180
                  ....*....|....*....|..
gi 299473744  650 HKGVFNIEVQAVSSVHTQDNHL 671
Cdd:cd08696   158 HKGVFSVSVEAVSSVHTQDSYL 179
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1539-1957 1.96e-108

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: 352.79  E-value: 1.96e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1539 DLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMledHSYLPVGSVSFQNISSNVLEESVVSEDTLSPDedgvc 1618
Cdd:cd11698     1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTR---KGMFRQGCTAFRVITPNIDEEASMMEDVGMQD----- 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1619 agQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVNKDH--KRMFGTYFR 1696
Cdd:cd11698    73 --VHFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVMHsgKRLLGTYFR 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1697 VGFFGSKF-GDLDEQEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVEVIKDSTPVDKTKLDPNKAYIQITFVEPYFDEY 1775
Cdd:cd11698   151 VAFFGQGFfEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDEK 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1776 EMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKK 1855
Cdd:cd11698   231 ELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKK 310

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1856 TLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 1935
Cdd:cd11698   311 VAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERLI 390

                         410       420
                  ....*....|....*....|..
gi 299473744 1936 TADQREYQQELKKNYNKLKENL 1957
Cdd:cd11698   391 KEDQLEYQEEMKANYREMAKEL 412
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1538-1957 5.38e-106

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: 347.03  E-value: 5.38e-106
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1538 PDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYL--------------SMLEDHSYLP----------------V 1587
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLkrkgywkmekictsSMLPEDSQVYdsnlllttstggsmfsM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1588 GSVSFQNISSNVLEESVVSEDTLSPDEDgvcagqyFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRK 1667
Cdd:cd11699    81 GWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1668 LTLTHSKLQRAF---DSIVNKDhKRMFGTYFRVGFFGSKFGDLDE-QEFVYKEPAITKLPEISHRLEAFYGQCFGAEFVE 1743
Cdd:cd11699   154 LSELYYDIHRSYlkvAEVVNSE-KRLFGRYYRVAFYGQGFFEEEEgKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVK 232

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1744 VIKDSTPVDKTKLDPNKAYIQITFVEPYFDEYEMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMH 1823
Cdd:cd11699   233 IIQDSNKVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSH 312

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1824 AFPYIKTRISVIQKEEFVLTPIEVAIEDMKKKTLQLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPAD 1903
Cdd:cd11699   313 SFPYVKKRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAK 392

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....
gi 299473744 1904 PKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11699   393 KYPDNQVKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 488-670 2.61e-63

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: 214.00  E-value: 2.61e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744   488 HTVYRNLLYVYPQRLNFVN-KLASARNITIKIQFMCGEdaSNAMP-VIFGKSSGPeFLQEVYTAVTYHNKSPDFYEEVKI 565
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKqKKSSARNIEVTVEVRDSD--GEPLPnCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744   566 KLPAKLTVNHHLLFTFYHISCQQKQGaSVETLLGYSWLPILLNER--LQTGSYCLPVAL-EKLPPNY----SMHSAEKVP 638
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKKD-KVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKyDELPPGYlslpWSSGGEKES 156

                          170       180       190
                   ....*....|....*....|....*....|..
gi 299473744   639 LQNPPIKwaeGHKGVFNIEVQAVSSVHTQDNH 670
Cdd:pfam14429  157 SALPGLK---GGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1525-1683 1.39e-62

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: 210.61  E-value: 1.39e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  1525 DLMYRIAKSYQASPDLRLTWLQNMAEKHTKKKCYTEAAMCLVHAAALVAEYLSMLeDHSYLPVGSVSFQNISSNVL-EES 1603
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  1604 VVSEDTlspdedGVCAGQYFTESGLVGLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIV 1683
Cdd:pfam06920   80 ALKDDS------GVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIV 153
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 491-671 1.40e-53

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: 185.99  E-value: 1.40e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  491 YRNLLYVYPQRLNFVNK--LASARNITIKIQFMCGEDAsNAMPV--IFGKSSGPeFLQEVYTAVTYHNKSPDFYEEVKIK 566
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQktFAKARNIAVCIEFRDSDEE-DAKPLkcIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  567 LPAKLTVNHHLLFTFYHISCQQ----KQGASVETLLGYSWLPILLNE-RLQTGSYCLPVALekLPPNYSMHSAEKVPLQn 641
Cdd:cd08697    79 LPTQLHEKHHLLFTFYHVSCDInkkgKKKDGVETPVGYAWLPLLKDKgRLNSEEQTPPVAN--LLPNYPDGYLSIQPHG- 155

                         170       180       190
                  ....*....|....*....|....*....|
gi 299473744  642 PPIKWAEGHKGVFNIEVQAVSSVHTQDNHL 671
Cdd:cd08697   156 PEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 491-671 2.35e-45

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: 162.11  E-value: 2.35e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  491 YRNLLYVYPQRLNFVNKLASARNITIKIQFMCGEDASNAMPVIFGKSSgpEFLQEVYTAVTYHNKSPDFYEEVKIKLPAK 570
Cdd:cd08679     1 LRNDLYVYPQSGELSKAKSKGRNIEITVEVRDDDGDIIEPCISAPGSG--SELRSEYTSVVYYHKNPVFNDEIKIQLPAD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  571 LTVNHHLLFTFYHISCQQKQGASVETLLGYSWLPIL--LNERLQTGSYCLPVALE-KLPPNYSMHSAEKVPLQNPPikwa 647
Cdd:cd08679    79 LTPQHHLLFTFYHVSSKKKQGDKEETPFGYAFLPLMdkDGAFIKDGDHTLPVYKYdKRPDVGPSGYLSLPSTLANG---- 154

                         170       180
                  ....*....|....*....|....
gi 299473744  648 EGHKGVFNIEVQAVSSVHTQDNHL 671
Cdd:cd08679   155 KSSKDTFKIKTRLCSTILTQDKSL 178
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1858-1960 4.44e-45

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: 158.53  E-value: 4.44e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  1858 QLAVAINQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITA 1937
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|...
gi 299473744  1938 DQREYQQELKKNYNKLKENLRPM 1960
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEPY 103
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1748-1824 3.71e-37

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: 134.66  E-value: 3.71e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 299473744  1748 STPVDKTKLDPNKAYIQITFVEPYFDEYEMKDRVTYFEKNFNLRRFMYTTPFTLEGRPRGELHEQYRRNTVLTTMHA 1824
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEHS 77
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 1-98 3.11e-33

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 125.07  E-value: 3.11e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744     1 MTHLNSLDVQLAQELGDFTDDDLDVVFTPKECRTLQPSLPEEG-VELDPHVRDCVQTYIREWLIVNRKNQGSPEICGFKK 79
Cdd:pfam11878   14 SQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAeKEADPLVRECIKTYTSDWHVVNYKYEDYSGDFRQLP 93

                           90
                   ....*....|....*....
gi 299473744    80 TGSRKDFHKTLPKQTFESE 98
Cdd:pfam11878   94 KSKRRERPEKLPKQVFEID 112
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1670-1957 1.39e-15

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: 80.95  E-value: 1.39e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1670 LTHSKLQRA--FDSIVnkDHKRMFGTYFRVGFFGSKFGD-LDEQEFVYKEPAITKLPEISHRLEAFYGQcfgaefVEVIK 1746
Cdd:cd11696    96 LSHILRMEAsfYDNIL--TQLRPEPEYFRVGFYGKGFPLfLRNKQFVYRGLDYERIGAFTQRLQSEFPQ------AHILT 167

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1747 DSTPVDKTKLDPNKAYIQITFVEP------YFDEYEMKDRVTYFEKNFNLRRFMYTTPFTLEGRPR-GELHEQYRRNTVL 1819
Cdd:cd11696   168 KNTPPDDAILQADGQYIQICNVKPvperrpVLQMVGVPDKVRSFYRVNDVRKFQYDRPIHKGPIDKdNEFKSLWIERTTL 247

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1820 TTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKKTLQLAVAINQEPPDAK----MLQMVLQGSVGATVNQGPLEVAQV 1895
Cdd:cd11696   248 VTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTrninPFSMRLQGVIDAAVNGGIAKYQEA 327

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 299473744 1896 FLAE--IPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11696   328 FFTPefILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVERFTQMKQSL 391
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1694-1963 1.02e-14

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: 78.52  E-value: 1.02e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1694 YFRVGFFGSKFGD-LDEQEFVYKEPAITKLPEISHRLEAFYGQcfgaefVEVIKDSTPVDKTKLDPNKAYIQITFVEPYF 1772
Cdd:cd11697   125 YFRVGYYGQGFPSfLRNKVFIYRGKEYERLSDFSARLLNQFPN------AELMNTLTPPGDEIKESPGQYLQINKVDPVM 198

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1773 DEY-EMKDR------VTYFEKNfNLRRFMYTTPFTLEGR-PRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTP 1844
Cdd:cd11697   199 DERpRFKGKpvsdqiLNYYKVN-EVQRFTFSRPFRRGTKdPDNEFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISP 277

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1845 IEVAIEDMKKKTLQLAVAINQEPPDAKM----LQMVLQGSVGATVNQGPLEVAQVFLaeipADPKLYRHHNKlrlcfkef 1920
Cdd:cd11697   278 LENAIETMEDTNKKIRDLILQHQSDPTLpinpLSMLLNGIVDAAVMGGIANYEKAFF----TEEYLDEHPED-------- 345

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 299473744 1921 imrcGEAVEKNKRLItADQREYQQE-LKKNYNKLKENLRPMIER 1963
Cdd:cd11697   346 ----QELIERLKDLI-AEQIPLLEAgLKIHKQKAPESLRPLHER 384
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1630-1957 1.81e-13

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: 74.66  E-value: 1.81e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1630 GLLEQAAELFSTGGLYETVNEVYKLVIPILEAHREFRKLTLTHSKLQRAFDSIVnkDHKRMFGTYFRVGFFGSKFG-DLD 1708
Cdd:cd11704    58 GLCRKIIHYFNKGKSWEFGIPLCRELAFQYESLYDYQSLSWIRKMEAAYYDNIM--EQQRLEPEFFRVGFYGRKFPfFLR 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1709 EQEFVYKEpaitklpEISHRLEAFYGQCFGaEFVEVIKDSTP--VDKTKLDPNKAYIQITFVEP---YFDEYEMK---DR 1780
Cdd:cd11704   136 NKEYVCRG-------HDYERLEAFQQRMLS-EFPQAIAMQHPnhPDDGILQCDAQYLQIYAVTPipdNMDVLQMDrvpDR 207

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1781 VTYFEKNFNLRRFMYTTPFTLEGRPR-GELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKKTLQL 1859
Cdd:cd11704   208 IKSFYRVNNVRKFRYDRPFHKGPKDKeNEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQEL 287

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1860 AVAINQEP-----PDAKMLQMVLQGSVGATVNQGPLEVAQVFLAE--IPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNK 1932
Cdd:cd11704   288 RTLISQYQhkqlhGNINLLSMCLNGVIDAAVNGGIARYQEAFFDKdyISKHPGDAEKITQLKELMQEQVHVLGVGLAVHE 367

                         330       340
                  ....*....|....*....|....*
gi 299473744 1933 RLITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11704   368 KFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1660-1957 2.09e-12

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: 71.21  E-value: 2.09e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1660 EAHREFRKLTLTHSKLQRAFDSIVnkDHKRMFGTYFRVGFFGSKFGD-LDEQEFVYKEpaitklpEISHRLEAFYGQCFG 1738
Cdd:cd11705    88 ESYYDYRNLSKMRMMEASLYDKIM--DQQRLEPEFFRVGFYGKKFPFfLRNKEFVCRG-------HDYERLEAFQQRMLN 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1739 aEFVEVI--KDSTPVDKTKLDPNKAYIQITFVEPYFDEYEM------KDRVTYFEKNFNLRRFMYTTPFTLEGRPR-GEL 1809
Cdd:cd11705   159 -EFPHAIamQHANQPDETIFQAEAQYLQIYAVTPIPESQEVlqrdgvPDNIKSFYKVNHIWRFRYDRPFHKGTKDKeNEF 237

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1810 HEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKKTLQLAVAINQ----EPPDAKMLQMVLQGSVGATV 1885
Cdd:cd11705   238 KSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQcqtrQMQNINPLTMCLNGVIDAAV 317

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 299473744 1886 NQGPLEVAQVFLAE--IPADPKLYRHHNKLR-LCFKE-FIMRCGEAVekNKRLITADQREYQQELKKNYNKLKENL 1957
Cdd:cd11705   318 NGGVSRYQEAFFVKeyILNHPEDGDKITRLReLMLEQaQILEFGLAV--HEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1694-1954 2.41e-11

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: 68.09  E-value: 2.41e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1694 YFRVGFFGSKFGD-LDEQEFVYKEPAITKLPEISHRLEAfygQCFGAEFVEVIkdSTPVDKTKLDPNKaYIQITFVEPYF 1772
Cdd:cd11706   143 YFAVGYYGQGFPSfLRNKVFIYRGKEYERREDFQMQLMS---QFPNAEKLNTT--SAPGDDIKNSPGQ-YIQCFTVQPVL 216

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1773 DEY------EMKDRVTYFEKNFNLRRFMYTTPFTLEGR-PRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPI 1845
Cdd:cd11706   217 EEHprlknkPVPDQIINFYKSNYVQRFHYSRPVRKGPVdPENEFASMWIERTTFVTAYKLPGILRWFEVTHMSQTTISPL 296

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1846 EVAIEDMKKKTLQLAVAINQEPPDAKM----LQMVLQGSVGATVNQGPLEVAQVFLAEipadPKLYRHH----NKLRLcf 1917
Cdd:cd11706   297 ENAIETMSTTNEKILMMINQYQSDESLpinpLSMLLNGIVDPAVMGGFAKYEKAFFTE----EYVRDHPedqdKLTRL-- 370

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 299473744 1918 KEFIM----RCGEAVEKNKRLITADQREYQQELKKNYNKLK 1954
Cdd:cd11706   371 KDLIAwqipLLGAGIKIHGKRVTDDLRPFHERMEECFKQLK 411
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1539-1963 1.50e-10

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: 65.35  E-value: 1.50e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1539 DLRLTWLQNMAEKHTKKKCYTEAAMCLVhaaaLVAEYLSMLEDhsylPVGSVSFQNISSNVLEESVVSEDtlspdedgvc 1618
Cdd:cd11708     1 DIYIRYLYKLRDLHLDCENYTEAAYTLL----LHAELLQWSEK----PCVPHLLQRDSYYVYTQQELKER---------- 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1619 agqyftesglvgLLEQAAELFSTGGLYETVNEVYKLVIPILEAHR-EFRKLTLTHSKLQRAFDSIVNKdhKRMFGTYFRV 1697
Cdd:cd11708    63 ------------LYQEIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFYENIMKA--MRPQPEYFAV 128

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1698 GFFGSKFGD-LDEQEFVYKEPAITKLPEISHRLeafYGQCFGAEfvEVIKDSTPVDKTKLDPnKAYIQITFVEP------ 1770
Cdd:cd11708   129 GYYGQGFPSfLRNKIFIYRGKEYERLEDFSLKL---LTQFPNAE--KMTSTSPPGDEIKSST-KQYVQCFTVKPvmnlps 202

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1771 -YFDEYEMKDRVTYFEKNfNLRRFMYTTPFTL-EGRPRGELHEQYRRNTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVA 1848
Cdd:cd11708   203 hYKDKPVPEQILNYYRAN-EVQQFQYSRPFRKgEKDPDNEFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLENA 281

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1849 IEDMKKKTLQLAVAINQEPPDAKM----LQMVLQGSVGATVNQGPLEVAQVFLAEipadPKLYRHHNKLrlcfkefimrc 1924
Cdd:cd11708   282 IETMELTNEKISNLVQQHAWDRSLpvhpLSMLLNGIVDPAVMGGFSNYEKAFFTE----KYLQEHPEDQ----------- 346

                         410       420       430
                  ....*....|....*....|....*....|....*....
gi 299473744 1925 gEAVEKNKRLITADQREYQQELKKNYNKLKENLRPMIER 1963
Cdd:cd11708   347 -EKIELLKQLIALQMPLLAEGIRIHGEKLTEQLKPLHER 384
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1664-1963 1.41e-08

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: 59.28  E-value: 1.41e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1664 EFRKLTLTHSKLQRAFDSIVNKDHKRmfGTYFRVGFFGSKFGD-LDEQEFVYKEPAITKLPEISHRLEAFYGQcfgaefV 1742
Cdd:cd11707    97 DYEQLSELLKKQAQFYENIVKVIRPK--PDYFAVGYYGQGFPTfLRNKMFIYRGKEYERREDFEARLLTQFPN------A 168

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1743 EVIKDSTPVDKTKLDPNKAYIQITFVEPYFD------EYEMKDRVTYFEKNFNLRRFMYTTPFTL-EGRPRGELHEQYRR 1815
Cdd:cd11707   169 EKMKTTSPPGDDIKNSSGQYIQCFTVKPLLElppkfqNKPVSEQIVSFYRVNEVQRFQYSRPVRKgEKDPDNEFANMWIE 248

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744 1816 NTVLTTMHAFPYIKTRISVIQKEEFVLTPIEVAIEDMKKKTLQLAVAINQEPPDAKM----LQMVLQGSVGATVNQGPLE 1891
Cdd:cd11707   249 RTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNEKINNMVQQHLNDPNLpinpLSMLLNGIVDPAVMGGFAN 328

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 299473744 1892 VAQVFLAEipadpKLYRHHNKLRlcfkefimrcgEAVEKNKRLITADQREYQQELKKNYNKLKENLRPMIER 1963
Cdd:cd11707   329 YEKAFFTE-----KYMQEHPEDH-----------EKIEKLKDLIAWQIPFLAEGIRIHGEKVTEALRPFHER 384
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 510-588 9.36e-07

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: 51.25  E-value: 9.36e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 299473744  510 SARNITIKIQfMCGEDASnAMPVIFGKSSGPEFLQEVYTAVTYHNKSPDFYEEVKIKLPAKLTVNHHLLFTFYHISCQQ 588
Cdd:cd08694    21 SDKNVEVTVS-VCNEDGK-IIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIEDFKSSHLRFTFKHRSSNE 97
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 492-606 1.51e-04

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: 44.68  E-value: 1.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299473744  492 RNLLYVYPQRLNF--VNKlASARNITIKIqFMCGEDASNAMPVIFGkSSGPEFLQEVYTAVTYHNKSPDFYEEVKIKLPA 569
Cdd:cd08695     2 RNDLYLTLERGEFekGGK-STAKNIEVTM-VVLDADGQVLKDCISL-GSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPI 78

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 299473744  570 KLTVNHHLLFTFYHISCQQKqgaSVETLLGYSWLPIL 606
Cdd:cd08695    79 DKFRGSHLRFEFRHCSTKDK---GEKKLFGFSFVPLM 112
 
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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