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Conserved domains on  [gi|119604588|gb|EAW84182|]
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dedicator of cytokinesis 6, isoform CRA_d [Homo sapiens]

Protein Classification

DUF3398 and C2_Dock-C domain-containing protein( domain architecture ID 10570939)

protein containing domains DUF3398, C2_Dock-C, and DHR2_DOCK

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK super family cl06123
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1592-1790 1.71e-131

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.


The actual alignment was detected with superfamily member cd11702:

Pssm-ID: 471388  Cd Length: 423  Bit Score: 417.49  E-value: 1.71e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1592 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEG 1671
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1672 FCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQPfSQPQRVFGT 1751
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQS-SGWERMFGT 159

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 119604588 1752 YFRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEAF 1790
Cdd:cd11702   160 YFRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEF 198
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 547-724 7.28e-104

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: 329.70  E-value: 7.28e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  547 YRNLLYVYPHSLNFSSRQGSVRNLAVRVQYMTGEDPSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 626
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  627 VTENHHLLFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 705
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                         170
                  ....*....|....*....
gi 119604588  706 VFSVELTAVSSVHPQDPYL 724
Cdd:cd08696   161 VFSVSVEAVSSVHTQDSYL 179
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 48-157 8.55e-46

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: 160.51  E-value: 8.55e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588    48 TEVVEPLDFEDVLLSRPPDAEPGPLRDLVEFPADDLELLLQPRECRTTEPGIPKD--EKLDAQVRAAVEMYIEDWVIVHR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 119604588   126 RYQYLSAAYSPVTTDTQRERQKGLPRQVFEQD 157
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1592-1790 1.71e-131

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: 417.49  E-value: 1.71e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1592 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEG 1671
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1672 FCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQPfSQPQRVFGT 1751
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQS-SGWERMFGT 159

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 119604588 1752 YFRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEAF 1790
Cdd:cd11702   160 YFRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEF 198
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 547-724 7.28e-104

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: 329.70  E-value: 7.28e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  547 YRNLLYVYPHSLNFSSRQGSVRNLAVRVQYMTGEDPSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 626
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  627 VTENHHLLFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 705
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                         170
                  ....*....|....*....
gi 119604588  706 VFSVELTAVSSVHPQDPYL 724
Cdd:cd08696   161 VFSVSVEAVSSVHTQDSYL 179
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1580-1737 1.23e-69

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: 230.64  E-value: 1.23e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  1580 DLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLeDHRHLPVGCVSFQNISSNVL-EES 1658
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119604588  1659 AISDDilspdeEGFCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKI 1737
Cdd:pfam06920   80 ALKDD------SGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKI 152
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 544-723 1.21e-61

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: 209.00  E-value: 1.21e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588   544 HTSYRNLLYVYPHSLNFSSRQGSV-RNLAVRVQYMTGEdpSQALP-VIFGKSSCsEFTREAFTPVVYHNKSPEFYEEFKL 621
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSaRNIEVTVEVRDSD--GEPLPnCIYGGSGG-PFVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588   622 HLPACVTENHHLLFTFYHVSCQPRPgTALETPVGFTWIPLLQHGR--LRTGPFCLPVS-VDQPPPSYSVLT-------PD 691
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKK-DKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYkYDELPPGYLSLPwssggekES 156

                          170       180       190
                   ....*....|....*....|....*....|..
gi 119604588   692 VALPGMRwvdGHKGVFSVELTAVSSVHPQDPY 723
Cdd:pfam14429  157 SALPGLK---GGKDLFKVRTRLCSTKYTQDEH 185
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 48-157 8.55e-46

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: 160.51  E-value: 8.55e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588    48 TEVVEPLDFEDVLLSRPPDAEPGPLRDLVEFPADDLELLLQPRECRTTEPGIPKD--EKLDAQVRAAVEMYIEDWVIVHR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 119604588   126 RYQYLSAAYSPVTTDTQRERQKGLPRQVFEQD 157
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1592-1790 1.71e-131

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: 417.49  E-value: 1.71e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1592 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEG 1671
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1672 FCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQPfSQPQRVFGT 1751
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQS-SGWERMFGT 159

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 119604588 1752 YFRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEAF 1790
Cdd:cd11702   160 YFRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEF 198
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1553-1794 4.26e-128

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: 409.85  E-value: 4.26e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1553 DLMFNLHMILTDTVKMKEHQEDPEMLIDLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLA 1632
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1633 LLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEGFCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIP 1712
Cdd:cd11703    81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1713 ILEAHRDYKKLAAVHGKLQEAFTKIMHQpfsQPQRVFGTYFRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEAFlH 1792
Cdd:cd11703   161 IHEANRDAKKLATIHGKLQEAFSKIVHQ---DGKRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGF-Y 236


                  ..
gi 119604588 1793 GE 1794
Cdd:cd11703   237 GE 238
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 547-724 7.28e-104

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: 329.70  E-value: 7.28e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  547 YRNLLYVYPHSLNFSSRQGSVRNLAVRVQYMTGEDPSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 626
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  627 VTENHHLLFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 705
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                         170
                  ....*....|....*....
gi 119604588  706 VFSVELTAVSSVHPQDPYL 724
Cdd:cd08696   161 VFSVSVEAVSSVHTQDSYL 179
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1592-1790 1.88e-103

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: 338.55  E-value: 1.88e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1592 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEG 1671
Cdd:cd11701     2 SPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDEDG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1672 FCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQpfsQPQRVFGT 1751
Cdd:cd11701    82 VCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINK---GHKRMFGT 158

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 119604588 1752 YFRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEAF 1790
Cdd:cd11701   159 YFRVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGF 197
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1592-1790 1.00e-77

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: 262.62  E-value: 1.00e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1592 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALvaeylalledhrhlpvgcvsfqnissnvleesaisddilspdeeg 1671
Cdd:cd11695     1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1672 fcsgkhftelGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQpfSQPQRVFGT 1751
Cdd:cd11695    36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQ--QGGKRMFGT 103

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 119604588 1752 YFRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEAF 1790
Cdd:cd11695   104 YFRVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETF 142
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1580-1737 1.23e-69

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: 230.64  E-value: 1.23e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  1580 DLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLeDHRHLPVGCVSFQNISSNVL-EES 1658
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119604588  1659 AISDDilspdeEGFCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKI 1737
Cdd:pfam06920   80 ALKDD------SGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKI 152
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 544-723 1.21e-61

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: 209.00  E-value: 1.21e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588   544 HTSYRNLLYVYPHSLNFSSRQGSV-RNLAVRVQYMTGEdpSQALP-VIFGKSSCsEFTREAFTPVVYHNKSPEFYEEFKL 621
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSaRNIEVTVEVRDSD--GEPLPnCIYGGSGG-PFVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588   622 HLPACVTENHHLLFTFYHVSCQPRPgTALETPVGFTWIPLLQHGR--LRTGPFCLPVS-VDQPPPSYSVLT-------PD 691
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKK-DKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYkYDELPPGYLSLPwssggekES 156

                          170       180       190
                   ....*....|....*....|....*....|..
gi 119604588   692 VALPGMRwvdGHKGVFSVELTAVSSVHPQDPY 723
Cdd:pfam14429  157 SALPGLK---GGKDLFKVRTRLCSTKYTQDEH 185
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 547-724 4.65e-47

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: 166.74  E-value: 4.65e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  547 YRNLLYVYPHSLNFSSRQGSVRNLAVRVQYMTGEDPSqALPVIFGkSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 626
Cdd:cd08679     1 LRNDLYVYPQSGELSKAKSKGRNIEITVEVRDDDGDI-IEPCISA-PGSGSELRSEYTSVVYYHKNPVFNDEIKIQLPAD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  627 VTENHHLLFTFYHVSCQPRPGTALETPVGFTWIPLL--QHGRLRTGPFCLPVSVDQPPPSYSVLTpDVALPGMRWVDGHK 704
Cdd:cd08679    79 LTPQHHLLFTFYHVSSKKKQGDKEETPFGYAFLPLMdkDGAFIKDGDHTLPVYKYDKRPDVGPSG-YLSLPSTLANGKSS 157

                         170       180
                  ....*....|....*....|.
gi 119604588  705 G-VFSVELTAVSSVHPQDPYL 724
Cdd:cd08679   158 KdTFKIKTRLCSTILTQDKSL 178
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 547-724 2.97e-46

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: 164.80  E-value: 2.97e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  547 YRNLLYVYPHSLNFSSRQGSV--RNLAVRVQYM-TGEDPSQALPVIFGKSSCSeFTREAFTPVVYHNKSPEFYEEFKLHL 623
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFAkaRNIAVCIEFRdSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  624 PACVTENHHLLFTFYHVSC-QPRPGT---ALETPVGFTWIPLLQ-HGRLRTGPFCLPVSVDQP--PPSYSVLTPDValPG 696
Cdd:cd08697    80 PTQLHEKHHLLFTFYHVSCdINKKGKkkdGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLPnyPDGYLSIQPHG--PE 157

                         170       180
                  ....*....|....*....|....*...
gi 119604588  697 MRWVDGHKGVFSVELTAVSSVHPQDPYL 724
Cdd:cd08697   158 VKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 48-157 8.55e-46

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: 160.51  E-value: 8.55e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588    48 TEVVEPLDFEDVLLSRPPDAEPGPLRDLVEFPADDLELLLQPRECRTTEPGIPKD--EKLDAQVRAAVEMYIEDWVIVHR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 119604588   126 RYQYLSAAYSPVTTDTQRERQKGLPRQVFEQD 157
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1594-1789 4.49e-44

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: 165.93  E-value: 4.49e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1594 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLalledhrhlpvgcvsfqnissnvleesaisDDILSPDEEGFC 1673
Cdd:cd11684     1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDL------------------------------KALVPALAESLS 50

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1674 SGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQpfsqpQRVFGTYF 1753
Cdd:cd11684    51 FPEQTSFERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEK-----DRLFPTYF 125

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 119604588 1754 RVGFYGAHF-GDLDEQEFVYKEPSITKLAEISHRLEA 1789
Cdd:cd11684   126 RVGFYGKGFpESLRGKEFIYRGPEFERLGDFCERLKS 162
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1593-1794 8.28e-43

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: 162.86  E-value: 8.28e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1593 PDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLalledHRH--LPVGCVSFQNISSNVLEESAISDDILSPDee 1670
Cdd:cd11700     1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFL-----HRKklFPSGCAAFKKITPNIDEEGAMKEDIGMMD-- 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1671 gfcsgKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMhQPFSQPQRVFG 1750
Cdd:cd11700    74 -----VHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKIL-EVMHTGKRLLG 147

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 119604588 1751 TYFRVGFYG-AHFGDLDEQEFVYKEPSITKLAEISHRLEAfLHGE 1794
Cdd:cd11700   148 TFFRVAFYGqGFFEEEDGKEYIYKEPKLTGLSEISHRLLK-LYGE 191
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1594-1787 1.68e-40

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: 155.96  E-value: 1.68e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1594 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHlpvGCVSFQNISSNVLEESAISDDILSPDeegfc 1673
Cdd:cd11698     1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTRKGMFRQ---GCTAFRVITPNIDEEASMMEDVGMQD----- 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1674 sgKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMhQPFSQPQRVFGTYF 1753
Cdd:cd11698    73 --VHFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVT-EVMHSGKRLLGTYF 149

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 119604588 1754 RVGFYGAH-FGDLDEQEFVYKEPSITKLAEISHRL 1787
Cdd:cd11698   150 RVAFFGQGfFEDEDGKEYIYKEPKLTPLSEISQRL 184
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1594-1789 3.19e-37

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: 145.18  E-value: 3.19e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1594 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDhrhlpvgcvsfqnissnvleesaisddilspdeegfc 1673
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKRKDL------------------------------------- 43

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1674 sgkhftelgLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQPFSQpQRVFGTYF 1753
Cdd:cd11694    44 ---------LLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESG-KRLLGTYY 113

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 119604588 1754 RVGFYG-AHFGDLDEQEFVYKEPSITKLAEISHRLEA 1789
Cdd:cd11694   114 RVAFYGqAFFEEEDGKEYIYKEPKVTSLSEISERLLK 150
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1593-1787 5.26e-32

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: 131.71  E-value: 5.26e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1593 PDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYL---------------------------ALLEDHR---HLPV 1642
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLkrkgywkmekictssmlpedsqvydsnLLLTTSTggsMFSM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1643 GCVSFQNISSNVLEESAISDDILSPDEEgfcsgkhFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKK 1722
Cdd:cd11699    81 GWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKR 153

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119604588 1723 LAAVHGKLQEAFTKIMHQPFSQpQRVFGTYFRVGFYGAHFGDLDE-QEFVYKEPSITKLAEISHRL 1787
Cdd:cd11699   154 LSELYYDIHRSYLKVAEVVNSE-KRLFGRYYRVAFYGQGFFEEEEgKEYIYKEPKLTGLSEISQRL 218
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 548-663 6.89e-06

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: 48.55  E-value: 6.89e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588  548 RNLLYVYPHSLNFSS-RQGSVRNLAVRVqYMTGEDpSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 626
Cdd:cd08694     2 RNDLYLTLVQGDFDKgSKTSDKNVEVTV-SVCNED-GKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIE 79

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 119604588  627 VTENHHLLFTFYHVSCQPRPGTAlETPVGFTWIPLLQ 663
Cdd:cd08694    80 DFKSSHLRFTFKHRSSNEAKDKS-EKPFALSFVKLMQ 115
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1693-1787 3.68e-03

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: 41.93  E-value: 3.68e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119604588 1693 YFTMGGLYEAVNEVYKNLIPILEAHR-DYKKLAAVHGKLQEAFTKIMHQPFSQPQrvfgtYFRVGFYGAHFGD-LDEQEF 1770
Cdd:cd11697    70 YFDKGKMWECAISLCKELAEQYENETfDYLQLSELLKRMATFYDNIMKTLRPEPE-----YFRVGYYGQGFPSfLRNKVF 144

                          90
                  ....*....|....*..
gi 119604588 1771 VYKEPSITKLAEISHRL 1787
Cdd:cd11697   145 IYRGKEYERLSDFSARL 161
 
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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