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Conserved domains on  [gi|768003225|ref|XP_011526452|]
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dedicator of cytokinesis protein 6 isoform X1 [Homo sapiens]

Protein Classification

C2_Dock-C and DHR2_DOCK6 domain-containing protein( domain architecture ID 10570937)

protein containing domains DOCK_C-D_N, C2_Dock-C, and DHR2_DOCK6

Graphical summary

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List of domain hits

 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 ...
 1638-2060 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: 943.28  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1638 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEG 1717
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1718 FCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTY 1797
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1798 FRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDT 1877
Cdd:cd11702   161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1878 YELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1957
Cdd:cd11702   241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1958 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 2037
Cdd:cd11702   321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                         410       420
                  ....*....|....*....|...
gi 768003225 2038 IGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11702   401 IGPDQKEYHRELERNYQRLREAL 423
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 558-735 8.99e-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: 8.99e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  558 YRNLLYVYPHSLNFSSRQGSVRNLAVRVQYMTGEDPSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 637
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  638 VTENHHLLFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 716
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                         170
                  ....*....|....*....
gi 768003225  717 VFSVELTAVSSVHPQDPYL 735
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 1.70e-45

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: 160.13  E-value: 1.70e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225    48 TEVVEPLDFEDVLLSRPPDAEPGPLRDLVEFPADDLELLLQPRECRTTEPGIPKD--EKLDAQVRAAVEMYIEDWVIVHR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 768003225   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 ...
 1638-2060 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: 943.28  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1638 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEG 1717
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1718 FCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTY 1797
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1798 FRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDT 1877
Cdd:cd11702   161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1878 YELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1957
Cdd:cd11702   241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1958 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 2037
Cdd:cd11702   321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                         410       420
                  ....*....|....*....|...
gi 768003225 2038 IGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11702   401 IGPDQKEYHRELERNYQRLREAL 423
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 558-735 8.99e-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: 8.99e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  558 YRNLLYVYPHSLNFSSRQGSVRNLAVRVQYMTGEDPSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 637
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  638 VTENHHLLFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 716
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                         170
                  ....*....|....*....
gi 768003225  717 VFSVELTAVSSVHPQDPYL 735
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 ...
 1626-1783 1.02e-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: 231.03  E-value: 1.02e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  1626 DLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLeDHRHLPVGCVSFQNISSNVL-EES 1704
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768003225  1705 AISDDilspdeEGFCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKI 1783
Cdd:pfam06920   80 ALKDD------SGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKI 152
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 555-734 2.11e-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: 208.61  E-value: 2.11e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225   555 HTSYRNLLYVYPHSLNFSSRQGSV-RNLAVRVQYMTGEdpSQALP-VIFGKSSCsEFTREAFTPVVYHNKSPEFYEEFKL 632
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSaRNIEVTVEVRDSD--GEPLPnCIYGGSGG-PFVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225   633 HLPACVTENHHLLFTFYHVSCQPRPgTALETPVGFTWIPLLQHGR--LRTGPFCLPVS-VDQPPPSYSVLT-------PD 702
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKK-DKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYkYDELPPGYLSLPwssggekES 156

                          170       180       190
                   ....*....|....*....|....*....|..
gi 768003225   703 VALPGMRwvdGHKGVFSVELTAVSSVHPQDPY 734
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 1.70e-45

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: 160.13  E-value: 1.70e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225    48 TEVVEPLDFEDVLLSRPPDAEPGPLRDLVEFPADDLELLLQPRECRTTEPGIPKD--EKLDAQVRAAVEMYIEDWVIVHR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 768003225   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 ...
 1638-2060 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: 943.28  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1638 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEG 1717
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1718 FCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTY 1797
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1798 FRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDT 1877
Cdd:cd11702   161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1878 YELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1957
Cdd:cd11702   241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1958 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 2037
Cdd:cd11702   321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                         410       420
                  ....*....|....*....|...
gi 768003225 2038 IGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11702   401 IGPDQKEYHRELERNYQRLREAL 423
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1599-2071 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: 816.63  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1599 DLMFNLHMILTDTVKMKEHQEDPEMLIDLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLA 1678
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1679 LLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEGFCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIP 1758
Cdd:cd11703    81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1759 ILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGweRVFGTYFRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEEFYTE 1838
Cdd:cd11703   161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGK--RMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1839 RFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDTYELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKR 1918
Cdd:cd11703   239 RFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 318

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1919 KTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQV 1998
Cdd:cd11703   319 KTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 398

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768003225 1999 FLAEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALIGPDQKEYHRELERNYCRLREALQPLLTQRLPQL 2071
Cdd:cd11703   399 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQL 471
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1638-2060 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: 732.22  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1638 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHLPVGCVSFQNISSNVLEESAISDDILSPDEEG 1717
Cdd:cd11701     2 SPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDEDG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1718 FCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQssGWERVFGTY 1797
Cdd:cd11701    82 VCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINK--GHKRMFGTY 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1798 FRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDT 1877
Cdd:cd11701   160 FRVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDD 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1878 YELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1957
Cdd:cd11701   240 YEMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQK 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1958 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 2037
Cdd:cd11701   320 KTRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRL 399

                         410       420
                  ....*....|....*....|...
gi 768003225 2038 IGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11701   400 ITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1638-2060 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: 728.71  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1638 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALvaeylalledhrhlpvgcvsfqnissnvleesaisddilspdeeg 1717
Cdd:cd11695     1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1718 fcsgkhftelGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSsGWERVFGTY 1797
Cdd:cd11695    36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQ-GGKRMFGTY 104

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1798 FRVGFYGAHFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDT 1877
Cdd:cd11695   105 FRVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDE 184

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1878 YELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1957
Cdd:cd11695   185 YELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQK 264

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1958 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPK-LFRHHNKLRLCFKDFCKKCEDALRKNKA 2036
Cdd:cd11695   265 KTRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKeLDRHQNKLRLCFKEFSKKCYDALEKNKE 344

                         410       420
                  ....*....|....*....|....
gi 768003225 2037 LIGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11695   345 LIGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1640-2060 1.06e-131

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: 417.90  E-value: 1.06e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1640 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDhrhlpvgcvsfqnissnvleesaisddilspdeegfc 1719
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKRKDL------------------------------------- 43

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1720 sgkhftelgLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTYFR 1799
Cdd:cd11694    44 ---------LLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESGKRLLGTYYR 114

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1800 VGFYG-AHFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDTY 1878
Cdd:cd11694   115 VAFYGqAFFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEK 194

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1879 ELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKK 1958
Cdd:cd11694   195 ELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSK 274

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1959 TRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLaeipeDPKLFRHHN-----KLRLCFKDFCKKCEDALRK 2033
Cdd:cd11694   275 VKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFL-----EPTTVKNYPddqveDLKDVFRDFIKACGQALEL 349

                         410       420
                  ....*....|....*....|....*..
gi 768003225 2034 NKALIGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11694   350 NERLIKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1640-2060 8.30e-123

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: 393.20  E-value: 8.30e-123
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1640 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLalledhrhlpvgcvsfqnissnvleesaisDDILSPDEEGFC 1719
Cdd:cd11684     1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDL------------------------------KALVPALAESLS 50

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1720 SGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQssgwERVFGTYFR 1799
Cdd:cd11684    51 FPEQTSFERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEK----DRLFPTYFR 126

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1800 VGFYGAHF-GDLDEQEFVYKEPSITKLAEISHRLEEFYTERfgddvvEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDTY 1878
Cdd:cd11684   127 VGFYGKGFpESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDE 200

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1879 ELK----DRVTYFDRNYGLRTFLFCTPFTPDGRA-HGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIE 1953
Cdd:cd11684   201 DLVsraaPGVRQFYRNNNINTFVYERPFTKGGKKsQNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIE 280

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1954 DMQKKTRELAFATEQ----DPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPKLFRHH-NKLRLCFKDFCKKCE 2028
Cdd:cd11684   281 DIEKKTEELRSLINKyrsgDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEEYLSNYPEAEKvKKLKEAFEEFLEILK 360

                         410       420       430
                  ....*....|....*....|....*....|..
gi 768003225 2029 DALRKNKALIGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11684   361 RGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1639-2053 5.95e-110

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: 357.38  E-value: 5.95e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1639 PDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLalledHRH--LPVGCVSFQNISSNVLEESAISDDILSPDee 1716
Cdd:cd11700     1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFL-----HRKklFPSGCAAFKKITPNIDEEGAMKEDIGMMD-- 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1717 gfcsgKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGT 1796
Cdd:cd11700    74 -----VHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMHTGKRLLGT 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1797 YFRVGFYG-AHFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYF 1875
Cdd:cd11700   149 FFRVAFYGqGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYF 228

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1876 DTYELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDM 1955
Cdd:cd11700   229 DDKEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEI 308

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1956 QKKTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNK 2035
Cdd:cd11700   309 KDKTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKKVKELKEMFRKFIQACSIALELNE 388

                         410
                  ....*....|....*...
gi 768003225 2036 ALIGPDQKEYHRELERNY 2053
Cdd:cd11700   389 RLIKEDQVEYHEGLKSNF 406
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1640-2060 6.54e-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: 351.64  E-value: 6.54e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1640 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDHRHlpvGCVSFQNISSNVLEESAISDDILSPDeegfc 1719
Cdd:cd11698     1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTRKGMFRQ---GCTAFRVITPNIDEEASMMEDVGMQD----- 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1720 sgKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTYFR 1799
Cdd:cd11698    73 --VHFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVMHSGKRLLGTYFR 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1800 VGFYGAHF-GDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDTY 1878
Cdd:cd11698   151 VAFFGQGFfEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDEK 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1879 ELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKK 1958
Cdd:cd11698   231 ELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKK 310

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1959 TRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALI 2038
Cdd:cd11698   311 VAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERLI 390

                         410       420
                  ....*....|....*....|..
gi 768003225 2039 GPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11698   391 KEDQLEYQEEMKANYREMAKEL 412
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 558-735 8.99e-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: 8.99e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  558 YRNLLYVYPHSLNFSSRQGSVRNLAVRVQYMTGEDPSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 637
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  638 VTENHHLLFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 716
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                         170
                  ....*....|....*....
gi 768003225  717 VFSVELTAVSSVHPQDPYL 735
Cdd:cd08696   161 VFSVSVEAVSSVHTQDSYL 179
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1639-2063 1.04e-100

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: 332.01  E-value: 1.04e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1639 PDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYL---------------------------ALLEDHR---HLPV 1688
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLkrkgywkmekictssmlpedsqvydsnLLLTTSTggsMFSM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1689 GCVSFQNISSNVLEESAISDDILSPDEEgfcsgkhFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKK 1768
Cdd:cd11699    81 GWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1769 LAAVHGKLQEAFTKIMHQSSGWERVFGTYFRVGFYGAHFGDLDE-QEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEI 1847
Cdd:cd11699   154 LSELYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEgKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKI 233

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1848 IKDSNPVDKSKLDSQKAYIQITYVEPYFDTYELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHA 1927
Cdd:cd11699   234 IQDSNKVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHS 313

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1928 FPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDP 2007
Cdd:cd11699   314 FPYVKKRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKK 393

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 768003225 2008 KLFRHHNKLRLCFKDFCKKCEDALRKNKALIGPDQKEYHRELERNYcrlREALQPL 2063
Cdd:cd11699   394 YPDNQVKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHY---RDMLSEL 446
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1626-1783 1.02e-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: 231.03  E-value: 1.02e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  1626 DLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLeDHRHLPVGCVSFQNISSNVL-EES 1704
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768003225  1705 AISDDilspdeEGFCSGKHFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKI 1783
Cdd:pfam06920   80 ALKDD------SGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKI 152
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 555-734 2.11e-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: 208.61  E-value: 2.11e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225   555 HTSYRNLLYVYPHSLNFSSRQGSV-RNLAVRVQYMTGEdpSQALP-VIFGKSSCsEFTREAFTPVVYHNKSPEFYEEFKL 632
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSaRNIEVTVEVRDSD--GEPLPnCIYGGSGG-PFVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225   633 HLPACVTENHHLLFTFYHVSCQPRPgTALETPVGFTWIPLLQHGR--LRTGPFCLPVS-VDQPPPSYSVLT-------PD 702
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKK-DKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYkYDELPPGYLSLPwssggekES 156

                          170       180       190
                   ....*....|....*....|....*....|..
gi 768003225   703 VALPGMRwvdGHKGVFSVELTAVSSVHPQDPY 734
Cdd:pfam14429  157 SALPGLK---GGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1961-2063 1.76e-47

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: 165.46  E-value: 1.76e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  1961 ELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALIGP 2040
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|...
gi 768003225  2041 DQKEYHRELERNYCRLREALQPL 2063
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEPY 103
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 558-735 5.46e-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: 5.46e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  558 YRNLLYVYPHSLNFSSRQGSVRNLAVRVQYMTGEDPSqALPVIFGkSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 637
Cdd:cd08679     1 LRNDLYVYPQSGELSKAKSKGRNIEITVEVRDDDGDI-IEPCISA-PGSGSELRSEYTSVVYYHKNPVFNDEIKIQLPAD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  638 VTENHHLLFTFYHVSCQPRPGTALETPVGFTWIPLL--QHGRLRTGPFCLPVSVDQPPPSYSVLTpDVALPGMRWVDGHK 715
Cdd:cd08679    79 LTPQHHLLFTFYHVSSKKKQGDKEETPFGYAFLPLMdkDGAFIKDGDHTLPVYKYDKRPDVGPSG-YLSLPSTLANGKSS 157

                         170       180
                  ....*....|....*....|.
gi 768003225  716 G-VFSVELTAVSSVHPQDPYL 735
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 ...
 558-735 5.23e-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: 164.42  E-value: 5.23e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  558 YRNLLYVYPHSLNFSSRQGSV--RNLAVRVQYM-TGEDPSQALPVIFGKSSCSeFTREAFTPVVYHNKSPEFYEEFKLHL 634
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFAkaRNIAVCIEFRdSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  635 PACVTENHHLLFTFYHVSC-QPRPGT---ALETPVGFTWIPLLQ-HGRLRTGPFCLPVSVDQP--PPSYSVLTPDValPG 707
Cdd:cd08697    80 PTQLHEKHHLLFTFYHVSCdINKKGKkkdGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLPnyPDGYLSIQPHG--PE 157

                         170       180
                  ....*....|....*....|....*...
gi 768003225  708 MRWVDGHKGVFSVELTAVSSVHPQDPYL 735
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 1.70e-45

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: 160.13  E-value: 1.70e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225    48 TEVVEPLDFEDVLLSRPPDAEPGPLRDLVEFPADDLELLLQPRECRTTEPGIPKD--EKLDAQVRAAVEMYIEDWVIVHR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 768003225   126 RYQYLSAAYSPVTTDTQRERQKGLPRQVFEQD 157
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1851-1927 1.40e-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: 136.20  E-value: 1.40e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 768003225  1851 SNPVDKSKLDSQKAYIQITYVEPYFDTYELKDRVTYFDRNYGLRTFLFCTPFTPDGRAHGELPEQHKRKTLLSTDHA 1927
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEHS 77
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1739-2060 1.22e-16

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: 84.42  E-value: 1.22e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1739 YFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAavHGKLQEA--FTKIMHQssgwERVFGTYFRVGFYGAHFGD-LDEQEF 1815
Cdd:cd11696    66 YFDRGKCWEKGIPLCRELAELYESLYDYAKLS--HILRMEAsfYDNILTQ----LRPEPEYFRVGFYGKGFPLfLRNKQF 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1816 VYKEPSITKLAEISHRLE-EFYTerfgddvVEIIKDSNPVDKSKLDSQKAYIQITYVEP------YFDTYELKDRVTYFD 1888
Cdd:cd11696   140 VYRGLDYERIGAFTQRLQsEFPQ-------AHILTKNTPPDDAILQADGQYIQICNVKPvperrpVLQMVGVPDKVRSFY 212

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1889 RNYGLRTFLFCTPF-TPDGRAHGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATE 1967
Cdd:cd11696   213 RVNDVRKFQYDRPIhKGPIDKDNEFKSLWIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLIS 292

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1968 QDPPDAK----MLQMVLQGSVGPTVNQGPLEVAQVFLAE--IPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALIGPD 2041
Cdd:cd11696   293 QYQADPTrninPFSMRLQGVIDAAVNGGIAKYQEAFFTPefILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPE 372

                         330
                  ....*....|....*....
gi 768003225 2042 QKEYHRELERNYCRLREAL 2060
Cdd:cd11696   373 VRPLHKRLVERFTQMKQSL 391
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1739-2006 5.07e-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: 76.60  E-value: 5.07e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1739 YFTMGGLYEAVNEVYKNLIPILEAHR-DYKKLAAVHGKLQEAFTKIMHQSsgweRVFGTYFRVGFYGAHFGD-LDEQEFV 1816
Cdd:cd11697    70 YFDKGKMWECAISLCKELAEQYENETfDYLQLSELLKRMATFYDNIMKTL----RPEPEYFRVGYYGQGFPSfLRNKVFI 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1817 YKEPSITKLAEISHRLEEFYTErfgddvVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDTY-ELKDR------VTYFDR 1889
Cdd:cd11697   146 YRGKEYERLSDFSARLLNQFPN------AELMNTLTPPGDEIKESPGQYLQINKVDPVMDERpRFKGKpvsdqiLNYYKV 219

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1890 NYgLRTFLFCTPF---TPDGRahGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFAT 1966
Cdd:cd11697   220 NE-VQRFTFSRPFrrgTKDPD--NEFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIETMEDTNKKIRDLI 296

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 768003225 1967 EQDPPDAKM----LQMVLQGSVGPTVNQGPLEVAQVF-----LAEIPED 2006
Cdd:cd11697   297 LQHQSDPTLpinpLSMLLNGIVDAAVMGGIANYEKAFfteeyLDEHPED 345
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1731-2060 3.44e-12

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: 70.81  E-value: 3.44e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1731 GLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQssgwERVFGTYFRVGFYGAHFG-D 1809
Cdd:cd11704    58 GLCRKIIHYFNKGKSWEFGIPLCRELAFQYESLYDYQSLSWIRKMEAAYYDNIMEQ----QRLEPEFFRVGFYGRKFPfF 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1810 LDEQEFVYKEPSITKLAEISHRLEEFYTERFGddvveiIKDSNPVDKSKLDSQKAYIQITYVEP---YFDTYELK---DR 1883
Cdd:cd11704   134 LRNKEYVCRGHDYERLEAFQQRMLSEFPQAIA------MQHPNHPDDGILQCDAQYLQIYAVTPipdNMDVLQMDrvpDR 207

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1884 VTYFDRNYGLRTFLFCTPF--TPDGRAHgELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRE 1961
Cdd:cd11704   208 IKSFYRVNNVRKFRYDRPFhkGPKDKEN-EFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQE 286

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1962 L-----AFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLAE--IPEDPKLFRHHNKLRLCFKDFCKKCEDALRKN 2034
Cdd:cd11704   287 LrtlisQYQHKQLHGNINLLSMCLNGVIDAAVNGGIARYQEAFFDKdyISKHPGDAEKITQLKELMQEQVHVLGVGLAVH 366

                         330       340
                  ....*....|....*....|....*.
gi 768003225 2035 KALIGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11704   367 EKFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1674-2006 8.02e-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: 66.55  E-value: 8.02e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1674 AEYLALLEDHRHLPVGCVSFQNISSNVLEESAI---SDDILSPDEEGFCSGKHFTELGLV-GLLEQAAGYFTMGGLYEAV 1749
Cdd:cd11706    19 AMYIRYLYKLRDLHLDCENYTEAAYTLLLHTRLlkwSDEQCASQVMQTGQQHPQTQRQLKeTLYETIIGYFDKGKMWEEA 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1750 NEVYKNLIPILEAH-RDYKKLAAV---HGKLQEAFTKIMHQSSgwervfgTYFRVGFYGAHFGD-LDEQEFVYKEPSITK 1824
Cdd:cd11706    99 ISLCKELAEQYEMEiFDYELLSQNliqQAKFYESIMKILRPKP-------DYFAVGYYGQGFPSfLRNKVFIYRGKEYER 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1825 LAEISHRLEEFYTerfgdDVVEIIKDSNPVDKSKlDSQKAYIQITYVEPYFDTY-ELKDR------VTYFDRNYgLRTFL 1897
Cdd:cd11706   172 REDFQMQLMSQFP-----NAEKLNTTSAPGDDIK-NSPGQYIQCFTVQPVLEEHpRLKNKpvpdqiINFYKSNY-VQRFH 244

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1898 FCTPFT-----PDGrahgELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATEQDPPD 1972
Cdd:cd11706   245 YSRPVRkgpvdPEN----EFASMWIERTTFVTAYKLPGILRWFEVTHMSQTTISPLENAIETMSTTNEKILMMINQYQSD 320

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 768003225 1973 AKM----LQMVLQGSVGPTVNQGPLEVAQVFLAEI-----PED 2006
Cdd:cd11706   321 ESLpinpLSMLLNGIVDPAVMGGFAKYEKAFFTEEyvrdhPED 363
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1732-2028 1.57e-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: 1.57e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1732 LLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHR-DYKKLAAVHGKLQEAFTKIMHQSsgweRVFGTYFRVGFYGAHFGD- 1809
Cdd:cd11708    63 LYQEIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFYENIMKAM----RPQPEYFAVGYYGQGFPSf 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1810 LDEQEFVYKEPSITKLAEISHRL-EEFyterfgDDVVEIIKDSNPVDKSKlDSQKAYIQITYVEP------YFDTYELKD 1882
Cdd:cd11708   139 LRNKIFIYRGKEYERLEDFSLKLlTQF------PNAEKMTSTSPPGDEIK-SSTKQYVQCFTVKPvmnlpsHYKDKPVPE 211

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1883 RVTYFDRNYGLRTFLFCTPF-----TPDGrahgELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1957
Cdd:cd11708   212 QILNYYRANEVQQFQYSRPFrkgekDPDN----EFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLENAIETMEL 287

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1958 KTRELAFATEQDPPDAKM----LQMVLQGSVGPTVNQGPLEVAQVF-----LAEIPEDP---KLFRH------------- 2012
Cdd:cd11708   288 TNEKISNLVQQHAWDRSLpvhpLSMLLNGIVDPAVMGGFSNYEKAFftekyLQEHPEDQekiELLKQlialqmpllaegi 367

                         330       340       350
                  ....*....|....*....|....*....|
gi 768003225 2013 --------------HNKLRLCFKDFCKKCE 2028
Cdd:cd11708   368 rihgeklteqlkplHERLVSCFKDLRAKVE 397
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1761-2060 1.87e-08

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: 58.89  E-value: 1.87e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1761 EAHRDYKKLAAVHGKLQEAFTKIMHQssgwERVFGTYFRVGFYGAHFGD-LDEQEFVYKEPSITKLAEISHRLEEFYTER 1839
Cdd:cd11705    88 ESYYDYRNLSKMRMMEASLYDKIMDQ----QRLEPEFFRVGFYGKKFPFfLRNKEFVCRGHDYERLEAFQQRMLNEFPHA 163

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1840 FGddvveiIKDSNPVDKSKLDSQKAYIQITYVEPYFDTYEL------KDRVTYFDRNYGLRTFLFCTPFTPDGR-AHGEL 1912
Cdd:cd11705   164 IA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVlqrdgvPDNIKSFYKVNHIWRFRYDRPFHKGTKdKENEF 237

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1913 PEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATEQ----DPPDAKMLQMVLQGSVGPTV 1988
Cdd:cd11705   238 KSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQcqtrQMQNINPLTMCLNGVIDAAV 317

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768003225 1989 NQGPLEVAQVFLAE--IPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALIGPDQKEYHRELERNYCRLREAL 2060
Cdd:cd11705   318 NGGVSRYQEAFFVKeyILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1732-2061 2.88e-07

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: 55.04  E-value: 2.88e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1732 LLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHR-DYKKLAAVHGKLQEAFTKIMHQSsgweRVFGTYFRVGFYGAHFGD- 1809
Cdd:cd11707    63 LYQEIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKVI----RPKPDYFAVGYYGQGFPTf 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1810 LDEQEFVYKEPSITKLAEISHRLeefyTERFGDdvVEIIKDSNPVDKSKLDSQKAYIQITYVEPYFDT------YELKDR 1883
Cdd:cd11707   139 LRNKMFIYRGKEYERREDFEARL----LTQFPN--AEKMKTTSPPGDDIKNSSGQYIQCFTVKPLLELppkfqnKPVSEQ 212

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1884 VTYFDRNYGLRTFLFCTPF-----TPDgrahGELPEQHKRKTLLSTDHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKK 1958
Cdd:cd11707   213 IVSFYRVNEVQRFQYSRPVrkgekDPD----NEFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLT 288

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225 1959 TRELAFATEQDPPDAKM----LQMVLQGSVGPTVNQGPLEVAQVFLAE--IPEDPKLFRHHNKLRLCFKDFCKKCEDALR 2032
Cdd:cd11707   289 NEKINNMVQQHLNDPNLpinpLSMLLNGIVDPAVMGGFANYEKAFFTEkyMQEHPEDHEKIEKLKDLIAWQIPFLAEGIR 368

                         330       340
                  ....*....|....*....|....*....
gi 768003225 2033 KNKALIGPDQKEYHRELERNYCRLREALQ 2061
Cdd:cd11707   369 IHGEKVTEALRPFHERMEACFRQLKEKVE 397
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 559-674 8.08e-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: 8.08e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768003225  559 RNLLYVYPHSLNFSS-RQGSVRNLAVRVqYMTGEDpSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLHLPAC 637
Cdd:cd08694     2 RNDLYLTLVQGDFDKgSKTSDKNVEVTV-SVCNED-GKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIE 79

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 768003225  638 VTENHHLLFTFYHVSCQPRPGTAlETPVGFTWIPLLQ 674
Cdd:cd08694    80 DFKSSHLRFTFKHRSSNEAKDKS-EKPFALSFVKLMQ 115
 
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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