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Conserved domains on  [gi|1370511304|ref|XP_024302774|]
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dedicator of cytokinesis protein 4 isoform X12 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1130-1520 0e+00

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


:

Pssm-ID: 212578  Cd Length: 391  Bit Score: 808.10  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLTYPMQTEWQRKEHLHLTIIQNFDRGKCWENGIILC 1209
Cdd:cd11705      1 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLSYPMQTEWQRKEYLHLTIIQNFDRGKCWENGIILC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1210 RKIAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 1289
Cdd:cd11705     81 RKLAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1290 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKENEFKSL 1369
Cdd:cd11705    161 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRDGVPDNIKSFYKVNHIWRFRYDRPFHKGTKDKENEFKSL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1370 WVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQNINPLTMCLNGVIDAAVNGG 1449
Cdd:cd11705    241 WVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQCQTRQMQNINPLTMCLNGVIDAAVNGG 320

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370511304 1450 VSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11705    321 VSRYQEAFFVKEYILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 324-508 7.94e-124

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


:

Pssm-ID: 176077  Cd Length: 189  Bit Score: 386.74  E-value: 7.94e-124
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  324 MRNDLYITIERGEFEKGGKSVARNVEVTMFIVDSSGQTLKDFISFGSGEPPASEYHSFVLYHNNSPRWSELLKLPIPVDK 403
Cdd:cd08695      1 VRNDLYLTLERGEFEKGGKSTAKNIEVTMVVLDADGQVLKDCISLGSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPIDK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  404 FRGAHIRFEFRHCSTKEKGEKKLFGFSFVPLMQEDGRTLPDGTHELIVHKCEENTNLQDTTRYLKLPFSKGIFLGNNNQA 483
Cdd:cd08695     81 FRGSHLRFEFRHCSTKDKGEKKLFGFSFVPLMREDGTTLPDGSHELYVYKCDENATFLDPALYLGLPCSKEDFQGCPNSP 160

                          170       180
                   ....*....|....*....|....*....
gi 1370511304  484 M----KATKESFCITSFLCSTKLTQNGDM 508
Cdd:cd08695    161 SplfsRSSKESFWIRTLLCSTKLTQNVDL 189
DOCK_N pfam16172
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 1-316 2.70e-117

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


:

Pssm-ID: 465040  Cd Length: 317  Bit Score: 373.77  E-value: 2.70e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304    1 MVIPTEDSVITEMTSTLRDWGTMWKQLYVRNEGDLFHRLWHIMNEILDLRRQVLVGHLTHDRMKDVKRHITARLDWGNEQ 80
Cdd:pfam16172    5 TPTSAEEPLVDEIASCLREWHSTLHELLLSRQYQLFDKLSQLIYELDLARRQLLHGVLTADELKELREKTVWDLVRGNKL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304   81 LGLDLVPRKE--YAMVDPEDISITELYRL------MEHRHRKKDTPVQASSHHLFVQMKSLMCSNLGEELEVIFSLFDSK 152
Cdd:pfam16172   85 LGLDVIVRDPtgRGRLLTDDDSVVELYKLqsemslLDEPPTPQVEPDATSLHHLLVDVKNFVGSSIGEDAELFFSLYDKK 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  153 ENRPISERFFLRLNRNGLPKAPDKPERHCSLFVDLGSSEL-RKDIYITVHIIRIgrmgagekknacsvqYRRPFGCAVLS 231
Cdd:pfam16172  165 ELKFLSENFVVRLPSNGMPKSLAQSLNLRTLFTDLSSSDLaRSKLYLVCKVIRN---------------VRRPFGVAVLD 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  232 IADLLTG----ETKDDLILKVYMCNTESEWYQIHENIIKKLNARYNLTGSNAGLAVSLQLLHGDIEQIRREYSSVFsHGV 307
Cdd:pfam16172  230 LTDILKGlkqsDEEVEHVVPIWSPNNESDFDELHRDIIKSITGKYEKSPRAERLWVSLKLFHGDAEQLRKENPTLL-HNV 308


                   ....*....
gi 1370511304  308 SITRKLGFS 316
Cdd:pfam16172  309 AITRKLGFP 317
 
Name Accession Description Interval E-value
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1130-1520 0e+00

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


Pssm-ID: 212578  Cd Length: 391  Bit Score: 808.10  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLTYPMQTEWQRKEHLHLTIIQNFDRGKCWENGIILC 1209
Cdd:cd11705      1 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLSYPMQTEWQRKEYLHLTIIQNFDRGKCWENGIILC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1210 RKIAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 1289
Cdd:cd11705     81 RKLAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1290 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKENEFKSL 1369
Cdd:cd11705    161 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRDGVPDNIKSFYKVNHIWRFRYDRPFHKGTKDKENEFKSL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1370 WVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQNINPLTMCLNGVIDAAVNGG 1449
Cdd:cd11705    241 WVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQCQTRQMQNINPLTMCLNGVIDAAVNGG 320

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370511304 1450 VSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11705    321 VSRYQEAFFVKEYILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 324-508 7.94e-124

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


Pssm-ID: 176077  Cd Length: 189  Bit Score: 386.74  E-value: 7.94e-124
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  324 MRNDLYITIERGEFEKGGKSVARNVEVTMFIVDSSGQTLKDFISFGSGEPPASEYHSFVLYHNNSPRWSELLKLPIPVDK 403
Cdd:cd08695      1 VRNDLYLTLERGEFEKGGKSTAKNIEVTMVVLDADGQVLKDCISLGSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPIDK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  404 FRGAHIRFEFRHCSTKEKGEKKLFGFSFVPLMQEDGRTLPDGTHELIVHKCEENTNLQDTTRYLKLPFSKGIFLGNNNQA 483
Cdd:cd08695     81 FRGSHLRFEFRHCSTKDKGEKKLFGFSFVPLMREDGTTLPDGSHELYVYKCDENATFLDPALYLGLPCSKEDFQGCPNSP 160

                          170       180
                   ....*....|....*....|....*....
gi 1370511304  484 M----KATKESFCITSFLCSTKLTQNGDM 508
Cdd:cd08695    161 SplfsRSSKESFWIRTLLCSTKLTQNVDL 189
DOCK_N pfam16172
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 1-316 2.70e-117

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


Pssm-ID: 465040  Cd Length: 317  Bit Score: 373.77  E-value: 2.70e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304    1 MVIPTEDSVITEMTSTLRDWGTMWKQLYVRNEGDLFHRLWHIMNEILDLRRQVLVGHLTHDRMKDVKRHITARLDWGNEQ 80
Cdd:pfam16172    5 TPTSAEEPLVDEIASCLREWHSTLHELLLSRQYQLFDKLSQLIYELDLARRQLLHGVLTADELKELREKTVWDLVRGNKL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304   81 LGLDLVPRKE--YAMVDPEDISITELYRL------MEHRHRKKDTPVQASSHHLFVQMKSLMCSNLGEELEVIFSLFDSK 152
Cdd:pfam16172   85 LGLDVIVRDPtgRGRLLTDDDSVVELYKLqsemslLDEPPTPQVEPDATSLHHLLVDVKNFVGSSIGEDAELFFSLYDKK 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  153 ENRPISERFFLRLNRNGLPKAPDKPERHCSLFVDLGSSEL-RKDIYITVHIIRIgrmgagekknacsvqYRRPFGCAVLS 231
Cdd:pfam16172  165 ELKFLSENFVVRLPSNGMPKSLAQSLNLRTLFTDLSSSDLaRSKLYLVCKVIRN---------------VRRPFGVAVLD 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  232 IADLLTG----ETKDDLILKVYMCNTESEWYQIHENIIKKLNARYNLTGSNAGLAVSLQLLHGDIEQIRREYSSVFsHGV 307
Cdd:pfam16172  230 LTDILKGlkqsDEEVEHVVPIWSPNNESDFDELHRDIIKSITGKYEKSPRAERLWVSLKLFHGDAEQLRKENPTLL-HNV 308


                   ....*....
gi 1370511304  308 SITRKLGFS 316
Cdd:pfam16172  309 AITRKLGFP 317
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 321-505 2.61e-67

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: 225.17  E-value: 2.61e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  321 PGEMRNDLYITIERGEFEKGGKSVARNVEVTMFIVDSSGQTLKDFISFGSGEPPASEYHSFVLYHNNSPRWSELLKLPIP 400
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSARNIEVTVEVRDSDGEPLPNCIYGGSGGPFVTEFKSTVYYHNKSPTWYEEIKIALP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  401 VDKFRGAHIRFEFRHCSTKEKGEK--KLFGFSFVPLMQEDGRTLPDGTHELIVHKCEEntnlqDTTRYLKLPFSKGIFLG 478
Cdd:pfam14429   81 AELTPKHHLLFTFYHVSCDEKKDKveKPFGYAFLPLLDDDGAFLRDGEHTLPVYKYDE-----LPPGYLSLPWSSGGEKE 155

                          170       180
                   ....*....|....*....|....*...
gi 1370511304  479 -NNNQAMKATKESFCITSFLCSTKLTQN 505
Cdd:pfam14429  156 sSALPGLKGGKDLFKVRTRLCSTKYTQD 183
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1430-1520 1.65e-21

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: 91.12  E-value: 1.65e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1430 NINPLTMCLNGVIDAAVNGGVSRYQEAFFVKEYILSHPEdgEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKL 1509
Cdd:pfam20421   12 NIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPA--EKVEKLKEEFRDFLKVCGEALRLNKKLISEDQREYQEEL 89

                           90
                   ....*....|.
gi 1370511304 1510 VDQFFVMKSSL 1520
Cdd:pfam20421   90 EEGFEKLKEKL 100
 
Name Accession Description Interval E-value
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1130-1520 0e+00

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


Pssm-ID: 212578  Cd Length: 391  Bit Score: 808.10  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLTYPMQTEWQRKEHLHLTIIQNFDRGKCWENGIILC 1209
Cdd:cd11705      1 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLSYPMQTEWQRKEYLHLTIIQNFDRGKCWENGIILC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1210 RKIAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 1289
Cdd:cd11705     81 RKLAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1290 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKENEFKSL 1369
Cdd:cd11705    161 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRDGVPDNIKSFYKVNHIWRFRYDRPFHKGTKDKENEFKSL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1370 WVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQNINPLTMCLNGVIDAAVNGG 1449
Cdd:cd11705    241 WVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQCQTRQMQNINPLTMCLNGVIDAAVNGG 320

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370511304 1450 VSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11705    321 VSRYQEAFFVKEYILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1130-1520 0e+00

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


Pssm-ID: 212569  Cd Length: 391  Bit Score: 744.27  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLTYPMQTEWQRKEHLHLTIIQNFDRGKCWENGIILC 1209
Cdd:cd11696      1 EMYLRYIYKLHDLHLQAENYTEAAFTLLLYAELLSWSSDPLPADLHHPSQPEWQRKEALYLKILQYFDRGKCWEKGIPLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1210 RKIAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 1289
Cdd:cd11696     81 RELAELYESLYDYAKLSHILRMEASFYDNILTQLRPEPEYFRVGFYGKGFPLFLRNKQFVYRGLDYERIGAFTQRLQSEF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1290 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKENEFKSL 1369
Cdd:cd11696    161 PQAHILTKNTPPDDAILQADGQYIQICNVKPVPERRPVLQMVGVPDKVRSFYRVNDVRKFQYDRPIHKGPIDKDNEFKSL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1370 WVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQNINPLTMCLNGVIDAAVNGG 1449
Cdd:cd11696    241 WIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTRNINPFSMRLQGVIDAAVNGG 320

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370511304 1450 VSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11696    321 IAKYQEAFFTPEFILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVERFTQMKQSL 391
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1130-1520 0e+00

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


Pssm-ID: 212577  Cd Length: 392  Bit Score: 609.32  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLTYPMQTEWQRKEHLHLTIIQNFDRGKCWENGIILC 1209
Cdd:cd11704      1 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWEDRPLREFLHYPSQSEWQRKEGLCRKIIHYFNKGKSWEFGIPLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1210 RKIAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEF 1289
Cdd:cd11704     81 RELAFQYESLYDYQSLSWIRKMEAAYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1290 PHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKENEFKSL 1369
Cdd:cd11704    161 PQAIAMQHPNHPDDGILQCDAQYLQIYAVTPIPDNMDVLQMDRVPDRIKSFYRVNNVRKFRYDRPFHKGPKDKENEFKSL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1370 WVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQ-NINPLTMCLNGVIDAAVNG 1448
Cdd:cd11704    241 WIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQHKQLHgNINLLSMCLNGVIDAAVNG 320

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370511304 1449 GVSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11704    321 GIARYQEAFFDKDYISKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1130-1519 1.45e-154

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


Pssm-ID: 212570  Cd Length: 400  Bit Score: 480.67  E-value: 1.45e-154
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLT---YPM-QTEWQRKEHLHLTIIQNFDRGKCWENG 1205
Cdd:cd11697      1 EMYIRYLYKLCDLHLECDNYTEAAYTLQLHAELLKWSDEPLPTLLRsrrYPEaQTHRQLKEALYYDIIDYFDKGKMWECA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1206 IILCRKIAEQYES-YYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQR 1284
Cdd:cd11697     81 ISLCKELAEQYENeTFDYLQLSELLKRMATFYDNIMKTLRPEPEYFRVGYYGQGFPSFLRNKVFIYRGKEYERLSDFSAR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1285 MLNEFPHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKEN 1364
Cdd:cd11697    161 LLNQFPNAELMNTLTPPGDEIKESPGQYLQINKVDPVMDERPRFKGKPVSDQILNYYKVNEVQRFTFSRPFRRGTKDPDN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1365 EFKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQNINPLTMCLNGVIDA 1444
Cdd:cd11697    241 EFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIETMEDTNKKIRDLILQHQSDPTLPINPLSMLLNGIVDA 320

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370511304 1445 AVNGGVSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSS 1519
Cdd:cd11697    321 AVMGGIANYEKAFFTEEYLDEHPEDQELIERLKDLIAEQIPLLEAGLKIHKQKAPESLRPLHERMEECFAKMKEH 395
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1130-1520 1.12e-142

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: 447.90  E-value: 1.12e-142
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDR----PLREFLTYPMQTEWQRKEHLHLTIIQNFDRGKCWENG 1205
Cdd:cd11684      1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKalvpALAESLSFPEQTSFERKEALYKKAIDLFDKGKAWEFA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1206 IILCRKIAEQYESYYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRM 1285
Cdd:cd11684     81 IALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEKDRLFPTYFRVGFYGKGFPESLRGKEFIYRGPEFERLGDFCERL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1286 LNEFPHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEvlQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKENE 1365
Cdd:cd11684    161 KSLYPGAEIIQSSEEPDDEILDSEGQYIQITSVEPYFDDED--LVSRAAPGVRQFYRNNNINTFVYERPFTKGGKKSQNE 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1366 FKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQNINPLTMCLNGVIDAA 1445
Cdd:cd11684    239 ITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIEDIEKKTEELRSLINKYRSGDSPNVNPLQMLLQGTVDAA 318

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370511304 1446 VNGGVSRYQEAFFVKEYILSHPEDgEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11684    319 VNGGPVAYAEAFLSEEYLSNYPEA-EKVKKLKEAFEEFLEILKRGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1111-1517 4.54e-138

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: 436.34  E-value: 4.54e-138
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1111 KIGCTVSLLNFYKtELNKEEMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSD----RPLREFLTYPMQTEWQRKE 1186
Cdd:cd11706      1 RMSCTVNLLNFYK-DINREAMYIRYLYKLRDLHLDCENYTEAAYTLLLHTRLLKWSDeqcaSQVMQTGQQHPQTQRQLKE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1187 HLHLTIIQNFDRGKCWENGIILCRKIAEQYES-YYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRN 1265
Cdd:cd11706     80 TLYETIIGYFDKGKMWEEAISLCKELAEQYEMeIFDYELLSQNLIQQAKFYESIMKILRPKPDYFAVGYYGQGFPSFLRN 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1266 KEFVCRGHDYERLEAFQQRMLNEFPHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNH 1345
Cdd:cd11706    160 KVFIYRGKEYERREDFQMQLMSQFPNAEKLNTTSAPGDDIKNSPGQYIQCFTVQPVLEEHPRLKNKPVPDQIINFYKSNY 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1346 IWKFRYDRPFHKGTKDKENEFKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQT 1425
Cdd:cd11706    240 VQRFHYSRPVRKGPVDPENEFASMWIERTTFVTAYKLPGILRWFEVTHMSQTTISPLENAIETMSTTNEKILMMINQYQS 319

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1426 RQMQNINPLTMCLNGVIDAAVNGGVSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPL 1505
Cdd:cd11706    320 DESLPINPLSMLLNGIVDPAVMGGFAKYEKAFFTEEYVRDHPEDQDKLTRLKDLIAWQIPLLGAGIKIHGKRVTDDLRPF 399

                          410
                   ....*....|..
gi 1370511304 1506 HKKLVDQFFVMK 1517
Cdd:cd11706    400 HERMEECFKQLK 411
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 324-508 7.94e-124

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


Pssm-ID: 176077  Cd Length: 189  Bit Score: 386.74  E-value: 7.94e-124
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  324 MRNDLYITIERGEFEKGGKSVARNVEVTMFIVDSSGQTLKDFISFGSGEPPASEYHSFVLYHNNSPRWSELLKLPIPVDK 403
Cdd:cd08695      1 VRNDLYLTLERGEFEKGGKSTAKNIEVTMVVLDADGQVLKDCISLGSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPIDK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  404 FRGAHIRFEFRHCSTKEKGEKKLFGFSFVPLMQEDGRTLPDGTHELIVHKCEENTNLQDTTRYLKLPFSKGIFLGNNNQA 483
Cdd:cd08695     81 FRGSHLRFEFRHCSTKDKGEKKLFGFSFVPLMREDGTTLPDGSHELYVYKCDENATFLDPALYLGLPCSKEDFQGCPNSP 160

                          170       180
                   ....*....|....*....|....*....
gi 1370511304  484 M----KATKESFCITSFLCSTKLTQNGDM 508
Cdd:cd08695    161 SplfsRSSKESFWIRTLLCSTKLTQNVDL 189
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1130-1518 7.39e-120

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


Pssm-ID: 212581  Cd Length: 400  Bit Score: 384.68  E-value: 7.39e-120
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFL----TYPMQTEWQRKEHLHLTIIQNFDRGKCWENG 1205
Cdd:cd11708      1 DIYIRYLYKLRDLHLDCENYTEAAYTLLLHAELLQWSEKPCVPHLlqrdSYYVYTQQELKERLYQEIISFFDKGKMWEKA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1206 IILCRKIAEQYES-YYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQR 1284
Cdd:cd11708     81 IELSKELADMYENqVFDYEGLGNLLKKQAQFYENIMKAMRPQPEYFAVGYYGQGFPSFLRNKIFIYRGKEYERLEDFSLK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1285 MLNEFPHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKEN 1364
Cdd:cd11708    161 LLTQFPNAEKMTSTSPPGDEIKSSTKQYVQCFTVKPVMNLPSHYKDKPVPEQILNYYRANEVQQFQYSRPFRKGEKDPDN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1365 EFKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQNINPLTMCLNGVIDA 1444
Cdd:cd11708    241 EFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLENAIETMELTNEKISNLVQQHAWDRSLPVHPLSMLLNGIVDP 320

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370511304 1445 AVNGGVSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKS 1518
Cdd:cd11708    321 AVMGGFSNYEKAFFTEKYLQEHPEDQEKIELLKQLIALQMPLLAEGIRIHGEKLTEQLKPLHERLVSCFKDLRA 394
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1130-1509 4.21e-119

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: 382.46  E-value: 4.21e-119
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1130 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLT----YPMQTEWQRKEHLHLTIIQNFDRGKCWENG 1205
Cdd:cd11707      1 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEEACAAHLTqrdgYQATTQGQLKDQLYQEIIHYFDKGKMWEEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1206 IILCRKIAEQYES-YYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQR 1284
Cdd:cd11707     81 IALGKELAEQYENeMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRNKMFIYRGKEYERREDFEAR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1285 MLNEFPHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKEN 1364
Cdd:cd11707    161 LLTQFPNAEKMKTTSPPGDDIKNSSGQYIQCFTVKPLLELPPKFQNKPVSEQIVSFYRVNEVQRFQYSRPVRKGEKDPDN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1365 EFKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQNINPLTMCLNGVIDA 1444
Cdd:cd11707    241 EFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNEKINNMVQQHLNDPNLPINPLSMLLNGIVDP 320

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370511304 1445 AVNGGVSRYQEAFFVKEYILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKL 1509
Cdd:cd11707    321 AVMGGFANYEKAFFTEKYMQEHPEDHEKIEKLKDLIAWQIPFLAEGIRIHGEKVTEALRPFHERM 385
DOCK_N pfam16172
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 1-316 2.70e-117

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


Pssm-ID: 465040  Cd Length: 317  Bit Score: 373.77  E-value: 2.70e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304    1 MVIPTEDSVITEMTSTLRDWGTMWKQLYVRNEGDLFHRLWHIMNEILDLRRQVLVGHLTHDRMKDVKRHITARLDWGNEQ 80
Cdd:pfam16172    5 TPTSAEEPLVDEIASCLREWHSTLHELLLSRQYQLFDKLSQLIYELDLARRQLLHGVLTADELKELREKTVWDLVRGNKL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304   81 LGLDLVPRKE--YAMVDPEDISITELYRL------MEHRHRKKDTPVQASSHHLFVQMKSLMCSNLGEELEVIFSLFDSK 152
Cdd:pfam16172   85 LGLDVIVRDPtgRGRLLTDDDSVVELYKLqsemslLDEPPTPQVEPDATSLHHLLVDVKNFVGSSIGEDAELFFSLYDKK 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  153 ENRPISERFFLRLNRNGLPKAPDKPERHCSLFVDLGSSEL-RKDIYITVHIIRIgrmgagekknacsvqYRRPFGCAVLS 231
Cdd:pfam16172  165 ELKFLSENFVVRLPSNGMPKSLAQSLNLRTLFTDLSSSDLaRSKLYLVCKVIRN---------------VRRPFGVAVLD 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  232 IADLLTG----ETKDDLILKVYMCNTESEWYQIHENIIKKLNARYNLTGSNAGLAVSLQLLHGDIEQIRREYSSVFsHGV 307
Cdd:pfam16172  230 LTDILKGlkqsDEEVEHVVPIWSPNNESDFDELHRDIIKSITGKYEKSPRAERLWVSLKLFHGDAEQLRKENPTLL-HNV 308


                   ....*....
gi 1370511304  308 SITRKLGFS 316
Cdd:pfam16172  309 AITRKLGFP 317
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 321-505 2.61e-67

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: 225.17  E-value: 2.61e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  321 PGEMRNDLYITIERGEFEKGGKSVARNVEVTMFIVDSSGQTLKDFISFGSGEPPASEYHSFVLYHNNSPRWSELLKLPIP 400
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSARNIEVTVEVRDSDGEPLPNCIYGGSGGPFVTEFKSTVYYHNKSPTWYEEIKIALP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  401 VDKFRGAHIRFEFRHCSTKEKGEK--KLFGFSFVPLMQEDGRTLPDGTHELIVHKCEEntnlqDTTRYLKLPFSKGIFLG 478
Cdd:pfam14429   81 AELTPKHHLLFTFYHVSCDEKKDKveKPFGYAFLPLLDDDGAFLRDGEHTLPVYKYDE-----LPPGYLSLPWSSGGEKE 155

                          170       180
                   ....*....|....*....|....*...
gi 1370511304  479 -NNNQAMKATKESFCITSFLCSTKLTQN 505
Cdd:pfam14429  156 sSALPGLKGGKDLFKVRTRLCSTKYTQD 183
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 325-508 1.84e-64

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: 217.66  E-value: 1.84e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  325 RNDLYITIERGEFEKGGKSVARNVEVTMFIVDSSGQTLKDFISFGSGEPPASEYHSFVLYHNNSPRWSELLKLPIPVDKF 404
Cdd:cd08694      2 RNDLYLTLVQGDFDKGSKTSDKNVEVTVSVCNEDGKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIEDF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  405 RGAHIRFEFRHCSTKEKGEK--KLFGFSFVPLMQEDGRTLPDGTHELIVHKCEENTNLQDTTRYLKLPFSK------GIF 476
Cdd:cd08694     82 KSSHLRFTFKHRSSNEAKDKseKPFALSFVKLMQENGTTLTDGEHDLIVYKVDAKKKLEDAKAYLSLPSTRaelearKSS 161

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1370511304  477 LGNNNQAMK---ATKESFCITSFLCSTKLTQNGDM 508
Cdd:cd08694    162 PSGSASNLGlslSSKDSFQISTLVCSTKLTQNVDL 196
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 324-505 7.32e-50

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: 174.83  E-value: 7.32e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  324 MRNDLYITIERGEFEKGgKSVARNVEVTMFIVDSSGQTLKD-FISFGSGEPPASEYHSfVLYHNNSPRWSELLKLPIPVD 402
Cdd:cd08679      1 LRNDLYVYPQSGELSKA-KSKGRNIEITVEVRDDDGDIIEPcISAPGSGSELRSEYTS-VVYYHKNPVFNDEIKIQLPAD 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  403 KFRGAHIRFEFRHCSTKEKG---EKKLFGFSFVPLMQEDGRTLPDGTHELIVHKCEENT-NLQDTtrYLKLPFSKGIflg 478
Cdd:cd08679     79 LTPQHHLLFTFYHVSSKKKQgdkEETPFGYAFLPLMDKDGAFIKDGDHTLPVYKYDKRPdVGPSG--YLSLPSTLAN--- 153

                          170       180
                   ....*....|....*....|....*..
gi 1370511304  479 nnnqaMKATKESFCITSFLCSTKLTQN 505
Cdd:cd08679    154 -----GKSSKDTFKIKTRLCSTILTQD 175
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1430-1520 1.65e-21

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: 91.12  E-value: 1.65e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1430 NINPLTMCLNGVIDAAVNGGVSRYQEAFFVKEYILSHPEdgEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKL 1509
Cdd:pfam20421   12 NIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPA--EKVEKLKEEFRDFLKVCGEALRLNKKLISEDQREYQEEL 89

                           90
                   ....*....|.
gi 1370511304 1510 VDQFFVMKSSL 1520
Cdd:pfam20421   90 EEGFEKLKEKL 100
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1216-1509 1.91e-19

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: 93.17  E-value: 1.91e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1216 YESYYDYRNLSKMRMMEASLYDKIMD----QQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEFPH 1291
Cdd:cd11698    111 YEKRRDFERLAHLYDTLHRAYSKVTEvmhsGKRLLGTYFRVAFFGQGFFEDEDGKEYIYKEPKLTPLSEISQRLLKLYSD 190

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1292 AIA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREgvpdniKSFYKVNHIWKFRYDRPFHKGTKdKENE 1365
Cdd:cd11698    191 KFGsenvkmIQDSGKVNPKDLDSKYAYIQVTHVTPYFDEKELQERK------TDFERSHNIRRFMFEMPFTQSGK-RQGG 263

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1366 FKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLisqCQTRQMQNINpLTMCLNGVIDAA 1445
Cdd:cd11698    264 VEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKKVAELRQL---CSSAEVDMIK-LQLKLQGSVSVQ 339

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370511304 1446 VNGGVSRYQEAFFVKEYILSHPEDgeKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKL 1509
Cdd:cd11698    340 VNAGPLAYARAFLDDTNTKRYPDN--KVKLLKEVFRQFVEACGQALAVNERLIKEDQLEYQEEM 401
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1208-1520 4.95e-17

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: 85.82  E-value: 4.95e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1208 LCRKIAEQYESYYDYRNLSKMRMMEASLYDKIMD----QQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQ 1283
Cdd:cd11700    104 ISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEvmhtGKRLLGTFFRVAFYGQGFFEEEDGKEYIYKEPKLTGLSEISH 183

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1284 RMLNEFPHAIA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREgvpdniKSFYKVNHIWKFRYDRPFHK 1357
Cdd:cd11700    184 RLLKLYGEKFGsenvkiIQDSNKVNQKDLDPKYAHIQVTYVKPYFDDKEMAERK------TEFERNHNIQRFVFETPYTL 257

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1358 GTKdKENEFKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQCQTRQMQninpLTMC 1437
Cdd:cd11700    258 SGK-KQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKDKTAELQKLCSNQDVDMIQ----LQLK 332

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1438 LNGVIDAAVNGGVSRYQEAFFVKEYILSHPedGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMK 1517
Cdd:cd11700    333 LQGCVSVQVNAGPLAYARAFLDDSQASKYP--NKKVKELKEMFRKFIQACSIALELNERLIKEDQVEYHEGLKSNFRDMV 410


                   ...
gi 1370511304 1518 SSL 1520
Cdd:cd11700    411 KEL 413
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1216-1520 9.50e-17

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: 85.10  E-value: 9.50e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1216 YESYYDYRNLSKMRMMEASLYDKIMD----QQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEFPH 1291
Cdd:cd11699    145 FEKQRDFKRLSELYYDIHRSYLKVAEvvnsEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYAD 224

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1292 AIA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREgvpdniKSFYKVNHIWKFRYDRPFHKGTKdKENE 1365
Cdd:cd11699    225 KFGadnvkiIQDSNKVNPKELDPKFAYIQVTYVTPYFDEKEQEDRK------TDFEMHHNINRFVFETPFTLSGK-KHGG 297

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1366 FKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLisqCQTRQMQNINpLTMCLNGVIDAA 1445
Cdd:cd11699    298 VEEQCKRRTILTTSHSFPYVKKRIQVVSQTSTELNPIEVAIDEMSKKVSELNQL---CTMEEVDMIR-LQLKLQGSVSVK 373

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370511304 1446 VNGGVSRYQEAFFVKEYILSHPEDgeKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11699    374 VNAGPMAYARAFLEETNAKKYPDN--QVKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1216-1520 9.72e-17

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: 84.27  E-value: 9.72e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1216 YESYYDYRNLSK--MRMMEAslYDKIMDQQ---RLEPEFFRVGFYGKKFPFfLRNKEFVCR----------GHdyeRLEA 1280
Cdd:cd11695     68 LEANRDYKKLAEihGKLQDA--FTKIEKQQggkRMFGTYFRVGFYGSKFGD-LDGKEFIYKepaitklpeiSH---RLET 141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1281 FQQRMLNEfPHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQREGVpdniksFYKVNHIWKFRYDRPFHKGTK 1360
Cdd:cd11695    142 FYGERFGE-ERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEYELKERTTY------FERNYNLRRFMYATPFTPDGK 214

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1361 ---DKENEFKslwvERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQcqtrQMQNINPLTMC 1437
Cdd:cd11695    215 ahgELAEQYK----RKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKKTRELAAATTQ----EPPDPKMLQMV 286

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1438 LNGVIDAAVNggvsryQEAFFVKEYILSHPEDGEKIA-------RL--RELMLEQAQILEfglaVHEKFVPQDMRPLHKK 1508
Cdd:cd11695    287 LQGSIGTTVN------QGPLEVANVFLSDIPLDPKELdrhqnklRLcfKEFSKKCYDALE----KNKELIGPDQKEYQKE 356

                          330
                   ....*....|..
gi 1370511304 1509 LVDQFFVMKSSL 1520
Cdd:cd11695    357 LERNYENFKEKL 368
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1217-1520 4.94e-15

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: 79.69  E-value: 4.94e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1217 ESYYDYRNLSKMRMMEASLYDKIM--DQQRLEPEFFRVGFYGKKFPfFLRNKEFVCRGHDYERLEAFQQRMLNEFPH--- 1291
Cdd:cd11701    125 EAHRDFRKLASTHDKLQKAFDNIInkGHKRMFGTYFRVGFYGSKFG-DLDEQEFIYKEPAITKLPEISHRLEGFYGQcfg 203

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1292 --AIAMQHANQP-DETIFQAEAQYLQIYAVTPIPESQEvlqregVPDNIKSFYKVNHIWKFRYDRPFHKGTKDKeNEFKS 1368
Cdd:cd11701    204 ddVVEVIKDSTPvDKSKLDPNKAYIQITFVEPYFDDYE------MKDRVTYFEKNFNLRRFMYTTPFTLDGRPR-GELSE 276

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1369 LWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLktliSQCQTRQMQNINPLTMCLNGVIDAAVNG 1448
Cdd:cd11701    277 QYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTREL----AEATHQEPPDAKMLQMVLQGSVGATVNQ 352

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370511304 1449 GVSRYQEAFFVKeyILSHPEDGEKIARLRELMLEqaQILEFGLAV--HEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11701    353 GPLEVAQVFLAE--IPADPKLYRHHNKLRLCFKE--FIMRCGEAVekNKRLITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1211-1520 5.62e-14

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: 75.84  E-value: 5.62e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1211 KIAEQYES-----------YYDYRNLSKM----RMMEASlYDKIMDQQ----RLEPEFFRVGFYGKKFPFFLRNKEFVCR 1271
Cdd:cd11694     56 WKAERYELlgelykliipiYEKRRDFEQLadcyRTLHRA-YEKVVEVMesgkRLLGTYYRVAFYGQAFFEEEDGKEYIYK 134

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1272 GHDYERLEAFQQRMLNEF-----PHAIAM-QHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRegvpdnIKSFYKVNH 1345
Cdd:cd11694    135 EPKVTSLSEISERLLKLYgdkfgSENVKLiQDSGKVNPKDLDPKYAYIQVTHVTPYFDEKELEDR------KTEFERNHN 208

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1346 IWKFRYDRPFHKGTKdKENEFKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISqcqt 1425
Cdd:cd11694    209 IRRFVFETPFTLSGK-ARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSKVKELEELIS---- 283

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1426 RQMQNINPLTMCLNGVIDAAVNGGVSRYQEAFFVKEYILSHPEDgeKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPL 1505
Cdd:cd11694    284 TEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTVKNYPDD--QVEDLKDVFRDFIKACGQALELNERLIKEDQREY 361

                          330
                   ....*....|....*
gi 1370511304 1506 HKKLVDQFFVMKSSL 1520
Cdd:cd11694    362 HEVLKENYRKMVKEL 376
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1299-1376 1.26e-13

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: 67.63  E-value: 1.26e-13
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370511304 1299 NQPDETIFQAEAQYLQIYAVTPIPESQEVlqregvPDNIKSFYKVNHIWKFRYDRPFHKGTKdKENEFKSLWVERTSL 1376
Cdd:pfam20422    2 NPVDESILDPDKAYIQITSVEPYFDDSEL------NDRVTYFERNNNVNRFVFETPFTKSGK-AQGEFEEQWKRRTIL 72
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1216-1520 6.36e-13

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: 73.12  E-value: 6.36e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1216 YESYYDYRNLSKMRMMEASLYDKIMDQ----QRLEPEFFRVGFYGKKFPfFLRNKEFVCR-------GHDYERLEAFQQR 1284
Cdd:cd11702    123 HEANRDYKKLAVVHGKLQEAFNKITNQssgwERMFGTYFRVGFYGCKFG-DLDEQEFVYKepsitklAEISHRLEEFYTE 201

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1285 MLNEFPHAIaMQHANQPDETIFQAEAQYLQIYAVTPIPESQEvlqregVPDNIKSFYKVNHIWKFRYDRPFhkgTKD--K 1362
Cdd:cd11702    202 RFGDEVVEI-IKDSNPVDKSKLDPNKAYIQITYVEPFFDTYE------LKDRVTYFDKNYNLRTFLFCTPF---TLDgrA 271

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1363 ENEFKSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQcqtrQMQNINPLTMCLNGVI 1442
Cdd:cd11702    272 HGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQKKTQELAFATHQ----DPADAKMLQMVLQGCV 347

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1443 DAAVNGGVSRYQEAFFVKEyilshPEDgEKIAR----LRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKS 1518
Cdd:cd11702    348 GTTVNQGPLEVAQVFLSEI-----PED-PKLFRhhnkLRLCFKDFTKRCEDALRKNKALIGPDQKEYHRELERNYQRLRE 421


                   ..
gi 1370511304 1519 SL 1520
Cdd:cd11702    422 AL 423
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1216-1520 1.09e-10

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: 66.26  E-value: 1.09e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1216 YESYYDYRNLSKMRMMEASLYDKIMDQ--QRLEPEFFRVGFYGKKFPFfLRNKEFVCR-------GHDYERLEAFQQRML 1286
Cdd:cd11703    162 HEANRDAKKLATIHGKLQEAFSKIVHQdgKRMFGTYFRVGFYGTKFGD-LDEQEFVYKepaitklAEISHRLEGFYGERF 240

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1287 NEfPHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVlqregvPDNIKSFYKVNHIWKFRYDRPFHKGTKdKENEF 1366
Cdd:cd11703    241 GE-DVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEM------KDRITYFDKNYNLRRFMYCTPFTLDGR-AHGEL 312

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1367 KSLWVERTSLYLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLKTLISQcqtrQMQNINPLTMCLNGVIDAAV 1446
Cdd:cd11703    313 HEQFKRKTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQ----DPADPKMLQMVLQGSVGTTV 388

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370511304 1447 NGGVSRYQEAFFVKeyILSHPEDGEKIARLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 1520
Cdd:cd11703    389 NQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEAL 460
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1117-1239 1.58e-10

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: 61.15  E-value: 1.58e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304 1117 SLLNFYKtelNKEEMYIRYIHKLYDLHLKAQNFTEAAYTLL----LYDELLEWSDRPLR--------------------- 1171
Cdd:pfam06920    5 SLANSYK---SSPDLRLTWLENLAEKHLENGNFSEAAQCLIhiaaLIAEYLKLKGKIPNplgasafekispnilreesal 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370511304 1172 ----EFLTYPMQTEWQRKEHLHLtIIQNFDRGKCWENGIILCRKIAEQYESYYDYRNLSKMRMMEASLYDKI 1239
Cdd:pfam06920   82 kddsGVCDSPHFTEDGLVGLLEE-AIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKI 152
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 324-451 2.76e-08

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: 55.44  E-value: 2.76e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  324 MRNDLYITIERGEFEKGGKSvARNVEVTMFIVDSSGQTLK-DFISFGSGEPPAS-EYHSFVLYHNNSPRWSELLKLPIPV 401
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRLGS-ARNIAVKVQLMSGEDESQAlPVIFKGSSPEEFLtEAYTAVTYHNKSPDFYDEIKIKLPA 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1370511304  402 DKFRGAHIRFEFRHCSTKEKGE----KKLFGFSFVPLMqEDGRtLPDGTHELIV 451
Cdd:cd08696     80 DLTDNHHLLFTFYHISCQKKQEggsvETPIGYTWLPLL-RNGR-LQSGEFNLPV 131
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 345-504 1.08e-07

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: 53.86  E-value: 1.08e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  345 ARNVEVTMFIVDS---SGQTLKdFISFGSGEPPASEYHSFVLYHNNSPRWSELLKLPIPVDKFRGAHIRFEFRH--CSTK 419
Cdd:cd08697     23 ARNIAVCIEFRDSdeeDAKPLK-CIYYGPGGGFTTSAYAAVLHHNQNPEFYDEIKIELPTQLHEKHHLLFTFYHvsCDIN 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370511304  420 EKGEKK-----LFGFSFVPLMQEDGRtLPDGTHELIVHKCEENTNLQDTTRYLKLPFSKGIfLGNnnqamkatKESFCIT 494
Cdd:cd08697    102 KKGKKKdgvetPVGYAWLPLLKDKGR-LNSEEQTPPVANLLPNYPDGYLSIQPHGPEVKWV-DGG--------KPLFKVS 171

                          170
                   ....*....|
gi 1370511304  495 SFLCSTKLTQ 504
Cdd:cd08697    172 THLVSTVYTQ 181
 
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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