UniProtKB - Q14185 (DOCK1_HUMAN)
Protein
Dedicator of cytokinesis protein 1
Gene
DOCK1
Organism
Homo sapiens (Human)
Status
Functioni
Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen (PubMed:19004829). Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1 (PubMed:8657152).2 Publications
GO - Molecular functioni
- GTPase activator activity Source: ProtInc
- Rho guanyl-nucleotide exchange factor activity Source: Reactome
- SH3 domain binding Source: UniProtKB-KW
GO - Biological processi
- apoptotic process Source: ProtInc
- blood coagulation Source: Reactome
- Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
- integrin-mediated signaling pathway Source: ProtInc
- phagocytosis, engulfment Source: ProtInc
- positive regulation of epithelial cell migration Source: UniProtKB
- positive regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
- signal transduction Source: ProtInc
- small GTPase mediated signal transduction Source: ProtInc
- vascular endothelial growth factor receptor signaling pathway Source: Reactome
Keywordsi
Molecular function | Guanine-nucleotide releasing factor |
Biological process | Apoptosis, Phagocytosis |
Enzyme and pathway databases
PathwayCommonsi | Q14185 |
Reactomei | R-HSA-2029482, Regulation of actin dynamics for phagocytic cup formation R-HSA-418885, DCC mediated attractive signaling R-HSA-4420097, VEGFA-VEGFR2 Pathway R-HSA-8849471, PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases R-HSA-9664422, FCGR3A-mediated phagocytosis R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
Names & Taxonomyi
Protein namesi | Recommended name: Dedicator of cytokinesis protein 1Alternative name(s): 180 kDa protein downstream of CRK Short name: DOCK180 |
Gene namesi | Name:DOCK1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2987, DOCK1 |
MIMi | 601403, gene |
neXtProti | NX_Q14185 |
VEuPathDBi | HostDB:ENSG00000150760.12 |
Subcellular locationi
Cytosol
- cytosol Source: HPA
Nucleus
- nuclear speck Source: HPA
- nucleoplasm Source: HPA
Other locations
- cytoplasm Source: CAFA
- guanyl-nucleotide exchange factor complex Source: WormBase
- membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1401 – 1402 | YI → AA: Abolishes Rac GEF activity. 1 Publication | 2 | |
Mutagenesisi | 1487 – 1489 | ISP → AAA: Abolishes Rac GEF activity. 1 Publication | 3 |
Organism-specific databases
DisGeNETi | 1793 |
OpenTargetsi | ENSG00000150760 |
PharmGKBi | PA27453 |
Miscellaneous databases
Pharosi | Q14185, Tbio |
Genetic variation databases
BioMutai | DOCK1 |
DMDMi | 209572608 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000189984 | 1 – 1865 | Dedicator of cytokinesis protein 1Add BLAST | 1865 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1681 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1743 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1751 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1756 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1761 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1764 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1767 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1772 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1858 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q14185 |
jPOSTi | Q14185 |
MassIVEi | Q14185 |
MaxQBi | Q14185 |
PaxDbi | Q14185 |
PeptideAtlasi | Q14185 |
PRIDEi | Q14185 |
ProteomicsDBi | 59903 |
PTM databases
iPTMneti | Q14185 |
PhosphoSitePlusi | Q14185 |
Expressioni
Tissue specificityi
Highly expressed in placenta, lung, kidney, pancreas and ovary. Expressed at intermediate level in thymus, testes and colon.
Gene expression databases
Bgeei | ENSG00000150760, Expressed in lung and 239 other tissues |
ExpressionAtlasi | Q14185, baseline and differential |
Genevisiblei | Q14185, HS |
Organism-specific databases
HPAi | ENSG00000150760, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with the SH3 domains of CRK and NCK2 via multiple sites (PubMed:8657152, PubMed:8662907, PubMed:11240126).
Interacts with nucleotide-free RAC1 via its DOCKER domain (PubMed:9808620, PubMed:12134158).
Interacts with ELMO1, ELMO2 and probably ELMO3 via its SH3 domain (PubMed:12134158).
Interacts with ADGRB1.
Identified in a complex with AUTS2 and ELMO2 (By similarity).
By similarity6 PublicationsBinary interactionsi
Hide detailsQ14185
GO - Molecular functioni
- Rho guanyl-nucleotide exchange factor activity Source: Reactome
- SH3 domain binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 108128, 29 interactors |
CORUMi | Q14185 |
DIPi | DIP-29391N |
IntActi | Q14185, 25 interactors |
MINTi | Q14185 |
STRINGi | 9606.ENSP00000280333 |
Miscellaneous databases
RNActi | Q14185, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | Q14185 |
SMRi | Q14185 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q14185 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 9 – 70 | SH3PROSITE-ProRule annotationAdd BLAST | 62 | |
Domaini | 425 – 609 | C2 DOCK-typePROSITE-ProRule annotationAdd BLAST | 185 | |
Domaini | 1207 – 1617 | DOCKERPROSITE-ProRule annotationAdd BLAST | 411 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1687 – 1695 | Phosphoinositide-bindingSequence analysis | 9 | |
Regioni | 1793 – 1819 | Interaction with NCK2 second and third SH3 domain (minor)Add BLAST | 27 | |
Regioni | 1820 – 1836 | Interaction with NCK2 third SH3 domain (major)Add BLAST | 17 | |
Regioni | 1837 – 1852 | Interaction with NCK2 (minor)Add BLAST | 16 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 1799 – 1805 | SH3-binding; interaction with CRKSequence analysis | 7 | |
Motifi | 1838 – 1843 | SH3-binding; interaction with CRKSequence analysis | 6 |
Domaini
The DOCKER domain is necessary and sufficient for the GEF activity.
Sequence similaritiesi
Belongs to the DOCK family.PROSITE-ProRule annotation
Keywords - Domaini
SH3 domain, SH3-bindingPhylogenomic databases
eggNOGi | KOG1998, Eukaryota |
GeneTreei | ENSGT00940000154974 |
HOGENOMi | CLU_000595_2_1_1 |
InParanoidi | Q14185 |
OrthoDBi | 102580at2759 |
PhylomeDBi | Q14185 |
TreeFami | TF300423 |
Family and domain databases
Gene3Di | 1.20.1270.350, 1 hit 1.20.58.740, 1 hit 1.25.40.410, 1 hit 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR016024, ARM-type_fold IPR035892, C2_domain_sf IPR027007, DHR-1_domain IPR027357, DHR-2 IPR026791, DOCK IPR010703, DOCK_C IPR043161, DOCK_C_lobe_A IPR043162, DOCK_C_lobe_C IPR032376, DOCK_N IPR042455, DOCK_N_sub1 IPR036028, SH3-like_dom_sf IPR001452, SH3_domain |
PANTHERi | PTHR45653, PTHR45653, 1 hit |
Pfami | View protein in Pfam PF06920, DHR-2, 1 hit PF14429, DOCK-C2, 1 hit PF16172, DOCK_N, 1 hit PF00018, SH3_1, 1 hit |
SMARTi | View protein in SMART SM00326, SH3, 1 hit |
SUPFAMi | SSF48371, SSF48371, 1 hit SSF50044, SSF50044, 1 hit |
PROSITEi | View protein in PROSITE PS51650, C2_DOCK, 1 hit PS51651, DOCKER, 1 hit PS50002, SH3, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q14185-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTRWVPTKRE EKYGVAFYNY DARGADELSL QIGDTVHILE TYEGWYRGYT
60 70 80 90 100
LRKKSKKGIF PASYIHLKEA IVEGKGQHET VIPGDLPLIQ EVTTTLREWS
110 120 130 140 150
TIWRQLYVQD NREMFRSVRH MIYDLIEWRS QILSGTLPQD ELKELKKKVT
160 170 180 190 200
AKIDYGNRIL DLDLVVRDED GNILDPELTS TISLFRAHEI ASKQVEERLQ
210 220 230 240 250
EEKSQKQNID INRQAKFAAT PSLALFVNLK NVVCKIGEDA EVLMSLYDPV
260 270 280 290 300
ESKFISENYL VRWSSSGLPK DIDRLHNLRA VFTDLGSKDL KREKISFVCQ
310 320 330 340 350
IVRVGRMELR DNNTRKLTSG LRRPFGVAVM DVTDIINGKV DDEDKQHFIP
360 370 380 390 400
FQPVAGENDF LQTVINKVIA AKEVNHKGQG LWVTLKLLPG DIHQIRKEFP
410 420 430 440 450
HLVDRTTAVA RKTGFPEIIM PGDVRNDIYV TLVQGDFDKG SKTTAKNVEV
460 470 480 490 500
TVSVYDEDGK RLEHVIFPGA GDEAISEYKS VIYYQVKQPR WFETVKVAIP
510 520 530 540 550
IEDVNRSHLR FTFRHRSSQD SKDKSEKIFA LAFVKLMRYD GTTLRDGEHD
560 570 580 590 600
LIVYKAEAKK LEDAATYLSL PSTKAELEEK GHSATGKSMQ SLGSCTISKD
610 620 630 640 650
SFQISTLVCS TKLTQNVDLL GLLKWRSNTS LLQQNLRQLM KVDGGEVVKF
660 670 680 690 700
LQDTLDALFN IMMENSESET FDTLVFDALV FIIGLIADRK FQHFNPVLET
710 720 730 740 750
YIKKHFSATL AYTKLTKVLK NYVDGAEKPG VNEQLYKAMK ALESIFKFIV
760 770 780 790 800
RSRILFNQLY ENKGEADFVE SLLQLFRSIN DMMSSMSDQT VRVKGAALKY
810 820 830 840 850
LPTIVNDVKL VFDPKELSKM FTEFILNVPM GLLTIQKLYC LIEIVHSDLF
860 870 880 890 900
TQHDCREILL PMMTDQLKYH LERQEDLEAC CQLLSHILEV LYRKDVGPTQ
910 920 930 940 950
RHVQIIMEKL LRTVNRTVIS MGRDSELIGN FVACMTAILR QMEDYHYAHL
960 970 980 990 1000
IKTFGKMRTD VVDFLMETFI MFKNLIGKNV YPFDWVIMNM VQNKVFLRAI
1010 1020 1030 1040 1050
NQYADMLNKK FLDQANFELQ LWNNYFHLAV AFLTQESLQL ENFSSAKRAK
1060 1070 1080 1090 1100
ILNKYGDMRR QIGFEIRDMW YNLGQHKIKF IPEMVGPILE MTLIPETELR
1110 1120 1130 1140 1150
KATIPIFFDM MQCEFHSTRS FQMFENEIIT KLDHEVEGGR GDEQYKVLFD
1160 1170 1180 1190 1200
KILLEHCRKH KYLAKTGETF VKLVVRLMER LLDYRTIMHD ENKENRMSCT
1210 1220 1230 1240 1250
VNVLNFYKEI EREEMYIRYL YKLCDLHKEC DNYTEAAYTL LLHAKLLKWS
1260 1270 1280 1290 1300
EDVCVAHLTQ RDGYQATTQG QLKEQLYQEI IHYFDKGKMW EEAIALGKEL
1310 1320 1330 1340 1350
AEQYENEMFD YEQLSELLKK QAQFYENIVK VIRPKPDYFA VGYYGQGFPT
1360 1370 1380 1390 1400
FLRGKVFIYR GKEYERREDF EARLLTQFPN AEKMKTTSPP GDDIKNSPGQ
1410 1420 1430 1440 1450
YIQCFTVKPK LDLPPKFHRP VSEQIVSFYR VNEVQRFEYS RPIRKGEKNP
1460 1470 1480 1490 1500
DNEFANMWIE RTIYTTAYKL PGILRWFEVK SVFMVEISPL ENAIETMQLT
1510 1520 1530 1540 1550
NDKINSMVQQ HLDDPSLPIN PLSMLLNGIV DPAVMGGFAN YEKAFFTDRY
1560 1570 1580 1590 1600
LQEHPEAHEK IEKLKDLIAW QIPFLAEGIR IHGDKVTEAL RPFHERMEAC
1610 1620 1630 1640 1650
FKQLKEKVEK EYGVRIMPSS LDDRRGSRPR SMVRSFTMPS SSRPLSVASV
1660 1670 1680 1690 1700
SSLSSDSTPS RPGSDGFALE PLLPKKMHSR SQDKLDKDDL EKEKKDKKKE
1710 1720 1730 1740 1750
KRNSKHQEIF EKEFKPTDIS LQQSEAVILS ETISPLRPQR PKSQVMNVIG
1760 1770 1780 1790 1800
SERRFSVSPS SPSSQQTPPP VTPRAKLSFS MQSSLELNGM TGADVADVPP
1810 1820 1830 1840 1850
PLPLKGSVAD YGNLMENQDL LGSPTPPPPP PHQRHLPPPL PSKTPPPPPP
1860
KTTRKQASVD SGIVQ
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A096LNH6 | A0A096LNH6_HUMAN | Dedicator of cytokinesis protein 1 | DOCK1 | 1,886 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 1857 | A → T in BAA09454 (PubMed:8657152).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_059971 | 1793 | A → T. Corresponds to variant dbSNP:rs869801Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D50857 mRNA Translation: BAA09454.1 AL157711 Genomic DNA No translation available. AL359094 Genomic DNA No translation available. BX470201 Genomic DNA No translation available. AL390920 Genomic DNA No translation available. AL607029 Genomic DNA No translation available. AL355316 Genomic DNA No translation available. BX470155 Genomic DNA No translation available. |
CCDSi | CCDS73222.1 |
RefSeqi | NP_001371.1, NM_001380.4 |
Genome annotation databases
Ensembli | ENST00000280333; ENSP00000280333; ENSG00000150760 |
GeneIDi | 1793 |
KEGGi | hsa:1793 |
UCSCi | uc001ljt.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D50857 mRNA Translation: BAA09454.1 AL157711 Genomic DNA No translation available. AL359094 Genomic DNA No translation available. BX470201 Genomic DNA No translation available. AL390920 Genomic DNA No translation available. AL607029 Genomic DNA No translation available. AL355316 Genomic DNA No translation available. BX470155 Genomic DNA No translation available. |
CCDSi | CCDS73222.1 |
RefSeqi | NP_001371.1, NM_001380.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3L4C | X-ray | 2.37 | A/B | 422-619 | [»] | |
BMRBi | Q14185 | |||||
SMRi | Q14185 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108128, 29 interactors |
CORUMi | Q14185 |
DIPi | DIP-29391N |
IntActi | Q14185, 25 interactors |
MINTi | Q14185 |
STRINGi | 9606.ENSP00000280333 |
PTM databases
iPTMneti | Q14185 |
PhosphoSitePlusi | Q14185 |
Genetic variation databases
BioMutai | DOCK1 |
DMDMi | 209572608 |
Proteomic databases
EPDi | Q14185 |
jPOSTi | Q14185 |
MassIVEi | Q14185 |
MaxQBi | Q14185 |
PaxDbi | Q14185 |
PeptideAtlasi | Q14185 |
PRIDEi | Q14185 |
ProteomicsDBi | 59903 |
Protocols and materials databases
Antibodypediai | 3822, 257 antibodies |
Genome annotation databases
Ensembli | ENST00000280333; ENSP00000280333; ENSG00000150760 |
GeneIDi | 1793 |
KEGGi | hsa:1793 |
UCSCi | uc001ljt.4, human |
Organism-specific databases
CTDi | 1793 |
DisGeNETi | 1793 |
GeneCardsi | DOCK1 |
HGNCi | HGNC:2987, DOCK1 |
HPAi | ENSG00000150760, Low tissue specificity |
MIMi | 601403, gene |
neXtProti | NX_Q14185 |
OpenTargetsi | ENSG00000150760 |
PharmGKBi | PA27453 |
VEuPathDBi | HostDB:ENSG00000150760.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1998, Eukaryota |
GeneTreei | ENSGT00940000154974 |
HOGENOMi | CLU_000595_2_1_1 |
InParanoidi | Q14185 |
OrthoDBi | 102580at2759 |
PhylomeDBi | Q14185 |
TreeFami | TF300423 |
Enzyme and pathway databases
PathwayCommonsi | Q14185 |
Reactomei | R-HSA-2029482, Regulation of actin dynamics for phagocytic cup formation R-HSA-418885, DCC mediated attractive signaling R-HSA-4420097, VEGFA-VEGFR2 Pathway R-HSA-8849471, PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases R-HSA-9664422, FCGR3A-mediated phagocytosis R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
Miscellaneous databases
BioGRID-ORCSi | 1793, 6 hits in 143 CRISPR screens |
ChiTaRSi | DOCK1, human |
EvolutionaryTracei | Q14185 |
GeneWikii | Dock180 |
GenomeRNAii | 1793 |
Pharosi | Q14185, Tbio |
PROi | PR:Q14185 |
RNActi | Q14185, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000150760, Expressed in lung and 239 other tissues |
ExpressionAtlasi | Q14185, baseline and differential |
Genevisiblei | Q14185, HS |
Family and domain databases
Gene3Di | 1.20.1270.350, 1 hit 1.20.58.740, 1 hit 1.25.40.410, 1 hit 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR016024, ARM-type_fold IPR035892, C2_domain_sf IPR027007, DHR-1_domain IPR027357, DHR-2 IPR026791, DOCK IPR010703, DOCK_C IPR043161, DOCK_C_lobe_A IPR043162, DOCK_C_lobe_C IPR032376, DOCK_N IPR042455, DOCK_N_sub1 IPR036028, SH3-like_dom_sf IPR001452, SH3_domain |
PANTHERi | PTHR45653, PTHR45653, 1 hit |
Pfami | View protein in Pfam PF06920, DHR-2, 1 hit PF14429, DOCK-C2, 1 hit PF16172, DOCK_N, 1 hit PF00018, SH3_1, 1 hit |
SMARTi | View protein in SMART SM00326, SH3, 1 hit |
SUPFAMi | SSF48371, SSF48371, 1 hit SSF50044, SSF50044, 1 hit |
PROSITEi | View protein in PROSITE PS51650, C2_DOCK, 1 hit PS51651, DOCKER, 1 hit PS50002, SH3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DOCK1_HUMAN | |
Accessioni | Q14185Primary (citable) accession number: Q14185 Secondary accession number(s): A9Z1Z5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 3, 2003 |
Last sequence update: | October 14, 2008 | |
Last modified: | February 10, 2021 | |
This is version 185 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families