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Protein

Dedicator of cytokinesis protein 1

Gene

DOCK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Biological processi

  • apoptotic process Source: ProtInc
  • blood coagulation Source: Reactome
  • cell migration Source: InterPro
  • cytoskeleton organization Source: InterPro
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Apoptosis, Phagocytosis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000150760-MONOMER.
ReactomeiR-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-983231. Factors involved in megakaryocyte development and platelet production.

Names & Taxonomyi

Protein namesi
Recommended name:
Dedicator of cytokinesis protein 1
Alternative name(s):
180 kDa protein downstream of CRK
Short name:
DOCK180
Gene namesi
Name:DOCK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:2987. DOCK1.

Subcellular locationi

  • Cytoplasm Curated
  • Membrane Curated

  • Note: Recruited to membranes via its interaction with phosphatidylinositol 3,4,5-trisphosphate.Curated

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • guanyl-nucleotide exchange factor complex Source: WormBase
  • membrane Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1401 – 1402YI → AA: Abolishes Rac GEF activity. 1 Publication2
Mutagenesisi1487 – 1489ISP → AAA: Abolishes Rac GEF activity. 1 Publication3

Organism-specific databases

DisGeNETi1793.
OpenTargetsiENSG00000150760.
PharmGKBiPA27453.

Polymorphism and mutation databases

BioMutaiDOCK1.
DMDMi209572608.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001899841 – 1865Dedicator of cytokinesis protein 1Add BLAST1865

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1681PhosphoserineCombined sources1
Modified residuei1743PhosphoserineBy similarity1
Modified residuei1751PhosphoserineCombined sources1
Modified residuei1756PhosphoserineBy similarity1
Modified residuei1761PhosphoserineBy similarity1
Modified residuei1764PhosphoserineBy similarity1
Modified residuei1767PhosphothreonineBy similarity1
Modified residuei1772PhosphothreonineBy similarity1
Modified residuei1858PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ14185.
MaxQBiQ14185.
PaxDbiQ14185.
PeptideAtlasiQ14185.
PRIDEiQ14185.

PTM databases

iPTMnetiQ14185.
PhosphoSitePlusiQ14185.

Expressioni

Tissue specificityi

Highly expressed in placenta, lung, kidney, pancreas and ovary. Expressed at intermediate level in thymus, testes and colon.

Gene expression databases

BgeeiENSG00000150760.
CleanExiHS_DOCK1.
ExpressionAtlasiQ14185. baseline and differential.
GenevisibleiQ14185. HS.

Organism-specific databases

HPAiCAB004378.
HPA048692.
HPA053277.

Interactioni

Subunit structurei

Interacts with the SH3 domains of CRK and NCK2 via multiple sites. Interacts with nucleotide-free RAC1 via its DHR-2 domain. Interacts with ELMO1, ELMO2 and probably ELMO3 via its SH3 domain. Interacts with RAC1 and BAI1.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ANKRD28O150844EBI-446740,EBI-359567
ELMO1Q9255616EBI-446740,EBI-346417
GRB2P629932EBI-446740,EBI-401755
RAC1P6300010EBI-446740,EBI-413628

Protein-protein interaction databases

BioGridi108128. 20 interactors.
DIPiDIP-29391N.
IntActiQ14185. 15 interactors.
MINTiMINT-190985.
STRINGi9606.ENSP00000280333.

Structurei

Secondary structure

11865
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi426 – 436Combined sources11
Beta strandi440 – 444Combined sources5
Beta strandi448 – 456Combined sources9
Beta strandi493 – 499Combined sources7
Beta strandi507 – 515Combined sources9
Beta strandi528 – 537Combined sources10
Beta strandi546 – 555Combined sources10
Helixi558 – 561Combined sources4
Helixi564 – 567Combined sources4
Helixi574 – 578Combined sources5
Beta strandi595 – 608Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L4CX-ray2.37A/B422-619[»]
ProteinModelPortaliQ14185.
SMRiQ14185.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14185.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 70SH3PROSITE-ProRule annotationAdd BLAST62
Domaini425 – 609DHR-1PROSITE-ProRule annotationAdd BLAST185
Domaini1207 – 1617DHR-2PROSITE-ProRule annotationAdd BLAST411

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1687 – 1695Phosphoinositide-bindingSequence analysis9
Regioni1793 – 1819Interaction with NCK2 second and third SH3 domain (minor)Add BLAST27
Regioni1820 – 1836Interaction with NCK2 third SH3 domain (major)Add BLAST17
Regioni1837 – 1852Interaction with NCK2 (minor)Add BLAST16

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1799 – 1805SH3-binding; interaction with CRKSequence analysis7
Motifi1838 – 1843SH3-binding; interaction with CRKSequence analysis6

Domaini

The DHR-2 domain is necessary and sufficient for the GEF activity.

Sequence similaritiesi

Belongs to the DOCK family.PROSITE-ProRule annotation
Contains 1 DHR-1 domain.PROSITE-ProRule annotation
Contains 1 DHR-2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain, SH3-binding

Phylogenomic databases

eggNOGiKOG1998. Eukaryota.
ENOG410XQH7. LUCA.
GeneTreeiENSGT00610000085806.
HOGENOMiHOG000006631.
HOVERGENiHBG051389.
InParanoidiQ14185.
KOiK13708.
PhylomeDBiQ14185.
TreeFamiTF300423.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR027007. DHR-1_domain.
IPR027357. DHR-2.
IPR026791. DOCK.
IPR030717. DOCK1.
IPR010703. DOCK_C.
IPR032376. DOCK_N.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR23317. PTHR23317. 1 hit.
PTHR23317:SF79. PTHR23317:SF79. 1 hit.
PfamiPF06920. DHR-2. 1 hit.
PF14429. DOCK-C2. 1 hit.
PF16172. DOCK_N. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
SMARTiSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
SSF50044. SSF50044. 1 hit.
PROSITEiPS51650. DHR_1. 1 hit.
PS51651. DHR_2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q14185-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:1,865
Mass (Da):215,346
Last modified:October 14, 2008 - v2
Checksum:i940C5AFD047EBEDE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1857A → T in BAA09454 (PubMed:8657152).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0599711793A → T.Corresponds to variant rs869801dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D50857 mRNA. Translation: BAA09454.1.
AL157711
, AL355316, AL359094, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH71463.2.
AL359094
, AL157711, AL355316, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH71477.2.
BX470201
, AL157711, AL355316, AL359094, AL390920, AL607029, BX470155 Genomic DNA. Translation: CAH72560.2.
AL390920
, AL157711, AL355316, AL359094, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH73231.2.
AL607029
, AL157711, AL355316, AL359094, AL390920, BX470155, BX470201 Genomic DNA. Translation: CAI15329.2.
AL355316
, AL157711, AL359094, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAI16871.2.
BX470155
, AL157711, AL355316, AL359094, AL390920, AL607029, BX470201 Genomic DNA. Translation: CAI22477.2.
CCDSiCCDS73222.1.
RefSeqiNP_001371.1. NM_001380.4.
UniGeneiHs.159195.

Genome annotation databases

EnsembliENST00000280333; ENSP00000280333; ENSG00000150760.
GeneIDi1793.
KEGGihsa:1793.
UCSCiuc001ljt.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D50857 mRNA. Translation: BAA09454.1.
AL157711
, AL355316, AL359094, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH71463.2.
AL359094
, AL157711, AL355316, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH71477.2.
BX470201
, AL157711, AL355316, AL359094, AL390920, AL607029, BX470155 Genomic DNA. Translation: CAH72560.2.
AL390920
, AL157711, AL355316, AL359094, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH73231.2.
AL607029
, AL157711, AL355316, AL359094, AL390920, BX470155, BX470201 Genomic DNA. Translation: CAI15329.2.
AL355316
, AL157711, AL359094, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAI16871.2.
BX470155
, AL157711, AL355316, AL359094, AL390920, AL607029, BX470201 Genomic DNA. Translation: CAI22477.2.
CCDSiCCDS73222.1.
RefSeqiNP_001371.1. NM_001380.4.
UniGeneiHs.159195.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L4CX-ray2.37A/B422-619[»]
ProteinModelPortaliQ14185.
SMRiQ14185.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108128. 20 interactors.
DIPiDIP-29391N.
IntActiQ14185. 15 interactors.
MINTiMINT-190985.
STRINGi9606.ENSP00000280333.

PTM databases

iPTMnetiQ14185.
PhosphoSitePlusiQ14185.

Polymorphism and mutation databases

BioMutaiDOCK1.
DMDMi209572608.

Proteomic databases

EPDiQ14185.
MaxQBiQ14185.
PaxDbiQ14185.
PeptideAtlasiQ14185.
PRIDEiQ14185.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000280333; ENSP00000280333; ENSG00000150760.
GeneIDi1793.
KEGGihsa:1793.
UCSCiuc001ljt.4. human.

Organism-specific databases

CTDi1793.
DisGeNETi1793.
GeneCardsiDOCK1.
HGNCiHGNC:2987. DOCK1.
HPAiCAB004378.
HPA048692.
HPA053277.
MIMi601403. gene.
neXtProtiNX_Q14185.
OpenTargetsiENSG00000150760.
PharmGKBiPA27453.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1998. Eukaryota.
ENOG410XQH7. LUCA.
GeneTreeiENSGT00610000085806.
HOGENOMiHOG000006631.
HOVERGENiHBG051389.
InParanoidiQ14185.
KOiK13708.
PhylomeDBiQ14185.
TreeFamiTF300423.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000150760-MONOMER.
ReactomeiR-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-983231. Factors involved in megakaryocyte development and platelet production.

Miscellaneous databases

ChiTaRSiDOCK1. human.
EvolutionaryTraceiQ14185.
GeneWikiiDock180.
GenomeRNAii1793.
PROiQ14185.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150760.
CleanExiHS_DOCK1.
ExpressionAtlasiQ14185. baseline and differential.
GenevisibleiQ14185. HS.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR027007. DHR-1_domain.
IPR027357. DHR-2.
IPR026791. DOCK.
IPR030717. DOCK1.
IPR010703. DOCK_C.
IPR032376. DOCK_N.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR23317. PTHR23317. 1 hit.
PTHR23317:SF79. PTHR23317:SF79. 1 hit.
PfamiPF06920. DHR-2. 1 hit.
PF14429. DOCK-C2. 1 hit.
PF16172. DOCK_N. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
SMARTiSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
SSF50044. SSF50044. 1 hit.
PROSITEiPS51650. DHR_1. 1 hit.
PS51651. DHR_2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDOCK1_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.