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Protein

Dedicator of cytokinesis protein 1

Gene

DOCK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
Biological processApoptosis, Phagocytosis

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000150760.12
HGNCiHGNC:2987 DOCK1
MIMi601403 gene
neXtProtiNX_Q14185

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi59903

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 Expressed in 234 organ(s), highest expression level in lung
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 (PubMed:8657152, PubMed:8662907, PubMed:11240126). Interacts with nucleotide-free RAC1 via its DHR-2 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 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108128, 23 interactors
CORUMiQ14185
DIPiDIP-29391N
IntActiQ14185, 16 interactors
MINTiQ14185
STRINGi9606.ENSP00000280333

Structurei

Secondary structure

11865
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

SH3 domain, SH3-binding

Phylogenomic databases

eggNOGiKOG1998 Eukaryota
ENOG410XQH7 LUCA
GeneTreeiENSGT00610000085806
HOGENOMiHOG000006631
HOVERGENiHBG051389
InParanoidiQ14185
KOiK13708
PhylomeDBiQ14185
TreeFamiTF300423

Family and domain databases

Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR035892 C2_domain_sf
IPR027007 DHR-1_domain
IPR027357 DHR-2
IPR026791 DOCK
IPR030717 DOCK1
IPR010703 DOCK_C
IPR032376 DOCK_N
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR23317 PTHR23317, 1 hit
PTHR23317:SF79 PTHR23317:SF79, 1 hit
PfamiView protein in Pfam
PF06920 DHR-2, 1 hit
PF14429 DOCK-C2, 1 hit
PF16172 DOCK_N, 1 hit
PF14604 SH3_9, 1 hit
SMARTiView protein in SMART
SM00326 SH3, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
SSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS51650 DHR_1, 1 hit
PS51651 DHR_2, 1 hit
PS50002 SH3, 1 hit

Sequence (1+)i

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
« 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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A096LNH6A0A096LNH6_HUMAN
Dedicator of cytokinesis protein 1
DOCK1
1,886Annotation score:

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 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.
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

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.
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, 23 interactors
CORUMiQ14185
DIPiDIP-29391N
IntActiQ14185, 16 interactors
MINTiQ14185
STRINGi9606.ENSP00000280333

PTM databases

iPTMnetiQ14185
PhosphoSitePlusiQ14185

Polymorphism and mutation databases

BioMutaiDOCK1
DMDMi209572608

Proteomic databases

EPDiQ14185
MaxQBiQ14185
PaxDbiQ14185
PeptideAtlasiQ14185
PRIDEiQ14185
ProteomicsDBi59903

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1793
DisGeNETi1793
EuPathDBiHostDB:ENSG00000150760.12
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

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
PROiPR:Q14185
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150760 Expressed in 234 organ(s), highest expression level in lung
CleanExiHS_DOCK1
ExpressionAtlasiQ14185 baseline and differential
GenevisibleiQ14185 HS

Family and domain databases

Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR035892 C2_domain_sf
IPR027007 DHR-1_domain
IPR027357 DHR-2
IPR026791 DOCK
IPR030717 DOCK1
IPR010703 DOCK_C
IPR032376 DOCK_N
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR23317 PTHR23317, 1 hit
PTHR23317:SF79 PTHR23317:SF79, 1 hit
PfamiView protein in Pfam
PF06920 DHR-2, 1 hit
PF14429 DOCK-C2, 1 hit
PF16172 DOCK_N, 1 hit
PF14604 SH3_9, 1 hit
SMARTiView protein in SMART
SM00326 SH3, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
SSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS51650 DHR_1, 1 hit
PS51651 DHR_2, 1 hit
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDOCK1_HUMAN
AccessioniPrimary (citable) accession number: Q14185
Secondary accession number(s): A9Z1Z5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: October 14, 2008
Last modified: November 7, 2018
This is version 169 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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