Seroatlas · Human Serome Atlas

DOCK4

Dedicator of cytokinesis protein 4

Also known as: DOCK4_HUMAN, FLJ34238, KIAA0716

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q8N1I0
Gene: DOCK4
Ensembl: ENSG00000128512
Chromosome: 7
Canonical length: 1966 aa
Protein class: Plasma proteins, Predicted intracellular proteins
Subcellular location: Nucleoli,Golgi apparatus,Plasma membrane,Cytosol

OverviewNCBI Gene

This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1966 residues, UniProt reviewed canonical sequence.

>Q8N1I0|DOCK4
     1  MWIPTEHEKY GVVIASFRGT VPYGLSLEIG DTVQILEKCD GWYRGFALKN PNIKGIFPSS
    61  YVHLKNACVK NKGQFEMVIP TEDSVITEMT STLRDWGTMW KQLYVRNEGD LFHRLWHIMN
   121  EILDLRRQVL VGHLTHDRMK DVKRHITARL DWGNEQLGLD LVPRKEYAMV DPEDISITEL
   181  YRLMEHRHRK KDTPVQASSH HLFVQMKSLM CSNLGEELEV IFSLFDSKEN RPISERFFLR
   241  LNRNGLPKAP DKPERHCSLF VDLGSSELRK DIYITVHIIR IGRMGAGEKK NACSVQYRRP
   301  FGCAVLSIAD LLTGETKDDL ILKVYMCNTE SEWYQIHENI IKKLNARYNL TGSNAGLAVS
   361  LQLLHGDIEQ IRREYSSVFS HGVSITRKLG FSNIIMPGEM RNDLYITIER GEFEKGGKSV
   421  ARNVEVTMFI VDSSGQTLKD FISFGSGEPP ASEYHSFVLY HNNSPRWSEL LKLPIPVDKF
   481  RGAHIRFEFR HCSTKEKGEK KLFGFSFVPL MQEDGRTLPD GTHELIVHKC EENTNLQDTT
   541  RYLKLPFSKG IFLGNNNQAM KATKESFCIT SFLCSTKLTQ NGDMLDLLKW RTHPDKITGC
   601  LSKLKEIDGS EIVKFLQDTL DTLFGILDEN SQKYGSKVFD SLVHIINLLQ DSKFHHFKPV
   661  MDTYIESHFA GALAYRDLIK VLKWYVDRIT EAERQEHIQE VLKAQEYIFK YIVQSRRLFS
   721  LATGGQNEEE FRCCIQELLM SVRFFLSQES KGSGALSQSQ AVFLSSFPAV YSELLKLFDV
   781  REVANLVQDT LGSLPTILHV DDSLQAIKLQ CIGKTVESQL YTNPDSRYIL LPVVLHHLHI
   841  HLQEQKDLIM CARILSNVFC LIKKNSSEKS VLEEIDVIVA SLLDILLRTI LEITSRPQPS
   901  SSAMRFQFQD VTGEFVACLL SLLRQMTDRH YQQLLDSFNT KEELRDFLLQ IFTVFRILIR
   961  PEMFPKDWTV MRLVANNVII TTVLYLSDAL RKNFLNENFD YKIWDSYFYL AVIFINQLCL
  1021  QLEMFTPSKK KKVLEKYGDM RVTMGCEIFS MWQNLGEHKL HFIPALIGPF LEVTLIPQPD
  1081  LRNVMIPIFH DMMDWEQRRS GNFKQVEAKL IDKLDSLMSE GKGDETYREL FNSILLKKIE
  1141  RETWRESGVS LIATVTRLME RLLDYRDCMK MGEVDGKKIG CTVSLLNFYK TELNKEEMYI
  1201  RYIHKLYDLH LKAQNFTEAA YTLLLYDELL EWSDRPLREF LTYPMQTEWQ RKEHLHLTII
  1261  QNFDRGKCWE NGIILCRKIA EQYESYYDYR NLSKMRMMEA SLYDKIMDQQ RLEPEFFRVG
  1321  FYGKKFPFFL RNKEFVCRGH DYERLEAFQQ RMLNEFPHAI AMQHANQPDE TIFQAEAQYL
  1381  QIYAVTPIPE SQEVLQREGV PDNIKSFYKV NHIWKFRYDR PFHKGTKDKE NEFKSLWVER
  1441  TSLYLVQSLP GISRWFEVEK REVVEMSPLE NAIEVLENKN QQLKTLISQC QTRQMQNINP
  1501  LTMCLNGVID AAVNGGVSRY QEAFFVKEYI LSHPEDGEKI ARLRELMLEQ AQILEFGLAV
  1561  HEKFVPQDMR PLHKKLVDQF FVMKSSLGIQ EFSACMQASP VHFPNGSPRV CRNSAPASVS
  1621  PDGTRVIPRR SPLSYPAVNR YSSSSLSSQA SAEVSNITGQ SESSDEVFNM QPSPSTSSLS
  1681  STHSASPNVT SSAPSSARAS PLLSDKHKHS RENSCLSPRE RPCSAIYPTP VEPSQRMLFN
  1741  HIGDGALPRS DPNLSAPEKA VNPTPSSWSL DSGKEAKNMS DSGKLISPPV PPRPTQTASP
  1801  ARHTTSVSPS PAGRSPLKGS VQSFTPSPVE YHSPGLISNS PVLSGSYSSG ISSLSRCSTS
  1861  ETSGFENQVN EQSAPLPVPV PVPVPSYGGE EPVRKESKTP PPYSVYERTL RRPVPLPHSL
  1921  SIPVTSEPPA LPPKPLAARS SHLENGARRT DPGPRPRPLP RKVSQL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DOCK4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.34
Highest tissue expression: 28 nTPM

Expression across tissuesHPA

Tissue

basal ganglia: 28 nTPM
hippocampal formation: 20 nTPM
cerebral cortex: 20 nTPM
lung: 19 nTPM
amygdala: 14 nTPM
midbrain: 13 nTPM

Single-cell type

microglia: 6,744 nCPM
neutrophils: 3,894 nCPM
monocytes: 1,634 nCPM
macrophages: 1,540 nCPM
astrocytes: 1,167 nCPM
oligodendrocytes: 1,144 nCPM

Immune cell

neutrophil: 0.8 nTPM
intermediate monocyte: 0.3 nTPM
classical monocyte: 0.1 nTPM
basophil: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM

Brain region

basal ganglia: 117 nTPM
hippocampal formation: 110 nTPM
cerebral cortex: 77 nTPM
white matter: 72 nTPM
thalamus: 67 nTPM
hypothalamus: 64 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DOCK4.

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 366 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Neurodevelopmental disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.3
gnomAD pLI: 0.83
gnomAD missense Z: 2.52
DepMap mean gene effect: 0.05
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

SH3 domain
Dedicator of cytokinesis
C2 DOCK-type domain
DOCKER domain
Dedicator of cytokinesis, N-terminal domain
C2 domain superfamily
SH3-like domain superfamily
Dedicator of cytokinesis B, C2 domain
Dedicator of cytokinesis, N-terminal, subdomain 1
Dedicator of cytokinesis, C-terminal, lobe A
Dedicator of cytokinesis, C-terminal, lobe C
DOCKER, Lobe A
DOCKER, Lobe B
DOCKER, Lobe C
Dedicator of cytokinesis, TPR repeats region
DHR-2, Lobe A
Variant SH3 domain
C2 domain in Dock180 and Zizimin proteins
DOCK N-terminus
DHR-2, Lobe C
DHR-2, Lobe B
Dedicator of cytokinesis (DOCK) TPR region
Dedicator of cytokinesis 4, SH3 domain
Dedicator of cytokinesis protein 4, DHR2 domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of DOCK4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads DOCK4 as an antibody target. Whether an autoantibody or antibody against DOCK4 could matter depends on whether native DOCK4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

DOCK4 is annotated at the cell surface, where native DOCK4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label DOCK4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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