Seroatlas · Human Serome Atlas

DOCK8

Dedicator of cytokinesis protein 8

Also known as: DOCK8_HUMAN, FLJ00026, FLJ00152, FLJ00346, ZIR8

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

Protein identityUniProt · HPA

UniProt accession: Q8NF50
Gene: DOCK8
Ensembl: ENSG00000107099
Chromosome: 9
Canonical length: 2099 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location: Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010]

Canonical amino-acid sequenceUniProt

2099 residues, UniProt reviewed canonical sequence.

>Q8NF50|DOCK8
     1  MATLPSAERR AFALKINRYS SAEIRKQFTL PPNLGQYHRQ SISTSGFPSL QLPQFYDPVE
    61  PVDFEGLLMT HLNSLDVQLA QELGDFTDDD LDVVFTPKEC RTLQPSLPEE GVELDPHVRD
   121  CVQTYIREWL IVNRKNQGSP EICGFKKTGS RKDFHKTLPK QTFESETLEC SEPAAQAGPR
   181  HLNVLCDVSG KGPVTACDFD LRSLQPDKRL ENLLQQVSAE DFEKQNEEAR RTNRQAELFA
   241  LYPSVDEEDA VEIRPVPECP KEHLGNRILV KLLTLKFEIE IEPLFASIAL YDVKERKKIS
   301  ENFHCDLNSD QFKGFLRAHT PSVAASSQAR SAVFSVTYPS SDIYLVVKIE KVLQQGEIGD
   361  CAEPYTVIKE SDGGKSKEKI EKLKLQAESF CQRLGKYRMP FAWAPISLSS FFNVSTLERE
   421  VTDVDSVVGR SSVGERRTLA QSRRLSERAL SLEENGVGSN FKTSTLSVSS FFKQEGDRLS
   481  DEDLFKFLAD YKRSSSLQRR VKSIPGLLRL EISTAPEIIN CCLTPEMLPV KPFPENRTRP
   541  HKEILEFPTR EVYVPHTVYR NLLYVYPQRL NFVNKLASAR NITIKIQFMC GEDASNAMPV
   601  IFGKSSGPEF LQEVYTAVTY HNKSPDFYEE VKIKLPAKLT VNHHLLFTFY HISCQQKQGA
   661  SVETLLGYSW LPILLNERLQ TGSYCLPVAL EKLPPNYSMH SAEKVPLQNP PIKWAEGHKG
   721  VFNIEVQAVS SVHTQDNHLE KFFTLCHSLE SQVTFPIRVL DQKISEMALE HELKLSIICL
   781  NSSRLEPLVL FLHLVLDKLF QLSVQPMVIA GQTANFSQFA FESVVAIANS LHNSKDLSKD
   841  QHGRNCLLAS YVHYVFRLPE VQRDVPKSGA PTALLDPRSY HTYGRTSAAA VSSKLLQARV
   901  MSSSNPDLAG THSAADEEVK NIMSSKIADR NCSRMSYYCS GSSDAPSSPA APRPASKKHF
   961  HEELALQMVV STGMVRETVF KYAWFFFELL VKSMAQHVHN MDKRDSFRRT RFSDRFMDDI
  1021  TTIVNVVTSE IAALLVKPQK ENEQAEKMNI SLAFFLYDLL SLMDRGFVFN LIRHYCSQLS
  1081  AKLSNLPTLI SMRLEFLRIL CSHEHYLNLN LFFMNADTAP TSPCPSISSQ NSSSCSSFQD
  1141  QKIASMFDLT SEYRQQHFLT GLLFTELAAA LDAEGEGISK VQRKAVSAIH SLLSSHDLDP
  1201  RCVKPEVKVK IAALYLPLVG IILDALPQLC DFTVADTRRY RTSGSDEEQE GAGAINQNVA
  1261  LAIAGNNFNL KTSGIVLSSL PYKQYNMLNA DTTRNLMICF LWIMKNADQS LIRKWIADLP
  1321  STQLNRILDL LFICVLCFEY KGKQSSDKVS TQVLQKSRDV KARLEEALLR GEGARGEMMR
  1381  RRAPGNDRFP GLNENLRWKK EQTHWRQANE KLDKTKAELD QEALISGNLA TEAHLIILDM
  1441  QENIIQASSA LDCKDSLLGG VLRVLVNSLN CDQSTTYLTH CFATLRALIA KFGDLLFEEE
  1501  VEQCFDLCHQ VLHHCSSSMD VTRSQACATL YLLMRFSFGA TSNFARVKMQ VTMSLASLVG
  1561  RAPDFNEEHL RRSLRTILAY SEEDTAMQMT PFPTQVEELL CNLNSILYDT VKMREFQEDP
  1621  EMLMDLMYRI AKSYQASPDL RLTWLQNMAE KHTKKKCYTE AAMCLVHAAA LVAEYLSMLE
  1681  DHSYLPVGSV SFQNISSNVL EESVVSEDTL SPDEDGVCAG QYFTESGLVG LLEQAAELFS
  1741  TGGLYETVNE VYKLVIPILE AHREFRKLTL THSKLQRAFD SIVNKDHKRM FGTYFRVGFF
  1801  GSKFGDLDEQ EFVYKEPAIT KLPEISHRLE AFYGQCFGAE FVEVIKDSTP VDKTKLDPNK
  1861  AYIQITFVEP YFDEYEMKDR VTYFEKNFNL RRFMYTTPFT LEGRPRGELH EQYRRNTVLT
  1921  TMHAFPYIKT RISVIQKEEF VLTPIEVAIE DMKKKTLQLA VAINQEPPDA KMLQMVLQGS
  1981  VGATVNQGPL EVAQVFLAEI PADPKLYRHH NKLRLCFKEF IMRCGEAVEK NKRLITADQR
  2041  EYQQELKKNY NKLKENLRPM IERKIPELYK PIFRVESQKR DSFHRSSFRK CETQLSQGS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DOCK8 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): 0.32
Highest tissue expression: 58 nTPM

Expression across tissuesHPA

Tissue

thymus: 58 nTPM
tonsil: 41 nTPM
lymph node: 40 nTPM
bone marrow: 36 nTPM
spleen: 35 nTPM
appendix: 31 nTPM

Single-cell type

microglia: 2,809 nCPM
neutrophils: 2,638 nCPM
choroid plexus epithelial cells: 1,462 nCPM
neutrophil progenitors: 1,122 nCPM
monocytes: 638 nCPM
monocyte progenitors: 606 nCPM

Immune cell

neutrophil: 98 nTPM
basophil: 57 nTPM
non-classical monocyte: 55 nTPM
intermediate monocyte: 38 nTPM
eosinophil: 38 nTPM
naive B-cell: 38 nTPM

Brain region

choroid plexus: 65 nTPM
white matter: 20 nTPM
spinal cord: 16 nTPM
medulla oblongata: 15 nTPM
pons: 13 nTPM
thalamus: 13 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DOCK8.

Disease | AllUniProt

Conditions DOCK8 is implicated in, by any mechanism.

Hyper-IgE syndrome 2, autosomal recessive, with recurrent infections (HIES2) MIM:243700
Intellectual developmental disorder, autosomal dominant 2 (MRD2) MIM:614113

Disease | GeneticClinVar

142 pathogenic / likely-pathogenic of 3,073 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Combined immunodeficiency due to DOCK8 deficiency
Hyper-IgE recurrent infection syndrome 3, autosomal recessive
Severe combined immunodeficiency disease
DOCK8-related disorder
Inherited Immunodeficiency Diseases

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): 0.48
gnomAD pLI: 0
gnomAD missense Z: -2.54
DepMap mean gene effect: -0.01
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

guanyl-nucleotide exchange factor activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of DOCK8 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 DOCK8 as an antibody target. Whether an autoantibody or antibody against DOCK8 could matter depends on whether native DOCK8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

DOCK8 is annotated at the cell surface, where native DOCK8 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 DOCK8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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