DOCK3

Protein identityUniProt · HPA

UniProt accession

Q8IZD9

Gene

DOCK3

Ensembl

ENSG00000088538

Chromosome

3

Canonical length

2030 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

This gene is specifically expressed in the central nervous system (CNS). It encodes a member of the DOCK (dedicator of cytokinesis) family of guanine nucleotide exchange factors (GEFs). This protein, dedicator of cytokinesis 3 (DOCK3), is also known as modifier of cell adhesion (MOCA) and presenilin-binding protein (PBP). The DOCK3 and DOCK1, -2 and -4 share several conserved amino acids in their DHR-2 (DOCK homology region 2) domains that are required for GEF activity, and bind directly to WAVE proteins [Wiskott-Aldrich syndrome protein (WASP) family Verprolin-homologous proteins] via their DHR-1 domains. The DOCK3 induces axonal outgrowth in CNS by stimulating membrane recruitment of the WAVE complex and activating the small G protein Rac1. This gene is associated with an attention deficit hyperactivity disorder-like phenotype by a complex chromosomal rearrangement. [provided by RefSeq, Aug 2010]

Canonical amino-acid sequenceUniProt

2030 residues, UniProt reviewed canonical sequence.

>Q8IZD9|DOCK3
     1  MWTPTEEEKY GVVICSFRGS VPQGLVLEIG ETVQILEKCE GWYRGVSTKK PNVKGIFPAN
    61  YIHLKKAIVS NRGQYETVVP LEDSIVTEVT ATLQEWASLW KQLYVKHKVD LFYKLRHVMN
   121  ELIDLRRQLL SGHLTQDQVR EVKRHITVRL DWGNEHLGLD LVPRKDFEVV DSDQISVSDL
   181  YKMHLSSRQS VQQSTSQVDT MRPRHGETCR MPVPHHFFLS LKSFTYNTIG EDTDVFFSLY
   241  DMREGKQISE RFLVRLNKNG GPRNPEKIER MCALFTDLSS KDMKRDLYIV AHVIRIGRML
   301  LNDSKKGPPH LHYRRPYGCA VLSILDVLQS LTEVKEEKDF VLKVYTCNNE SEWSQIHENI
   361  IRKSSAKYSA PSASHGLIIS LQLLRGDMEQ IRRENPMIFN RGLAITRKLG FPDVIMPGDI
   421  RNDLYLTLEK GDFERGGKSV QKNIEVTMYV LYADGEILKD CISLGSGEPN RSSYHSFVLY
   481  HSNSPRWGEI IKLPIPIDRF RGSHLRFEFR HCSTKDKGEK KLFGFAFSTL MRDDGTTLSD
   541  DIHELYVYKC DENSTFNNHA LYLGLPCCKE DYNGCPNIPS SLIFQRSTKE SFFISTQLSS
   601  TKLTQNVDLL ALLKWKAFPD RIMDVLGRLR HVSGEEIVKF LQDILDTLFV ILDDNTEKYG
   661  LLVFQSLVFI INLLRDIKYF HFRPVMDTYI QKHFAGALAY KELIRCLKWY MDCSAELIRQ
   721  DHIQEAMRAL EYLFKFIVQS RILYSRATCG MEEEQFRSSI QELFQSIRFV LSLDSRNSET
   781  LLFTQAALLN SFPTIFDELL QMFTVQEVAE FVRGTLGSMP STVHIGQSMD VVKLQSIART
   841  VDSRLFSFSE SRRILLPVVL HHIHLHLRQQ KELLICSGIL GSIFSIVKTS SLEADVMEEV
   901  EMMVESLLDV LLQTLLTIMS KSHAQEAVRG QRCPQCTAEI TGEYVSCLLS LLRQMCDTHF
   961  QHLLDNFQSK DELKEFLLKI FCVFRNLMKM SVFPRDWMVM RLLTSNIIVT TVQYLSSALH
  1021  KNFTETDFDF KVWNSYFSLA VLFINQPSLQ LEIITSAKRK KILDKYGDMR VMMAYELFSM
  1081  WQNLGEHKIH FIPGMIGPFL GVTLVPQPEV RNIMIPIFHD MMDWEQRKNG NFKQVEAELI
  1141  DKLDSMVSEG KGDESYRELF SLLTQLFGPY PSLLEKVEQE TWRETGISFV TSVTRLMERL
  1201  LDYRDCMKGE ETENKKIGCT VNLMNFYKSE INKEEMYIRY IHKLCDMHLQ AENYTEAAFT
  1261  LLLYCELLQW EDRPLREFLH YPSQTEWQRK EGLCRKIIHY FNKGKSWEFG IPLCRELACQ
  1321  YESLYDYQSL SWIRKMEASY YDNIMEQQRL EPEFFRVGFY GRKFPFFLRN KEYVCRGHDY
  1381  ERLEAFQQRM LSEFPQAVAM QHPNHPDDAI LQCDAQYLQI YAVTPIPDYV DVLQMDRVPD
  1441  RVKSFYRVNN VRKFRYDRPF HKGPKDKENE FKSLWIERTT LTLTHSLPGI SRWFEVERRE
  1501  LVEVSPLENA IQVVENKNQE LRSLISQYQH KQVHGNINLL SMCLNGVIDA AVNGGIARYQ
  1561  EAFFDKDYIN KHPGDAEKIT QLKELMQEQV HVLGVGLAVH EKFVHPEMRP LHKKLIDQFQ
  1621  MMRASLYHEF PGLDKLSPAC SGTSTPRGNV LASHSPMSPE SIKMTHRHSP MNLMGTGRHS
  1681  SSSLSSHASS EAGNMVMLGD GSMGDAPEDL YHHMQLAYPN PRYQGSVTNV SVLSSSQASP
  1741  SSSSLSSTHS APSQMITSAP SSARGSPSLP DKYRHAREMM LLLPTYRDRP SSAMYPAAIL
  1801  ENGQPPNFQR ALFQQVVGAC KPCSDPNLSV AEKGHYSLHF DAFHHPLGDT PPALPARTLR
  1861  KSPLHPIPAS PTSPQSGLDG SNSTLSGSAS SGVSSLSESN FGHSSEAPPR TDTMDSMPSQ
  1921  AWNADEDLEP PYLPVHYSLS ESAVLDSIKA QPCRSHSAPG CVIPQDPMDP PALPPKPYHP
  1981  RLPALEHDEG VLLREETERP RGLHRKAPLP PGSAKEEQAR MAWEHGRGEQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DOCK3 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DOCK3.

Disease | AllUniProt

Conditions DOCK3 is implicated in, by any mechanism.

• Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia (NEDIDHA) MIM:618292

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 340 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia
• DOCK3-related disorder
• Inborn genetic diseases
• Hypotonia
• Global developmental delay

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)

0.16

gnomAD pLI

1

gnomAD missense Z

3.94

DepMap mean gene effect

-0.05

DepMap dependency class

none

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

• neurotrophin TRK receptor signaling pathway
• regulation of small GTPase mediated signal transduction
• small GTPase-mediated signal transduction

Molecular functions

• GTPase activator activity
• guanyl-nucleotide exchange factor activity
• SH3 domain binding
• small GTPase binding

Cellular components

• cytoplasm
• cytosol
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• SH3 domain
• Armadillo-type fold
• 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 protein 3, DHR2 domain
• Dedicator of cytokinesis 3, SH3 domain

KeywordsUniProt

• Chromosomal rearrangement
• Cytoplasm
• Guanine-nucleotide releasing factor
• Phosphoprotein
• SH3 domain
• SH3-binding

InteractionsUniProt · HPA

Protein binding partners of DOCK3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CRK
• PSEN1
• PSEN2
• ELMO1