DOCK3 dedicator of cytokinesis 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DOCK3provided by HGNC
Official Full Name: dedicator of cytokinesis 3provided by HGNC
Primary source: HGNC:HGNC:2989
See related: Ensembl:ENSG00000088538 MIM:603123; AllianceGenome:HGNC:2989
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PBP; MOCA; NEDIDHA
Summary: 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]
Expression: Biased expression in brain (RPKM 7.9), thyroid (RPKM 4.0) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.2

Exon count:: 61

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (50674927..51384198)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (50704905..51414618)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (50712358..51421629)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies.
Title: DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies.
hree patients with genetic variants in the dedicator of cytokinesis 3 (DOCK3) who presented with global developmental delay (GDD), hypotonia, and wide-based or uncoordinated gait.
Title: Variants in DOCK3 cause developmental delay and hypotonia.
here we report a second case of biallelic DOCK3 mutation due to homozygous deletion. Given the clinical similarities among the cases with DOCK3 mutations, we provided further evidence that biallelic mutations of DOCK3 lead to a specific DOCK3-related neurodevelopmental syndrome
Title: DOCK3-related neurodevelopmental syndrome: Biallelic intragenic deletion of DOCK3 in a boy with developmental delay and hypotonia.
Common features in both affected individuals include severe developmental disability, ataxic gait, and severe hypotonia, which recapitulates the Dock3 knockout mouse phenotype. We show that complete DOCK3 deficiency in humans leads to developmental disability with significant hypotonia and gait ataxia, probably due to abnormal axonal development
Title: Biallelic loss-of-function variants in DOCK3 cause muscle hypotonia, ataxia, and intellectual disability.
Inhibition of Dock3 by Dock3 shRNA impaired the severity of status epilepticus in the acute stage and decreased the spontaneous recurrent seizures times in the chronic stage of lithium-pilocarpine model and decreased the expression of rac1-GTP.
Title: Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models.
Results supported that miR-512-3p could inhibit tumor cell adhesion, migration, and invasion by regulating the RAC1 activity via DOCK3 in NSCLC A549 and H1299 cell lines.
Title: Inhibition of RAC1-GEF DOCK3 by miR-512-3p contributes to suppression of metastasis in non-small cell lung cancer.
It plays a role in axonal regeneration. (review)
Title: [Role of Dock3 in axonal regeneration].
MOCA is a key molecule of the Alzheimer disease-relevant neuronal death signals that links the presenilin-mediated death signal with the APP-mediated death signal at a point between Rac1 or Cdc42 and ASK1.
Title: MOCA is an integrator of the neuronal death signals that are activated by familial Alzheimer's disease-related mutants of amyloid β precursor protein and presenilins.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex
Title: Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia MedGen: C4749014 OMIM: 618292 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of a melanoma susceptibility locus and somatic mutation in TET2. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3S3151 (e-PCR)
- UniSTS:62722

DOCK3__4766 (e-PCR)
- UniSTS:462877

fk95g07.x1 (e-PCR)
- UniSTS:201785

D3S1573 (e-PCR), detects polymorphism
- UniSTS:78138

D3S1235 (e-PCR), detects polymorphism
- UniSTS:43090

SHGC-107368 (e-PCR)
- UniSTS:170341

RH18533 (e-PCR)
- UniSTS:1654

RH12752 (e-PCR)
- UniSTS:15480

D3S2928E (e-PCR)
- UniSTS:150912

D3S3306E (e-PCR)
- UniSTS:153740

RH121275 (e-PCR)
- UniSTS:138386

D3S3188 (e-PCR)
- UniSTS:153513

SHGC-156153 (e-PCR)
- UniSTS:185281

D3S1573 (e-PCR), detects polymorphism
- UniSTS:91588

D3S3060 (e-PCR)
- UniSTS:48883

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase activator activity	IEA Inferred from Electronic Annotation more info
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small GTPase binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in neurotrophin TRK receptor signaling pathway	TAS Traceable Author Statement more info
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info
involved_in small GTPase-mediated signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: dedicator of cytokinesis protein 3

Names: modifier of cell adhesion; presenilin-binding protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_028012.2 RefSeqGene

Range

4687..713958

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004947.5 → NP_004938.1 dedicator of cytokinesis protein 3

See identical proteins and their annotated locations for NP_004938.1

Status: REVIEWED

Source sequence(s)

AC096920, AY254099, BC045793

Consensus CDS

CCDS46835.1

UniProtKB/Swiss-Prot

O15017, Q8IZD9

UniProtKB/TrEMBL

A0A2X0SFH6

Related

ENSP00000266037.8, ENST00000266037.10

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:1235 → 1626

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

50674927..51384198

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005264914.4 → XP_005264971.1 dedicator of cytokinesis protein 3 isoform X1

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:1235 → 1626

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus
XM_006713010.4 → XP_006713073.1 dedicator of cytokinesis protein 3 isoform X19

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:1235 → 1626

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus
XM_005264915.4 → XP_005264972.1 dedicator of cytokinesis protein 3 isoform X2

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:1235 → 1626

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus
XM_017005825.3 → XP_016861314.1 dedicator of cytokinesis protein 3 isoform X9

UniProtKB/TrEMBL

A0A2X0SFH6
XM_006713008.4 → XP_006713071.1 dedicator of cytokinesis protein 3 isoform X5

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:1235 → 1626

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus
XM_047447600.1 → XP_047303556.1 dedicator of cytokinesis protein 3 isoform X14
XM_006713009.4 → XP_006713072.1 dedicator of cytokinesis protein 3 isoform X8

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus

cl06123
Location:1235 → 1597

DHR2_DOCK; Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins
XM_047447602.1 → XP_047303558.1 dedicator of cytokinesis protein 3 isoform X16
XM_047447603.1 → XP_047303559.1 dedicator of cytokinesis protein 3 isoform X17
XM_005264916.5 → XP_005264973.1 dedicator of cytokinesis protein 3 isoform X3

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:1226 → 1617

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus
XM_047447597.1 → XP_047303553.1 dedicator of cytokinesis protein 3 isoform X11
XM_047447598.1 → XP_047303554.1 dedicator of cytokinesis protein 3 isoform X12
XM_047447604.1 → XP_047303560.1 dedicator of cytokinesis protein 3 isoform X20
XM_005264917.4 → XP_005264974.1 dedicator of cytokinesis protein 3 isoform X4

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:1221 → 1612

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus
XM_047447595.1 → XP_047303551.1 dedicator of cytokinesis protein 3 isoform X6
XM_047447596.1 → XP_047303552.1 dedicator of cytokinesis protein 3 isoform X7
XM_047447601.1 → XP_047303557.1 dedicator of cytokinesis protein 3 isoform X15
XM_005264918.5 → XP_005264975.1 dedicator of cytokinesis protein 3 isoform X10

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (4) summary

cd08695
Location:420 → 609

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:1186 → 1577

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cd12048
Location:10 → 65

SH3_DOCK3_B; Src Homology 3 domain of Class B Dedicator of Cytokinesis 3

pfam16172
Location:69 → 412

DOCK_N; DOCK N-terminus
XM_047447599.1 → XP_047303555.1 dedicator of cytokinesis protein 3 isoform X13
XM_017005826.3 → XP_016861315.1 dedicator of cytokinesis protein 3 isoform X18

UniProtKB/TrEMBL

A0A2X0SFH6
XM_047447605.1 → XP_047303561.1 dedicator of cytokinesis protein 3 isoform X21
XM_017005827.3 → XP_016861316.1 dedicator of cytokinesis protein 3 isoform X22

UniProtKB/TrEMBL

A0A2X0SFH6
XM_047447606.1 → XP_047303562.1 dedicator of cytokinesis protein 3 isoform X24
XM_011533441.4 → XP_011531743.1 dedicator of cytokinesis protein 3 isoform X23

UniProtKB/TrEMBL

A0A2X0SFH6

Conserved Domains (3) summary

cd08695
Location:75 → 264

C2_Dock-B; C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins

cd11704
Location:890 → 1281

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

pfam16172
Location:2 → 67

DOCK_N; DOCK N-terminus
XM_011533443.3 → XP_011531745.1 dedicator of cytokinesis protein 3 isoform X25

See identical proteins and their annotated locations for XP_011531745.1

Conserved Domains (2) summary

cd11704
Location:339 → 730

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cl09913
Location:233 → 349

Csn2_like; CRISPR/Cas system-associated protein Csn2
XM_011533445.3 → XP_011531747.1 dedicator of cytokinesis protein 3 isoform X26

Conserved Domains (2) summary

cd11704
Location:281 → 672

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cl09913
Location:175 → 291

Csn2_like; CRISPR/Cas system-associated protein Csn2
XM_011533444.3 → XP_011531746.1 dedicator of cytokinesis protein 3 isoform X25

See identical proteins and their annotated locations for XP_011531746.1

Conserved Domains (2) summary

cd11704
Location:339 → 730

DHR2_DOCK3; Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3

cl09913
Location:233 → 349

Csn2_like; CRISPR/Cas system-associated protein Csn2