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    DOCK8 dedicator of cytokinesis 8 [ Homo sapiens ]

    Gene ID: 81704, updated on 11-May-2012
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    Summary

    Official Symbol
    DOCK8provided by HGNC
    Official Full Name
    dedicator of cytokinesis 8provided by HGNC
    Primary source
    HGNC:19191
    Locus tag
    RP11-165F24.7
    See related
    Ensembl:ENSG00000107099; HPRD:10920; MIM:611432; Vega:OTTHUMG00000078789
    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
    MRD2; ZIR8; FLJ00026; FLJ00152; FLJ00346
    Summary
    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]
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    Genomic context

    Location :
    9p24.3
    Sequence :
    Chromosome: 9; NC_000009.11 (214865..465259)
    See DOCK8 in Epigenomics, MapViewer

    Chromosome 9 - NC_000009.11Genomic Context describing neighboring genes Neighboring gene forkhead box D4 Neighboring gene COBW domain containing 1 Neighboring gene chromosome 9 open reading frame 66 Neighboring gene chromosome 6 open reading frame 146 pseudogene Neighboring gene ribosomal protein L12 pseudogene 25

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice. Randall KL, et al. J Exp Med, 2011 Oct 24. PMID 22006977.
    2. DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory. Lambe T, et al. Eur J Immunol, 2011 Dec. PMID 21969276.
    3. Cutaneous manifestations of DOCK8 deficiency syndrome. Chu EY, et al. Arch Dermatol, 2012 Jan. PMID 21931011.
    4. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Wagner SA, et al. Mol Cell Proteomics, 2011 Oct. PMID 21890473.
    5. Deficient T Cell Receptor Excision Circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: implications for pathogenesis and potential detection by newborn screening. Dasouki M, et al. Clin Immunol, 2011 Nov. PMID 21763205.

    See all (26) citations in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Findings help to explain why DOCK8-deficient patients are susceptible to recurrent infections and provide new insights into how T-cell memory is sustained.
      Title: DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory.
    2. Rates of malignancy and overall mortality in patients with DOCK8 deficiency were higher than in those with Job's syndrome
      Title: Cutaneous manifestations of DOCK8 deficiency syndrome.
    3. These findings highlight a key role for DOCK8 in the survival and function of human and mouse CD8 T cells.
      Title: DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice.
    4. A 2-bp deletion at codon 510 in exon 14 causing a frameshift mutation was found in 3 homozygous siblings with Job syndrome and their heterozygous first-cousin parents.
      Title: Deficient T Cell Receptor Excision Circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: implications for pathogenesis and potential detection by newborn screening.
    5. Mutations in DOCK8 lead to DOCK8 immunodeficiency syndrome characterized by recurrent viral infections, severe atopy, and early onset malignancy. (Review)
      Title: Genetic, clinical, and laboratory markers for DOCK8 immunodeficiency syndrome.
    6. DOCK8 deficiency and clinical manifestations of hyper IgE syndromes (Review)
      Title: Clinical manifestations of hyper IgE syndromes.
    7. Several AR-HIES patients have recently been shown to harbour mutations in the gene for dedicator of cytokinesis 8 (DOCK8). Here, we present the long-term outcome of a girl having received a hematopoietic stem cell graft.
      Title: Successful long-term correction of autosomal recessive hyper-IgE syndrome due to DOCK8 deficiency by hematopoietic stem cell transplantation.
    8. Chromosome 9p loss is the hallmark of squamous cell carcinoma, and DMRT1, DMRT3 and DOCK8 genes at 9p24.3 might be of interest for the study of the pathophysiology of SCC as potential targets for therapeutic measures.
      Title: Frequent silence of chromosome 9p, homozygous DOCK8, DMRT1 and DMRT3 deletion at 9p24.3 in squamous cell carcinoma of the lung.
    9. 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.
    10. Autosomal-recessive mutations in DOCK8 are responsible for many, although not all, cases of autosomal-recessive hyper-IgE syndrome.
      Title: Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome.
    Submit: New GeneRIF Correction See all (14)
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    Phenotypes

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

    Review eQTL and phenotype association data in this region using PheGenI

    Hyper-IgE recurrent infection syndrome, autosomal recessive

    Mental retardation, autosomal dominant 2

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q8NF50 P60953 CDC42    HPRD  PubMed  
    Q8NF50 P63000 RAC1    HPRD  PubMed  
    Q8NF50 Q9H4E5 RHOJ    HPRD  PubMed  
    Q8NF50 P17081 RHOQ    HPRD  PubMed  
    BioGRID:123577 BioGRID:107433 CDC42    BioGRID  PubMed Two-hybrid 
    BioGRID:123577 BioGRID:111817 RAC1    BioGRID  PubMed Two-hybrid 
    BioGRID:123577 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Factors involved in megakaryocyte development and platelet production, organism-specific biosystem (from REACTOME)
      Factors involved in megakaryocyte development and platelet production, organism-specific biosystemMegakaryocytes (MKs) give rise to circulating platelets (thrombocytes) through terminal differentiation of MKs which release cytoplasmic fragments as circulating platelets. As MKs mature they underg...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    GTP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    GTPase binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    guanyl-nucleotide exchange factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    blood coagulation TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    cytosol TAS
    Traceable Author Statement
    more info
    		  
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    General protein information

    Preferred Names
    dedicator of cytokinesis protein 8
    Names
    dedicator of cytokinesis protein 8
    1200017A24Rik
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    NCBI Reference Sequences (RefSeq)

    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

    1. NG_017007.1 RefSeqGene

      Range
      5001..255395
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_196

    mRNA and Protein(s)

    1. NM_001190458.1 → NP_001177387.1  dedicator of cytokinesis protein 8 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. This variant also lacks an in-frame exon in the middle portion of the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AB191037, AK090429, AL583913, AY117695, BC143929, BM680510, BU532484, DB147029
      Consensus CDS
      CCDS55284.1
      UniProtKB/TrEMBL
      B7ZLP0
      UniProtKB/TrEMBL
      E9PH09
      UniProtKB/Swiss-Prot
      Q8NF50
      Related
      ENSP00000419438, OTTHUMP00000214870, ENST00000469391, OTTHUMT00000354646
      Conserved Domains (3) summary
      pfam11878
      Location:1 – 96
      Blast Score: 251
      DUF3398; Domain of unknown function (DUF3398)
      cd08696
      Location:491 – 671
      Blast Score: 849
      C2_Dock-C; C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins
      pfam06920
      Location:1782 – 1944
      Blast Score: 656
      Ded_cyto; Dedicator of cytokinesis

    2. NM_001193536.1 → NP_001180465.1  dedicator of cytokinesis protein 8 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AK090429, AY117695, BC143929, CA503173, HM991479, HM991480
      Consensus CDS
      CCDS55283.1
      UniProtKB/TrEMBL
      B7ZLP0
      UniProtKB/TrEMBL
      E2J6M5
      UniProtKB/TrEMBL
      E2J6M6
      UniProtKB/Swiss-Prot
      Q8NF50
      Related
      ENSP00000394888, ENST00000432829
      Conserved Domains (3) summary
      pfam11878
      Location:1 – 96
      Blast Score: 251
      DUF3398; Domain of unknown function (DUF3398)
      cd08696
      Location:491 – 671
      Blast Score: 849
      C2_Dock-C; C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins
      pfam06920
      Location:1814 – 1976
      Blast Score: 656
      Ded_cyto; Dedicator of cytokinesis

    3. NM_203447.3 → NP_982272.2  dedicator of cytokinesis protein 8 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AB191037, AK090429, CA503173, DR004867
      Consensus CDS
      CCDS6440.2
      UniProtKB/Swiss-Prot
      Q8NF50
      Related
      ENSP00000408464, OTTHUMP00000096442, ENST00000453981, OTTHUMT00000171792
      Conserved Domains (3) summary
      pfam11878
      Location:69 – 164
      Blast Score: 251
      DUF3398; Domain of unknown function (DUF3398)
      cd08696
      Location:559 – 739
      Blast Score: 848
      C2_Dock-C; C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins
      pfam06920
      Location:1882 – 2044
      Blast Score: 656
      Ded_cyto; Dedicator of cytokinesis

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000009.11 Reference GRCh37.p5 Primary Assembly

      Range
      214865..465259
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000141.1 Alternate HuRef

      Range
      168609..417080
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL158832.13 CAM22535.1
      CAM22536.1
      CAM22537.1
    genomic AL158832.13 CAM22535.1
      CAM22536.1
      CAM22537.1
    genomic AL161725.13 CAM13232.1
      CAM13233.1
      CAM13234.1
    genomic CH471071.2 EAW58825.1
      EAW58826.1
      EAW58827.1
      EAW58828.1
      EAW58829.1
      EAW58830.1
    mRNA AB191037.1 BAE45254.1
    mRNA AF194407.1 AAG42221.1
    mRNA AK024436.1 BAB15726.1
    mRNA AK074081.1 BAB84907.1
    mRNA AK090429.1 BAC03410.1
    mRNA AK093572.1 BAC04199.1
    mRNA AK293353.1 BAG56869.1
    mRNA AK310555.1 None
    mRNA AL583913.1 CAC29497.1
    mRNA AY117695.1 None
    mRNA BC019102.2 AAH19102.2
    mRNA BC030518.1 None
    mRNA BC043265.2 None
    mRNA BC045629.1 AAH45629.1
    mRNA BC112894.1 AAI12895.1
    mRNA BC130518.1 AAI30519.1
    mRNA BC143929.1 AAI43930.1
    mRNA BG388288.1 None
    mRNA BM680510.1 None
    mRNA BU532484.1 None
    mRNA CA503173.1 None
    mRNA DB147029.1 None
    mRNA DR004867.1 None
    mRNA HM991479.1 ADK91777.1
    mRNA HM991480.1 ADK91778.1
    mRNA AL832270.1 CAI46160.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q86XD0 GenPept UniProtKB/TrEMBL:Q86XD0
    Q8N227 GenPept UniProtKB/TrEMBL:Q8N227
    Q8NF50.3 GenPept UniProtKB/Swiss-Prot:Q8NF50
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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