Human Gene DOCK2 (uc003maf.3)
  Description: Homo sapiens dedicator of cytokinesis 2 (DOCK2), mRNA.
RefSeq Summary (NM_004946): The protein encoded by this gene belongs to the CDM protein family. It is specifically expressed in hematopoietic cells and is predominantly expressed in peripheral blood leukocytes. The protein is involved in remodeling of the actin cytoskeleton required for lymphocyte migration in response to chemokine signaling. It activates members of the Rho family of GTPases, for example RAC1 and RAC2, by acting as a guanine nucleotide exchange factor (GEF) to exchange bound GDP for free GTP. Mutations in this gene result in immunodeficiency 40 (IMD40), a combined form of immunodeficiency that affects T cell number and function, also with variable defects in B cell and NK cell function. [provided by RefSeq, May 2018].
Transcript (Including UTRs)
   Position: hg19 chr5:169,064,251-169,510,386 Size: 446,136 Total Exon Count: 52 Strand: +
Coding Region
   Position: hg19 chr5:169,064,331-169,509,862 Size: 445,532 Coding Exon Count: 52 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:169,064,251-169,510,386)mRNA (may differ from genome)Protein (1830 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: DOCK2_HUMAN
DESCRIPTION: RecName: Full=Dedicator of cytokinesis protein 2;
FUNCTION: Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2.
SUBUNIT: Homodimer (Probable). Interacts with RAC1 and RAC2. Interacts with CRKL and VAV. Interacts with CD3Z.
SUBCELLULAR LOCATION: Endomembrane system; Peripheral membrane protein. Cytoplasm, cytoskeleton. Note=Colocalizes with F-actin.
TISSUE SPECIFICITY: Specifically expressed in hematopoietic cells. Highly expressed in peripheral blood leukocytes, and expressed at intermediate level in thymus and spleen. Expressed at very low level in the small intestine and colon.
DOMAIN: The DHR-2 domain may mediate the GEF activity (By similarity).
SIMILARITY: Belongs to the DOCK family.
SIMILARITY: Contains 1 DHR-1 domain.
SIMILARITY: Contains 1 DHR-2 domain.
SIMILARITY: Contains 1 SH3 domain.
SEQUENCE CAUTION: Sequence=BAA13200.1; Type=Erroneous initiation;

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): DOCK2
CDC HuGE Published Literature: DOCK2
Positive Disease Associations: Asthma , Body Height , Eosinophils , Heart Failure , Leptin , Myocardial Infarction , protein quantitative trait loci , Stroke
Related Studies:
  1. Asthma
    C Ober et al. American journal of human genetics 2000, A second-generation genomewide screen for asthma-susceptibility alleles in a founder population., American journal of human genetics. [PubMed 11022011]
  2. Asthma
    C Ober et al. American journal of human genetics 2000, A second-generation genomewide screen for asthma-susceptibility alleles in a founder population., American journal of human genetics. [PubMed 11022011]
  3. Body Height
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: DOCK2
Diseases sorted by gene-association score: immunodeficiency 40* (1578), dock2 deficiency (18), childhood pilocytic astrocytoma (11), usher syndrome, type 1c (7)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 47.50 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 165.04 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -33.1080-0.414 Picture PostScript Text
3' UTR -148.06524-0.283 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009056 - Cyt_c_dom
IPR026791 - DOCK
IPR026799 - DOCK_A
IPR010703 - DOCK_C
IPR011511 - SH3_2
IPR001452 - SH3_domain

Pfam Domains:
PF06920 - Dock homology region 2
PF14429 - C2 domain in Dock180 and Zizimin proteins
PF16172 - DOCK N-terminus

SCOP Domains:
46626 - Cytochrome c
50044 - SH3-domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2RQR - NMR MuPIT 2YIN - X-ray 3A98 - X-ray MuPIT 3B13 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q92608
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
 Gene Details    
 Gene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005096 GTPase activator activity
GO:0005515 protein binding
GO:0030676 Rac guanyl-nucleotide exchange factor activity
GO:0042608 T cell receptor binding

Biological Process:
GO:0001766 membrane raft polarization
GO:0001768 establishment of T cell polarity
GO:0001771 immunological synapse formation
GO:0002277 myeloid dendritic cell activation involved in immune response
GO:0006935 chemotaxis
GO:0007010 cytoskeleton organization
GO:0007264 small GTPase mediated signal transduction
GO:0030036 actin cytoskeleton organization
GO:0042098 T cell proliferation
GO:0042110 T cell activation
GO:0043312 neutrophil degranulation
GO:0043547 positive regulation of GTPase activity
GO:0044351 macropinocytosis
GO:0045059 positive thymic T cell selection
GO:0045060 negative thymic T cell selection
GO:0046631 alpha-beta T cell activation
GO:0046633 alpha-beta T cell proliferation
GO:0050690 regulation of defense response to virus by virus
GO:0050766 positive regulation of phagocytosis

Cellular Component:
GO:0005576 extracellular region
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0012505 endomembrane system
GO:0016020 membrane
GO:0035580 specific granule lumen
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  D86964 - Homo sapiens mRNA for KIAA0209 gene.
BC104900 - Homo sapiens dedicator of cytokinesis 2, mRNA (cDNA clone MGC:132560 IMAGE:8143903), complete cds.
BC113457 - Homo sapiens dedicator of cytokinesis 2, mRNA (cDNA clone MGC:142017 IMAGE:8322509), complete cds.
BC143358 - Homo sapiens cDNA clone IMAGE:9051863.
AB463008 - Synthetic construct DNA, clone: pF1KA0209, Homo sapiens DOCK2 gene for dedicator of cytokinesis 2, without stop codon, in Flexi system.
BC016996 - Homo sapiens dedicator of cytokinesis 2, mRNA (cDNA clone IMAGE:4413481), complete cds.
AK128107 - Homo sapiens cDNA FLJ46228 fis, clone TESTI4014908, highly similar to Dedicator of cytokinesis protein 2.
BC035613 - Homo sapiens dedicator of cytokinesis 2, mRNA (cDNA clone IMAGE:4385164), partial cds.
BC084556 - Homo sapiens dedicator of cytokinesis 2, mRNA (cDNA clone IMAGE:5933446), partial cds.
JD216123 - Sequence 197147 from Patent EP1572962.
AK128449 - Homo sapiens cDNA FLJ46592 fis, clone THYMU3045510, highly similar to Dedicator of cytokinesis protein 2.
AK130744 - Homo sapiens cDNA FLJ27234 fis, clone SYN07051.
JD323286 - Sequence 304310 from Patent EP1572962.
JD427461 - Sequence 408485 from Patent EP1572962.
JD479699 - Sequence 460723 from Patent EP1572962.
JD456118 - Sequence 437142 from Patent EP1572962.
JD376416 - Sequence 357440 from Patent EP1572962.
JD503341 - Sequence 484365 from Patent EP1572962.
JD242413 - Sequence 223437 from Patent EP1572962.
JD284821 - Sequence 265845 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04062 - Chemokine signaling pathway
hsa04666 - Fc gamma R-mediated phagocytosis

Reactome (by CSHL, EBI, and GO)

Protein Q92608 (Reactome details) participates in the following event(s):

R-HSA-200952 Nef binds a ternary complex comprising DOCK2 guanine nucleotide exchange factor for small Rho-family GTPase Rac, its cofactor ELMO1, and Rac, and activates Rac through this interaction
R-HSA-1011598 DOCKs bind to RhoGEFs
R-HSA-6798749 Exocytosis of specific granule lumen proteins
R-HSA-164944 Nef and signal transduction
R-HSA-983231 Factors involved in megakaryocyte development and platelet production
R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis
R-HSA-6798695 Neutrophil degranulation
R-HSA-109582 Hemostasis
R-HSA-162909 Host Interactions of HIV factors
R-HSA-168249 Innate Immune System
R-HSA-162906 HIV Infection
R-HSA-168256 Immune System
R-HSA-5663205 Infectious disease
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: DOCK2_HUMAN, KIAA0209, NM_004946, NP_004937, Q2M3I0, Q92608, Q96AK7
UCSC ID: uc003maf.3
RefSeq Accession: NM_004946
Protein: Q92608 (aka DOCK2_HUMAN or DOC2_HUMAN)
CCDS: CCDS4371.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_004946.2
exon count: 52CDS single in 3' UTR: no RNA size: 6117
ORF size: 5493CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 10492.00frame shift in genome: no % Coverage: 99.67
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.