GENOMIC
Mapping
4qC6. View the map and BAC clones (data from UCSC genome browser).
Structure
(assembly 07/2007)
Dock7 (NM_026082): 48 exons, 184,251 bp, chr4:98,603,356-98,787,606
The figure below shows the structure of the Dock7 gene (data from UCSC genome browser).
Regulatory Element
TRANSCRIPT
RefSeq/ORF
Dock7 (NM_026082), 7,043 bp, view ORF and the alignment to genomic.
Expression Pattern
DOCK7 protein is highly expressed in the developing brain and the heart, and is expressed at lower levels in the lung, kidney, skeletal muscle, liver, and spleen. In the brain, DOCK7 protein levels were higher at late embryonic and early postnatal stages and decreased gradually with age.
Browse more information in Entrez Gene, UCSC Gene Sorter, MGI.
PROTEIN
Sequence
Dock7 (Dedicator of cytokinesis protein 7, Kiaa1771) (NP_080358): 2130 aa, UniProtKB/Swiss-Prot entry Q8R1A4.
Ortholog
View NCBI HomoloGene of DOCK7.
Domain
Domain: Pfam:PF06920.
Two domains are shared amongst all DOCK proteins, the catalytic DHR-2 (DOCK homology region 2) or CZH-2 (CDM-zizimin homology 2) domain and the DHR-1 or CZH-1domain. For all DOCK proteins, the DHR-1 domain is located N-terminal to the DHR-2 domain. The DHR-1 domain is probably involved in the binding with PtdIns, while the DHR-2 domain may be responsible for the GEF activity through the interaction with Rho GTPase.
Motif/Site
View annotated motifs in UniProt.
3D Model
ModBase predicted 3D structure of Q8R1A4 from UCSC Gene Sorter: (none).
2D-PAGE
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=241,438Da, pI=6.25.
View NCBI HomoloGene of DOCK7.
Domain
Domain: Pfam:PF06920.
Two domains are shared amongst all DOCK proteins, the catalytic DHR-2 (DOCK homology region 2) or CZH-2 (CDM-zizimin homology 2) domain and the DHR-1 or CZH-1domain. For all DOCK proteins, the DHR-1 domain is located N-terminal to the DHR-2 domain. The DHR-1 domain is probably involved in the binding with PtdIns, while the DHR-2 domain may be responsible for the GEF activity through the interaction with Rho GTPase.
Motif/Site
View annotated motifs in UniProt.
3D Model
ModBase predicted 3D structure of Q8R1A4 from UCSC Gene Sorter: (none).
2D-PAGE
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=241,438Da, pI=6.25.
FUNCTION
Ontology
(1) Biological process: differentiation, neurogenesis.
(2) Guanine-nucleotide releasing factor, guanyl-nucleotide exchange factor activity.
(3) GTP binding, Rac GTPase binding.
(4) Regulation of pigmentation during development.
Location
Cell projection.
Interaction
Interacts with TSC1. Interacts with nucleotide-free RAC1 and RAC3.
View interactions in HPRD
View co-occured partners in literature searched by PPI Finder.
Pathway
Functions as a guanine nucleotide exchange factor (GEF), which activates Rac and Cdc42 small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for RhoA. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization.
MUTATION
Allele or SNP
2 phenotypic alleles of Dock7 are described in MGI:1914549.
SNPs deposited in dbSNP Build 128.
Distribution
m/m and mnlt/mnlt phenotypes both result from mutations that truncate the Dock7 protein with a large insertion in the case of
m/m and a large deletion in the case of mnlt/mnlt (Blasius et al.). See the description of mutational sites in Mutagenetix.
(Numbering of cDNA sequence is based on the start codon of RefSeq NM_026086. view ORF here.)
Effect
Cis-acting effects of either of these two mutations might elicit phenotypic differences that are not related to the Dock7 locus itself (Blasius et al.).
PHENOTYPE
The misty(m) was first described in 1941. The moonlight (mnlt), a second hypopigmentation and white-spotting mutation identified on the C57BL/6J background, yields a phenotypic copy of m/m coat color traits (Blasius et al.). Not all of the phenotypic anomalies observed in m/m and mnlt/mnlt mice are shared. For instance, mnlt/mnlt mice do not show the bleeding phenotype seen in m/m animals (Sviderskaya et al.). On the other hand, mnlt/mnlt females are unable to raise their offspring, while m/m mice are adequate mothers (Blasius et al.). The m allele arose spontaneously in the DBA/J strain. The strain is described in more detail in JAX Mice database (B6.D-Tyrp16m/J). The mnlt allele is described in detail in Mutagenetix.
Although Dock7 is transcribed at high levels in the developing brain and has been implicated in both axon development and myelination by in vitro studies, there is no requirement for Dock7 in neurobehavioral function in vivo. However, Dock7 has non-redundant role(s) related to the distribution and function of dermal and follicular melanocytes (Blasius et al.).
REFERENCE
- Blasius AL, Brandl K, Crozat K, Xia Y, Khovananth K, Krebs P, Smart NG, Zampolli A, Ruggeri ZM, Beutler BA. Mice with mutations of Dock7 have generalized hypopigmentation and white-spotting but show normal neurological function. Proc Natl Acad Sci U S A 2009; 106:2706-11. PMID: 19202056
- Sviderskaya EV, Novak EK, Swank RT, Bennett DC. The murine misty mutation: phenotypic effects on melanocytes, platelets and brown fat. Genetics 1998; 148:381-90. PMID: 9475748