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UniProtKB - Q18PE0 (DOK7_MOUSE)

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Protein

Protein Dok-7

Gene

Dok7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable muscle-intrinsic activator of MUSK that plays an essential role in neuromuscular synaptogenesis. Acts in aneural activation of MUSK and subsequent acetylcholine receptor (AchR) clustering in myotubes. Induces autophosphorylation of MUSK.2 Publications

GO - Molecular functioni

  • insulin receptor binding Source: InterPro
  • phosphatidylinositol binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  • neuromuscular junction development Source: MGI
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of protein tyrosine kinase activity Source: UniProtKB
  • receptor clustering Source: MGI
Complete GO annotation...

Keywordsi

LigandLipid-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protein Dok-7
Alternative name(s):
Downstream of tyrosine kinase 7
Gene namesi
Name:Dok7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:3584043. Dok7.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • neuromuscular junction Source: MGI
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice are immobile at birth and die shortly thereafter. They do not form neither acetylcholine receptor clusters nor neuromuscular synapses.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi158 – 159RR → AA: Abolishes interaction with MUSK and function; when associated with A-174. 1 Publication2
Mutagenesisi174R → A: Abolishes interaction with MUSK and function; when associated with A-158 and A-159. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002503721 – 504Protein Dok-7Add BLAST504

Proteomic databases

PaxDbiQ18PE0.
PRIDEiQ18PE0.

PTM databases

iPTMnetiQ18PE0.
PhosphoSitePlusiQ18PE0.

Expressioni

Developmental stagei

Expressed in the central region encompassing the endplate area of the diaphragm muscles at day 14.5 of embryonic development (E14.5), when AChRs cluster in a nerve- and agrin-independent manner.1 Publication

Gene expression databases

BgeeiENSMUSG00000044716.
CleanExiMM_DOK7.
ExpressionAtlasiQ18PE0. baseline and differential.
GenevisibleiQ18PE0. MM.

Interactioni

Subunit structurei

Homodimer. Forms a heterotetramer composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-autophosphorylation on tyrosine residue and activation. Interacts (via IRS-type PTB domain) with MUSK (via cytoplasmic part); requires MUSK phosphorylation.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MuskQ610063EBI-3989091,EBI-3989087

GO - Molecular functioni

  • insulin receptor binding Source: InterPro
  • protein kinase binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

IntActiQ18PE0. 2 interactors.
STRINGi10090.ENSMUSP00000059538.

Structurei

Secondary structure

1504
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 13Combined sources8
Beta strandi15 – 17Combined sources3
Beta strandi20 – 27Combined sources8
Beta strandi36 – 44Combined sources9
Helixi45 – 48Combined sources4
Beta strandi54 – 59Combined sources6
Beta strandi62 – 71Combined sources10
Beta strandi74 – 84Combined sources11
Beta strandi86 – 90Combined sources5
Helixi94 – 107Combined sources14
Beta strandi109 – 118Combined sources10
Beta strandi120 – 124Combined sources5
Beta strandi127 – 134Combined sources8
Beta strandi137 – 142Combined sources6
Turni143 – 146Combined sources4
Beta strandi147 – 153Combined sources7
Helixi154 – 156Combined sources3
Beta strandi157 – 163Combined sources7
Beta strandi166 – 171Combined sources6
Helixi173 – 178Combined sources6
Beta strandi180 – 185Combined sources6
Helixi189 – 199Combined sources11
Turni200 – 202Combined sources3
Turni205 – 207Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3ML4X-ray2.60A/B/C/D1-220[»]
ProteinModelPortaliQ18PE0.
SMRiQ18PE0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ18PE0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 109PHPROSITE-ProRule annotationAdd BLAST106
Domaini105 – 210IRS-type PTBPROSITE-ProRule annotationAdd BLAST106

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi246 – 358Ser-richAdd BLAST113

Domaini

The PH domain mediated binding to phospholipids with phosphoinositol headgroups. Affinity is highest for phosphatidyl 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate.1 Publication

Phylogenomic databases

eggNOGiENOG410IHI2. Eukaryota.
ENOG4111MP1. LUCA.
GeneTreeiENSGT00390000015386.
HOGENOMiHOG000230953.
HOVERGENiHBG080009.
InParanoidiQ18PE0.
PhylomeDBiQ18PE0.
TreeFamiTF332288.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiView protein in InterPro
IPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
PfamiView protein in Pfam
PF02174. IRS. 1 hit.
SMARTiView protein in SMART
SM00233. PH. 1 hit.
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiView protein in PROSITE
PS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q18PE0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTEAALVEGQ VKLRDGKKWK SRWLVLRKPS PVADCLLMLV YKDKCERSKG 
        60         70         80         90        100
LRERSSLTLE DICGLEPALP YEGLAHTLAI ICLSQAVMLG FDSHEAMCAW 
       110        120        130        140        150
DTRIRYALGE VHRFHVTVAP GTKLESGPAT LHLCNDILVL ARDIPPTVMG 
       160        170        180        190        200
QWKLSDLRRY GAVPNGFIFE GGTRCGYWAG VFFLSSAEGE QMSFLFDCIV 
       210        220        230        240        250
RGISPTKGPF GLRPVLPDPS SGGPSASEER VAQEALEALQ LEKRLSLLSH 
       260        270        280        290        300
SGRPGSGGDD RSLSSSSSEA SHSDISASSR LTAWPEQSSS SAGTSQEGPG 
       310        320        330        340        350
LVAAQGPGEA MLGASRPPLK PLRPRQLQEV GRQSSSDSGI ATGSHSSYSG 
       360        370        380        390        400
SFSSYAGSNL DVWRAGEEFG SLLSLPPGAS APEPRLCACP PGAAEYQVPT 
       410        420        430        440        450
SLRHHYDTPR SLRQAPRDPS PASQGSSDHG SATDLGGQAP TGCPSSWLGA 
       460        470        480        490        500
RRRGQATEGP GSDAALPSPS PGESWEAGSP HAGPPPAFFL SCSICGGLKV 

KPPP
Length:504
Mass (Da):53,177
Last modified:July 25, 2006 - v1
Checksum:iAB0FC717F6C1A5B2
GO
Isoform 2 (identifier: Q18PE0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     34-178: DCLLMLVYKD...FEGGTRCGYW → G

Note: No experimental confirmation available.
Show »
Length:360
Mass (Da):37,098
Checksum:iF8E9ABE394D5F37E
GO
Isoform 3 (identifier: Q18PE0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     501-504: KPPP → MATSSPGFTV...PELEQRKKGP

Note: No experimental confirmation available.
Show »
Length:607
Mass (Da):64,260
Checksum:iA481EB490F5F9F96
GO

Sequence cautioni

The sequence AAH89590 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC31923 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02063634 – 178DCLLM…RCGYW → G in isoform 2. 1 PublicationAdd BLAST145
Alternative sequenceiVSP_020637501 – 504KPPP → MATSSPGFTVTHPGSPGRVA ADSPGPERPHSEMPTYVNIP ISPISRPQLHYMDLELPGAS AGVRGASTSRYAQIDIAATE TAHRVGVRHAQTREERLPEL EQRKKGP in isoform 3. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB220919 mRNA. Translation: BAE96740.1.
AK044445 mRNA. Translation: BAC31923.1. Different initiation.
AK170454 mRNA. Translation: BAE41809.1.
BC089590 mRNA. Translation: AAH89590.1. Different initiation.
RefSeqiNP_001335203.1. NM_001348274.1. [Q18PE0-1]
NP_001335204.1. NM_001348275.1.
NP_001335205.1. NM_001348276.1. [Q18PE0-2]
NP_001335407.1. NM_001348478.1. [Q18PE0-3]
XP_006503961.1. XM_006503898.3. [Q18PE0-3]
XP_006503963.1. XM_006503900.2.
UniGeneiMm.205483.

Genome annotation databases

EnsembliENSMUST00000101298; ENSMUSP00000098856; ENSMUSG00000044716. [Q18PE0-2]
ENSMUST00000114270; ENSMUSP00000109909; ENSMUSG00000044716. [Q18PE0-1]
GeneIDi231134.
KEGGimmu:231134.
UCSCiuc008xdk.1. mouse. [Q18PE0-1]
uc008xdl.1. mouse. [Q18PE0-2]
uc008xdm.1. mouse. [Q18PE0-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiDOK7_MOUSE
AccessioniPrimary (citable) accession number: Q18PE0
Secondary accession number(s): Q3TCZ6, Q5FW70, Q8C8U7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: July 25, 2006
Last modified: May 10, 2017
This is version 93 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references