Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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

  • phosphatidylinositol binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

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...

Keywords - Ligandi

Lipid-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi158 – 1592RR → AA: Abolishes interaction with MUSK and function; when associated with A-174. 1 Publication
Mutagenesisi174 – 1741R → A: Abolishes interaction with MUSK and function; when associated with A-158 and A-159. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 504504Protein Dok-7PRO_0000250372Add
BLAST

Proteomic databases

MaxQBiQ18PE0.
PaxDbiQ18PE0.
PRIDEiQ18PE0.

PTM databases

iPTMnetiQ18PE0.
PhosphoSiteiQ18PE0.

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

BgeeiQ18PE0.
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

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

IntActiQ18PE0. 2 interactions.
STRINGi10090.ENSMUSP00000059538.

Structurei

Secondary structure

1
504
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 138Combined sources
Beta strandi15 – 173Combined sources
Beta strandi20 – 278Combined sources
Beta strandi36 – 449Combined sources
Helixi45 – 484Combined sources
Beta strandi54 – 596Combined sources
Beta strandi62 – 7110Combined sources
Beta strandi74 – 8411Combined sources
Beta strandi86 – 905Combined sources
Helixi94 – 10714Combined sources
Beta strandi109 – 11810Combined sources
Beta strandi120 – 1245Combined sources
Beta strandi127 – 1348Combined sources
Beta strandi137 – 1426Combined sources
Turni143 – 1464Combined sources
Beta strandi147 – 1537Combined sources
Helixi154 – 1563Combined sources
Beta strandi157 – 1637Combined sources
Beta strandi166 – 1716Combined sources
Helixi173 – 1786Combined sources
Beta strandi180 – 1856Combined sources
Helixi189 – 19911Combined sources
Turni200 – 2023Combined sources
Turni205 – 2073Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3ML4X-ray2.60A/B/C/D1-220[»]
ProteinModelPortaliQ18PE0.
SMRiQ18PE0. Positions 3-210.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ18PE0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 109106PHPROSITE-ProRule annotationAdd
BLAST
Domaini105 – 210106IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi246 – 358113Ser-richAdd
BLAST

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

Sequence similaritiesi

Contains 1 IRS-type PTB domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IHI2. Eukaryota.
ENOG4111MP1. LUCA.
GeneTreeiENSGT00390000015386.
HOGENOMiHOG000230953.
HOVERGENiHBG080009.
InParanoidiQ18PE0.
OrthoDBiEOG75B84J.
PhylomeDBiQ18PE0.
TreeFamiTF332288.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

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 AAH89590.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAC31923.1 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei34 – 178145DCLLM…RCGYW → G in isoform 2. 1 PublicationVSP_020636Add
BLAST
Alternative sequencei501 – 5044KPPP → MATSSPGFTVTHPGSPGRVA ADSPGPERPHSEMPTYVNIP ISPISRPQLHYMDLELPGAS AGVRGASTSRYAQIDIAATE TAHRVGVRHAQTREERLPEL EQRKKGP in isoform 3. 1 PublicationVSP_020637

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_766296.1. NM_172708.3.
XP_006503961.1. XM_006503898.2. [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

Cross-referencesi

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_766296.1. NM_172708.3.
XP_006503961.1. XM_006503898.2. [Q18PE0-3]
XP_006503963.1. XM_006503900.2.
UniGeneiMm.205483.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3ML4X-ray2.60A/B/C/D1-220[»]
ProteinModelPortaliQ18PE0.
SMRiQ18PE0. Positions 3-210.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ18PE0. 2 interactions.
STRINGi10090.ENSMUSP00000059538.

PTM databases

iPTMnetiQ18PE0.
PhosphoSiteiQ18PE0.

Proteomic databases

MaxQBiQ18PE0.
PaxDbiQ18PE0.
PRIDEiQ18PE0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi285489.
MGIiMGI:3584043. Dok7.

Phylogenomic databases

eggNOGiENOG410IHI2. Eukaryota.
ENOG4111MP1. LUCA.
GeneTreeiENSGT00390000015386.
HOGENOMiHOG000230953.
HOVERGENiHBG080009.
InParanoidiQ18PE0.
OrthoDBiEOG75B84J.
PhylomeDBiQ18PE0.
TreeFamiTF332288.

Miscellaneous databases

EvolutionaryTraceiQ18PE0.
PROiQ18PE0.
SOURCEiSearch...

Gene expression databases

BgeeiQ18PE0.
CleanExiMM_DOK7.
ExpressionAtlasiQ18PE0. baseline and differential.
GenevisibleiQ18PE0. MM.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MUSK, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, MUTAGENESIS OF 158-ARG-ARG-159 AND ARG-174.
    Strain: C57BL/6J.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 19-504 (ISOFORM 3).
    Strain: C57BL/6J and NOD.
    Tissue: Retina.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Heart.
  4. "The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization."
    Bergamin E., Hallock P.T., Burden S.J., Hubbard S.R.
    Mol. Cell 39:100-109(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-220 IN COMPLEX WITH MUSK PEPTIDE, HOMODIMERIZATION, FUNCTION IN MUSK AUTOPHOSPHORYLATION, DOMAIN, INTERACTION WITH MUSK.

Entry informationi

Entry nameiDOK7_MOUSE
AccessioniPrimary (citable) accession number: Q18PE0
Secondary accession number(s): Q3TCZ6, Q5FW70, Q8C8U7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: July 25, 2006
Last modified: June 8, 2016
This is version 87 of the entry and version 1 of the sequence. [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
  3. SIMILARITY comments
    Index of protein domains and families

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.