DOK7_MOUSE
ID DOK7_MOUSE Reviewed; 504 AA.
AC Q18PE0; Q3TCZ6; Q5FW70; Q8C8U7;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Protein Dok-7;
DE AltName: Full=Downstream of tyrosine kinase 7;
GN Name=Dok7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH MUSK, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF 158-ARG-ARG-159 AND ARG-174.
RC STRAIN=C57BL/6J;
RX PubMed=16794080; DOI=10.1126/science.1127142;
RA Okada K., Inoue A., Okada M., Murata Y., Kakuta S., Jigami T., Kubo S.,
RA Shiraishi H., Eguchi K., Motomura M., Akiyama T., Iwakura Y., Higuchi O.,
RA Yamanashi Y.;
RT "The muscle protein Dok-7 is essential for neuromuscular synaptogenesis.";
RL Science 312:1802-1805(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 19-504 (ISOFORM 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Retina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-220 IN COMPLEX WITH MUSK
RP PEPTIDE, HOMODIMERIZATION, FUNCTION IN MUSK AUTOPHOSPHORYLATION, DOMAIN,
RP AND INTERACTION WITH MUSK.
RX PubMed=20603078; DOI=10.1016/j.molcel.2010.06.007;
RA Bergamin E., Hallock P.T., Burden S.J., Hubbard S.R.;
RT "The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine
RT kinase MuSK via dimerization.";
RL Mol. Cell 39:100-109(2010).
CC -!- FUNCTION: Probable muscle-intrinsic activator of MUSK that plays an
CC essential role in neuromuscular synaptogenesis. Acts in aneural
CC activation of MUSK and subsequent acetylcholine receptor (AchR)
CC clustering in myotubes. Induces autophosphorylation of MUSK.
CC {ECO:0000269|PubMed:16794080, ECO:0000269|PubMed:20603078}.
CC -!- SUBUNIT: Homodimer. Forms a heterotetramer composed of 2 DOK7 and 2
CC MUSK molecules which facilitates MUSK trans-autophosphorylation on
CC tyrosine residue and activation. Interacts (via IRS-type PTB domain)
CC with MUSK (via cytoplasmic part); requires MUSK phosphorylation.
CC {ECO:0000269|PubMed:16794080, ECO:0000269|PubMed:20603078}.
CC -!- INTERACTION:
CC Q18PE0; Q61006: Musk; NbExp=3; IntAct=EBI-3989091, EBI-3989087;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16794080};
CC Peripheral membrane protein {ECO:0000269|PubMed:16794080}. Synapse
CC {ECO:0000269|PubMed:16794080}. Note=Accumulates at neuromuscular
CC junctions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q18PE0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q18PE0-2; Sequence=VSP_020636;
CC Name=3;
CC IsoId=Q18PE0-3; Sequence=VSP_020637;
CC -!- DEVELOPMENTAL STAGE: Expressed in the central region encompassing the
CC endplate area of the diaphragm muscles at day 14.5 of embryonic
CC development (14.5 dpc), when AChRs cluster in a nerve- and agrin-
CC independent manner. {ECO:0000269|PubMed:16794080}.
CC -!- DOMAIN: The PH domain mediated binding to phospholipids with
CC phosphoinositol headgroups. Affinity is highest for phosphatidyl 3,4,5-
CC trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and
CC phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:20603078}.
CC -!- DISRUPTION PHENOTYPE: Mice are immobile at birth and die shortly
CC thereafter. They do not form neither acetylcholine receptor clusters
CC nor neuromuscular synapses. {ECO:0000269|PubMed:16794080}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH89590.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC31923.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB220919; BAE96740.1; -; mRNA.
DR EMBL; AK044445; BAC31923.1; ALT_INIT; mRNA.
DR EMBL; AK170454; BAE41809.1; -; mRNA.
DR EMBL; BC089590; AAH89590.1; ALT_INIT; mRNA.
DR CCDS; CCDS89911.1; -. [Q18PE0-1]
DR CCDS; CCDS89912.1; -. [Q18PE0-2]
DR RefSeq; NP_001335203.1; NM_001348274.1. [Q18PE0-1]
DR RefSeq; NP_001335204.1; NM_001348275.1.
DR RefSeq; NP_001335205.1; NM_001348276.1. [Q18PE0-2]
DR RefSeq; NP_001335407.1; NM_001348478.1. [Q18PE0-3]
DR RefSeq; XP_006503961.1; XM_006503898.3.
DR RefSeq; XP_006503963.1; XM_006503900.2.
DR PDB; 3ML4; X-ray; 2.60 A; A/B/C/D=1-220.
DR PDBsum; 3ML4; -.
DR AlphaFoldDB; Q18PE0; -.
DR SMR; Q18PE0; -.
DR BioGRID; 231089; 1.
DR ELM; Q18PE0; -.
DR IntAct; Q18PE0; 2.
DR STRING; 10090.ENSMUSP00000059538; -.
DR iPTMnet; Q18PE0; -.
DR PhosphoSitePlus; Q18PE0; -.
DR PaxDb; Q18PE0; -.
DR PRIDE; Q18PE0; -.
DR ProteomicsDB; 277394; -. [Q18PE0-1]
DR ProteomicsDB; 277395; -. [Q18PE0-2]
DR ProteomicsDB; 277396; -. [Q18PE0-3]
DR Antibodypedia; 55035; 450 antibodies from 28 providers.
DR DNASU; 231134; -.
DR Ensembl; ENSMUST00000101298; ENSMUSP00000098856; ENSMUSG00000044716. [Q18PE0-2]
DR Ensembl; ENSMUST00000114270; ENSMUSP00000109909; ENSMUSG00000044716. [Q18PE0-1]
DR GeneID; 231134; -.
DR KEGG; mmu:231134; -.
DR UCSC; uc008xdk.1; mouse. [Q18PE0-1]
DR UCSC; uc008xdl.1; mouse. [Q18PE0-2]
DR UCSC; uc008xdm.1; mouse. [Q18PE0-3]
DR CTD; 285489; -.
DR MGI; MGI:3584043; Dok7.
DR VEuPathDB; HostDB:ENSMUSG00000044716; -.
DR eggNOG; ENOG502QQBI; Eukaryota.
DR GeneTree; ENSGT00390000015386; -.
DR HOGENOM; CLU_024931_1_0_1; -.
DR InParanoid; Q18PE0; -.
DR OrthoDB; 317220at2759; -.
DR PhylomeDB; Q18PE0; -.
DR TreeFam; TF332288; -.
DR BioGRID-ORCS; 231134; 1 hit in 60 CRISPR screens.
DR ChiTaRS; Dok7; mouse.
DR EvolutionaryTrace; Q18PE0; -.
DR PRO; PR:Q18PE0; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q18PE0; protein.
DR Bgee; ENSMUSG00000044716; Expressed in interventricular septum and 146 other tissues.
DR ExpressionAtlas; Q18PE0; baseline and differential.
DR Genevisible; Q18PE0; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0031594; C:neuromuscular junction; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR GO; GO:0007528; P:neuromuscular junction development; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:MGI.
DR GO; GO:0043113; P:receptor clustering; IDA:MGI.
DR CDD; cd14677; PH_DOK7; 1.
DR CDD; cd13165; PTB_DOK7; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR037746; Dok-7.
DR InterPro; IPR037747; Dok-7_PH.
DR InterPro; IPR037748; Dok-7_PTB.
DR InterPro; IPR002404; IRS_PTB.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR21636; PTHR21636; 1.
DR Pfam; PF02174; IRS; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS51064; IRS_PTB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Lipid-binding; Membrane;
KW Reference proteome; Synapse.
FT CHAIN 1..504
FT /note="Protein Dok-7"
FT /id="PRO_0000250372"
FT DOMAIN 4..109
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 105..210
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 210..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 248..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 371..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..298
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..348
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..440
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 34..178
FT /note="DCLLMLVYKDKCERSKGLRERSSLTLEDICGLEPALPYEGLAHTLAIICLSQ
FT AVMLGFDSHEAMCAWDTRIRYALGEVHRFHVTVAPGTKLESGPATLHLCNDILVLARDI
FT PPTVMGQWKLSDLRRYGAVPNGFIFEGGTRCGYW -> G (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020636"
FT VAR_SEQ 501..504
FT /note="KPPP -> MATSSPGFTVTHPGSPGRVAADSPGPERPHSEMPTYVNIPISPI
FT SRPQLHYMDLELPGASAGVRGASTSRYAQIDIAATETAHRVGVRHAQTREERLPELEQR
FT KKGP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020637"
FT MUTAGEN 158..159
FT /note="RR->AA: Abolishes interaction with MUSK and
FT function; when associated with A-174."
FT /evidence="ECO:0000269|PubMed:16794080"
FT MUTAGEN 174
FT /note="R->A: Abolishes interaction with MUSK and function;
FT when associated with A-158 and A-159."
FT /evidence="ECO:0000269|PubMed:16794080"
FT STRAND 6..13
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 20..27
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 36..44
FT /evidence="ECO:0007829|PDB:3ML4"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 54..59
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 62..71
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 74..84
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:3ML4"
FT HELIX 94..107
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 109..118
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 127..134
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:3ML4"
FT TURN 143..146
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:3ML4"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:3ML4"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:3ML4"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:3ML4"
FT HELIX 189..199
FT /evidence="ECO:0007829|PDB:3ML4"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:3ML4"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:3ML4"
SQ SEQUENCE 504 AA; 53177 MW; AB0FC717F6C1A5B2 CRC64;
MTEAALVEGQ VKLRDGKKWK SRWLVLRKPS PVADCLLMLV YKDKCERSKG LRERSSLTLE
DICGLEPALP YEGLAHTLAI ICLSQAVMLG FDSHEAMCAW DTRIRYALGE VHRFHVTVAP
GTKLESGPAT LHLCNDILVL ARDIPPTVMG QWKLSDLRRY GAVPNGFIFE GGTRCGYWAG
VFFLSSAEGE QMSFLFDCIV RGISPTKGPF GLRPVLPDPS SGGPSASEER VAQEALEALQ
LEKRLSLLSH SGRPGSGGDD RSLSSSSSEA SHSDISASSR LTAWPEQSSS SAGTSQEGPG
LVAAQGPGEA MLGASRPPLK PLRPRQLQEV GRQSSSDSGI ATGSHSSYSG SFSSYAGSNL
DVWRAGEEFG SLLSLPPGAS APEPRLCACP PGAAEYQVPT SLRHHYDTPR SLRQAPRDPS
PASQGSSDHG SATDLGGQAP TGCPSSWLGA RRRGQATEGP GSDAALPSPS PGESWEAGSP
HAGPPPAFFL SCSICGGLKV KPPP
