ID   DOK4_MOUSE              Reviewed;         325 AA.
AC   Q99KE3; Q3U0X3;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   03-AUG-2022, entry version 134.
DE   RecName: Full=Docking protein 4;
DE   AltName: Full=Downstream of tyrosine kinase 4;
GN   Name=Dok4;
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], INTERACTION WITH RET, TISSUE SPECIFICITY, AND
RP   DEVELOPMENTAL STAGE.
RX   PubMed=11470823; DOI=10.1083/jcb.200102032;
RA   Grimm J., Sachs M., Britsch S., Di Cesare S., Schwarz-Romond T.,
RA   Alitalo K., Birchmeier W.;
RT   "Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret
RT   receptor tyrosine kinase and mediate neuronal differentiation.";
RL   J. Cell Biol. 154:345-354(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD;
RC   TISSUE=Brain cortex, Mammary gland, Olfactory bulb, and Spleen;
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].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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).
CC   -!- FUNCTION: DOK proteins are enzymatically inert adaptor or scaffolding
CC       proteins. They provide a docking platform for the assembly of
CC       multimolecular signaling complexes. DOK4 functions in RET-mediated
CC       neurite outgrowth and plays a positive role in activation of the MAP
CC       kinase pathway (By similarity). Putative link with downstream effectors
CC       of RET in neuronal differentiation. May be involved in the regulation
CC       of the immune response induced by T-cells (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with RET and TEK/TIE2. Interaction with RET is
CC       mediated through the PTB domain and requires phosphorylation of RET
CC       'Tyr-1062'. {ECO:0000269|PubMed:11470823}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. Highest levels in heart, lung and
CC       kidney. {ECO:0000269|PubMed:11470823}.
CC   -!- DEVELOPMENTAL STAGE: At 12.5 dpc and 13.5 dpc, expressed in the central
CC       and peripheral nervous system and in endothelia. In the nervous system,
CC       expression localized to the ventral portion of the neural tube and the
CC       dorsal root and cranial sensory ganglia. Expression confined to
CC       neurons. {ECO:0000269|PubMed:11470823}.
CC   -!- DOMAIN: PTB domain mediates receptor interaction. {ECO:0000250}.
CC   -!- PTM: Phosphorylated on tyrosine residues in response to insulin, IGF1
CC       or RET stimulation. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the DOK family. Type B subfamily. {ECO:0000305}.
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DR   EMBL; AF418207; AAL14626.1; -; mRNA.
DR   EMBL; AK032352; BAC27829.1; -; mRNA.
DR   EMBL; AK043670; BAC31613.1; -; mRNA.
DR   EMBL; AK142621; BAE25134.1; -; mRNA.
DR   EMBL; AK156485; BAE33728.1; -; mRNA.
DR   EMBL; BC004705; AAH04705.1; -; mRNA.
DR   CCDS; CCDS40443.1; -.
DR   RefSeq; NP_444476.1; NM_053246.3.
DR   RefSeq; XP_006530642.1; XM_006530579.3.
DR   AlphaFoldDB; Q99KE3; -.
DR   SMR; Q99KE3; -.
DR   BioGRID; 227631; 3.
DR   STRING; 10090.ENSMUSP00000043554; -.
DR   iPTMnet; Q99KE3; -.
DR   PhosphoSitePlus; Q99KE3; -.
DR   PaxDb; Q99KE3; -.
DR   PRIDE; Q99KE3; -.
DR   ProteomicsDB; 277588; -.
DR   Antibodypedia; 28881; 249 antibodies from 29 providers.
DR   DNASU; 114255; -.
DR   Ensembl; ENSMUST00000046461; ENSMUSP00000043554; ENSMUSG00000040631.
DR   Ensembl; ENSMUST00000212810; ENSMUSP00000148355; ENSMUSG00000040631.
DR   GeneID; 114255; -.
DR   KEGG; mmu:114255; -.
DR   UCSC; uc009mxf.2; mouse.
DR   CTD; 55715; -.
DR   MGI; MGI:2148865; Dok4.
DR   VEuPathDB; HostDB:ENSMUSG00000040631; -.
DR   eggNOG; KOG4047; Eukaryota.
DR   GeneTree; ENSGT00940000160143; -.
DR   HOGENOM; CLU_057256_1_0_1; -.
DR   InParanoid; Q99KE3; -.
DR   OMA; KMLSIEC; -.
DR   OrthoDB; 1224728at2759; -.
DR   PhylomeDB; Q99KE3; -.
DR   TreeFam; TF324994; -.
DR   Reactome; R-MMU-8853659; RET signaling.
DR   BioGRID-ORCS; 114255; 6 hits in 72 CRISPR screens.
DR   ChiTaRS; Dok4; mouse.
DR   PRO; PR:Q99KE3; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; Q99KE3; protein.
DR   Bgee; ENSMUSG00000040631; Expressed in lumbar dorsal root ganglion and 155 other tissues.
DR   ExpressionAtlas; Q99KE3; baseline and differential.
DR   Genevisible; Q99KE3; MM.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0007399; P:nervous system development; IDA:MGI.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IPI:MGI.
DR   CDD; cd14678; PH_DOK4_DOK5_DOK6; 1.
DR   Gene3D; 2.30.29.30; -; 2.
DR   InterPro; IPR037816; DOK4/5/6_PH.
DR   InterPro; IPR002404; IRS_PTB.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   Pfam; PF02174; IRS; 1.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00310; PTBI; 1.
DR   PROSITE; PS51064; IRS_PTB; 1.
PE   1: Evidence at protein level;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..325
FT                   /note="Docking protein 4"
FT                   /id="PRO_0000187275"
FT   DOMAIN          7..112
FT                   /note="PH"
FT   DOMAIN          132..237
FT                   /note="IRS-type PTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT   MOTIF           265..275
FT                   /note="DKFBH motif"
SQ   SEQUENCE   325 AA;  37040 MW;  B925D9F11BA7093A CRC64;
     MATNFNDIVK QGYVKMKSRK LGIYRRCWLV FRKSSSKGPQ RLEKYPDEKS VCLRGCPKVT
     EISNVKCVTR LPKETKRQAV AIIFTDDSAR TFTCDSELEA EEWYKTLSVE CLGSRLNDIS
     LGEPDLLAPG VQCEQTDRFN VFLLPCPNLD VYGECKLQIT HENIYLWDIH NPRVKLVSWP
     LCSLRRYGRD ATRFTFEAGR MCDAGEGLYT FQTQEGEQIY QRVHSATLAI AEQHKRVLLE
     MEKNVRLLNK GTEHYSYPCT PTAMLPRSAY WHHITGSQNI AEASSYGESY GAAQASSETD
     LLNRFILLKP KPSQEDSSEA KTPAQ