ID F7F370_MONDO Unreviewed; 1378 AA.
AC F7F370;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 09-JAN-2013, sequence version 2.
DT 24-JAN-2024, entry version 92.
DE RecName: Full=Tyrosine-protein kinase receptor {ECO:0000256|RuleBase:RU000312};
DE EC=2.7.10.1 {ECO:0000256|RuleBase:RU000312};
GN Name=INSR {ECO:0000313|Ensembl:ENSMODP00000018879.3};
OS Monodelphis domestica (Gray short-tailed opossum).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Didelphimorphia; Didelphidae; Monodelphis.
OX NCBI_TaxID=13616 {ECO:0000313|Ensembl:ENSMODP00000018879.3, ECO:0000313|Proteomes:UP000002280};
RN [1] {ECO:0000313|Ensembl:ENSMODP00000018879.3, ECO:0000313|Proteomes:UP000002280}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=17495919; DOI=10.1038/nature05805;
RA Mikkelsen T.S., Wakefield M.J., Aken B., Amemiya C.T., Chang J.L., Duke S.,
RA Garber M., Gentles A.J., Goodstadt L., Heger A., Jurka J., Kamal M.,
RA Mauceli E., Searle S.M., Sharpe T., Baker M.L., Batzer M.A., Benos P.V.,
RA Belov K., Clamp M., Cook A., Cuff J., Das R., Davidow L., Deakin J.E.,
RA Fazzari M.J., Glass J.L., Grabherr M., Greally J.M., Gu W., Hore T.A.,
RA Huttley G.A., Kleber M., Jirtle R.L., Koina E., Lee J.T., Mahony S.,
RA Marra M.A., Miller R.D., Nicholls R.D., Oda M., Papenfuss A.T., Parra Z.E.,
RA Pollock D.D., Ray D.A., Schein J.E., Speed T.P., Thompson K.,
RA VandeBerg J.L., Wade C.M., Walker J.A., Waters P.D., Webber C.,
RA Weidman J.R., Xie X., Zody M.C., Baldwin J., Abdouelleil A., Abdulkadir J.,
RA Abebe A., Abera B., Abreu J., Acer S.C., Aftuck L., Alexander A., An P.,
RA Anderson E., Anderson S., Arachi H., Azer M., Bachantsang P., Barry A.,
RA Bayul T., Berlin A., Bessette D., Bloom T., Bloom T., Boguslavskiy L.,
RA Bonnet C., Boukhgalter B., Bourzgui I., Brown A., Cahill P., Channer S.,
RA Cheshatsang Y., Chuda L., Citroen M., Collymore A., Cooke P., Costello M.,
RA D'Aco K., Daza R., De Haan G., DeGray S., DeMaso C., Dhargay N., Dooley K.,
RA Dooley E., Doricent M., Dorje P., Dorjee K., Dupes A., Elong R., Falk J.,
RA Farina A., Faro S., Ferguson D., Fisher S., Foley C.D., Franke A.,
RA Friedrich D., Gadbois L., Gearin G., Gearin C.R., Giannoukos G., Goode T.,
RA Graham J., Grandbois E., Grewal S., Gyaltsen K., Hafez N., Hagos B.,
RA Hall J., Henson C., Hollinger A., Honan T., Huard M.D., Hughes L.,
RA Hurhula B., Husby M.E., Kamat A., Kanga B., Kashin S., Khazanovich D.,
RA Kisner P., Lance K., Lara M., Lee W., Lennon N., Letendre F., LeVine R.,
RA Lipovsky A., Liu X., Liu J., Liu S., Lokyitsang T., Lokyitsang Y.,
RA Lubonja R., Lui A., MacDonald P., Magnisalis V., Maru K., Matthews C.,
RA McCusker W., McDonough S., Mehta T., Meldrim J., Meneus L., Mihai O.,
RA Mihalev A., Mihova T., Mittelman R., Mlenga V., Montmayeur A., Mulrain L.,
RA Navidi A., Naylor J., Negash T., Nguyen T., Nguyen N., Nicol R., Norbu C.,
RA Norbu N., Novod N., O'Neill B., Osman S., Markiewicz E., Oyono O.L.,
RA Patti C., Phunkhang P., Pierre F., Priest M., Raghuraman S., Rege F.,
RA Reyes R., Rise C., Rogov P., Ross K., Ryan E., Settipalli S., Shea T.,
RA Sherpa N., Shi L., Shih D., Sparrow T., Spaulding J., Stalker J.,
RA Stange-Thomann N., Stavropoulos S., Stone C., Strader C., Tesfaye S.,
RA Thomson T., Thoulutsang Y., Thoulutsang D., Topham K., Topping I.,
RA Tsamla T., Vassiliev H., Vo A., Wangchuk T., Wangdi T., Weiand M.,
RA Wilkinson J., Wilson A., Yadav S., Young G., Yu Q., Zembek L., Zhong D.,
RA Zimmer A., Zwirko Z., Jaffe D.B., Alvarez P., Brockman W., Butler J.,
RA Chin C., Gnerre S., MacCallum I., Graves J.A., Ponting C.P., Breen M.,
RA Samollow P.B., Lander E.S., Lindblad-Toh K.;
RT "Genome of the marsupial Monodelphis domestica reveals innovation in non-
RT coding sequences.";
RL Nature 447:167-177(2007).
RN [2] {ECO:0000313|Ensembl:ENSMODP00000018879.3}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (JUL-2023) to UniProtKB.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000256|ARBA:ARBA00001171,
CC ECO:0000256|RuleBase:RU000312};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004479}; Single-
CC pass type I membrane protein {ECO:0000256|ARBA:ARBA00004479}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily.
CC {ECO:0000256|RuleBase:RU000312}.
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DR RefSeq; XP_001377572.2; XM_001377535.4.
DR STRING; 13616.ENSMODP00000018879; -.
DR Ensembl; ENSMODT00000019220.4; ENSMODP00000018879.3; ENSMODG00000015101.4.
DR GeneID; 100027215; -.
DR KEGG; mdo:100027215; -.
DR CTD; 3643; -.
DR eggNOG; KOG4258; Eukaryota.
DR GeneTree; ENSGT00940000155404; -.
DR HOGENOM; CLU_000288_166_0_1; -.
DR InParanoid; F7F370; -.
DR OMA; WTEATHF; -.
DR OrthoDB; 1614410at2759; -.
DR TreeFam; TF351636; -.
DR Proteomes; UP000002280; Chromosome 3.
DR Bgee; ENSMODG00000015101; Expressed in adult mammalian kidney and 17 other cell types or tissues.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0005899; C:insulin receptor complex; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR GO; GO:0031981; C:nuclear lumen; IEA:Ensembl.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0005525; F:GTP binding; IEA:Ensembl.
DR GO; GO:0043559; F:insulin binding; IEA:Ensembl.
DR GO; GO:0005009; F:insulin receptor activity; IBA:GO_Central.
DR GO; GO:0043560; F:insulin receptor substrate binding; IBA:GO_Central.
DR GO; GO:0031994; F:insulin-like growth factor I binding; IEA:Ensembl.
DR GO; GO:0031995; F:insulin-like growth factor II binding; IEA:Ensembl.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0051425; F:PTB domain binding; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IBA:GO_Central.
DR GO; GO:0003007; P:heart morphogenesis; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0048639; P:positive regulation of developmental growth; IEA:Ensembl.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IEA:Ensembl.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IEA:Ensembl.
DR GO; GO:0060267; P:positive regulation of respiratory burst; IEA:Ensembl.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; IEA:Ensembl.
DR GO; GO:0045995; P:regulation of embryonic development; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0046718; P:viral entry into host cell; IEA:Ensembl.
DR CDD; cd00063; FN3; 2.
DR CDD; cd00064; FU; 1.
DR CDD; cd05061; PTKc_InsR; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 4.
DR Gene3D; 3.80.20.20; Receptor L-domain; 2.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR040969; Insulin_TMD.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR000494; Rcpt_L-dom.
DR InterPro; IPR036941; Rcpt_L-dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016246; Tyr_kinase_insulin-like_rcpt.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR PANTHER; PTHR24416:SF535; INSULIN RECEPTOR; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF17870; Insulin_TMD; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PIRSF; PIRSF000620; Insulin_receptor; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 3.
DR SMART; SM00261; FU; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; Fibronectin type III; 3.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF52058; L domain-like; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 3: Inferred from homology;
KW ATP-binding {ECO:0000256|PIRSR:PIRSR000620-2, ECO:0000256|PROSITE-
KW ProRule:PRU10141}; Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Kinase {ECO:0000256|ARBA:ARBA00023137};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius};
KW Nucleotide-binding {ECO:0000256|PIRSR:PIRSR000620-2, ECO:0000256|PROSITE-
KW ProRule:PRU10141};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553,
KW ECO:0000256|RuleBase:RU000312};
KW Receptor {ECO:0000256|ARBA:ARBA00023170, ECO:0000256|RuleBase:RU000312};
KW Reference proteome {ECO:0000313|Proteomes:UP000002280};
KW Signal {ECO:0000256|SAM:SignalP};
KW Transferase {ECO:0000256|ARBA:ARBA00023137};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW ECO:0000256|RuleBase:RU000312};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|SAM:Phobius};
KW Tyrosine-protein kinase {ECO:0000256|ARBA:ARBA00023137}.
FT SIGNAL 1..31
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 32..1378
FT /note="Tyrosine-protein kinase receptor"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5003352790"
FT TRANSMEM 959..980
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 623..725
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000259|PROSITE:PS50853"
FT DOMAIN 853..948
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000259|PROSITE:PS50853"
FT DOMAIN 1019..1294
FT /note="Protein kinase"
FT /evidence="ECO:0000259|PROSITE:PS50011"
FT REGION 685..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1323..1378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1155
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR000620-1"
FT BINDING 1029
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000620-2"
FT BINDING 1053
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000620-2,
FT ECO:0000256|PROSITE-ProRule:PRU10141"
FT BINDING 1100..1106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000620-2"
FT BINDING 1159..1160
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000620-2"
FT BINDING 1173
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000620-2"
SQ SEQUENCE 1378 AA; 156111 MW; F1CF6504EA99B85E CRC64;
MGAARPLTVG LPPLLLLLLL LLSSSCSLSS GEVCPSMDIR NNLTQLNMLE RCSVIEGSLQ
ILLMFKTKPE DFRDLSFPRL TMITEYLLLF RVYGLESLKD LFPNLTVIRG SRLFFNYALV
IFEMVHLKEI GLYNLMNITR GAVRIEKNNE LCYLSTIDWS QILDSVEDNY IVDNKDGKEE
CGDVCPGAVK GVNSCKSTVI NGQFIERCWT HSHCQKVCPP SCKWQGCTAS GQCCHSECLG
NCIEPNNPEK CVACRNFYLD GKCVETCPPN YYHFQDWRCV NFSVCQELHN KCKNSRQSSC
SQYVIHNNKC IPECPSGYTM NSTNLHCSPC SGPCPKVCDI VADQTIDSVH AAQALRGCTV
INGSLIINIR GGNNIAAELE ANLGLIEEIT GYLKIRRSYA LVSLSFFRKL HLIRGETLEI
GNYSFYALDN QNLRQLWDWS KHNLTITKGK LFFHYNPKLC LSEIHKMEEV SGTKGRQERN
DIALKTNGDQ ASCENELLRF SSIRTTHDKI LLRWEPYWPP DFRDLLGFML FYKEAPYQNV
TEFDGQDACG SNSWTVIDVE PPVRSNDPKT QNQHPGWLMR NLKPWTQYAI FVKTLVTFSD
ERRTYGAKSE IIYVQTNATV PSVPLDPISV SNSSSQIILK WKPPSEPNGN ITHYLVYWEK
QAEDVELYEL DYCLKGLKLP SRTWSPPFES EDSQKHNQSN HEDPNGECCS CPKTDSQILK
ELEESSFRKT FENYLHNEVF IPRKASSGIG ADDSRPSRRR RDLRFRVANV TVVTPTGSSF
FNASSTTAPA STEEPKPFEK VKSKESLVIS GLQHFTGYRI ELQACNHDEQ ESRCGLAAYV
SARTMPEAKA DDIVGAVTHE VLEHNIVHLR WQEPKHPNGL IILYEVNYWR VGDTEELHLC
VSRKHYANEQ GCRLRGLQPG NYTVRIRATS LAGNGSWTEH TYFYVADYLD VPSNIAKIII
GPVIIAIFLV SMVGAIYVFV KKRQTEGPTG PLFASSNPEY LSASDVYVPD EWEVAREKIS
LLRELGQGSF GMVYEGNAKD IVKGEAETRV AVKTVNESAS LRERIEFLNE ASVMKGFSCH
HVVRLLGVVS KGQPTLVVME LMVHGDLKSY LRSLRPEAEN NPGRPPPTLR EIIQMAVEIA
DGMAYLNAKK FVHRDLAARN CMVAEDFTVK IGDFGMTRDI YETDYYRKGG KGLLPVRWMA
PESLKDGVFT TYSDVWSFGV VLWEISSLAE QPYQGLSNEQ VLKFVMDGGY LDQPDNCPER
VNSLMQMCWQ YNPKMRPTFI EIIEMLKDDL HPSFREVSFF YSEENKPPES EEFEMDFENM
ESIPLDPSSY SQRDEVLGRD NGPSLGLKGN YEERIPYTHM NGGKKNGRIL SLPRSNPS
//