ID INSRR_RAT Reviewed; 1300 AA.
AC Q64716; Q63146;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 3.
DT 27-MAR-2024, entry version 162.
DE RecName: Full=Insulin receptor-related protein;
DE Short=IRR;
DE EC=2.7.10.1;
DE AltName: Full=IR-related receptor;
DE Flags: Precursor;
GN Name=Insrr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-481, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley, and Wistar; TISSUE=Kidney, Liver, and Stomach;
RX PubMed=1603082; DOI=10.1210/mend.6.5.1603082;
RA Shier P., Watt V.M.;
RT "Tissue-specific expression of the rat insulin receptor-related receptor
RT gene.";
RL Mol. Endocrinol. 6:723-729(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 896-996, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=1530648; DOI=10.1016/0006-291x(92)91287-z;
RA Kurachi H., Jobo K., Ohta M., Kawasaki T., Itoh N.;
RT "A new member of the insulin receptor family, insulin receptor-related
RT receptor, is expressed preferentially in the kidney.";
RL Biochem. Biophys. Res. Commun. 187:934-939(1992).
RN [4]
RP FUNCTION, AND AUTOPHOSPHORYLATION.
RX PubMed=21641549; DOI=10.1016/j.cmet.2011.03.022;
RA Deyev I.E., Sohet F., Vassilenko K.P., Serova O.V., Popova N.V.,
RA Zozulya S.A., Burova E.B., Houillier P., Rzhevsky D.I., Berchatova A.A.,
RA Murashev A.N., Chugunov A.O., Efremov R.G., Nikol'sky N.N., Bertelli E.,
RA Eladari D., Petrenko A.G.;
RT "Insulin receptor-related receptor as an extracellular alkali sensor.";
RL Cell Metab. 13:679-689(2011).
CC -!- FUNCTION: Receptor with tyrosine-protein kinase activity. Functions as
CC a pH sensing receptor which is activated by increased extracellular pH.
CC Activates an intracellular signaling pathway that involves IRS1 and
CC AKT1/PKB. {ECO:0000269|PubMed:21641549}.
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:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Probable tetramer of 2 alpha and 2 beta chains linked by
CC disulfide bonds. The alpha chains contribute to the formation of the
CC ligand-binding domain, while the beta chains carry the kinase domain
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed preferentially in the kidney. Also found
CC in stomach and thymus but not in skeletal muscle, brain, intestine, and
CC uterus. {ECO:0000269|PubMed:1530648, ECO:0000269|PubMed:1603082}.
CC -!- DOMAIN: The extracellular domain is required for sensing alterations in
CC external pH. {ECO:0000250}.
CC -!- PTM: Autophosphorylated on tyrosine residues between pH 7.9 and pH
CC 10.5.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AABR03012734; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M90661; AAB59692.1; -; mRNA.
DR EMBL; M90660; AAA41452.1; -; Genomic_DNA.
DR EMBL; D12678; BAA20982.1; -; mRNA.
DR PIR; PC1130; PC1130.
DR RefSeq; NP_071548.2; NM_022212.2.
DR AlphaFoldDB; Q64716; -.
DR SMR; Q64716; -.
DR STRING; 10116.ENSRNOP00000073224; -.
DR GlyCosmos; Q64716; 10 sites, No reported glycans.
DR GlyGen; Q64716; 10 sites.
DR iPTMnet; Q64716; -.
DR PhosphoSitePlus; Q64716; -.
DR jPOST; Q64716; -.
DR PaxDb; 10116-ENSRNOP00000018638; -.
DR Ensembl; ENSRNOT00000080693.3; ENSRNOP00000073224.1; ENSRNOG00000057702.3.
DR GeneID; 60663; -.
DR KEGG; rno:60663; -.
DR UCSC; RGD:67399; rat.
DR AGR; RGD:67399; -.
DR CTD; 3645; -.
DR RGD; 67399; Insrr.
DR eggNOG; KOG1095; Eukaryota.
DR eggNOG; KOG4258; Eukaryota.
DR GeneTree; ENSGT00940000160437; -.
DR HOGENOM; CLU_000288_166_0_1; -.
DR InParanoid; Q64716; -.
DR OMA; IQRGHVY; -.
DR OrthoDB; 1614410at2759; -.
DR TreeFam; TF351636; -.
DR PRO; PR:Q64716; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000057702; Expressed in kidney and 6 other cell types or tissues.
DR Genevisible; Q64716; RN.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005899; C:insulin receptor complex; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0043548; F:phosphatidylinositol 3-kinase binding; IEA:InterPro.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0071469; P:cellular response to alkaline pH; ISO:RGD.
DR GO; GO:0030238; P:male sex determination; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00063; FN3; 3.
DR CDD; cd00064; FU; 1.
DR CDD; cd05032; PTKc_InsR_like; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 3.
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; 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:SF338; INSULIN RECEPTOR-RELATED PROTEIN; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR Pfam; PF00757; Furin-like; 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; 1.
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; 3.
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 1: Evidence at protein level;
KW ATP-binding; Disulfide bond; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1300
FT /note="Insulin receptor-related protein"
FT /id="PRO_0000016707"
FT TOPO_DOM 747..921
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 922..942
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 943..1300
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 483..603
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 607..707
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 818..913
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 979..1254
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1270..1300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1115
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 985..993
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1013
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1145
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1146
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 492
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 528
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 616
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 634
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 756
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 885
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 898
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 214..222
FT /evidence="ECO:0000250"
FT DISULFID 216..228
FT /evidence="ECO:0000250"
FT DISULFID 229..237
FT /evidence="ECO:0000250"
FT DISULFID 233..246
FT /evidence="ECO:0000250"
FT DISULFID 249..258
FT /evidence="ECO:0000250"
FT DISULFID 262..274
FT /evidence="ECO:0000250"
FT DISULFID 280..300
FT /evidence="ECO:0000250"
FT DISULFID 304..317
FT /evidence="ECO:0000250"
FT DISULFID 320..324
FT /evidence="ECO:0000250"
FT DISULFID 657..864
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000255"
FT CONFLICT 261
FT /note="T -> A (in Ref. 2; AAB59692)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="L -> M (in Ref. 2; AAB59692)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1300 AA; 144846 MW; 0CF24D5B96D68225 CRC64;
MAVPALWPWG VYLLMSLLSL GSCLDTLEVC PSLDIRSEVT ELRRLENCSV VEGHLQILLM
FAATGEDFRG LSFPRLTQVT DYLLLFRVYG LESLRDLFPN LAVIRGARLF LGYALIIFEM
PHLRDIGLPS LGAVLRGAVR VEKNQELCHL STIDWGLLQP APGANHIVGN KLGEECADVC
PGVLGAAGEP CVRTTFGGHT DYRCWTSSHC QRVCPCPRGL ACTVGGECCH SECLGGCSQP
EDPRACVACR HLYFQGVCLP TCPPGTYQYE SWRCVTAELC GHLREVPGHA TAFGIYEGSC
LAQCPPGFTR NGSSIFCHKC EGLCPKECKV GTKTIDSVQA TQDLVGCTHV EGSLILNLRQ
GYNLEPELQR NLGLVETITG FLKIKHSFAL VTLGFFKNLK LIRGDSMVDG NYTLYVLDNQ
NLQQLGSWVA AGLTIPVGKI YFAFNPRLCL EHIYQLEEVT GTRGRQSKAE INPRTNGDRA
ACQTRTLRFV FNLTEEDRIL LRWERYEPLE ARDLLSFIVY YKESPFQNAT EHVGPDACGT
QSWNLLDVEL PLSRTQEPGV TLAPLKPWTQ YAVFVRAITL TTAEDSPHQG AQSPIVYLRT
LPAAPTVPQD VISTSNSSSH LLVRWKPPVQ RNGNITYYLV LWQRLAEDGD LYINDYCHRG
LRLPTSSHDT RFDREDPALE AEPEQGCCPC QHSPPGQALP ALEAQEVTFQ KKFENFLHHA
ITIPKAPWKV TSINKNPQRD SERHRRETGL LRLGKNNSDF EIHEDKVPRE RAVLSGLRHF
TEYRIDIHAC NHAAHTVGCS AATFVFARTM PHREADGIPG KVVWKAVGKS SVILHWLEPP
DPNGLILKYE IKYRRLGEEA TVLCVSRLRY AKVGGVHLAL LPPGNYSAKV RATSLAGNGS
WTDGVAFYIT GPEEEDTGGL RILLTVTPVG FMLLVMLAAL GFFYSKKRNS TLYTSVNPEY
FSASHMYVPD EWEVPREQIA IIRELGQGSF GMVYEGLARG LEAGEESTPV ALKTVNELAS
ARERVEFLKE ASVMKAFKCH HVVRLLGVVS QGQPTLVIME LMTRGDLKSH LRSLRPEAEN
NPGLPQPALS DMIQMAGEIA DGMAYLAAKK FVHRDLAARN CMVSQDFTVK IGDFGMTRDV
YETDYYRKGG KGLLPVRWMA PESLKDGIFT THSDVWSFGV VLWEIVTLAE QPYQGLSNEQ
VLKFVMDGGV LEEQEDCPIQ LQELMRRCWQ HTPRLRPTFV HILDRIQDEL RPSFRLCSFY
YSPECQRGQA SLLPTEAEPD SPPTLNGASD YGPPNGDPGH
//
