INSRR_MOUSE
ID INSRR_MOUSE Reviewed; 1300 AA.
AC Q9WTL4; B2RQC5;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Insulin receptor-related protein;
DE Short=IRR;
DE EC=2.7.10.1;
DE AltName: Full=IR-related receptor;
DE Contains:
DE RecName: Full=Insulin receptor-related protein alpha chain;
DE Contains:
DE RecName: Full=Insulin receptor-related protein beta chain;
DE Flags: Precursor;
GN Name=Insrr; Synonyms=Irr;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Pancreas;
RX PubMed=10342810; DOI=10.2337/diabetes.48.6.1237;
RA Hirayama I., Tamemoto H., Yokota H., Kubo S.-K., Wang J., Kuwano H.,
RA Nagamachi Y., Takeuchi T., Izumi T.;
RT "Insulin receptor-related receptor is expressed in pancreatic beta-cells
RT and stimulates tyrosine phosphorylation of insulin receptor substrate-1
RT and-2.";
RL Diabetes 48:1237-1244(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 DISRUPTION PHENOTYPE.
RX PubMed=11463843; DOI=10.1128/mcb.21.16.5624-5630.2001;
RA Kitamura T., Kido Y., Nef S., Merenmies J., Parada L.F., Accili D.;
RT "Preserved pancreatic beta-cell development and function in mice lacking
RT the insulin receptor-related receptor.";
RL Mol. Cell. Biol. 21:5624-5630(2001).
RN [5]
RP DISRUPTION PHENOTYPE, 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: Highly expressed in the islets as well as in
CC pancreatic beta-cells. {ECO:0000269|PubMed:10342810}.
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 -!- DISRUPTION PHENOTYPE: Renal function is impaired, with reduced ability
CC of the collecting duct to adapt to alkalosis.
CC {ECO:0000269|PubMed:11463843, ECO:0000269|PubMed:21641549}.
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; AB007135; BAA77835.1; -; mRNA.
DR EMBL; CH466547; EDL15346.1; -; Genomic_DNA.
DR EMBL; BC137855; AAI37856.1; -; mRNA.
DR CCDS; CCDS17454.1; -.
DR RefSeq; NP_035962.2; NM_011832.2.
DR AlphaFoldDB; Q9WTL4; -.
DR SMR; Q9WTL4; -.
DR BioGRID; 204794; 3.
DR STRING; 10090.ENSMUSP00000029711; -.
DR GlyGen; Q9WTL4; 11 sites.
DR iPTMnet; Q9WTL4; -.
DR PhosphoSitePlus; Q9WTL4; -.
DR PaxDb; Q9WTL4; -.
DR PeptideAtlas; Q9WTL4; -.
DR PRIDE; Q9WTL4; -.
DR ProteomicsDB; 267251; -.
DR Antibodypedia; 20446; 393 antibodies from 34 providers.
DR DNASU; 23920; -.
DR Ensembl; ENSMUST00000029711; ENSMUSP00000029711; ENSMUSG00000005640.
DR Ensembl; ENSMUST00000107582; ENSMUSP00000103208; ENSMUSG00000005640.
DR GeneID; 23920; -.
DR KEGG; mmu:23920; -.
DR UCSC; uc008psy.2; mouse.
DR CTD; 3645; -.
DR MGI; MGI:1346037; Insrr.
DR VEuPathDB; HostDB:ENSMUSG00000005640; -.
DR eggNOG; KOG1095; Eukaryota.
DR eggNOG; KOG4258; Eukaryota.
DR GeneTree; ENSGT00940000160437; -.
DR HOGENOM; CLU_000288_166_0_1; -.
DR InParanoid; Q9WTL4; -.
DR OMA; GTRGRWQ; -.
DR OrthoDB; 223327at2759; -.
DR PhylomeDB; Q9WTL4; -.
DR TreeFam; TF351636; -.
DR BioGRID-ORCS; 23920; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Insrr; mouse.
DR PRO; PR:Q9WTL4; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9WTL4; protein.
DR Bgee; ENSMUSG00000005640; Expressed in islet of Langerhans and 45 other tissues.
DR Genevisible; Q9WTL4; MM.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005899; C:insulin receptor complex; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
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:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0071469; P:cellular response to alkaline pH; IDA:UniProtKB.
DR GO; GO:0030238; P:male sex determination; IMP:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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 Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.80.20.20; -; 2.
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; IPR028792; INSRR.
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; PTHR24416:SF338; 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; SSF49265; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 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; Cleavage on pair of basic residues; Disulfide bond;
KW Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1300
FT /note="Insulin receptor-related protein"
FT /id="PRO_0000016704"
FT CHAIN 27..742
FT /note="Insulin receptor-related protein alpha chain"
FT /evidence="ECO:0000305"
FT /id="PRO_0000016705"
FT CHAIN 747..1300
FT /note="Insulin receptor-related protein beta chain"
FT /evidence="ECO:0000305"
FT /id="PRO_0000016706"
FT TOPO_DOM 747..921
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 922..943
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 944..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 1273..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 100
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 272
FT /note="W -> G (in Ref. 1; BAA77835)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1300 AA; 144875 MW; 3DE9FC3C53DB96BB CRC64;
MAVPALWPWG VHLLMSLLSL GSGLDTLEVC PSLDIRSEVT ELRRLENCSV VEGHLQILLM
FAATGEDFRG LSFPRLTQVT DYLLLFRVYG LESLRDLFPN LTVIRGTRLF LGYALIIFEM
PHLRDVGLPS LGAVLRGAVR VEKNQELCHL STIDWGLLQP APGTNHIVGN KLGEECADVC
PGVLGAAGEP CSRTTFSGRT DYRCWTSSHC QKVCPCPRGM ACTAGGDCCH SECLGGCSQP
EDPRACVACR HLYFQGVCLR ACPPGTYQYE SWRCVTAELC AHLREVPGLA TTFGIYEGSC
LAQCPPGFTR NGSSIFCHKC EGLCPKECKV GTKTIDSVQA TQDLVGCTHV EGNLILNLRQ
GYNLEPELQR NLGLVETITG FLKIKHSFAL VTLGFFKNLK LIRGDSMVDG NYTLYVLDNQ
NLQQLGSWVT 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 SERHRREAGL LRLGKNNSDF EIQEDKVPRE RAILSGLRHF
TEYRIDIHAC NHAAHTVGCS AATFVFARTM PHREADGIPG KVAWKAAGKS SVTLHWLEPP
DPNGLILKYE IKYRRLGEEA TVLCVSRLRY AKVGGVHLAL LPPGNYSAKV RATSLAGNGS
WTDGVTFYIT DLEEEDTGGM RIFLTVTPVG FMLLVTLAAL GFFYSRKRNS 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 LEELENCPIQ LQELMRLCWQ HSPRLRPTFV HILDRIQDEL RPSFRLCSFY
YSPECQRGQA SLLPTEAEPD SPPTLNGASD YSAPNGGPGH
