INSRR_CAVPO
ID INSRR_CAVPO Reviewed; 1300 AA.
AC P14617;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 164.
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;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2768234; DOI=10.1016/s0021-9258(18)63737-8;
RA Shier P., Watt V.M.;
RT "Primary structure of a putative receptor for a ligand of the insulin
RT family.";
RL J. Biol. Chem. 264:14605-14608(1989).
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 (By similarity). {ECO:0000250}.
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 -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
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. {ECO:0000250}.
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; J05047; AAA37044.1; -; Genomic_DNA.
DR PIR; A36502; A36502.
DR RefSeq; XP_003475448.1; XM_003475400.2.
DR AlphaFoldDB; P14617; -.
DR SMR; P14617; -.
DR STRING; 10141.ENSCPOP00000017876; -.
DR Ensembl; ENSCPOT00000003232; ENSCPOP00000002888; ENSCPOG00000003189.
DR GeneID; 100716566; -.
DR KEGG; cpoc:100716566; -.
DR CTD; 3645; -.
DR eggNOG; KOG1095; Eukaryota.
DR eggNOG; KOG4258; Eukaryota.
DR GeneTree; ENSGT00940000160437; -.
DR HOGENOM; CLU_000288_166_0_1; -.
DR InParanoid; P14617; -.
DR OrthoDB; 223327at2759; -.
DR BRENDA; 2.7.10.1; 1225.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000003189; Expressed in adult mammalian kidney and 3 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0043235; C:receptor complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043560; F:insulin receptor substrate binding; IEA:InterPro.
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; ISS:UniProtKB.
DR GO; GO:0030238; P:male sex determination; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro.
DR CDD; cd00063; FN3; 3.
DR CDD; cd00064; FU; 1.
DR Gene3D; 2.60.40.10; -; 4.
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 3: Inferred from homology;
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 CHAIN 27..746
FT /note="Insulin receptor-related protein alpha chain"
FT /evidence="ECO:0000305"
FT /id="PRO_0000016699"
FT CHAIN 747..1300
FT /note="Insulin receptor-related protein beta chain"
FT /evidence="ECO:0000305"
FT /id="PRO_0000016700"
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..912
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 740..762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1270..1300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1270..1292
FT /note="Polar residues"
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 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"
SQ SEQUENCE 1300 AA; 144518 MW; 3344DF4B6A57B24F CRC64;
MARPKLWPWG ILLLVSLLSA GFNLDTMNVC PSLDIRSEVA ELRRLENCSV VEGHLQILLM
FTATGEDFRS LSFPHLTQVT DYLLLFRVYG LESLRDLFPN LAVIRGAHLF LGYALVIFEM
PHLRDVGLPA LGAVLHGSVR VEKNQELCHL STIDWGLLQP TPSTNYIVGN KLGEECADVC
PGTLGAAGEP CARTTFNGHT DYRCWTSSHC QRVCPCPQGL ACTISGECCH TECLGGCSQP
EDPRACVACR HFYYQSACHR ACPLGTYEHE SWRCVTAESC ANLRSVPGRA STFGIHQGKC
LAQCPPGFTR NGSSIFCHKC EGLCPKECKV GTKTIDSVQA AQDLVGCTHV EGSLILNLRR
GYNLEPELQR SLGLVETITG FLKIKHSFAL VSLSFFKNLK LIRGDTMVDG NYTLYVLDNQ
NLQQLGPWVS AGLTIPVGKI YFAFNPRLCL EHIYRLEEVT GTRGRQNKAE INPRTNGDRA
ACQTRTLRFV SNVTEADRIL LRWERYEPLE ARDLLSFIVY YKESPFQNAT EHVGPDACGS
QSWNLLDVEL PLSRTQEPGV ILAPLKPWTQ YAVFVRAITL TTAEDSPHQG AQSPIVYLWT
LPAAPTVPQD VISSSNSSSH LLVRWKPPTQ RNGNITYYLV LWQRLAEDGD LYLNDYCHRG
LRLPTSNHDP RFDREDGDLE AELELGCCPC QHAPPGQVLP ALEAQEASFQ KKFENFLHNA
ITIPKPPWKV TSIHRNLQRD AGRHRRAIGS PRPGGNSSDF EIQEDKVPRE RAVLGGLRHF
TEYRIDIHAC NHAAHIVGCS AATFVFARTM PRREADDIPG KLSWEAASKS SVLLRWFEPP
DPNGLILKYE IKYRRLGEEA TVLCVSRLRY AKVGGVQLAL LPPGNYSARV RATSLAGNGS
WTDSVAFYIP GPEEEDSGGL HILLTVTPAG LMLLIILAAL GFFYSRKRNG TLYTSVNPEY
LSASDMYIPD EWEVPREQIS IIRELGQGSF GMVYEGVAKG LEAGEESTPV ALKTVNELAS
PRERIEFLKE ASVMKAFQCH HVVRLLGVVS QGQPTLVIME LMTRGDLKSH LRSLRPEAEN
NPGIPRPALG DMIQMAGEIA DGMAYLAANK FVHRDLAARN CMVSQDFTVK IGDFGMTRDV
YETDYYRKGG KGLLPVRWMA PESLKDGIFT THSDVWSFGV VLWEIVTLAE QPYQGLSNEQ
VLKFVMDGGV LEELEDCPHQ LQELMSSCWQ QNPRLRPTFT QILNSIQKEL RPSFRLLSFY
HSPECQGGCG LQPTTDAESS SPPTSKGASD CSLQNGGPEH
