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Q9WTL4 (INSRR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Insulin receptor-related protein
Short name=IRR
EC=2.7.10.1
Alternative name(s):
IR-related receptor

Cleaved into the following 2 chains:

  1. Insulin receptor-related protein alpha chain
  2. Insulin receptor-related protein beta chain
Gene names
Name:Insrr
Synonyms:Irr
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length1300 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB. Ref.5

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Probable tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chains carry the kinase domain By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein By similarity.

Tissue specificity

Highly expressed in the islets as well as in pancreatic beta-cells. Ref.1

Domain

The extracellular domain is required for sensing alterations in external pH By similarity.

Post-translational modification

Autophosphorylated on tyrosine residues between pH 7.9 and pH 10.5. Ref.5

Disruption phenotype

Renal function is impaired, with reduced ability of the collecting duct to adapt to alkalosis. Ref.4 Ref.5

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 3 fibronectin type-III domains.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 13001274Insulin receptor-related protein
PRO_0000016704
Chain27 – 742716Insulin receptor-related protein alpha chain Probable
PRO_0000016705
Chain747 – 1300554Insulin receptor-related protein beta chain Probable
PRO_0000016706

Regions

Topological domain747 – 921175Extracellular Potential
Transmembrane922 – 94322Helical; Potential
Topological domain944 – 1300357Cytoplasmic Potential
Domain484 – 594111Fibronectin type-III 1
Domain605 – 69591Fibronectin type-III 2
Domain815 – 91197Fibronectin type-III 3
Domain979 – 1254276Protein kinase
Nucleotide binding985 – 9939ATP By similarity

Sites

Active site11151Proton acceptor By similarity
Binding site10131ATP By similarity

Amino acid modifications

Modified residue11451Phosphotyrosine; by autocatalysis By similarity
Modified residue11461Phosphotyrosine; by autocatalysis By similarity
Glycosylation471N-linked (GlcNAc...) Potential
Glycosylation1001N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Potential
Glycosylation4111N-linked (GlcNAc...) Potential
Glycosylation4921N-linked (GlcNAc...) Potential
Glycosylation5281N-linked (GlcNAc...) Potential
Glycosylation6161N-linked (GlcNAc...) Potential
Glycosylation6341N-linked (GlcNAc...) Potential
Glycosylation7561N-linked (GlcNAc...) Potential
Glycosylation8851N-linked (GlcNAc...) Potential
Glycosylation8981N-linked (GlcNAc...) Potential
Disulfide bond214 ↔ 222 By similarity
Disulfide bond216 ↔ 228 By similarity
Disulfide bond229 ↔ 237 By similarity
Disulfide bond233 ↔ 246 By similarity
Disulfide bond249 ↔ 258 By similarity
Disulfide bond262 ↔ 274 By similarity
Disulfide bond280 ↔ 300 By similarity
Disulfide bond304 ↔ 317 By similarity
Disulfide bond320 ↔ 324 By similarity
Disulfide bond657 ↔ 864Interchain (between alpha and beta chains) Potential

Experimental info

Sequence conflict2721W → G in BAA77835. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9WTL4 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 3DE9FC3C53DB96BB

FASTA1,300144,875
        10         20         30         40         50         60 
MAVPALWPWG VHLLMSLLSL GSGLDTLEVC PSLDIRSEVT ELRRLENCSV VEGHLQILLM 

        70         80         90        100        110        120 
FAATGEDFRG LSFPRLTQVT DYLLLFRVYG LESLRDLFPN LTVIRGTRLF LGYALIIFEM 

       130        140        150        160        170        180 
PHLRDVGLPS LGAVLRGAVR VEKNQELCHL STIDWGLLQP APGTNHIVGN KLGEECADVC 

       190        200        210        220        230        240 
PGVLGAAGEP CSRTTFSGRT DYRCWTSSHC QKVCPCPRGM ACTAGGDCCH SECLGGCSQP 

       250        260        270        280        290        300 
EDPRACVACR HLYFQGVCLR ACPPGTYQYE SWRCVTAELC AHLREVPGLA TTFGIYEGSC 

       310        320        330        340        350        360 
LAQCPPGFTR NGSSIFCHKC EGLCPKECKV GTKTIDSVQA TQDLVGCTHV EGNLILNLRQ 

       370        380        390        400        410        420 
GYNLEPELQR NLGLVETITG FLKIKHSFAL VTLGFFKNLK LIRGDSMVDG NYTLYVLDNQ 

       430        440        450        460        470        480 
NLQQLGSWVT AGLTIPVGKI YFAFNPRLCL EHIYQLEEVT GTRGRQSKAE INPRTNGDRA 

       490        500        510        520        530        540 
ACQTRTLRFV FNLTEEDRIL LRWERYEPLE ARDLLSFIVY YKESPFQNAT EHVGPDACGT 

       550        560        570        580        590        600 
QSWNLLDVEL PLSRTQEPGV TLAPLKPWTQ YAVFVRAITL TTAEDSPHQG AQSPIVYLRT 

       610        620        630        640        650        660 
LPAAPTVPQD VISTSNSSSH LLVRWKPPVQ RNGNITYYLV LWQRLAEDGD LYINDYCHRG 

       670        680        690        700        710        720 
LRLPTSSHDT RFDREDPALE AEPEQGCCPC QHSPPGQALP ALEAQEVTFQ KKFENFLHHA 

       730        740        750        760        770        780 
ITIPKAPWKV TSINKNPQRD SERHRREAGL LRLGKNNSDF EIQEDKVPRE RAILSGLRHF 

       790        800        810        820        830        840 
TEYRIDIHAC NHAAHTVGCS AATFVFARTM PHREADGIPG KVAWKAAGKS SVTLHWLEPP 

       850        860        870        880        890        900 
DPNGLILKYE IKYRRLGEEA TVLCVSRLRY AKVGGVHLAL LPPGNYSAKV RATSLAGNGS 

       910        920        930        940        950        960 
WTDGVTFYIT DLEEEDTGGM RIFLTVTPVG FMLLVTLAAL GFFYSRKRNS TLYTSVNPEY 

       970        980        990       1000       1010       1020 
FSASHMYVPD EWEVPREQIA IIRELGQGSF GMVYEGLARG LEAGEESTPV ALKTVNELAS 

      1030       1040       1050       1060       1070       1080 
ARERVEFLKE ASVMKAFKCH HVVRLLGVVS QGQPTLVIME LMTRGDLKSH LRSLRPEAEN 

      1090       1100       1110       1120       1130       1140 
NPGLPQPALS DMIQMAGEIA DGMAYLAAKK FVHRDLAARN CMVSQDFTVK IGDFGMTRDV 

      1150       1160       1170       1180       1190       1200 
YETDYYRKGG KGLLPVRWMA PESLKDGIFT THSDVWSFGV VLWEIVTLAE QPYQGLSNEQ 

      1210       1220       1230       1240       1250       1260 
VLKFVMDGGV LEELENCPIQ LQELMRLCWQ HSPRLRPTFV HILDRIQDEL RPSFRLCSFY 

      1270       1280       1290       1300 
YSPECQRGQA SLLPTEAEPD SPPTLNGASD YSAPNGGPGH

« Hide

References

« Hide 'large scale' references
[1]"Insulin receptor-related receptor is expressed in pancreatic beta-cells and stimulates tyrosine phosphorylation of insulin receptor substrate-1 and-2."
Hirayama I., Tamemoto H., Yokota H., Kubo S.-K., Wang J., Kuwano H., Nagamachi Y., Takeuchi T., Izumi T.
Diabetes 48:1237-1244(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Pancreas.
[2]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[4]"Preserved pancreatic beta-cell development and function in mice lacking the insulin receptor-related receptor."
Kitamura T., Kido Y., Nef S., Merenmies J., Parada L.F., Accili D.
Mol. Cell. Biol. 21:5624-5630(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"Insulin receptor-related receptor as an extracellular alkali sensor."
Deyev I.E., Sohet F., Vassilenko K.P., Serova O.V., Popova N.V., Zozulya S.A., Burova E.B., Houillier P., Rzhevsky D.I., Berchatova A.A., Murashev A.N., Chugunov A.O., Efremov R.G., Nikol'sky N.N., Bertelli E., Eladari D., Petrenko A.G.
Cell Metab. 13:679-689(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, AUTOPHOSPHORYLATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AB007135 mRNA. Translation: BAA77835.1.
CH466547 Genomic DNA. Translation: EDL15346.1.
BC137855 mRNA. Translation: AAI37856.1.
IPIIPI00123516.
RefSeqNP_035962.2. NM_011832.2.
UniGeneMm.42041.

3D structure databases

ProteinModelPortalQ9WTL4.
SMRQ9WTL4. Positions 28-911, 913-1262.
ModBaseSearch...

PTM databases

PhosphoSiteQ9WTL4.

Proteomic databases

PaxDbQ9WTL4.
PRIDEQ9WTL4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029711; ENSMUSP00000029711; ENSMUSG00000005640.
ENSMUST00000107582; ENSMUSP00000103208; ENSMUSG00000005640.
GeneID23920.
KEGGmmu:23920.

Organism-specific databases

CTD3645.
MGIMGI:1346037. Insrr.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00690000101688.
HOGENOMHOG000038045.
HOVERGENHBG006134.
InParanoidB2RQC5.
KOK05086.
OMAARTMPHR.
OrthoDBEOG4DFPMM.

Gene expression databases

ArrayExpressQ9WTL4.
BgeeQ9WTL4.
CleanExMM_INSRR.
GenevestigatorQ9WTL4.
GermOnlineENSMUSG00000005640. Mus musculus.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR000494. EGF_rcpt_L.
IPR003961. Fibronectin_type3.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016246. Tyr_kinase_insulin-like_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PfamPF00041. fn3. 1 hit.
PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFPIRSF000620. Insulin_receptor. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 3 hits.
SM00261. FU. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. FN_III-like. 3 hits.
SSF57184. Grow_fac_recept. 1 hit.
SSF56112. Kinase_like. 1 hit.
PROSITEPS50853. FN3. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio303697.
SOURCESearch...

Entry information

Entry nameINSRR_MOUSE
AccessionPrimary (citable) accession number: Q9WTL4
Secondary accession number(s): B2RQC5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: July 27, 2011
Last modified: May 1, 2013
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents