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Q9WTL4

- INSRR_MOUSE

UniProt

Q9WTL4 - INSRR_MOUSE

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Protein

Insulin receptor-related protein

Gene
Insrr, Irr
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei1013 – 10131ATP By similarity
Active sitei1115 – 11151Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi985 – 9939ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. actin cytoskeleton reorganization Source: UniProtKB
  2. cellular response to alkalinity Source: UniProtKB
  3. male sex determination Source: MGI
  4. peptidyl-tyrosine phosphorylation Source: GOC
  5. protein autophosphorylation Source: UniProtKB
  6. transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin receptor-related protein (EC:2.7.10.1)
Short name:
IRR
Alternative name(s):
IR-related receptor
Cleaved into the following 2 chains:
Gene namesi
Name:Insrr
Synonyms:Irr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 3

Organism-specific databases

MGIiMGI:1346037. Insrr.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini747 – 921175Extracellular Reviewed predictionAdd
BLAST
Transmembranei922 – 94322Helical; Reviewed predictionAdd
BLAST
Topological domaini944 – 1300357Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: InterPro
  2. receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

Renal function is impaired, with reduced ability of the collecting duct to adapt to alkalosis.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626 Reviewed predictionAdd
BLAST
Chaini27 – 13001274Insulin receptor-related proteinPRO_0000016704Add
BLAST
Chaini27 – 742716Insulin receptor-related protein alpha chain InferredPRO_0000016705Add
BLAST
Chaini747 – 1300554Insulin receptor-related protein beta chain InferredPRO_0000016706Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi47 – 471N-linked (GlcNAc...) Reviewed prediction
Glycosylationi100 – 1001N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi214 ↔ 222 By similarity
Disulfide bondi216 ↔ 228 By similarity
Disulfide bondi229 ↔ 237 By similarity
Disulfide bondi233 ↔ 246 By similarity
Disulfide bondi249 ↔ 258 By similarity
Disulfide bondi262 ↔ 274 By similarity
Disulfide bondi280 ↔ 300 By similarity
Disulfide bondi304 ↔ 317 By similarity
Glycosylationi311 – 3111N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi320 ↔ 324 By similarity
Glycosylationi411 – 4111N-linked (GlcNAc...) Reviewed prediction
Glycosylationi492 – 4921N-linked (GlcNAc...) Reviewed prediction
Glycosylationi528 – 5281N-linked (GlcNAc...) Reviewed prediction
Glycosylationi616 – 6161N-linked (GlcNAc...) Reviewed prediction
Glycosylationi634 – 6341N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi657 ↔ 864Interchain (between alpha and beta chains) Reviewed prediction
Glycosylationi756 – 7561N-linked (GlcNAc...) Reviewed prediction
Glycosylationi885 – 8851N-linked (GlcNAc...) Reviewed prediction
Glycosylationi898 – 8981N-linked (GlcNAc...) Reviewed prediction
Modified residuei1145 – 11451Phosphotyrosine; by autocatalysis By similarity
Modified residuei1146 – 11461Phosphotyrosine; by autocatalysis By similarity

Post-translational modificationi

Autophosphorylated on tyrosine residues between pH 7.9 and pH 10.5.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9WTL4.
PRIDEiQ9WTL4.

PTM databases

PhosphoSiteiQ9WTL4.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ9WTL4.
CleanExiMM_INSRR.
GenevestigatoriQ9WTL4.

Interactioni

Subunit structurei

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.

Structurei

3D structure databases

ProteinModelPortaliQ9WTL4.
SMRiQ9WTL4. Positions 28-911, 913-1262.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini483 – 603121Fibronectin type-III 1Add
BLAST
Domaini607 – 707101Fibronectin type-III 2Add
BLAST
Domaini818 – 91396Fibronectin type-III 3Add
BLAST
Domaini979 – 1254276Protein kinaseAdd
BLAST

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00750000117239.
HOGENOMiHOG000038045.
HOVERGENiHBG006134.
InParanoidiB2RQC5.
KOiK05086.
OMAiFARTMPH.
OrthoDBiEOG73RB9N.
TreeFamiTF351636.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProiIPR000494. EGF_rcpt_L.
IPR003961. Fibronectin_type3.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR028792. INSRR.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PANTHERiPTHR24416:SF107. PTHR24416:SF107. 1 hit.
PfamiPF00041. fn3. 1 hit.
PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000620. Insulin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00060. FN3. 3 hits.
SM00261. FU. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS50853. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9WTL4-1 [UniParc]FASTAAdd to Basket

« Hide

MAVPALWPWG VHLLMSLLSL GSGLDTLEVC PSLDIRSEVT ELRRLENCSV     50
VEGHLQILLM FAATGEDFRG LSFPRLTQVT DYLLLFRVYG LESLRDLFPN 100
LTVIRGTRLF LGYALIIFEM PHLRDVGLPS LGAVLRGAVR VEKNQELCHL 150
STIDWGLLQP APGTNHIVGN KLGEECADVC PGVLGAAGEP CSRTTFSGRT 200
DYRCWTSSHC QKVCPCPRGM ACTAGGDCCH SECLGGCSQP EDPRACVACR 250
HLYFQGVCLR ACPPGTYQYE SWRCVTAELC AHLREVPGLA TTFGIYEGSC 300
LAQCPPGFTR NGSSIFCHKC EGLCPKECKV GTKTIDSVQA TQDLVGCTHV 350
EGNLILNLRQ GYNLEPELQR NLGLVETITG FLKIKHSFAL VTLGFFKNLK 400
LIRGDSMVDG NYTLYVLDNQ NLQQLGSWVT AGLTIPVGKI YFAFNPRLCL 450
EHIYQLEEVT GTRGRQSKAE INPRTNGDRA ACQTRTLRFV FNLTEEDRIL 500
LRWERYEPLE ARDLLSFIVY YKESPFQNAT EHVGPDACGT QSWNLLDVEL 550
PLSRTQEPGV TLAPLKPWTQ YAVFVRAITL TTAEDSPHQG AQSPIVYLRT 600
LPAAPTVPQD VISTSNSSSH LLVRWKPPVQ RNGNITYYLV LWQRLAEDGD 650
LYINDYCHRG LRLPTSSHDT RFDREDPALE AEPEQGCCPC QHSPPGQALP 700
ALEAQEVTFQ KKFENFLHHA ITIPKAPWKV TSINKNPQRD SERHRREAGL 750
LRLGKNNSDF EIQEDKVPRE RAILSGLRHF TEYRIDIHAC NHAAHTVGCS 800
AATFVFARTM PHREADGIPG KVAWKAAGKS SVTLHWLEPP DPNGLILKYE 850
IKYRRLGEEA TVLCVSRLRY AKVGGVHLAL LPPGNYSAKV RATSLAGNGS 900
WTDGVTFYIT DLEEEDTGGM RIFLTVTPVG FMLLVTLAAL GFFYSRKRNS 950
TLYTSVNPEY FSASHMYVPD EWEVPREQIA IIRELGQGSF GMVYEGLARG 1000
LEAGEESTPV ALKTVNELAS ARERVEFLKE ASVMKAFKCH HVVRLLGVVS 1050
QGQPTLVIME LMTRGDLKSH LRSLRPEAEN NPGLPQPALS DMIQMAGEIA 1100
DGMAYLAAKK FVHRDLAARN CMVSQDFTVK IGDFGMTRDV YETDYYRKGG 1150
KGLLPVRWMA PESLKDGIFT THSDVWSFGV VLWEIVTLAE QPYQGLSNEQ 1200
VLKFVMDGGV LEELENCPIQ LQELMRLCWQ HSPRLRPTFV HILDRIQDEL 1250
RPSFRLCSFY YSPECQRGQA SLLPTEAEPD SPPTLNGASD YSAPNGGPGH 1300
Length:1,300
Mass (Da):144,875
Last modified:July 27, 2011 - v2
Checksum:i3DE9FC3C53DB96BB
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti272 – 2721W → G in BAA77835. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB007135 mRNA. Translation: BAA77835.1.
CH466547 Genomic DNA. Translation: EDL15346.1.
BC137855 mRNA. Translation: AAI37856.1.
CCDSiCCDS17454.1.
RefSeqiNP_035962.2. NM_011832.2.
UniGeneiMm.42041.

Genome annotation databases

EnsembliENSMUST00000029711; ENSMUSP00000029711; ENSMUSG00000005640.
ENSMUST00000107582; ENSMUSP00000103208; ENSMUSG00000005640.
GeneIDi23920.
KEGGimmu:23920.
UCSCiuc008psy.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB007135 mRNA. Translation: BAA77835.1 .
CH466547 Genomic DNA. Translation: EDL15346.1 .
BC137855 mRNA. Translation: AAI37856.1 .
CCDSi CCDS17454.1.
RefSeqi NP_035962.2. NM_011832.2.
UniGenei Mm.42041.

3D structure databases

ProteinModelPortali Q9WTL4.
SMRi Q9WTL4. Positions 28-911, 913-1262.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei Q9WTL4.

Proteomic databases

PaxDbi Q9WTL4.
PRIDEi Q9WTL4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000029711 ; ENSMUSP00000029711 ; ENSMUSG00000005640 .
ENSMUST00000107582 ; ENSMUSP00000103208 ; ENSMUSG00000005640 .
GeneIDi 23920.
KEGGi mmu:23920.
UCSCi uc008psy.2. mouse.

Organism-specific databases

CTDi 3645.
MGIi MGI:1346037. Insrr.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00750000117239.
HOGENOMi HOG000038045.
HOVERGENi HBG006134.
InParanoidi B2RQC5.
KOi K05086.
OMAi FARTMPH.
OrthoDBi EOG73RB9N.
TreeFami TF351636.

Miscellaneous databases

NextBioi 303697.
PROi Q9WTL4.
SOURCEi Search...

Gene expression databases

Bgeei Q9WTL4.
CleanExi MM_INSRR.
Genevestigatori Q9WTL4.

Family and domain databases

Gene3Di 2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProi IPR000494. EGF_rcpt_L.
IPR003961. Fibronectin_type3.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR028792. INSRR.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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 ]
PANTHERi PTHR24416:SF107. PTHR24416:SF107. 1 hit.
Pfami PF00041. fn3. 1 hit.
PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view ]
PIRSFi PIRSF000620. Insulin_receptor. 1 hit.
PRINTSi PR00109. TYRKINASE.
SMARTi SM00060. FN3. 3 hits.
SM00261. FU. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF49265. SSF49265. 4 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEi PS50853. 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: DISRUPTION PHENOTYPE, FUNCTION, AUTOPHOSPHORYLATION.

Entry informationi

Entry nameiINSRR_MOUSE
AccessioniPrimary (citable) accession number: Q9WTL4
Secondary accession number(s): B2RQC5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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