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Protein

Insulin receptor-related protein

Gene

Insrr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1013ATPPROSITE-ProRule annotation1
Active sitei1115Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi985 – 993ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton reorganization Source: UniProtKB
  • cellular response to alkaline pH Source: UniProtKB
  • male sex determination Source: MGI
  • protein autophosphorylation Source: UniProtKB
  • 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
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1346037. Insrr.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini747 – 921ExtracellularSequence analysisAdd BLAST175
Transmembranei922 – 943HelicalSequence analysisAdd BLAST22
Topological domaini944 – 1300CytoplasmicSequence analysisAdd BLAST357

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000001670427 – 1300Insulin receptor-related proteinAdd BLAST1274
ChainiPRO_000001670527 – 742Insulin receptor-related protein alpha chainCuratedAdd BLAST716
ChainiPRO_0000016706747 – 1300Insulin receptor-related protein beta chainCuratedAdd BLAST554

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi47N-linked (GlcNAc...)Sequence analysis1
Glycosylationi100N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi214 ↔ 222By similarity
Disulfide bondi216 ↔ 228By similarity
Disulfide bondi229 ↔ 237By similarity
Disulfide bondi233 ↔ 246By similarity
Disulfide bondi249 ↔ 258By similarity
Disulfide bondi262 ↔ 274By similarity
Disulfide bondi280 ↔ 300By similarity
Disulfide bondi304 ↔ 317By similarity
Glycosylationi311N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi320 ↔ 324By similarity
Glycosylationi411N-linked (GlcNAc...)Sequence analysis1
Glycosylationi492N-linked (GlcNAc...)Sequence analysis1
Glycosylationi528N-linked (GlcNAc...)Sequence analysis1
Glycosylationi616N-linked (GlcNAc...)Sequence analysis1
Glycosylationi634N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi657 ↔ 864Interchain (between alpha and beta chains)Sequence analysis
Glycosylationi756N-linked (GlcNAc...)Sequence analysis1
Glycosylationi885N-linked (GlcNAc...)Sequence analysis1
Glycosylationi898N-linked (GlcNAc...)Sequence analysis1
Modified residuei1145Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1146Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated on tyrosine residues between pH 7.9 and pH 10.5.

Keywords - PTMi

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

Proteomic databases

PaxDbiQ9WTL4.
PeptideAtlasiQ9WTL4.
PRIDEiQ9WTL4.

PTM databases

iPTMnetiQ9WTL4.
PhosphoSitePlusiQ9WTL4.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000005640.
CleanExiMM_INSRR.
GenevisibleiQ9WTL4. MM.

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).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000029711.

Structurei

3D structure databases

ProteinModelPortaliQ9WTL4.
SMRiQ9WTL4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini483 – 603Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST121
Domaini607 – 707Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST101
Domaini818 – 913Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST96
Domaini979 – 1254Protein kinasePROSITE-ProRule annotationAdd BLAST276

Domaini

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

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
Contains 3 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
KOG4258. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000038045.
HOVERGENiHBG006134.
InParanoidiQ9WTL4.
KOiK05086.
OMAiFARTMPH.
OrthoDBiEOG091G00GE.
TreeFamiTF351636.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProiIPR003961. FN3_dom.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR028792. INSRR.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
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:SF338. PTHR24416:SF338. 3 hits.
PfamiPF00757. 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.
SSF52058. SSF52058. 3 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

        10         20         30         40         50
MAVPALWPWG VHLLMSLLSL GSGLDTLEVC PSLDIRSEVT ELRRLENCSV
60 70 80 90 100
VEGHLQILLM FAATGEDFRG LSFPRLTQVT DYLLLFRVYG LESLRDLFPN
110 120 130 140 150
LTVIRGTRLF LGYALIIFEM PHLRDVGLPS LGAVLRGAVR VEKNQELCHL
160 170 180 190 200
STIDWGLLQP APGTNHIVGN KLGEECADVC PGVLGAAGEP CSRTTFSGRT
210 220 230 240 250
DYRCWTSSHC QKVCPCPRGM ACTAGGDCCH SECLGGCSQP EDPRACVACR
260 270 280 290 300
HLYFQGVCLR ACPPGTYQYE SWRCVTAELC AHLREVPGLA TTFGIYEGSC
310 320 330 340 350
LAQCPPGFTR NGSSIFCHKC EGLCPKECKV GTKTIDSVQA TQDLVGCTHV
360 370 380 390 400
EGNLILNLRQ GYNLEPELQR NLGLVETITG FLKIKHSFAL VTLGFFKNLK
410 420 430 440 450
LIRGDSMVDG NYTLYVLDNQ NLQQLGSWVT AGLTIPVGKI YFAFNPRLCL
460 470 480 490 500
EHIYQLEEVT GTRGRQSKAE INPRTNGDRA ACQTRTLRFV FNLTEEDRIL
510 520 530 540 550
LRWERYEPLE ARDLLSFIVY YKESPFQNAT EHVGPDACGT QSWNLLDVEL
560 570 580 590 600
PLSRTQEPGV TLAPLKPWTQ YAVFVRAITL TTAEDSPHQG AQSPIVYLRT
610 620 630 640 650
LPAAPTVPQD VISTSNSSSH LLVRWKPPVQ RNGNITYYLV LWQRLAEDGD
660 670 680 690 700
LYINDYCHRG LRLPTSSHDT RFDREDPALE AEPEQGCCPC QHSPPGQALP
710 720 730 740 750
ALEAQEVTFQ KKFENFLHHA ITIPKAPWKV TSINKNPQRD SERHRREAGL
760 770 780 790 800
LRLGKNNSDF EIQEDKVPRE RAILSGLRHF TEYRIDIHAC NHAAHTVGCS
810 820 830 840 850
AATFVFARTM PHREADGIPG KVAWKAAGKS SVTLHWLEPP DPNGLILKYE
860 870 880 890 900
IKYRRLGEEA TVLCVSRLRY AKVGGVHLAL LPPGNYSAKV RATSLAGNGS
910 920 930 940 950
WTDGVTFYIT DLEEEDTGGM RIFLTVTPVG FMLLVTLAAL GFFYSRKRNS
960 970 980 990 1000
TLYTSVNPEY FSASHMYVPD EWEVPREQIA IIRELGQGSF GMVYEGLARG
1010 1020 1030 1040 1050
LEAGEESTPV ALKTVNELAS ARERVEFLKE ASVMKAFKCH HVVRLLGVVS
1060 1070 1080 1090 1100
QGQPTLVIME LMTRGDLKSH LRSLRPEAEN NPGLPQPALS DMIQMAGEIA
1110 1120 1130 1140 1150
DGMAYLAAKK FVHRDLAARN CMVSQDFTVK IGDFGMTRDV YETDYYRKGG
1160 1170 1180 1190 1200
KGLLPVRWMA PESLKDGIFT THSDVWSFGV VLWEIVTLAE QPYQGLSNEQ
1210 1220 1230 1240 1250
VLKFVMDGGV LEELENCPIQ LQELMRLCWQ HSPRLRPTFV HILDRIQDEL
1260 1270 1280 1290 1300
RPSFRLCSFY YSPECQRGQA SLLPTEAEPD SPPTLNGASD YSAPNGGPGH
Length:1,300
Mass (Da):144,875
Last modified:July 27, 2011 - v2
Checksum:i3DE9FC3C53DB96BB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti272W → G in BAA77835 (PubMed:10342810).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ9WTL4.
SMRiQ9WTL4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000029711.

PTM databases

iPTMnetiQ9WTL4.
PhosphoSitePlusiQ9WTL4.

Proteomic databases

PaxDbiQ9WTL4.
PeptideAtlasiQ9WTL4.
PRIDEiQ9WTL4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3645.
MGIiMGI:1346037. Insrr.

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
KOG4258. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000038045.
HOVERGENiHBG006134.
InParanoidiQ9WTL4.
KOiK05086.
OMAiFARTMPH.
OrthoDBiEOG091G00GE.
TreeFamiTF351636.

Miscellaneous databases

PROiQ9WTL4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000005640.
CleanExiMM_INSRR.
GenevisibleiQ9WTL4. MM.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProiIPR003961. FN3_dom.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR028792. INSRR.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
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:SF338. PTHR24416:SF338. 3 hits.
PfamiPF00757. 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.
SSF52058. SSF52058. 3 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]
ProtoNetiSearch...

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: November 30, 2016
This is version 141 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.