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Protein

Insulin receptor-related protein

Gene

INSRR

Organism
Homo sapiens (Human)
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

  • ATP binding Source: UniProtKB-KW
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton reorganization Source: UniProtKB
  • cellular response to alkaline pH Source: UniProtKB
  • male sex determination Source: Ensembl
  • protein autophosphorylation Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00457-MONOMER.
BRENDAi2.7.10.1. 2681.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6093. INSRR.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini747 – 921ExtracellularSequence analysisAdd BLAST175
Transmembranei922 – 943HelicalSequence analysisAdd BLAST22
Topological domaini944 – 1297CytoplasmicSequence analysisAdd BLAST354

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1145 – 1146YY → FF: Abolishes autophosphorylation. 1 Publication2

Organism-specific databases

DisGeNETi3645.
OpenTargetsiENSG00000027644.
PharmGKBiPA29899.

Chemistry databases

ChEMBLiCHEMBL5483.
GuidetoPHARMACOLOGYi1802.

Polymorphism and mutation databases

BioMutaiINSRR.
DMDMi12644000.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000001670127 – 1297Insulin receptor-related proteinAdd BLAST1271
ChainiPRO_000001670227 – 742Insulin receptor-related protein alpha chainCuratedAdd BLAST716
ChainiPRO_0000016703747 – 1297Insulin receptor-related protein beta chainCuratedAdd BLAST551

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi47N-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 autocatalysisCurated1
Modified residuei1146Phosphotyrosine; by autocatalysisCurated1

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

MaxQBiP14616.
PaxDbiP14616.
PeptideAtlasiP14616.
PRIDEiP14616.

PTM databases

iPTMnetiP14616.
PhosphoSitePlusiP14616.

Expressioni

Gene expression databases

BgeeiENSG00000027644.
CleanExiHS_INSRR.
GenevisibleiP14616. HS.

Organism-specific databases

HPAiHPA025285.

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.

Protein-protein interaction databases

BioGridi109856. 2 interactors.
IntActiP14616. 2 interactors.
STRINGi9606.ENSP00000357178.

Chemistry databases

BindingDBiP14616.

Structurei

3D structure databases

ProteinModelPortaliP14616.
SMRiP14616.
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.

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.
InParanoidiP14616.
KOiK05086.
OMAiFARTMPH.
OrthoDBiEOG091G00GE.
PhylomeDBiP14616.
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.

P14616-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVPSLWPWG ACLPVIFLSL GFGLDTVEVC PSLDIRSEVA ELRQLENCSV
60 70 80 90 100
VEGHLQILLM FTATGEDFRG LSFPRLTQVT DYLLLFRVYG LESLRDLFPN
110 120 130 140 150
LAVIRGTRLF LGYALVIFEM PHLRDVALPA LGAVLRGAVR VEKNQELCHL
160 170 180 190 200
STIDWGLLQP APGANHIVGN KLGEECADVC PGVLGAAGEP CAKTTFSGHT
210 220 230 240 250
DYRCWTSSHC QRVCPCPHGM ACTARGECCH TECLGGCSQP EDPRACVACR
260 270 280 290 300
HLYFQGACLW ACPPGTYQYE SWRCVTAERC ASLHSVPGRA STFGIHQGSC
310 320 330 340 350
LAQCPSGFTR NSSSIFCHKC EGLCPKECKV GTKTIDSIQA AQDLVGCTHV
360 370 380 390 400
EGSLILNLRQ GYNLEPQLQH SLGLVETITG FLKIKHSFAL VSLGFFKNLK
410 420 430 440 450
LIRGDAMVDG NYTLYVLDNQ NLQQLGSWVA AGLTIPVGKI YFAFNPRLCL
460 470 480 490 500
EHIYRLEEVT GTRGRQNKAE INPRTNGDRA ACQTRTLRFV SNVTEADRIL
510 520 530 540 550
LRWERYEPLE ARDLLSFIVY YKESPFQNAT EHVGPDACGT QSWNLLDVEL
560 570 580 590 600
PLSRTQEPGV TLASLKPWTQ YAVFVRAITL TTEEDSPHQG AQSPIVYLRT
610 620 630 640 650
LPAAPTVPQD VISTSNSSSH LLVRWKPPTQ RNGNLTYYLV LWQRLAEDGD
660 670 680 690 700
LYLNDYCHRG LRLPTSNNDP RFDGEDGDPE AEMESDCCPC QHPPPGQVLP
710 720 730 740 750
PLEAQEASFQ KKFENFLHNA ITIPISPWKV TSINKSPQRD SGRHRRAAGP
760 770 780 790 800
LRLGGNSSDF EIQEDKVPRE RAVLSGLRHF TEYRIDIHAC NHAAHTVGCS
810 820 830 840 850
AATFVFARTM PHREADGIPG KVAWEASSKN SVLLRWLEPP DPNGLILKYE
860 870 880 890 900
IKYRRLGEEA TVLCVSRLRY AKFGGVHLAL LPPGNYSARV RATSLAGNGS
910 920 930 940 950
WTDSVAFYIL GPEEEDAGGL HVLLTATPVG LTLLIVLAAL GFFYGKKRNR
960 970 980 990 1000
TLYASVNPEY FSASDMYVPD EWEVPREQIS IIRELGQGSF GMVYEGLARG
1010 1020 1030 1040 1050
LEAGEESTPV ALKTVNELAS PRECIEFLKE ASVMKAFKCH HVVRLLGVVS
1060 1070 1080 1090 1100
QGQPTLVIME LMTRGDLKSH LRSLRPEAEN NPGLPQPALG EMIQMAGEIA
1110 1120 1130 1140 1150
DGMAYLAANK FVHRDLAARN CMVSQDFTVK IGDFGMTRDV YETDYYRKGG
1160 1170 1180 1190 1200
KGLLPVRWMA PESLKDGIFT THSDVWSFGV VLWEIVTLAE QPYQGLSNEQ
1210 1220 1230 1240 1250
VLKFVMDGGV LEELEGCPLQ LQELMSRCWQ PNPRLRPSFT HILDSIQEEL
1260 1270 1280 1290
RPSFRLLSFY YSPECRGARG SLPTTDAEPD SSPTPRDCSP QNGGPGH
Length:1,297
Mass (Da):143,720
Last modified:January 11, 2001 - v2
Checksum:iBB22C7FF61E3065D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041434127A → E.1 PublicationCorresponds to variant rs55757706dbSNPEnsembl.1
Natural variantiVAR_041435161A → V.1 PublicationCorresponds to variant rs55971900dbSNPEnsembl.1
Natural variantiVAR_041436244R → H.1 PublicationCorresponds to variant rs55951840dbSNPEnsembl.1
Natural variantiVAR_041437246C → R.1 PublicationCorresponds to variant rs56377825dbSNPEnsembl.1
Natural variantiVAR_041438278E → Q in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041439554R → C.1 PublicationCorresponds to variant rs56068937dbSNPEnsembl.1
Natural variantiVAR_041440928P → L.1 PublicationCorresponds to variant rs56252149dbSNPEnsembl.1
Natural variantiVAR_0414411065G → E in a glioblastoma multiforme sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF064078 mRNA. Translation: AAC17167.1.
AL158169 Genomic DNA. Translation: CAH70009.1.
CH471121 Genomic DNA. Translation: EAW52903.1.
J05046 mRNA. Translation: AAC31759.1.
CCDSiCCDS1160.1.
PIRiB36502.
RefSeqiNP_055030.1. NM_014215.2.
UniGeneiHs.248138.

Genome annotation databases

EnsembliENST00000368195; ENSP00000357178; ENSG00000027644.
GeneIDi3645.
KEGGihsa:3645.
UCSCiuc010pht.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF064078 mRNA. Translation: AAC17167.1.
AL158169 Genomic DNA. Translation: CAH70009.1.
CH471121 Genomic DNA. Translation: EAW52903.1.
J05046 mRNA. Translation: AAC31759.1.
CCDSiCCDS1160.1.
PIRiB36502.
RefSeqiNP_055030.1. NM_014215.2.
UniGeneiHs.248138.

3D structure databases

ProteinModelPortaliP14616.
SMRiP14616.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109856. 2 interactors.
IntActiP14616. 2 interactors.
STRINGi9606.ENSP00000357178.

Chemistry databases

BindingDBiP14616.
ChEMBLiCHEMBL5483.
GuidetoPHARMACOLOGYi1802.

PTM databases

iPTMnetiP14616.
PhosphoSitePlusiP14616.

Polymorphism and mutation databases

BioMutaiINSRR.
DMDMi12644000.

Proteomic databases

MaxQBiP14616.
PaxDbiP14616.
PeptideAtlasiP14616.
PRIDEiP14616.

Protocols and materials databases

DNASUi3645.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368195; ENSP00000357178; ENSG00000027644.
GeneIDi3645.
KEGGihsa:3645.
UCSCiuc010pht.3. human.

Organism-specific databases

CTDi3645.
DisGeNETi3645.
GeneCardsiINSRR.
H-InvDBHIX0028530.
HGNCiHGNC:6093. INSRR.
HPAiHPA025285.
MIMi147671. gene.
neXtProtiNX_P14616.
OpenTargetsiENSG00000027644.
PharmGKBiPA29899.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
KOG4258. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000038045.
HOVERGENiHBG006134.
InParanoidiP14616.
KOiK05086.
OMAiFARTMPH.
OrthoDBiEOG091G00GE.
PhylomeDBiP14616.
TreeFamiTF351636.

Enzyme and pathway databases

BioCyciZFISH:HS00457-MONOMER.
BRENDAi2.7.10.1. 2681.

Miscellaneous databases

GeneWikiiINSRR.
GenomeRNAii3645.
PROiP14616.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000027644.
CleanExiHS_INSRR.
GenevisibleiP14616. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P14616
Secondary accession number(s): O60724, Q5VZS3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 11, 2001
Last modified: November 30, 2016
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.