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P14616 (INSRR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulin receptor-related protein

Short name=IRR
EC=2.7.10.1
Alternative name(s):
IR-related receptor
Gene names
Name:INSRR
Synonyms:IRR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1297 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.6

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.

Subcellular location

Membrane; Single-pass type I membrane protein.

Domain

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

Post-translational modification

Autophosphorylated on tyrosine residues between pH 7.9 and pH 10.5. Ref.6

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 – 12971271Insulin receptor-related protein
PRO_0000016701
Chain27 – 742716Insulin receptor-related protein alpha chain Probable
PRO_0000016702
Chain747 – 1297551Insulin receptor-related protein beta chain Probable
PRO_0000016703

Regions

Topological domain747 – 921175Extracellular Potential
Transmembrane922 – 94322Helical; Potential
Topological domain944 – 1297354Cytoplasmic Potential
Domain483 – 603121Fibronectin type-III 1
Domain607 – 707101Fibronectin type-III 2
Domain818 – 91396Fibronectin 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 Probable
Modified residue11461Phosphotyrosine; by autocatalysis Probable
Glycosylation471N-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

Natural variations

Natural variant1271A → E. Ref.5
Corresponds to variant rs55757706 [ dbSNP | Ensembl ].
VAR_041434
Natural variant1611A → V. Ref.5
Corresponds to variant rs55971900 [ dbSNP | Ensembl ].
VAR_041435
Natural variant2441R → H. Ref.5
Corresponds to variant rs55951840 [ dbSNP | Ensembl ].
VAR_041436
Natural variant2461C → R. Ref.5
Corresponds to variant rs56377825 [ dbSNP | Ensembl ].
VAR_041437
Natural variant2781E → Q in a lung adenocarcinoma sample; somatic mutation. Ref.5
VAR_041438
Natural variant5541R → C. Ref.5
Corresponds to variant rs56068937 [ dbSNP | Ensembl ].
VAR_041439
Natural variant9281P → L. Ref.5
Corresponds to variant rs56252149 [ dbSNP | Ensembl ].
VAR_041440
Natural variant10651G → E in a glioblastoma multiforme sample; somatic mutation. Ref.5
VAR_041441

Experimental info

Mutagenesis1145 – 11462YY → FF: Abolishes autophosphorylation. Ref.6

Sequences

Sequence LengthMass (Da)Tools
P14616 [UniParc].

Last modified January 11, 2001. Version 2.
Checksum: BB22C7FF61E3065D

FASTA1,297143,720
        10         20         30         40         50         60 
MAVPSLWPWG ACLPVIFLSL GFGLDTVEVC PSLDIRSEVA ELRQLENCSV VEGHLQILLM 

        70         80         90        100        110        120 
FTATGEDFRG LSFPRLTQVT DYLLLFRVYG LESLRDLFPN LAVIRGTRLF LGYALVIFEM 

       130        140        150        160        170        180 
PHLRDVALPA LGAVLRGAVR VEKNQELCHL STIDWGLLQP APGANHIVGN KLGEECADVC 

       190        200        210        220        230        240 
PGVLGAAGEP CAKTTFSGHT DYRCWTSSHC QRVCPCPHGM ACTARGECCH TECLGGCSQP 

       250        260        270        280        290        300 
EDPRACVACR HLYFQGACLW ACPPGTYQYE SWRCVTAERC ASLHSVPGRA STFGIHQGSC 

       310        320        330        340        350        360 
LAQCPSGFTR NSSSIFCHKC EGLCPKECKV GTKTIDSIQA AQDLVGCTHV EGSLILNLRQ 

       370        380        390        400        410        420 
GYNLEPQLQH SLGLVETITG FLKIKHSFAL VSLGFFKNLK LIRGDAMVDG NYTLYVLDNQ 

       430        440        450        460        470        480 
NLQQLGSWVA AGLTIPVGKI YFAFNPRLCL EHIYRLEEVT GTRGRQNKAE INPRTNGDRA 

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

       550        560        570        580        590        600 
QSWNLLDVEL PLSRTQEPGV TLASLKPWTQ YAVFVRAITL TTEEDSPHQG AQSPIVYLRT 

       610        620        630        640        650        660 
LPAAPTVPQD VISTSNSSSH LLVRWKPPTQ RNGNLTYYLV LWQRLAEDGD LYLNDYCHRG 

       670        680        690        700        710        720 
LRLPTSNNDP RFDGEDGDPE AEMESDCCPC QHPPPGQVLP PLEAQEASFQ KKFENFLHNA 

       730        740        750        760        770        780 
ITIPISPWKV TSINKSPQRD SGRHRRAAGP LRLGGNSSDF EIQEDKVPRE RAVLSGLRHF 

       790        800        810        820        830        840 
TEYRIDIHAC NHAAHTVGCS AATFVFARTM PHREADGIPG KVAWEASSKN SVLLRWLEPP 

       850        860        870        880        890        900 
DPNGLILKYE IKYRRLGEEA TVLCVSRLRY AKFGGVHLAL LPPGNYSARV RATSLAGNGS 

       910        920        930        940        950        960 
WTDSVAFYIL GPEEEDAGGL HVLLTATPVG LTLLIVLAAL GFFYGKKRNR TLYASVNPEY 

       970        980        990       1000       1010       1020 
FSASDMYVPD EWEVPREQIS IIRELGQGSF GMVYEGLARG LEAGEESTPV ALKTVNELAS 

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

      1090       1100       1110       1120       1130       1140 
NPGLPQPALG EMIQMAGEIA DGMAYLAANK FVHRDLAARN CMVSQDFTVK IGDFGMTRDV 

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

      1210       1220       1230       1240       1250       1260 
VLKFVMDGGV LEELEGCPLQ LQELMSRCWQ PNPRLRPSFT HILDSIQEEL RPSFRLLSFY 

      1270       1280       1290 
YSPECRGARG SLPTTDAEPD SSPTPRDCSP QNGGPGH 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and sequencing of the complete cDNA encoding the human insulin receptor related receptor."
Haenze J., Berthold A., Klammt J., Gallaher B., Siebler T., Kratzsch J., Elmlinger M., Kiess W.
Horm. Metab. Res. 31:77-79(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Primary structure of a putative receptor for a ligand of the insulin family."
Shier P., Watt V.M.
J. Biol. Chem. 264:14605-14608(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-1297.
[5]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLU-127; VAL-161; HIS-244; ARG-246; GLN-278; CYS-554; LEU-928 AND GLU-1065.
[6]"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: FUNCTION, MUTAGENESIS OF 1145-TYR-TYR-1146, AUTOPHOSPHORYLATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF064078 mRNA. Translation: AAC17167.1.
AL158169 Genomic DNA. Translation: CAH70009.1.
CH471121 Genomic DNA. Translation: EAW52903.1.
J05046 mRNA. Translation: AAC31759.1.
PIRB36502.
RefSeqNP_055030.1. NM_014215.2.
UniGeneHs.248138.

3D structure databases

ProteinModelPortalP14616.
SMRP14616. Positions 971-1262.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109856. 3 interactions.
IntActP14616. 1 interaction.
STRING9606.ENSP00000357178.

Chemistry

BindingDBP14616.
ChEMBLCHEMBL5483.
GuidetoPHARMACOLOGY1802.

PTM databases

PhosphoSiteP14616.

Polymorphism databases

DMDM12644000.

Proteomic databases

PaxDbP14616.
PRIDEP14616.

Protocols and materials databases

DNASU3645.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368195; ENSP00000357178; ENSG00000027644.
GeneID3645.
KEGGhsa:3645.
UCSCuc010pht.2. human.

Organism-specific databases

CTD3645.
GeneCardsGC01M156809.
H-InvDBHIX0028530.
HGNCHGNC:6093. INSRR.
HPAHPA025285.
MIM147671. gene.
neXtProtNX_P14616.
PharmGKBPA29899.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000038045.
HOVERGENHBG006134.
InParanoidP14616.
KOK05086.
OMAFARTMPH.
OrthoDBEOG73RB9N.
PhylomeDBP14616.
TreeFamTF351636.

Gene expression databases

ArrayExpressP14616.
BgeeP14616.
CleanExHS_INSRR.
GenevestigatorP14616.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProIPR000494. 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]
PANTHERPTHR24416:SF107. PTHR24416:SF107. 1 hit.
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. SSF49265. 4 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 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

GeneWikiINSRR.
GenomeRNAi3645.
NextBio14267.
PROP14616.
SOURCESearch...

Entry information

Entry nameINSRR_HUMAN
AccessionPrimary (citable) accession number: P14616
Secondary accession number(s): O60724, Q5VZS3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 11, 2001
Last modified: April 16, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM