P14616 (INSRR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1297 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton reorganization Inferred from direct assay Ref.6. Source: UniProtKB cellular response to alkalinity Inferred from direct assay Ref.6. Source: UniProtKB male sex determination Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from mutant phenotype Ref.6. Source: UniProtKB transmembrane receptor protein tyrosine kinase signaling pathway Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase activity Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 1297	1271	Insulin receptor-related protein		PRO_0000016701
	Chain	27 – 742	716	Insulin receptor-related protein alpha chain Probable		PRO_0000016702
	Chain	747 – 1297	551	Insulin receptor-related protein beta chain Probable		PRO_0000016703
Regions
	Topological domain	747 – 921	175	Extracellular Potential
	Transmembrane	922 – 943	22	Helical; Potential
	Topological domain	944 – 1297	354	Cytoplasmic Potential
	Domain	484 – 594	111	Fibronectin type-III 1
	Domain	605 – 686	82	Fibronectin type-III 2
	Domain	815 – 909	95	Fibronectin type-III 3
	Domain	979 – 1254	276	Protein kinase
	Nucleotide binding	985 – 993	9	ATP By similarity
Sites
	Active site	1115	1	Proton acceptor By similarity
	Binding site	1013	1	ATP By similarity
Amino acid modifications
	Modified residue	1145	1	Phosphotyrosine; by autocatalysis Probable
	Modified residue	1146	1	Phosphotyrosine; by autocatalysis Probable
	Glycosylation	47	1	N-linked (GlcNAc...) Potential
	Glycosylation	311	1	N-linked (GlcNAc...) Potential
	Glycosylation	411	1	N-linked (GlcNAc...) Potential
	Glycosylation	492	1	N-linked (GlcNAc...) Potential
	Glycosylation	528	1	N-linked (GlcNAc...) Potential
	Glycosylation	616	1	N-linked (GlcNAc...) Potential
	Glycosylation	634	1	N-linked (GlcNAc...) Potential
	Glycosylation	756	1	N-linked (GlcNAc...) Potential
	Glycosylation	885	1	N-linked (GlcNAc...) Potential
	Glycosylation	898	1	N-linked (GlcNAc...) Potential
	Disulfide bond	214 ↔ 222		By similarity
	Disulfide bond	216 ↔ 228		By similarity
	Disulfide bond	229 ↔ 237		By similarity
	Disulfide bond	233 ↔ 246		By similarity
	Disulfide bond	249 ↔ 258		By similarity
	Disulfide bond	262 ↔ 274		By similarity
	Disulfide bond	280 ↔ 300		By similarity
	Disulfide bond	304 ↔ 317		By similarity
	Disulfide bond	320 ↔ 324		By similarity
	Disulfide bond	657 ↔ 864		Interchain (between alpha and beta chains) Potential
Natural variations
	Natural variant	127	1	A → E. Ref.5 Corresponds to variant rs55757706 [ dbSNP | Ensembl ].		VAR_041434
	Natural variant	161	1	A → V. Ref.5 Corresponds to variant rs55971900 [ dbSNP | Ensembl ].		VAR_041435
	Natural variant	244	1	R → H. Ref.5 Corresponds to variant rs55951840 [ dbSNP | Ensembl ].		VAR_041436
	Natural variant	246	1	C → R. Ref.5 Corresponds to variant rs56377825 [ dbSNP | Ensembl ].		VAR_041437
	Natural variant	278	1	E → Q in a lung adenocarcinoma sample; somatic mutation. Ref.5		VAR_041438
	Natural variant	554	1	R → C. Ref.5 Corresponds to variant rs56068937 [ dbSNP | Ensembl ].		VAR_041439
	Natural variant	928	1	P → L. Ref.5 Corresponds to variant rs56252149 [ dbSNP | Ensembl ].		VAR_041440
	Natural variant	1065	1	G → E in a glioblastoma multiforme sample; somatic mutation. Ref.5		VAR_041441
Experimental info
	Mutagenesis	1145 – 1146	2	YY → FF: Abolishes autophosphorylation. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P14616 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: BB22C7FF61E3065D	FASTA	1,297	143,720
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00027212.
PIR	B36502.
RefSeq	NP_055030.1. NM_014215.2.
UniGene	Hs.248138.
3D structure databases
ProteinModelPortal	P14616.
ModBase	Search...
Protein-protein interaction databases
IntAct	P14616. 1 interaction.
STRING	9606.ENSP00000357178.
PTM databases
PhosphoSite	P14616.
Polymorphism databases
DMDM	12644000.
Proteomic databases
PaxDb	P14616.
PRIDE	P14616.
Protocols and materials databases
DNASU	3645.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368195; ENSP00000357178; ENSG00000027644.
GeneID	3645.
KEGG	hsa:3645.
UCSC	uc010pht.2. human.
Organism-specific databases
CTD	3645.
GeneCards	GC01M156809.
H-InvDB	HIX0028530.
HGNC	HGNC:6093. INSRR.
HPA	HPA025285.
MIM	147671. gene.
neXtProt	NX_P14616.
PharmGKB	PA29899.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000038045.
HOVERGEN	HBG006134.
InParanoid	P14616.
KO	K05086.
OMA	ARTMPHR.
OrthoDB	EOG4DFPMM.
PhylomeDB	P14616.
Gene expression databases
Bgee	P14616.
CleanEx	HS_INSRR.
Genevestigator	P14616.
GermOnline	ENSG00000027644. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 4 hits. 3.80.20.20. 2 hits.
InterPro	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. 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]
Pfam	PF00041. fn3. 1 hit. PF00757. Furin-like. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF01030. Recep_L_domain. 2 hits. [Graphical view]
PIRSF	PIRSF000620. Insulin_receptor. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00060. FN3. 3 hits. SM00261. FU. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 3 hits. SSF57184. Grow_fac_recept. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	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]
ProtoNet	Search...
Other
BindingDB	P14616.
ChEMBL	CHEMBL5483.
GenomeRNAi	3645.
NextBio	14267.
SOURCE	Search...

Entry information

Entry name

INSRR_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 139 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.