P30988 (CALCR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcitonin receptor
Short name=CT-R

Gene names

Name:

CALCR

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	490 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	This is a receptor for calcitonin. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The calcitonin receptor is thought to couple to the heterotrimeric guanosine triphosphate-binding protein that is sensitive to cholera toxin.
Subunit structure	Interacts with GPRASP2. Ref.12
Subcellular location	Cell membrane; Multi-pass membrane protein.
Polymorphism	Genetic variations in CALCR may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disrutption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 7619207. Source: UniProtKB elevation of cytosolic calcium ion concentration Inferred from direct assay Ref.2. Source: UniProtKB positive regulation of adenylate cyclase activity Inferred from direct assay PubMed 15563840Ref.3PubMed 7769107PubMed 7769107. Source: UniProtKB protein localization to plasma membrane Inferred from direct assay PubMed 14722252. Source: UniProtKB receptor internalization Inferred from direct assay PubMed 10882736. Source: UniProtKB response to glucocorticoid stimulus Inferred from direct assay PubMed 11250927. Source: UniProtKB
Cellular_component	integral to plasma membrane Non-traceable author statement Ref.3PubMed 7619207. Source: UniProtKB
Molecular_function	calcitonin binding Inferred from direct assay Ref.2PubMed 7769107PubMed 7769107. Source: UniProtKB calcitonin receptor activity Inferred from direct assay Ref.3. Source: UniProtKB protein transporter activity Inferred from direct assay PubMed 14722252. Source: UniProtKB receptor activity Inferred from direct assay PubMed 10882736PubMed 14722252. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P30988-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P30988-2)

The sequence of this isoform differs from the canonical sequence as follows:
     175-190: Missing.

Isoform 3 (identifier: P30988-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-47: Missing.
     175-190: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Ref.9
	Chain	25 – 490	466	Calcitonin receptor		PRO_0000012806
Regions
	Topological domain	25 – 153	129	Extracellular Potential
	Transmembrane	154 – 173	20	Helical; Name=1; Potential
	Topological domain	174 – 196	23	Cytoplasmic Potential
	Transmembrane	197 – 216	20	Helical; Name=2; Potential
	Topological domain	217 – 236	20	Extracellular Potential
	Transmembrane	237 – 259	23	Helical; Name=3; Potential
	Topological domain	260 – 276	17	Cytoplasmic Potential
	Transmembrane	277 – 296	20	Helical; Name=4; Potential
	Topological domain	297 – 312	16	Extracellular Potential
	Transmembrane	313 – 336	24	Helical; Name=5; Potential
	Topological domain	337 – 359	23	Cytoplasmic Potential
	Transmembrane	360 – 377	18	Helical; Name=6; Potential
	Topological domain	378 – 389	12	Extracellular Potential
	Transmembrane	390 – 411	22	Helical; Name=7; Potential
	Topological domain	412 – 490	79	Cytoplasmic Potential
	Compositional bias	444 – 449	6	Poly-Ala
Amino acid modifications
	Glycosylation	28	1	N-linked (GlcNAc...) Potential
	Glycosylation	73	1	N-linked (GlcNAc...) Potential
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
	Glycosylation	130	1	N-linked (GlcNAc...) Potential
	Disulfide bond	55 ↔ 81		By similarity
	Disulfide bond	72 ↔ 112		By similarity
	Disulfide bond	95 ↔ 134		By similarity
Natural variations
	Alternative sequence	1 – 47	47	Missing in isoform 3.		VSP_001991
	Alternative sequence	175 – 190	16	Missing in isoform 2 and isoform 3.		VSP_001992
	Natural variant	463	1	P → L May be correlated with low bone mineral density (BMD). Ref.4 Ref.6 Ref.8 Ref.14 Ref.15 Corresponds to variant rs1801197 [ dbSNP | Ensembl ].		VAR_003580
Experimental info
	Sequence conflict	363	1	I → T in AAC50301. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: 38EC7A4A9F07FF5D	FASTA	490	57,303
	10 20 30 40 50 60 MRFTFTSRCL ALFLLLNHPT PILPAFSNQT YPTIEPKPFL YVVGRKKMMD AQYKCYDRMQ 70 80 90 100 110 120 QLPAYQGEGP YCNRTWDGWL CWDDTPAGVL SYQFCPDYFP DFDPSEKVTK YCDEKGVWFK 130 140 150 160 170 180 HPENNRTWSN YTMCNAFTPE KLKNAYVLYY LAIVGHSLSI FTLVISLGIF VFFRKLTTIF 190 200 210 220 230 240 PLNWKYRKAL SLGCQRVTLH KNMFLTYILN SMIIIIHLVE VVPNGELVRR DPVSCKILHF 250 260 270 280 290 300 FHQYMMACNY FWMLCEGIYL HTLIVVAVFT EKQRLRWYYL LGWGFPLVPT TIHAITRAVY 310 320 330 340 350 360 FNDNCWLSVE THLLYIIHGP VMAALVVNFF FLLNIVRVLV TKMRETHEAE SHMYLKAVKA 370 380 390 400 410 420 TMILVPLLGI QFVVFPWRPS NKMLGKIYDY VMHSLIHFQG FFVATIYCFC NNEVQTTVKR 430 440 450 460 470 480 QWAQFKIQWN QRWGRRPSNR SARAAAAAAE AGDIPIYICH QEPRNEPANN QGEESAEIIP 490 LNIIEQESSA
	Isoform 2 [UniParc]. Checksum: 0D9FA80FF16E82D9	FASTA	474	55,329
	10 20 30 40 50 60 MRFTFTSRCL ALFLLLNHPT PILPAFSNQT YPTIEPKPFL YVVGRKKMMD AQYKCYDRMQ 70 80 90 100 110 120 QLPAYQGEGP YCNRTWDGWL CWDDTPAGVL SYQFCPDYFP DFDPSEKVTK YCDEKGVWFK 130 140 150 160 170 180 HPENNRTWSN YTMCNAFTPE KLKNAYVLYY LAIVGHSLSI FTLVISLGIF VFFRSLGCQR 190 200 210 220 230 240 VTLHKNMFLT YILNSMIIII HLVEVVPNGE LVRRDPVSCK ILHFFHQYMM ACNYFWMLCE 250 260 270 280 290 300 GIYLHTLIVV AVFTEKQRLR WYYLLGWGFP LVPTTIHAIT RAVYFNDNCW LSVETHLLYI 310 320 330 340 350 360 IHGPVMAALV VNFFFLLNIV RVLVTKMRET HEAESHMYLK AVKATMILVP LLGIQFVVFP 370 380 390 400 410 420 WRPSNKMLGK IYDYVMHSLI HFQGFFVATI YCFCNNEVQT TVKRQWAQFK IQWNQRWGRR 430 440 450 460 470 PSNRSARAAA AAAEAGDIPI YICHQEPRNE PANNQGEESA EIIPLNIIEQ ESSA
	Isoform 3 [UniParc]. Checksum: 733431C1963B7A83	FASTA	427	49,878
	10 20 30 40 50 60 MMDAQYKCYD RMQQLPAYQG EGPYCNRTWD GWLCWDDTPA GVLSYQFCPD YFPDFDPSEK 70 80 90 100 110 120 VTKYCDEKGV WFKHPENNRT WSNYTMCNAF TPEKLKNAYV LYYLAIVGHS LSIFTLVISL 130 140 150 160 170 180 GIFVFFRSLG CQRVTLHKNM FLTYILNSMI IIIHLVEVVP NGELVRRDPV SCKILHFFHQ 190 200 210 220 230 240 YMMACNYFWM LCEGIYLHTL IVVAVFTEKQ RLRWYYLLGW GFPLVPTTIH AITRAVYFND 250 260 270 280 290 300 NCWLSVETHL LYIIHGPVMA ALVVNFFFLL NIVRVLVTKM RETHEAESHM YLKAVKATMI 310 320 330 340 350 360 LVPLLGIQFV VFPWRPSNKM LGKIYDYVMH SLIHFQGFFV ATIYCFCNNE VQTTVKRQWA 370 380 390 400 410 420 QFKIQWNQRW GRRPSNRSAR AAAAAAEAGD IPIYICHQEP RNEPANNQGE ESAEIIPLNI IEQESSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line." Gorn A.H., Lin H.Y., Yamin M., Auron P.E., Flannery M.R., Tapp D.R., Manning C.A., Lodish H.F., Krane S.M., Goldring S.R. J. Clin. Invest. 90:1726-1735(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ovarian carcinoma.
[2]	"Cloning and characterization of an abundant subtype of the human calcitonin receptor." Kuestner R.E., Elrod R.D., Grant F.J., Hagen F.S., Kuijper J.L., Mathewes S.L., O'Hara P.J., Sheppard P.O., Stroop S.D., Thompson D.L., Whitmore T.E., Findlays D.M., Houssamis S., Sexton P.M., Moore E.E. Mol. Pharmacol. 46:246-255(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Molecular cloning and functional expression of a third isoform of the human calcitonin receptor and partial characterization of the calcitonin receptor gene." Albrandt K., Brady E.M.G., Moore C.X., Mull E., Sierzega M.E., Beaumont K. Endocrinology 136:5377-5384(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Mammary carcinoma.
[4]	"An isoform of the human calcitonin receptor is expressed in TT cells and in medullary carcinoma of the thyroid." Frendo J.L., Pichaud F., Delage-Mourroux R., Bouizar Z., Segond N., Moukhtar M.S., Jullienne A. FEBS Lett. 342:214-216(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-463.
[5]	"A novel calcitonin receptor gene in human osteoclasts from normal bone marrow." Nishikawa T., Ishikawa H., Yamamoto S., Koshihara Y. FEBS Lett. 458:409-414(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Mammary carcinoma.
[6]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." King M.M., Aronstam R.S., Sharma S.V. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT LEU-463. Tissue: Kidney.
[7]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] (ISOFORM 2), VARIANT LEU-463.
[9]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-39.
[10]	"Alternative splicing of a 48-nucleotide exon generates two isoforms of the human calcitonin receptor." Nussenzveig D.R., Mathew S., Gershengorn M.C. Endocrinology 136:2047-2051(1995) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING. Tissue: Placenta.
[11]	"A new type of human calcitonin receptor isoform generated by alternative splicing." Nakamura M., Hashimoto T., Nakajima T., Ichii S., Furuyama J., Ishihara Y., Kakudo K. Biochem. Biophys. Res. Commun. 209:744-751(1995) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
[12]	"Identification of a novel family of G protein-coupled receptor associated sorting proteins." Simonin F., Karcher P., Boeuf J.J.-M., Matifas A., Kieffer B.L. J. Neurochem. 89:766-775(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GPRASP2.
[13]	"Polymorphisms of the calcitonin receptor gene are associated with bone mineral density in postmenopausal Italian women." Masi L., Becherini L., Colli E., Gennari L., Mansani R., Falchetti A., Becorpi A.M., Cepollaro C., Gonnelli S., Tanini A., Brandi M.L. Biochem. Biophys. Res. Commun. 248:190-195(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LUMBAR BMD.
[14]	"Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women." Masi L., Becherini L., Gennari L., Colli E., Mansani R., Falchetti A., Cepollaro C., Gonnelli S., Tanini A., Brandi M.L. Biochem. Biophys. Res. Commun. 245:622-626(1998) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION OF VARIANT LEU-463 WITH LOWER LUMBAR BMD.
[15]	"Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women." Taboulet J., Frenkian M., Frendo J.L., Feingold N., Jullienne A., de Vernejoul M.-C. Hum. Mol. Genet. 7:2129-2133(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-463.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L00587 mRNA. Translation: AAA35640.1. X69920 mRNA. Translation: CAA49541.1. U26553 mRNA. Translation: AAC50300.1. U26554 mRNA. Translation: AAC50301.1. X82466 mRNA. Translation: CAA57849.1. S77876, S77875 Genomic DNA. Translation: AAD14268.1. AB022177 mRNA. Translation: BAA86929.1. AB022178 mRNA. Translation: BAA86928.1. AY430048 mRNA. Translation: AAR06949.1. AC003078 Genomic DNA. Translation: AAB83945.1. BC069611 mRNA. Translation: AAH69611.1. BC075028 mRNA. Translation: AAH75028.2.
IPI	IPI00187004. IPI00419304. IPI01015083.
PIR	I37217. S34486.
RefSeq	NP_001158209.1. NM_001164737.1. NP_001158210.1. NM_001164738.1. NP_001733.1. NM_001742.3.
UniGene	Hs.489127.
3D structure databases
ProteinModelPortal	P30988.
ModBase	Search...
Protein-protein interaction databases
IntAct	P30988. 2 interactions.
MINT	MINT-1217503.
STRING	9606.ENSP00000352561.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P30988.
Polymorphism databases
DMDM	399180.
Proteomic databases
PaxDb	P30988.
PRIDE	P30988.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360249; ENSP00000353385; ENSG00000004948. ENST00000421592; ENSP00000399552; ENSG00000004948.
GeneID	799.
KEGG	hsa:799.
Organism-specific databases
CTD	799.
GeneCards	GC07M093053.
H-InvDB	HIX0033513.
HGNC	HGNC:1440. CALCR.
HPA	HPA028962.
MIM	114131. gene.
neXtProt	NX_P30988.
PharmGKB	PA26032.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG255868.
HOGENOM	HOG000230695.
HOVERGEN	HBG102129.
InParanoid	P30988.
KO	K04576.
OrthoDB	EOG45QHD4.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P30988.
Bgee	P30988.
CleanEx	HS_CALCR.
Genevestigator	P30988.
GermOnline	ENSG00000004948. Homo sapiens.
Family and domain databases
InterPro	IPR003287. GCPR_2_calcitonin_rcpt_fam. IPR017981. GPCR_2-like. IPR001688. GPCR_2_calcitonin_rcpt. IPR001879. GPCR_2_extracellular_dom. IPR000832. GPCR_2_secretin-like. IPR017983. GPCR_2_secretin-like_CS. [Graphical view]
Pfam	PF00002. 7tm_2. 1 hit. PF02793. HRM. 1 hit. [Graphical view]
PRINTS	PR00361. CALCITONINR. PR01350. CTRFAMILY. PR00249. GPCRSECRETIN.
SMART	SM00008. HormR. 1 hit. [Graphical view]
PROSITE	PS00649. G_PROTEIN_RECEP_F2_1. 1 hit. PS00650. G_PROTEIN_RECEP_F2_2. 1 hit. PS50227. G_PROTEIN_RECEP_F2_3. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P30988.
ChEMBL	CHEMBL1832.
DrugBank	DB00017. Salmon Calcitonin.
GenomeRNAi	799.
NextBio	3248.
SOURCE	Search...

Entry information

Entry name

CALCR_HUMAN

Accession

Primary (citable) accession number: P30988
Secondary accession number(s): O14585 , Q13941, Q6DJU8, Q6T712

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	May 1, 2013
This is version 137 of the entry and version 1 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.