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P30988 (CALCR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 137. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcitonin receptor

Short name=CT-R
Gene names
Name:CALCR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length490 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate 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_componentintegral to plasma membrane

Non-traceable author statement Ref.3PubMed 7619207. Source: UniProtKB

   Molecular_functioncalcitonin 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Ref.9
Chain25 – 490466Calcitonin receptor
PRO_0000012806

Regions

Topological domain25 – 153129Extracellular Potential
Transmembrane154 – 17320Helical; Name=1; Potential
Topological domain174 – 19623Cytoplasmic Potential
Transmembrane197 – 21620Helical; Name=2; Potential
Topological domain217 – 23620Extracellular Potential
Transmembrane237 – 25923Helical; Name=3; Potential
Topological domain260 – 27617Cytoplasmic Potential
Transmembrane277 – 29620Helical; Name=4; Potential
Topological domain297 – 31216Extracellular Potential
Transmembrane313 – 33624Helical; Name=5; Potential
Topological domain337 – 35923Cytoplasmic Potential
Transmembrane360 – 37718Helical; Name=6; Potential
Topological domain378 – 38912Extracellular Potential
Transmembrane390 – 41122Helical; Name=7; Potential
Topological domain412 – 49079Cytoplasmic Potential
Compositional bias444 – 4496Poly-Ala

Amino acid modifications

Glycosylation281N-linked (GlcNAc...) Potential
Glycosylation731N-linked (GlcNAc...) Potential
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation1301N-linked (GlcNAc...) Potential
Disulfide bond55 ↔ 81 By similarity
Disulfide bond72 ↔ 112 By similarity
Disulfide bond95 ↔ 134 By similarity

Natural variations

Alternative sequence1 – 4747Missing in isoform 3.
VSP_001991
Alternative sequence175 – 19016Missing in isoform 2 and isoform 3.
VSP_001992
Natural variant4631P → 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 conflict3631I → T in AAC50301. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: 38EC7A4A9F07FF5D

FASTA49057,303
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 0D9FA80FF16E82D9
Show »

FASTA47455,329
Isoform 3 [UniParc].

Checksum: 733431C1963B7A83
Show »

FASTA42749,878

References

« Hide '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. expand/collapse author list , 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.
IPIIPI00187004.
IPI00419304.
IPI01015083.
PIRI37217.
S34486.
RefSeqNP_001158209.1. NM_001164737.1.
NP_001158210.1. NM_001164738.1.
NP_001733.1. NM_001742.3.
UniGeneHs.489127.

3D structure databases

ProteinModelPortalP30988.
ModBaseSearch...

Protein-protein interaction databases

IntActP30988. 2 interactions.
MINTMINT-1217503.
STRING9606.ENSP00000352561.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP30988.

Polymorphism databases

DMDM399180.

Proteomic databases

PaxDbP30988.
PRIDEP30988.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360249; ENSP00000353385; ENSG00000004948.
ENST00000421592; ENSP00000399552; ENSG00000004948.
GeneID799.
KEGGhsa:799.

Organism-specific databases

CTD799.
GeneCardsGC07M093053.
H-InvDBHIX0033513.
HGNCHGNC:1440. CALCR.
HPAHPA028962.
MIM114131. gene.
neXtProtNX_P30988.
PharmGKBPA26032.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG255868.
HOGENOMHOG000230695.
HOVERGENHBG102129.
InParanoidP30988.
KOK04576.
OrthoDBEOG45QHD4.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP30988.
BgeeP30988.
CleanExHS_CALCR.
GenevestigatorP30988.
GermOnlineENSG00000004948. Homo sapiens.

Family and domain databases

InterProIPR003287. 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]
PfamPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSPR00361. CALCITONINR.
PR01350. CTRFAMILY.
PR00249. GPCRSECRETIN.
SMARTSM00008. HormR. 1 hit.
[Graphical view]
PROSITEPS00649. 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]
ProtoNetSearch...

Other

BindingDBP30988.
ChEMBLCHEMBL1832.
DrugBankDB00017. Salmon Calcitonin.
GenomeRNAi799.
NextBio3248.
SOURCESearch...

Entry information

Entry nameCALCR_HUMAN
AccessionPrimary (citable) accession number: P30988
Secondary accession number(s): O14585 expand/collapse secondary AC list , 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 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

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families