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P30988 (CALCR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. 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 length508 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.14

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.

Sequence caution

The sequence AAA35640.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative promoter usage
Alternative 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_processG-protein coupled receptor signaling pathway

Inferred from direct assay Ref.3. Source: GOC

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 7619207. Source: UniProtKB

positive regulation of adenylate cyclase activity

Inferred from direct assay Ref.6Ref.3PubMed 7769107PubMed 7769107. Source: UniProtKB

positive regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 14722252. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from direct assay Ref.2. Source: UniProtKB

protein localization to plasma membrane

Inferred from direct assay PubMed 14722252. Source: UniProtKB

protein transport

Inferred from direct assay PubMed 14722252. Source: UniProtKB

receptor internalization

Inferred from direct assay PubMed 10882736. Source: UniProtKB

response to glucocorticoid

Inferred from direct assay PubMed 11250927. Source: UniProtKB

   Cellular_componentintegral component of plasma membrane

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

plasma membrane

Traceable author statement. Source: Reactome

   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 6 isoforms produced by alternative promoter usage and 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:
     1-18: Missing.
     193-208: Missing.
Isoform 3 (identifier: P30988-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.
     193-208: Missing.
Isoform 4 (identifier: P30988-4)

Also known as: Delta(1-47)hCT((a));

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.
Isoform 5 (identifier: P30988-5)

Also known as: HCTR-5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.
     302-308: GFPLVPT → APAFHRD
     309-508: Missing.
Isoform 6 (identifier: P30988-6)

Also known as: HCTR-6;

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.
     193-208: Missing.
     302-308: GFPLVPT → APAFHRD
     309-508: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4242 Ref.10
Chain43 – 508466Calcitonin receptor
PRO_0000012806

Regions

Topological domain43 – 171129Extracellular Potential
Transmembrane172 – 19120Helical; Name=1; Potential
Topological domain192 – 21423Cytoplasmic Potential
Transmembrane215 – 23420Helical; Name=2; Potential
Topological domain235 – 25420Extracellular Potential
Transmembrane255 – 27723Helical; Name=3; Potential
Topological domain278 – 29417Cytoplasmic Potential
Transmembrane295 – 31420Helical; Name=4; Potential
Topological domain315 – 33016Extracellular Potential
Transmembrane331 – 35424Helical; Name=5; Potential
Topological domain355 – 37723Cytoplasmic Potential
Transmembrane378 – 39518Helical; Name=6; Potential
Topological domain396 – 40712Extracellular Potential
Transmembrane408 – 42922Helical; Name=7; Potential
Topological domain430 – 50879Cytoplasmic Potential
Compositional bias462 – 4676Poly-Ala

Amino acid modifications

Glycosylation461N-linked (GlcNAc...) Potential
Glycosylation911N-linked (GlcNAc...) Potential
Glycosylation1431N-linked (GlcNAc...) Potential
Glycosylation1481N-linked (GlcNAc...) Potential
Disulfide bond73 ↔ 99 By similarity
Disulfide bond90 ↔ 130 By similarity
Disulfide bond113 ↔ 152 By similarity

Natural variations

Alternative sequence1 – 6565Missing in isoform 3 and isoform 4.
VSP_053289
Alternative sequence1 – 1818Missing in isoform 2, isoform 5 and isoform 6.
VSP_053290
Alternative sequence193 – 20816Missing in isoform 2, isoform 3 and isoform 6.
VSP_053291
Alternative sequence302 – 3087GFPLVPT → APAFHRD in isoform 5 and isoform 6.
VSP_053292
Alternative sequence309 – 508200Missing in isoform 5 and isoform 6.
VSP_053293
Natural variant4811P → L May be correlated with low bone mineral density (BMD). Ref.4 Ref.7 Ref.9 Ref.17 Ref.18
Corresponds to variant rs1801197 [ dbSNP | Ensembl ].
VAR_003580

Experimental info

Sequence conflict3811I → T in AAC50301. Ref.3

Sequences

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

Last modified October 16, 2013. Version 2.
Checksum: F76D13FD91BF61BA

FASTA50859,352
        10         20         30         40         50         60 
MQFSGEKISG QRDLQKSKMR FTFTSRCLAL FLLLNHPTPI LPAFSNQTYP TIEPKPFLYV 

        70         80         90        100        110        120 
VGRKKMMDAQ YKCYDRMQQL PAYQGEGPYC NRTWDGWLCW DDTPAGVLSY QFCPDYFPDF 

       130        140        150        160        170        180 
DPSEKVTKYC DEKGVWFKHP ENNRTWSNYT MCNAFTPEKL KNAYVLYYLA IVGHSLSIFT 

       190        200        210        220        230        240 
LVISLGIFVF FRKLTTIFPL NWKYRKALSL GCQRVTLHKN MFLTYILNSM IIIIHLVEVV 

       250        260        270        280        290        300 
PNGELVRRDP VSCKILHFFH QYMMACNYFW MLCEGIYLHT LIVVAVFTEK QRLRWYYLLG 

       310        320        330        340        350        360 
WGFPLVPTTI HAITRAVYFN DNCWLSVETH LLYIIHGPVM AALVVNFFFL LNIVRVLVTK 

       370        380        390        400        410        420 
MRETHEAESH MYLKAVKATM ILVPLLGIQF VVFPWRPSNK MLGKIYDYVM HSLIHFQGFF 

       430        440        450        460        470        480 
VATIYCFCNN EVQTTVKRQW AQFKIQWNQR WGRRPSNRSA RAAAAAAEAG DIPIYICHQE 

       490        500 
PRNEPANNQG EESAEIIPLN IIEQESSA 

« Hide

Isoform 2 [UniParc].

Checksum: 0D9FA80FF16E82D9
Show »

FASTA47455,329
Isoform 3 [UniParc].

Checksum: 733431C1963B7A83
Show »

FASTA42749,878
Isoform 4 (Delta(1-47)hCT((a))) [UniParc].

Checksum: AE090009967D7B08
Show »

FASTA44351,852
Isoform 5 (HCTR-5) [UniParc].

Checksum: B69ECF2AE4FAD38A
Show »

FASTA29034,397
Isoform 6 (HCTR-6) [UniParc].

Checksum: 83843885095D43EA
Show »

FASTA27432,423

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] (ISOFORM 1).
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] (ISOFORM 2).
[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] (ISOFORMS 2 AND 3), 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-481.
[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]"Molecular characterization of two novel isoforms of the human calcitonin receptor."
Beaudreuil J., Balasubramanian S., Chenais J., Taboulet J., Frenkian M., Orcel P., Jullienne A., Horne W., de Vernejoul M.C., Cressent M.
Gene 343:143-151(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6).
[7]"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-481.
Tissue: Kidney.
[8]"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].
[9]"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-481.
[10]"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 43-57.
[11]"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.
[12]"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.
[13]"Multiple promoters regulate human calcitonin receptor gene expression."
Hebden C., Smalt R., Chambers T., Pondel M.D.
Biochem. Biophys. Res. Commun. 272:738-743(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE PROMOTER USAGE.
[14]"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.
[15]"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.
[16]"Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant Delta(1-47)hCT((a)) function."
Qi T., Dong M., Watkins H.A., Wootten D., Miller L.J., Hay D.L.
Br. J. Pharmacol. 168:644-657(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 4).
[17]"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-481 WITH LOWER LUMBAR BMD.
[18]"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-481.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L00587 mRNA. Translation: AAA35640.1. Different initiation.
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.
AJ831406 mRNA. Translation: CAH40796.1.
AJ831407 mRNA. Translation: CAH40797.1.
AY430048 mRNA. Translation: AAR06949.1.
AC003078 Genomic DNA. Translation: AAB83945.1.
AC005024 Genomic DNA. No translation available.
BC069611 mRNA. Translation: AAH69611.1.
BC075028 mRNA. Translation: AAH75028.2.
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...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107250. 7 interactions.
IntActP30988. 2 interactions.
MINTMINT-1217503.
STRING9606.ENSP00000352561.

Chemistry

BindingDBP30988.
ChEMBLCHEMBL2111189.
DrugBankDB00017. Salmon Calcitonin.
GuidetoPHARMACOLOGY43.

Protein family/group databases

TCDB9.A.14.4.1. the g-protein-coupled receptor (gpcr) family.
GPCRDBSearch...

PTM databases

PhosphoSiteP30988.

Polymorphism databases

DMDM550544247.

Proteomic databases

PaxDbP30988.
PRIDEP30988.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000415529; ENSP00000413179; ENSG00000004948. [P30988-6]
ENST00000423724; ENSP00000391369; ENSG00000004948. [P30988-5]
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.
OrthoDBEOG712TW2.
TreeFamTF315710.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP30988.
BgeeP30988.
CleanExHS_CALCR.
GenevestigatorP30988.

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

GeneWikiCalcitonin_receptor.
GenomeRNAi799.
NextBio3248.
PROP30988.
SOURCESearch...

Entry information

Entry nameCALCR_HUMAN
AccessionPrimary (citable) accession number: P30988
Secondary accession number(s): F5H605 expand/collapse secondary AC list , O14585, Q13941, Q5ZGL8, Q659U6, Q6DJU8, Q6T712
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 16, 2013
Last modified: April 16, 2014
This is version 147 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

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 7

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

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries