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Protein

Calcitonin receptor

Gene

CALCR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • calcitonin binding Source: UniProtKB
  • calcitonin receptor activity Source: UniProtKB
  • protein transporter activity Source: UniProtKB
  • receptor activity Source: UniProtKB

GO - Biological processi

  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • cell surface receptor signaling pathway Source: InterPro
  • positive regulation of adenylate cyclase activity Source: UniProtKB
  • positive regulation of cAMP biosynthetic process Source: UniProtKB
  • positive regulation of cytosolic calcium ion concentration Source: UniProtKB
  • protein localization to plasma membrane Source: UniProtKB
  • protein transport Source: UniProtKB
  • receptor internalization Source: UniProtKB
  • response to glucocorticoid Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-418555. G alpha (s) signalling events.
R-HSA-419812. Calcitonin-like ligand receptors.

Protein family/group databases

TCDBi9.A.14.4.1. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcitonin receptor
Short name:
CT-R
Gene namesi
Name:CALCR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:1440. CALCR.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini43 – 171ExtracellularSequence analysisAdd BLAST129
Transmembranei172 – 191Helical; Name=1Sequence analysisAdd BLAST20
Topological domaini192 – 214CytoplasmicSequence analysisAdd BLAST23
Transmembranei215 – 234Helical; Name=2Sequence analysisAdd BLAST20
Topological domaini235 – 254ExtracellularSequence analysisAdd BLAST20
Transmembranei255 – 277Helical; Name=3Sequence analysisAdd BLAST23
Topological domaini278 – 294CytoplasmicSequence analysisAdd BLAST17
Transmembranei295 – 314Helical; Name=4Sequence analysisAdd BLAST20
Topological domaini315 – 330ExtracellularSequence analysisAdd BLAST16
Transmembranei331 – 354Helical; Name=5Sequence analysisAdd BLAST24
Topological domaini355 – 377CytoplasmicSequence analysisAdd BLAST23
Transmembranei378 – 395Helical; Name=6Sequence analysisAdd BLAST18
Topological domaini396 – 407ExtracellularSequence analysisAdd BLAST12
Transmembranei408 – 429Helical; Name=7Sequence analysisAdd BLAST22
Topological domaini430 – 508CytoplasmicSequence analysisAdd BLAST79

GO - Cellular componenti

  • cell Source: GOC
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi799.
MalaCardsiCALCR.
OpenTargetsiENSG00000004948.
PharmGKBiPA26032.

Chemistry databases

ChEMBLiCHEMBL1832.
DrugBankiDB01278. Pramlintide.
DB00017. Salmon Calcitonin.
GuidetoPHARMACOLOGYi43.

Polymorphism and mutation databases

BioMutaiCALCR.
DMDMi550544247.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 421 PublicationAdd BLAST42
ChainiPRO_000001280643 – 508Calcitonin receptorAdd BLAST466

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi46N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi73 ↔ 99By similarity
Disulfide bondi90 ↔ 130By similarity
Glycosylationi91N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi113 ↔ 152By similarity
Glycosylationi143N-linked (GlcNAc...)Sequence analysis1
Glycosylationi148N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP30988.
PeptideAtlasiP30988.
PRIDEiP30988.

PTM databases

iPTMnetiP30988.
PhosphoSitePlusiP30988.

Expressioni

Gene expression databases

BgeeiENSG00000004948.
CleanExiHS_CALCR.
ExpressionAtlasiP30988. baseline and differential.
GenevisibleiP30988. HS.

Organism-specific databases

HPAiHPA028962.

Interactioni

Subunit structurei

Interacts with GPRASP2.1 Publication

Protein-protein interaction databases

BioGridi107250. 5 interactors.
IntActiP30988. 8 interactors.
MINTiMINT-1217503.
STRINGi9606.ENSP00000352561.

Chemistry databases

BindingDBiP30988.

Structurei

Secondary structure

1508
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi59 – 79Combined sources21
Beta strandi85 – 87Combined sources3
Beta strandi108 – 112Combined sources5
Beta strandi115 – 117Combined sources3
Beta strandi124 – 130Combined sources7
Turni140 – 143Combined sources4
Helixi150 – 152Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5II0X-ray2.10A/B/C43-162[»]
ProteinModelPortaliP30988.
SMRiP30988.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi462 – 467Poly-Ala6

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
GeneTreeiENSGT00760000118800.
HOGENOMiHOG000230695.
HOVERGENiHBG102129.
InParanoidiP30988.
KOiK04576.
TreeFamiTF315710.

Family and domain databases

InterProiIPR003287. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR00361. CALCITONINR.
PR01350. CTRFAMILY.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P30988-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MQFSGEKISG QRDLQKSKMR FTFTSRCLAL FLLLNHPTPI LPAFSNQTYP
60 70 80 90 100
TIEPKPFLYV VGRKKMMDAQ YKCYDRMQQL PAYQGEGPYC NRTWDGWLCW
110 120 130 140 150
DDTPAGVLSY QFCPDYFPDF DPSEKVTKYC DEKGVWFKHP ENNRTWSNYT
160 170 180 190 200
MCNAFTPEKL KNAYVLYYLA IVGHSLSIFT LVISLGIFVF FRKLTTIFPL
210 220 230 240 250
NWKYRKALSL GCQRVTLHKN MFLTYILNSM IIIIHLVEVV PNGELVRRDP
260 270 280 290 300
VSCKILHFFH QYMMACNYFW MLCEGIYLHT LIVVAVFTEK QRLRWYYLLG
310 320 330 340 350
WGFPLVPTTI HAITRAVYFN DNCWLSVETH LLYIIHGPVM AALVVNFFFL
360 370 380 390 400
LNIVRVLVTK MRETHEAESH MYLKAVKATM ILVPLLGIQF VVFPWRPSNK
410 420 430 440 450
MLGKIYDYVM HSLIHFQGFF VATIYCFCNN EVQTTVKRQW AQFKIQWNQR
460 470 480 490 500
WGRRPSNRSA RAAAAAAEAG DIPIYICHQE PRNEPANNQG EESAEIIPLN

IIEQESSA
Length:508
Mass (Da):59,352
Last modified:October 16, 2013 - v2
Checksum:iF76D13FD91BF61BA
GO
Isoform 2 (identifier: P30988-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.
     193-208: Missing.

Show »
Length:474
Mass (Da):55,329
Checksum:i0D9FA80FF16E82D9
GO
Isoform 3 (identifier: P30988-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.
     193-208: Missing.

Show »
Length:427
Mass (Da):49,878
Checksum:i733431C1963B7A83
GO
Isoform 4 (identifier: P30988-4) [UniParc]FASTAAdd to basket
Also known as: Delta(1-47)hCT((a))

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.

Show »
Length:443
Mass (Da):51,852
Checksum:iAE090009967D7B08
GO
Isoform 5 (identifier: P30988-5) [UniParc]FASTAAdd to basket
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.

Show »
Length:290
Mass (Da):34,397
Checksum:iB69ECF2AE4FAD38A
GO
Isoform 6 (identifier: P30988-6) [UniParc]FASTAAdd to basket
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.

Show »
Length:274
Mass (Da):32,423
Checksum:i83843885095D43EA
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti381I → T in AAC50301 (PubMed:7588285).Curated1

Polymorphismi

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, disruption 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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003580481P → L May be correlated with low bone mineral density (BMD). 6 PublicationsCorresponds to variant rs1801197dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0532891 – 65Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST65
Alternative sequenceiVSP_0532901 – 18Missing in isoform 2, isoform 5 and isoform 6. 8 PublicationsAdd BLAST18
Alternative sequenceiVSP_053291193 – 208Missing in isoform 2, isoform 3 and isoform 6. 9 PublicationsAdd BLAST16
Alternative sequenceiVSP_053292302 – 308GFPLVPT → APAFHRD in isoform 5 and isoform 6. 1 Publication7
Alternative sequenceiVSP_053293309 – 508Missing in isoform 5 and isoform 6. 1 PublicationAdd BLAST200

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
FN994995 mRNA. Translation: CBN80567.1.
FN994996 mRNA. Translation: CBN80568.1.
AY430048 mRNA. Translation: AAR06949.1.
AK313996 mRNA. Translation: BAG36708.1.
AC003078 Genomic DNA. Translation: AAB83945.1.
AC005024 Genomic DNA. No translation available.
CH236949 Genomic DNA. Translation: EAL24142.1.
CH471091 Genomic DNA. Translation: EAW76814.1.
BC069611 mRNA. Translation: AAH69611.1.
BC075028 mRNA. Translation: AAH75028.2.
CCDSiCCDS55125.1. [P30988-1]
CCDS5631.1. [P30988-2]
PIRiI37217.
S34486.
RefSeqiNP_001158209.1. NM_001164737.1.
NP_001158210.1. NM_001164738.1.
NP_001733.1. NM_001742.3.
UniGeneiHs.489127.

Genome annotation databases

EnsembliENST00000415529; ENSP00000413179; ENSG00000004948. [P30988-6]
ENST00000423724; ENSP00000391369; ENSG00000004948. [P30988-5]
GeneIDi799.
KEGGihsa:799.
UCSCiuc003umw.3. human. [P30988-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
FN994995 mRNA. Translation: CBN80567.1.
FN994996 mRNA. Translation: CBN80568.1.
AY430048 mRNA. Translation: AAR06949.1.
AK313996 mRNA. Translation: BAG36708.1.
AC003078 Genomic DNA. Translation: AAB83945.1.
AC005024 Genomic DNA. No translation available.
CH236949 Genomic DNA. Translation: EAL24142.1.
CH471091 Genomic DNA. Translation: EAW76814.1.
BC069611 mRNA. Translation: AAH69611.1.
BC075028 mRNA. Translation: AAH75028.2.
CCDSiCCDS55125.1. [P30988-1]
CCDS5631.1. [P30988-2]
PIRiI37217.
S34486.
RefSeqiNP_001158209.1. NM_001164737.1.
NP_001158210.1. NM_001164738.1.
NP_001733.1. NM_001742.3.
UniGeneiHs.489127.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5II0X-ray2.10A/B/C43-162[»]
ProteinModelPortaliP30988.
SMRiP30988.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107250. 5 interactors.
IntActiP30988. 8 interactors.
MINTiMINT-1217503.
STRINGi9606.ENSP00000352561.

Chemistry databases

BindingDBiP30988.
ChEMBLiCHEMBL1832.
DrugBankiDB01278. Pramlintide.
DB00017. Salmon Calcitonin.
GuidetoPHARMACOLOGYi43.

Protein family/group databases

TCDBi9.A.14.4.1. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiP30988.
PhosphoSitePlusiP30988.

Polymorphism and mutation databases

BioMutaiCALCR.
DMDMi550544247.

Proteomic databases

PaxDbiP30988.
PeptideAtlasiP30988.
PRIDEiP30988.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000415529; ENSP00000413179; ENSG00000004948. [P30988-6]
ENST00000423724; ENSP00000391369; ENSG00000004948. [P30988-5]
GeneIDi799.
KEGGihsa:799.
UCSCiuc003umw.3. human. [P30988-1]

Organism-specific databases

CTDi799.
DisGeNETi799.
GeneCardsiCALCR.
H-InvDBHIX0033513.
HGNCiHGNC:1440. CALCR.
HPAiHPA028962.
MalaCardsiCALCR.
MIMi114131. gene.
neXtProtiNX_P30988.
OpenTargetsiENSG00000004948.
PharmGKBiPA26032.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
GeneTreeiENSGT00760000118800.
HOGENOMiHOG000230695.
HOVERGENiHBG102129.
InParanoidiP30988.
KOiK04576.
TreeFamiTF315710.

Enzyme and pathway databases

ReactomeiR-HSA-418555. G alpha (s) signalling events.
R-HSA-419812. Calcitonin-like ligand receptors.

Miscellaneous databases

ChiTaRSiCALCR. human.
GeneWikiiCalcitonin_receptor.
GenomeRNAii799.
PROiP30988.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000004948.
CleanExiHS_CALCR.
ExpressionAtlasiP30988. baseline and differential.
GenevisibleiP30988. HS.

Family and domain databases

InterProiIPR003287. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR00361. CALCITONINR.
PR01350. CTRFAMILY.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiCALCR_HUMAN
AccessioniPrimary (citable) accession number: P30988
Secondary accession number(s): A4D1G6
, F5H605, O14585, Q13941, Q5ZGL8, Q659U6, Q6DJU8, Q6T712
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 16, 2013
Last modified: November 30, 2016
This is version 174 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.