P06881 (CALCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcitonin gene-related peptide 1

Alternative name(s):
Alpha-type CGRP
Calcitonin gene-related peptide I
Short name=CGRP-I

Gene names

Name:	CALCA
Synonyms:	CALC1

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	128 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	CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role. It also elevates platelet cAMP. Ref.10
Subcellular location	Secreted.
Sequence similarities	Belongs to the calcitonin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Hormone
PTM	Amidation Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor internalization Inferred from direct assay PubMed 10882736. Source: UniProtKB activation of adenylate cyclase activity Inferred from direct assay PubMed 10822112PubMed 16014619. Source: UniProtKB cell-cell signaling Traceable author statement Ref.5. Source: ProtInc elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Inferred from direct assay PubMed 9685362. Source: UniProtKB endothelial cell migration Inferred from direct assay PubMed 17267696. Source: UniProtKB endothelial cell proliferation Inferred from direct assay PubMed 17267696. Source: UniProtKB leukocyte cell-cell adhesion Inferred from direct assay PubMed 1326102. Source: UniProtKB negative regulation of blood pressure Inferred from direct assay PubMed 10642343. Source: MGI negative regulation of bone resorption Inferred from direct assay PubMed 10822112. Source: UniProtKB negative regulation of calcium ion transport into cytosol Inferred from direct assay PubMed 16014619. Source: UniProtKB negative regulation of osteoclast differentiation Inferred from direct assay PubMed 10822112. Source: UniProtKB neurological system process involved in regulation of systemic arterial blood pressure Inferred from direct assay PubMed 10642343. Source: MGI positive regulation of interleukin-1 alpha production Inferred from direct assay PubMed 16904178. Source: UniProtKB positive regulation of interleukin-8 production Inferred from direct assay PubMed 16904178. Source: UniProtKB positive regulation of macrophage differentiation Inferred from direct assay PubMed 10822112. Source: UniProtKB positive regulation of vasodilation Inferred from direct assay PubMed 3266556. Source: UniProtKB protein phosphorylation Inferred from direct assay PubMed 20596610. Source: UniProtKB regulation of blood pressure Non-traceable author statement Ref.10. Source: UniProtKB vasculature development Inferred from direct assay PubMed 17267696. Source: UniProtKB vasodilation Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from direct assay PubMed 17267696. Source: UniProtKB extracellular space Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	protein complex binding Inferred from direct assay PubMed 14722252. Source: UniProtKB receptor binding Inferred from direct assay PubMed 16014619. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 3 (identifier: P06881-1)

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 1 (identifier: P01258-1)

The sequence of this isoform can be found in the external entry P01258.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Isoform 2 (identifier: P01258-2)

The sequence of this isoform can be found in the external entry P01258.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Potential

Propeptide

26 – 80

55

PRO_0000004053

Peptide

83 – 119

37

Calcitonin gene-related peptide 1 Ref.8

PRO_0000004054

Propeptide

125 – 128

4

PRO_0000004055

Amino acid modifications

Modified residue

119

1

Phenylalanine amide

Disulfide bond

84 ↔ 89

Natural variations

Natural variant

57

1

N → D. Ref.1 Ref.2 Ref.4
Corresponds to variant rs5239 [ dbSNP | Ensembl ].

VAR_048584

Secondary structure

1

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128

Helix Strand Turn

Details...

Helix

3 – 19

17

Helix

22 – 32

11

Helix

41 – 54

14

Helix

61 – 72

12

Helix

75 – 81

7

Turn

82 – 85

4

Helix

94 – 99

6

Helix

101 – 105

5

Beta strand

113 – 115

3

Helix

116 – 120

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 3 [UniParc]. Last modified October 5, 2010. Version 3. Checksum: 2AA1A9AC3060D9B6	FASTA	128	13,898
	10 20 30 40 50 60 MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL LAALVQNYVQ 70 80 90 100 110 120 MKASELEQEQ EREGSRIIAQ KRACDTATCV THRLAGLLSR SGGVVKNNFV PTNVGSKAFG RRRRDLQA
	Isoform 1 [UniParc]. See P01258.		–	–
	Isoform 2 [UniParc]. See P01258.		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Alternative RNA processing events in human calcitonin/calcitonin gene-related peptide gene expression." Jonas V., Lin C.R., Kawashima E., Semon D., Swanson L.W., Mermod J.-J., Evans R.M., Rosenfeld M.G. Proc. Natl. Acad. Sci. U.S.A. 82:1994-1998(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-57.
[2]	"Structure and methylation of the human calcitonin/alpha-CGRP gene." Broad P.M., Symes A.J., Thakker R.V., Craig R.K. Nucleic Acids Res. 17:6999-7011(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-57.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Structure and expression of a gene encoding human calcitonin and calcitonin gene related peptide." Nelkin B.D., Rosenfeld K.I., de Bustros A., Leong S.S., Roos B.A., Baylin S.B. Biochem. Biophys. Res. Commun. 123:648-655(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 48-119, VARIANT ASP-57.
[5]	"Expression of the human calcitonin/CGRP gene in lung and thyroid carcinoma." Edbrooke M.R., Parker D., McVey J.H., Riley J.H., Sorenson G.D., Pettengill O.S., Craig R.K. EMBO J. 4:715-724(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 76-128.
[6]	"Calcitonin gene related peptide coding sequence is conserved in the human genome and is expressed in medullary thyroid carcinoma." Steenbergh P.H., Hoppener J.W., Zandberg J., de Ven W.J., Jansz H.S., Lips C.J. J. Clin. Endocrinol. Metab. 59:358-360(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-128. Tissue: Thyroid carcinoma.
[7]	"Expression and function of the human calcitonin/alpha-CGRP gene in health and disease." Craig R.K., Riley J.H., Edbrooke M.R., Broad P.M., Foord S.M., Al-Kazwini S.J., Holman J.J., Marshall I. Biochem. Soc. Symp. 52:91-105(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-128.
[8]	"Isolation and characterization of human calcitonin gene-related peptide." Morris H.R., Panico M., Etienne T., Tippins J., Girgis S.I., McIntyre I. Nature 308:746-748(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 83-119.
[9]	"Identification in the human central nervous system, pituitary, and thyroid of a novel calcitonin gene-related peptide, and partial amino acid sequence in the spinal cord." Petermann J.B., Born W., Chang J.Y., Fischer J.A. J. Biol. Chem. 262:542-545(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 83-117.
[10]	"Isolation and characterization of peptides which act on rat platelets, from a pheochromocytoma." Kitamura K., Kangawa K., Kawamoto M., Ichiki Y., Matsuo H., Eto T. Biochem. Biophys. Res. Commun. 185:134-141(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 83-108, FUNCTION. Tissue: Pheochromocytoma.
[11]	"Solution structure of human calcitonin gene-related peptide by 1H NMR and distance geometry with restrained molecular dynamics." Breeze A.L., Harvey T.S., Bazzo R., Campbell I.D. Biochemistry 30:575-582(1991) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF CGRP.
[12]	"Solution structures of calcitonin-gene-related-peptide analogues of calcitonin-gene-related peptide and amylin." Hubbard J.A.M., Martin S.R., Chaplin L.C., Bose C., Kelly S.M., Price N.C. Biochem. J. 275:785-788(1991) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF CGRP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M12667, M12664, M12665 Genomic DNA. Translation: AAA51914.1.
X15943 Genomic DNA. Translation: CAA34070.1.
AC090835 Genomic DNA. No translation available.
K03512 mRNA. Translation: AAA52011.1.
X02330 mRNA. Translation: CAA26190.1.
M28637 Genomic DNA. Translation: AAA52012.1.
M26094 Genomic DNA. Translation: AAA51912.1.

IPI

IPI00027855.

PIR

TCHUR. S07644.

RefSeq

NP_001029125.1. NM_001033953.2.

UniGene

Hs.37058.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LS7	model	-	A	1-125	[»]

ProteinModelPortal

P06881.

SMR

P06881. Positions 83-119.

ModBase

Search...

Protein-protein interaction databases

IntAct

P06881. 3 interactions.

Protein family/group databases

TCDB

1.C.49.1.2. cytotoxic amylin family.

Polymorphism databases

DMDM

308153625.

Proteomic databases

PaxDb

P06881.

PRIDE

P06881.

Protocols and materials databases

DNASU

796.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000361010; ENSP00000354286; ENSG00000110680.
ENST00000486207; ENSP00000417833; ENSG00000110680.
ENST00000570728; ENSP00000461551; ENSG00000262933.

GeneID

796.

KEGG

hsa:796.

UCSC

uc001mlt.2. human.

Organism-specific databases

CTD

796.

GeneCards

GC11M014945.

HGNC

HGNC:1437. CALCA.

HPA

CAB000005.

MIM

114130. gene.

neXtProt

NX_P06881.

PharmGKB

PA26029.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40787.

HOGENOM

HOG000038203.

HOVERGEN

HBG031362.

KO

K12332.

OMA

RACDTAT.

OrthoDB

EOG4ZPDWQ.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P06881.

Bgee

P06881.

CleanEx

HS_CALCA.

Genevestigator

P06881.

GermOnline

ENSG00000110680. Homo sapiens.

Family and domain databases

InterPro

IPR018360. Calcitonin_CS.
IPR001693. Calcitonin_peptide-like.
IPR021117. Procalcitonin-like.
IPR021116. Procalcitonin/adrenomedullin.
IPR015476. Procalcitonin_gene-rel_peptide.
[Graphical view]

PANTHER

PTHR10505. PTHR10505. 1 hit.
PTHR10505:SF2. PTHR10505:SF2. 1 hit.

Pfam

PF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]

PRINTS

PR00817. CALCITONINB.

SMART

SM00113. CALCITONIN. 1 hit.
[Graphical view]

PROSITE

PS00258. CALCITONIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P06881.

ChEMBL

CHEMBL5293.

DrugBank

DB00692. Phentolamine.

GenomeRNAi

796.

NextBio

3234.

SOURCE

Search...

Entry information

Entry name

CALCA_HUMAN

Accession

Primary (citable) accession number: P06881
Secondary accession number(s): Q93048, Q9UCP0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	October 5, 2010
Last modified:	May 1, 2013
This is version 135 of the entry and version 3 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.