CALCA

Official Full Name

calcitonin related polypeptide alpha

Organism

Homo sapiens

Gene ID

796

Background

This gene encodes the peptide hormones calcitonin, calcitonin gene-related peptide and katacalcin by tissue-specific alternative RNA splicing of the gene transcripts and cleavage of inactive precursor proteins. Calcitonin is involved in calcium regulation and acts to regulate phosphorus metabolism. Calcitonin gene-related peptide functions as a vasodilator and as an antimicrobial peptide while katacalcin is a calcium-lowering peptide. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2014]

Synonyms

CT; KC; PCT; CGRP; CALC1; CGRP1; CGRP-I; CGRP-alpha

Cat.No.	Product Name	Price
CSC-DC002291	Panoply™ Human CALCA Knockdown Stable Cell Line	Inquiry
CSC-SC002291	Panoply™ Human CALCA Over-expressing Stable Cell Line	Inquiry
CLOE-0503	Human CALCA(Fc) HEK293 Cell Lysate	Inquiry
CLOE-0504	Human CALCA(His) HEK293 Cell Lysate	Inquiry
CSC-RO01411	Human CALCA Stable Cell Line - HCE-T	Inquiry

Cat.No.	Product Name	Price
AD02909Z	Human CALCA adenoviral particles	Inquiry
LV07774L	human CALCA (NM_001033953) lentivirus particles	Inquiry
LV07775L	human CALCA (NM_001033952) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHG136653	shRNA set against Rat Calca(NM_001033955.1)	Inquiry
SHG136649	shRNA set against Mouse Calca(NM_007587.2)	Inquiry
SHG136925	shRNA set against Rat Calca(NM_017338.2)	Inquiry
SHG136943	shRNA set against Rat Calca(NM_001033956.1)	Inquiry
SHG136961	shRNA set against Mouse Calca(NM_001033954.3)	Inquiry
SHG136979	shRNA set against Mouse Calca(NM_007587.2)	Inquiry
SHG136993	shRNA set against Rat Calca(NM_001033955.1)	Inquiry
SHH253693	shRNA set against Human CALCA (NM_001741.2)	Inquiry
SHH253697	shRNA set against Mouse CALCA (NM_007587.2)	Inquiry
SHH253701	shRNA set against Rat CALCA (NM_017338.2)	Inquiry
SHW002750	shRNA set against Chicken CALCA (NM_001113708)	Inquiry
SHW003632	shRNA set against Chicken CALCA (NM_001271964)	Inquiry
SHW003633	shRNA set against Chicken CALCA (NM_001271965)	Inquiry
SHW003634	shRNA set against Chicken CALCA (NM_001271966)	Inquiry
SHW006487	shRNA set against Danio rerio CALCA (NM_001002471)	Inquiry

Cat.No.	Product Name	Price
MiUTR4H-TG10790	CALCA miRNA 3'UTR clone	Inquiry
MiUTR1R-00689	CALCA miRNA 3'UTR clone	Inquiry
MiUTR1R-00688	CALCA miRNA 3'UTR clone	Inquiry
MiUTR1M-02467	CALCA miRNA 3'UTR clone	Inquiry
MiUTR1M-02466	CALCA miRNA 3'UTR clone	Inquiry
CDFR011051	Rat Calca cDNA Clone(NM_017338.2)	Inquiry
CDFR004302	Rat Calca cDNA Clone(NM_001033956.1)	Inquiry
CDCR040806	Mouse Calca ORF clone (NM_001033954.3)	Inquiry
CDFR004299	Rat Calca cDNA Clone(NM_001033955.1)	Inquiry
CDCR371328	Rat Calca ORF Clone(NM_001033955.1)	Inquiry
CDFH002613	Human CALCA cDNA Clone(NM_001741.2)	Inquiry
MiUTR1R-00690	CALCA miRNA 3'UTR clone	Inquiry
CDCR378437	Rat Calca ORF Clone(NM_017338.2)	Inquiry
CDCR371329	Rat Calca ORF Clone(NM_001033956.1)	Inquiry
CDCR281410	Human CALCA ORF Clone(NM_001741.2)	Inquiry
CDCL183019	Human CALCA ORF clone(NM_001033952.2)	Inquiry
CDCG012573	Mouse CALCA ORF clone(NM_007587.2)	Inquiry
CDCB167962	Danio rerio CALCA ORF Clone (NM_001002471)	Inquiry
CDCB165109	Chicken CALCA ORF Clone (NM_001271966)	Inquiry
CDCB165108	Chicken CALCA ORF Clone (NM_001271965)	Inquiry
CDCB165107	Chicken CALCA ORF Clone (NM_001271964)	Inquiry
CDCS406855	Human CALCA ORF Clone (BC069760)	Inquiry
CDCB164225	Chicken CALCA ORF Clone (NM_001113708)	Inquiry

Detailed Information

The CALCA gene, located on human chromosome 11p15.2, exemplifies the complexity and precision of eukaryotic gene expression. Through tissue-specific alternative RNA splicing, a single transcript gives rise to two distinct biologically active peptides: calcitonin (CT) and calcitonin gene-related peptide (CGRP). Additionally, post-translational proteolytic processing of the precursor protein can generate a third active peptide, katacalcin. This "one gene, multiple products" mechanism allows CALCA to perform divergent physiological roles depending on the tissue context.

In thyroid parafollicular cells, the primary transcript encodes the calcitonin precursor, which is processed into mature calcitonin. In contrast, in the nervous and cardiovascular systems, selective splicing skips the calcitonin exon, yielding CGRP, which exists in two major isoforms: α-CGRP, encoded by CALCA, and β-CGRP, encoded by the homologous CALCB gene. These isoforms have overlapping but subtly distinct functions, forming a finely tuned regulatory network. Such complex transcriptional and post-translational regulation ensures that CALCA products exert precise effects at the right time and place, underpinning their multifunctional biological roles.

Biological Significance

CALCA gene products are involved in calcium-phosphate homeostasis, neuro-immune-vascular communication, and more. Calcitonin primarily inhibits osteoclast-mediated bone resorption, promoting calcium and phosphate deposition in bone. This acute hypocalcemic effect counterbalances parathyroid hormone, maintaining mineral metabolism.

CGRP is recognized as one of the most potent endogenous vasodilators. By binding its specific receptor, CGRP induces relaxation of coronary, cerebral, and peripheral vessels, regulating local blood flow, blood pressure, and microcirculation. In the central and peripheral nervous systems, CGRP functions as a neurotransmitter and neuromodulator, modulating pain signaling, initiating and sustaining inflammation, and regulating autonomic functions.

Figure 1. Schematic representation of a CGRP receptor. (Iyengar S, et al., 2017)

Notably, CGRP released from sensory nerve terminals triggers neurogenic inflammation, causing vasodilation, plasma protein extravasation, and mast cell degranulation-critical mechanisms in pain and inflammatory disorders. CGRP also exhibits direct antimicrobial activity, suggesting a role in innate immune defense and forming a communication link between the nervous and immune systems. Katacalcin primarily contributes to calcium homeostasis, with mechanisms and physiological significance still under investigation. Together, CALCA products serve as multifunctional regulators in bone metabolism, cardiovascular homeostasis, neural signaling, immune defense, and inflammation, with dysregulation implicated in various diseases.

Clinical Relevance

The clinical importance of CALCA, particularly CGRP, is most prominent in migraine pathophysiology and treatment. During migraine attacks, abnormal activation of the trigeminovascular system leads to massive CGRP release from sensory nerve endings, causing severe intracranial vasodilation and neurogenic inflammation, producing throbbing headache and associated symptoms. This discovery established CGRP and its receptor as revolutionary therapeutic targets.

Clinically approved therapies include: CGRP receptor antagonists and monoclonal antibodies targeting CGRP or its receptor, which effectively and specifically block CGRP signaling, providing excellent efficacy and safety in prevention and treatment of migraine, transforming the clinical management of this condition.

Beyond migraine, CGRP plays important roles in cardiovascular physiology. In shock states, compensatory CGRP release may help maintain perfusion of vital organs, while excessive vasodilation may contribute to hypotension. In chronic conditions like atherosclerosis, hypertension, and heart failure, CGRP signaling may be disrupted, and loss of its protective function can exacerbate disease progression, making CGRP modulation a potential therapeutic avenue.

In oncology, aberrant CALCA expression and methylation patterns may serve as cancer biomarkers. Additionally, calcitonin analogs have long been used to inhibit bone resorption in osteoporosis and Paget's disease. However, systemic long-term CGRP blockade requires caution due to potential impacts on cardiovascular protection, immune surveillance, and bone metabolism. Future research aims to clarify the precise roles of CALCA-derived peptides in specific disease microenvironments and develop tissue-targeted modulation strategies.

References

Russell FA, King R, Smillie SJ, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94(4):1099–1142.
Iyengar S, Ossipov MH, Johnson KW. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine. Pain. 2017;158(4):543–559.

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