PTH

Protein identityUniProt · HPA

UniProt accession

P01270

Gene

PTH

Ensembl

ENSG00000152266

Chromosome

11

Canonical length

115 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a member of the parathyroid family of proteins. The encoded preproprotein is proteolytically processed to generate a protein that binds to the parathyroid hormone/parathyroid hormone-related peptide receptor and regulates blood calcium and phosphate levels. Excess production of the encoded protein, known as hyperparathyroidism, can result in hypercalcemia and kidney stones. On the other hand, defective processing of the encoded protein may lead to hypoparathyroidism, which can result in hypocalcemia and numbness. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

Canonical amino-acid sequenceUniProt

115 residues, UniProt reviewed canonical sequence.

>P01270|PTH
     1  MIPAKDMAKV MIVMLAICFL TKSDGKSVKK RSVSEIQLMH NLGKHLNSME RVEWLRKKLQ
    61  DVHNFVALGA PLAPRDAGSQ RPRKKEDNVL VESHEKSLGE ADKADVNVLT KAKSQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PTH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.59

Highest tissue expression

47,154 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PTH.

Disease | AllUniProt

Conditions PTH is implicated in, by any mechanism.

• Hypoparathyroidism, familial isolated, 1 (FIH1) MIM:146200

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 54 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypoparathyroidism, familial isolated 1
• Primary hyperparathyroidism
• Familial hypoparathyroidism

ReferencesPubMed · IEDB

Publications for PTH from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.7

gnomAD pLI

0.01

gnomAD missense Z

0.55

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway
• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• bone mineralization
• bone resorption
• cAMP metabolic process
• cell-cell signaling
• G protein-coupled receptor signaling pathway
• homeostasis of number of cells within a tissue
• hormone-mediated apoptotic signaling pathway
• intracellular calcium ion homeostasis
• magnesium ion homeostasis
• negative regulation of apoptotic process in bone marrow cell
• negative regulation of bone mineralization involved in bone maturation
• negative regulation of chondrocyte differentiation
• negative regulation of gene expression
• phosphate ion homeostasis
• positive regulation of bone mineralization
• positive regulation of cell proliferation in bone marrow
• positive regulation of D-glucose import
• positive regulation of gene expression
• positive regulation of glycogen biosynthetic process
• positive regulation of inositol phosphate biosynthetic process
• positive regulation of osteoclast proliferation
• positive regulation of signal transduction
• positive regulation of transcription by RNA polymerase II
• regulation of gene expression
• response to cadmium ion
• response to ethanol
• response to fibroblast growth factor
• response to lead ion
• response to parathyroid hormone
• response to vitamin D
• response to xenobiotic stimulus
• Rho protein signal transduction
• skeletal system development
• transcription by RNA polymerase II
• macromolecule biosynthetic process

Molecular functions

• hormone activity
• peptide hormone receptor binding
• receptor ligand activity
• parathyroid hormone receptor binding
• type 1 parathyroid hormone receptor binding

Cellular components

• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Parathyroid hormone/parathyroid hormone-related protein
• Parathyroid hormone family
• Parathyroid hormone

KeywordsUniProt

• Cleavage on pair of basic residues
• Hormone
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of PTH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PTH1R