PCSK1

Protein identityUniProt · HPA

UniProt accession

P29120

Gene

PCSK1

Ensembl

ENSG00000175426

Chromosome

5

Canonical length

753 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted in other tissues

OverviewNCBI Gene

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. The protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene [provided by RefSeq, Jan 2014]

Canonical amino-acid sequenceUniProt

753 residues, UniProt reviewed canonical sequence.

>P29120|PCSK1
     1  MERRAWSLQC TAFVLFCAWC ALNSAKAKRQ FVNEWAAEIP GGPEAASAIA EELGYDLLGQ
    61  IGSLENHYLF KHKNHPRRSR RSAFHITKRL SDDDRVIWAE QQYEKERSKR SALRDSALNL
   121  FNDPMWNQQW YLQDTRMTAA LPKLDLHVIP VWQKGITGKG VVITVLDDGL EWNHTDIYAN
   181  YDPEASYDFN DNDHDPFPRY DPTNENKHGT RCAGEIAMQA NNHKCGVGVA YNSKVGGIRM
   241  LDGIVTDAIE ASSIGFNPGH VDIYSASWGP NDDGKTVEGP GRLAQKAFEY GVKQGRQGKG
   301  SIFVWASGNG GRQGDNCDCD GYTDSIYTIS ISSASQQGLS PWYAEKCSST LATSYSSGDY
   361  TDQRITSADL HNDCTETHTG TSASAPLAAG IFALALEANP NLTWRDMQHL VVWTSEYDPL
   421  ANNPGWKKNG AGLMVNSRFG FGLLNAKALV DLADPRTWRS VPEKKECVVK DNDFEPRALK
   481  ANGEVIIEIP TRACEGQENA IKSLEHVQFE ATIEYSRRGD LHVTLTSAAG TSTVLLAERE
   541  RDTSPNGFKN WDFMSVHTWG ENPIGTWTLR ITDMSGRIQN EGRIVNWKLI LHGTSSQPEH
   601  MKQPRVYTSY NTVQNDRRGV EKMVDPGEEQ PTQENPKENT LVSKSPSSSS VGGRRDELEE
   661  GAPSQAMLRL LQSAFSKNSP PKQSPKKSPS AKLNIPYENF YEALEKLNKP SQLKDSEDSL
   721  YNDYVDVFYN TKPYKHRDDR LLQALVDILN EEN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PCSK1 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

31 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PCSK1.

Disease | AllUniProt

Conditions PCSK1 is implicated in, by any mechanism.

• Proprotein convertase 1 deficiency (PC1 deficiency) MIM:600955

Disease | GeneticClinVar

38 pathogenic / likely-pathogenic of 455 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Obesity due to prohormone convertase I deficiency
• PCSK1-related disorder
• Body mass index quantitative trait locus 12
• Obesity
• Early onset severe obesity

ReferencesPubMed · IEDB

Publications for PCSK1 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)

0.73

gnomAD pLI

0

gnomAD missense Z

1.47

DepMap mean gene effect

0.01

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

• cell-cell signaling
• insulin processing
• peptide biosynthetic process
• peptide hormone processing
• proteolysis

Molecular functions

• identical protein binding
• serine-type endopeptidase activity

Cellular components

• extracellular space
• membrane
• neuron projection
• secretory granule lumen
• transport vesicle

Protein domainsUniProt · Pfam · InterPro

• Peptidase S8/S53 domain
• P domain
• Galactose-binding-like domain superfamily
• Peptidase S8, subtilisin-related
• Peptidase S8, subtilisin, His-active site
• Peptidase S8, subtilisin, Asp-active site
• Peptidase S8, subtilisin, Ser-active site
• Peptidase S8, pro-domain
• Kexin/furin catalytic domain
• Peptidase S8/S53 domain superfamily
• Peptidase S8, pro-domain superfamily
• Subtilase family
• Proprotein convertase P-domain
• Peptidase S8 pro-domain
• Prohormone convertase enzyme
• Prohormone convertase enzyme

KeywordsUniProt

• Calcium
• Cleavage on pair of basic residues
• Cytoplasmic vesicle
• Disulfide bond
• Glycoprotein
• Hydrolase
• Obesity
• Protease
• Serine protease
• Signal
• Zymogen