PCSK1 proprotein convertase subtilisin/kexin type 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PCSK1provided by HGNC
Official Full Name: proprotein convertase subtilisin/kexin type 1provided by HGNC
Primary source: HGNC:HGNC:8743
See related: Ensembl:ENSG00000175426 MIM:162150; AllianceGenome:HGNC:8743
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PC1; PC3; NEC1; SPC3; PC1/3; BMIQ12
Summary: 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]
Expression: Biased expression in brain (RPKM 13.3), adrenal (RPKM 3.9) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q15

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (96390333..96433248, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (96891318..96934221, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (95726037..95768952, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differential sex-association between PCSK1 polymorphisms and obesity risk in Portuguese children.
Title: Differential sex-association between PCSK1 polymorphisms and obesity risk in Portuguese children.
The N221D variant in PCSK1 is highly prevalent in childhood obesity and can influence the metabolic profile.
Title: The N221D variant in PCSK1 is highly prevalent in childhood obesity and can influence the metabolic profile.
Association of PCSK1 and PPARG1 Allelic Variants with Obesity and Metabolic Syndrome in Mexican Adults.
Title: Association of PCSK1 and PPARG1 Allelic Variants with Obesity and Metabolic Syndrome in Mexican Adults.
Functional characterization of all missense variants in LEPR, PCSK1, and POMC genes arising from single-nucleotide variants.
Title: Functional characterization of all missense variants in LEPR, PCSK1, and POMC genes arising from single-nucleotide variants.
Contribution of heterozygous PCSK1 variants to obesity and implications for precision medicine: a case-control study.
Title: Contribution of heterozygous PCSK1 variants to obesity and implications for precision medicine: a case-control study.
Rare Heterozygous <i>PCSK1</i> Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.
Title: Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.
Novel Homozygous Inactivating Mutation in the PCSK1 Gene in an Infant with Congenital Malabsorptive Diarrhea.
Title: Novel Homozygous Inactivating Mutation in the PCSK1 Gene in an Infant with Congenital Malabsorptive Diarrhea.
GLP-1 receptor signaling increases PCSK1 and beta cell features in human alpha cells.
Title: GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells.
Revisiting Proinsulin Processing: Evidence That Human beta-Cells Process Proinsulin With Prohormone Convertase (PC) 1/3 but Not PC2.
Title: Revisiting Proinsulin Processing: Evidence That Human β-Cells Process Proinsulin With Prohormone Convertase (PC) 1/3 but Not PC2.
PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.
Title: PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.

Submit: New GeneRIF Correction See all GeneRIFs (69)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Body mass index quantitative trait locus 12 MedGen: C2676498 OMIM: 612362 GeneReviews: Not available	Compare labs
Obesity due to prohormone convertase I deficiency MedGen: C1833053 OMIM: 600955 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association of body fat distribution in African ancestry populations suggests new loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies common variants associated with body mass index in east Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. EBI GWAS Catalog EBI GWAS CatalogPubMed
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	PC1, one of the subtilisin/kexin family convertases, cleaves HIV-1 gp160 into gp120 and gp41 at amino acids 511-512	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH81073 (e-PCR)
- UniSTS:83969

G59132 (e-PCR)
- UniSTS:136453

PCSK1_1012 (e-PCR)
- UniSTS:277568

PCSK1_V280 (e-PCR)
- UniSTS:277568

NoName (e-PCR)
- UniSTS:486736

SHGC-112327 (e-PCR)
- UniSTS:168528

G59296 (e-PCR)
- UniSTS:136611

STS-X64810 (e-PCR)
- UniSTS:31153

RH92225 (e-PCR)
- UniSTS:92350

RH103693 (e-PCR)
- UniSTS:98018

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in insulin processing	IEA Inferred from Electronic Annotation more info
involved_in neurogenesis	IEA Inferred from Electronic Annotation more info
involved_in pancreas development	IEA Inferred from Electronic Annotation more info
involved_in peptide biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptide hormone processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in pituitary gland development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein secretion	IEA Inferred from Electronic Annotation more info
involved_in protein autoprocessing	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed
involved_in response to axon injury	IEA Inferred from Electronic Annotation more info
involved_in response to calcium ion	IEA Inferred from Electronic Annotation more info
involved_in response to chlorate	IEA Inferred from Electronic Annotation more info
involved_in response to fatty acid	IEA Inferred from Electronic Annotation more info
involved_in response to glucocorticoid	IEA Inferred from Electronic Annotation more info
involved_in response to glucose	IEA Inferred from Electronic Annotation more info
involved_in response to interleukin-1	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient levels	IEA Inferred from Electronic Annotation more info
involved_in response to peptide hormone	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in axon terminus	IEA Inferred from Electronic Annotation more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in secretory granule lumen	TAS Traceable Author Statement more info
located_in trans-Golgi network	IEA Inferred from Electronic Annotation more info
located_in transport vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: neuroendocrine convertase 1

Names: prohormone convertase 1; prohormone convertase 3; proprotein convertase 1/3

NP_000430.3

EC 3.4.21.93

NP_001171346.1

EC 3.4.21.93

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_021161.1 RefSeqGene

Range

5034..47949

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000439.5 → NP_000430.3 neuroendocrine convertase 1 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_000430.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest protein (isoform 1).

Source sequence(s)

AC008951, DA192592, X64810

Consensus CDS

CCDS4081.1

UniProtKB/Swiss-Prot

B7Z8T7, E9PHA1, P29120, P78478, Q92532

UniProtKB/TrEMBL

A1L3V6

Related

ENSP00000308024.2, ENST00000311106.8

Conserved Domains (5) summary

cd04059
Location:121 → 415

Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases

pfam00082
Location:158 → 432

Peptidase_S8; Subtilase family

pfam01483
Location:504 → 591

P_proprotein; Proprotein convertase P-domain

pfam12177
Location:715 → 751

Proho_convert; Prohormone convertase enzyme

pfam16470
Location:34 → 110

S8_pro-domain; Peptidase S8 pro-domain
NM_001177875.2 → NP_001171346.1 neuroendocrine convertase 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region, and initiates translation at an alternate start codon compared to variant 1. The resulting isoform (2) is shorter and has a distinct N-terminus compared to isoform 1.

Source sequence(s)

AC008951, AC108107, AK303888

Consensus CDS

CCDS54881.1

UniProtKB/TrEMBL

Q59H85

Related

ENSP00000421600.1, ENST00000508626.5

Conserved Domains (5) summary

cd04059
Location:74 → 368

Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases

pfam00082
Location:111 → 385

Peptidase_S8; Subtilase family

pfam01483
Location:457 → 544

P_proprotein; Proprotein convertase P-domain

pfam12177
Location:668 → 704

Proho_convert; Prohormone convertase enzyme

pfam16470
Location:8 → 63

S8_pro-domain; Peptidase S8 pro-domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

96390333..96433248 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060929.1 Alternate T2T-CHM13v2.0

Range

96891318..96934221 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001177876.1: Suppressed sequence

Description

NM_001177876.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.