Pcsk5 proprotein convertase subtilisin/kexin type 5 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pcsk5provided by MGI
Official Full Name: proprotein convertase subtilisin/kexin type 5provided by MGI
Primary source: MGI:MGI:97515
See related: Ensembl:ENSMUSG00000024713 AllianceGenome:MGI:97515
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: PC5; PC6; SPC6; b2b585Clo; b2b1549Clo
Summary: This gene encodes a subtilisin-like proprotein convertase that mediates posttranslational endoproteolytic processing of various proprotein substrates traversing the secretory pathway. The encoded protein is an inactive zymogen that undergoes autoproteolytic processing in the endoplasmic reticulum and the Golgi network to generate an active enzyme. Mice lacking the encoded protein die at an early embryonic stage. Conditional inactivation this gene in the epiblast but not in the extraembryonic tissue bypasses embryonic lethality but results in death at birth. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2015]
Expression: Broad expression in adrenal adult (RPKM 16.1), small intestine adult (RPKM 7.7) and 17 other tissues See more
Orthologs: human all
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Genomic context

Location:: 19 B; 19 12.86 cM

Exon count:: 42

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	19	NC_000085.7 (17409678..17815076, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	19	NC_000085.6 (17432314..17837712, complement)

Chromosome 19 - NC_000085.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

In Vivo Analysis of the Contribution of Proprotein Convertases to the Processing of FGF23.
Title: In Vivo Analysis of the Contribution of Proprotein Convertases to the Processing of FGF23.
Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix.
Title: Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix.
this study demonstrates that Pcsk5 is expressed in bone-forming cells, and that OPN is a novel substrate for PC5/6
Title: Osteopontin as a novel substrate for the proprotein convertase 5/6 (PCSK5) in bone.
Pcsk5 may have an essential and early role in the cranio-cardiac mesoderm for heart development.
Title: Pcsk5 is required in the early cranio-cardiac mesoderm for heart development.
loss of the convertase furin or PC5/6 in hepatocytes results in a approximately 30% decrease in APC levels, with no significant contribution from PACE4. We conclude that prior convertase cleavage of protein C in hepatocytes is critical for its thrombin activation.
Title: Thrombin activation of protein C requires prior processing by a liver proprotein convertase.
overexpression of PCs, furin and PC5, but not PC7, which are all expressed in SMC, increase PKGI cleavage in a dose-dependent manner
Title: Proprotein convertases play an important role in regulating PKGI endoproteolytic cleavage and nuclear transport.
Inactivation of endothelial proprotein convertase 5/6 decreases collagen deposition in the cardiovascular system: role of fibroblast autophagy.
Title: Inactivation of endothelial proprotein convertase 5/6 decreases collagen deposition in the cardiovascular system: role of fibroblast autophagy.
PCSK5 and GDF11 expression during hindgut morphogenesis could be key factors for normal anorectal development, which can be disturbed by the administration of an overdose of all-trans retinoic acid, leading to anorectal malformations.
Title: PCSK5 and GDF11 expression in the hindgut region of mouse embryos with anorectal malformations.
Latent transforming growth factor beta-binding proteins-2 and -3 inhibit the proprotein convertase 5/6A.
Title: Latent transforming growth factor beta-binding proteins-2 and -3 inhibit the proprotein convertase 5/6A.
These data support the role of proconvertase PCSK5 in the processing of ovarian inhibin subunits during folliculogenesis.
Title: Role of PCSK5 expression in mouse ovarian follicle development: identification of the inhibin α- and β-subunits as candidate substrates.

Submit: New GeneRIF Correction See all GeneRIFs (25)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (4) 1 citation
Endonuclease-mediated (2)
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Pcsk5 (e-PCR), detects polymorphism
- UniSTS:532493

Pcsk5 (e-PCR), detects polymorphism
- UniSTS:507429

Pcsk5 (e-PCR), detects polymorphism
- UniSTS:507430

RH126545 (e-PCR)
- UniSTS:142225

D19Dcr4 (e-PCR), detects polymorphism
- UniSTS:507557

D19Dcr5 (e-PCR), detects polymorphism
- UniSTS:507558

D17583 (e-PCR)
- UniSTS:181214

WI-15571 (e-PCR)
- UniSTS:5604

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables peptidase activity	ISO Inferred from Sequence Orthology more info	PubMed
enables peptide binding	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in anterior/posterior pattern specification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in anterior/posterior pattern specification	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cardiac septum development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within coronary vasculature development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cytokine precursor processing	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within determination of left/right symmetry	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryo implantation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic digestive tract development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic digestive tract development	ISO Inferred from Sequence Orthology more info
involved_in embryonic skeletal system development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic skeletal system development	ISO Inferred from Sequence Orthology more info
involved_in heart development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	ISO Inferred from Sequence Orthology more info
involved_in limb morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptide biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in peptide hormone processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptide hormone processing	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide hormone processing	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of integrin activation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of integrin-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of smooth muscle cell-matrix adhesion	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular associated smooth muscle cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein processing	ISO Inferred from Sequence Orthology more info	PubMed
involved_in protein processing	ISO Inferred from Sequence Orthology more info
involved_in respiratory tube development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal peptide processing	ISO Inferred from Sequence Orthology more info
involved_in viral life cycle	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in Golgi medial cisterna	ISO Inferred from Sequence Orthology more info
is_active_in Golgi membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in perikaryon	ISO Inferred from Sequence Orthology more info
located_in proximal dendrite	ISO Inferred from Sequence Orthology more info
is_active_in trans-Golgi network	IBA Inferred from Biological aspect of Ancestor more info
located_in trans-Golgi network	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: proprotein convertase subtilisin/kexin type 5

Names: proprotein convertase 5; proprotein convertase 6; proprotein convertase PC5; subtilisin-like proprotein convertase 6; subtilisin/kexin-like protease PC5

NP_001156616.1

EC 3.4.21.-

NP_001177412.1

EC 3.4.21.-

XP_006526822.1

EC 3.4.21.-

XP_006526823.1

EC 3.4.21.-

XP_006526824.1

EC 3.4.21.-

XP_011245464.1

EC 3.4.21.-

XP_036017351.1

EC 3.4.21.-

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.

mRNA and Protein(s)

NM_001163144.1 → NP_001156616.1 proprotein convertase subtilisin/kexin type 5 isoform 2 precursor

See identical proteins and their annotated locations for NP_001156616.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as PC6A) represents use of an alternate 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (2) has a substantially shorter and distinct C-terminus, compared to isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform 1.

Source sequence(s)

AC125203, AC126940, AC133509

Consensus CDS

CCDS50402.1

UniProtKB/TrEMBL

Q91VK0

Related

ENSMUSP00000050272.9, ENSMUST00000050715.10

Conserved Domains (9) summary

cd04059
Location:128 → 422

Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases

smart00261
Location:781 → 825

FU; Furin-like repeats

cd00064
Location:690 → 739

FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.

pfam00082
Location:164 → 447

Peptidase_S8; Subtilase family

pfam01483
Location:507 → 597

P_proprotein; Proprotein convertase P-domain

pfam08686
Location:888 → 912

PLAC; PLAC (protease and lacunin) domain

pfam14843
Location:691 → 855

GF_recep_IV; Growth factor receptor domain IV

pfam15913
Location:695 → 786

Furin-like_2; Furin-like repeat, cysteine-rich

pfam16470
Location:40 → 116

S8_pro-domain; Peptidase S8 pro-domain
NM_001190483.2 → NP_001177412.1 proprotein convertase subtilisin/kexin type 5 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_001177412.1

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as PC6B) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC125203, AC126940, AC133509, AC147369

Consensus CDS

CCDS50401.1

UniProtKB/Swiss-Prot

E9QPB7, Q04592, Q62040

Related

ENSMUSP00000025618.9, ENSMUST00000025618.16

Conserved Domains (8) summary

cd04059
Location:128 → 422

Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases

smart00261
Location:781 → 825

FU; Furin-like repeats

cd00064
Location:1546 → 1593

FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.

pfam00082
Location:164 → 447

Peptidase_S8; Subtilase family

pfam01483
Location:507 → 597

P_proprotein; Proprotein convertase P-domain

pfam14843
Location:1496 → 1611

GF_recep_IV; Growth factor receptor domain IV

pfam15913
Location:1214 → 1305

Furin-like_2; Furin-like repeat, cysteine-rich

pfam16470
Location:40 → 116

S8_pro-domain; Peptidase S8 pro-domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000085.7 Reference GRCm39 C57BL/6J

Range

17409678..17815076 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006526759.4 → XP_006526822.1 proprotein convertase subtilisin/kexin type 5 isoform X2

Conserved Domains (7) summary

pfam03302
Location:706 → 1063

VSP; Giardia variant-specific surface protein

cd04059
Location:128 → 422

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

smart00261
Location:1615 → 1657

FU; Furin-like repeats

cd00064
Location:1519 → 1566

FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.

pfam01483
Location:507 → 597

P_proprotein; Proprotein convertase P-domain

pfam14843
Location:637 → 746

GF_recep_IV; Growth factor receptor domain IV

pfam16470
Location:40 → 116

S8_pro-domain; Peptidase S8 pro-domain
XM_011247162.3 → XP_011245464.1 proprotein convertase subtilisin/kexin type 5 isoform X1

Conserved Domains (7) summary

pfam03302
Location:706 → 1063

VSP; Giardia variant-specific surface protein

cd04059
Location:128 → 422

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

smart00261
Location:1641 → 1683

FU; Furin-like repeats

cd00064
Location:1545 → 1592

FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.

pfam01483
Location:507 → 597

P_proprotein; Proprotein convertase P-domain

pfam14843
Location:637 → 746

GF_recep_IV; Growth factor receptor domain IV

pfam16470
Location:40 → 116

S8_pro-domain; Peptidase S8 pro-domain
XM_036161458.1 → XP_036017351.1 proprotein convertase subtilisin/kexin type 5 isoform X3

Conserved Domains (5) summary

pfam03302
Location:603 → 885

VSP; Giardia variant-specific surface protein

smart00261
Location:342 → 386

FU; Furin-like repeats

cd00064
Location:1107 → 1154

FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.

pfam01483
Location:68 → 158

P_proprotein; Proprotein convertase P-domain

pfam14843
Location:198 → 307

GF_recep_IV; Growth factor receptor domain IV
XM_006526760.3 → XP_006526823.1 proprotein convertase subtilisin/kexin type 5 isoform X4

Conserved Domains (5) summary

pfam03302
Location:706 → 1063

VSP; Giardia variant-specific surface protein

cd04059
Location:128 → 422

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

pfam01483
Location:507 → 597

P_proprotein; Proprotein convertase P-domain

pfam14843
Location:637 → 746

GF_recep_IV; Growth factor receptor domain IV

pfam16470
Location:40 → 116

S8_pro-domain; Peptidase S8 pro-domain
XM_006526761.4 → XP_006526824.1 proprotein convertase subtilisin/kexin type 5 isoform X5

Conserved Domains (6) summary

pfam03302
Location:674 → 959

VSP; Giardia variant-specific surface protein

cd04059
Location:128 → 422

Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

pfam01483
Location:507 → 597

P_proprotein; Proprotein convertase P-domain

pfam14843
Location:637 → 746

GF_recep_IV; Growth factor receptor domain IV

pfam15913
Location:968 → 1010

Furin-like_2; Furin-like repeat, cysteine-rich

pfam16470
Location:40 → 116

S8_pro-domain; Peptidase S8 pro-domain