Pcsk2 proprotein convertase subtilisin/kexin type 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pcsk2provided by MGI
Official Full Name: proprotein convertase subtilisin/kexin type 2provided by MGI
Primary source: MGI:MGI:97512
See related: Ensembl:ENSMUSG00000027419 AllianceGenome:MGI:97512
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: PC2; Nec2; SPC2; Nec-2; Phpp-2; 6330411F23Rik
Summary: Enables serine-type endopeptidase activity. Involved in enkephalin processing and protein autoprocessing. Acts upstream of or within nervous system development and proteolysis. Located in extracellular space. Is expressed in brain; endocrine gland; future brain; and gut. Human ortholog(s) of this gene implicated in myocardial infarction and type 2 diabetes mellitus. Orthologous to human PCSK2 (proprotein convertase subtilisin/kexin type 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in cortex adult (RPKM 46.1), frontal lobe adult (RPKM 33.5) and 4 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 G1; 2 70.89 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (143388053..143658204)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (143546133..143816284)

Chromosome 2 - NC_000068.8 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

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Replication Activities of Major 5' Terminally Deleted Group-B Coxsackievirus RNA Forms Decrease PCSK2 mRNA Expression Impairing Insulin Maturation in Pancreatic Beta Cells.
Title: Replication Activities of Major 5' Terminally Deleted Group-B Coxsackievirus RNA Forms Decrease PCSK2 mRNA Expression Impairing Insulin Maturation in Pancreatic Beta Cells.
A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing.
Title: A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing.
Hippocampal changes in mice lacking an active prohormone convertase 2.
Title: Hippocampal changes in mice lacking an active prohormone convertase 2.
Translation of insulin granule proteins are regulated by PDI and PABP.
Title: Translation of insulin granule proteins are regulated by PDI and PABP.
Study reveals a significant reduction of tachykinin and opioid neuropeptides level in proprotein convertase 1 and proprotein convertase 2 mutant mouse spinal cords.
Title: Targeted high-resolution quadrupole-Orbitrap mass spectrometry analyses reveal a significant reduction of tachykinin and opioid neuropeptides level in PC1 and PC2 mutant mouse spinal cords.
Study reports that PC2 null mice had increased number of mu opioid receptors in different brain areas. These mice also exhibited enhanced morphine-induced antinociception but reduced tolerance to and dependence on morphine.
Title: Prohormone convertase 2 (PC2) null mice have increased mu opioid receptor levels accompanied by altered morphine-induced antinociception, tolerance and dependence.
PC1 and PC2 are involved in the C-terminal processing of protachykinin peptides and suggest a major role in the maturation of the protachykinin-1 protein
Title: Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions.
activation of the hypothalamic GPR40/FFA1 signaling pathway may regulate beta-endorphin release via PC2, and regulate the endogenous pain control system
Title: Regulation of prohormone convertase 2 protein expression via GPR40/FFA1 in the hypothalamus.
Verified the roles of proprotein convertase subtilisin/kexin type 2 in regulating IGF1 and female sexual maturation, it also might be involved in the regulation of aging.
Title: Genetic Regulation of Female Sexual Maturation and Longevity Through Circulating IGF1.
Islets of Langerhans from prohormone convertase-2 knockout mice show alpha-cell hyperplasia and tumorigenesis with elevated alpha-cell neogenesis.
Title: Islets of Langerhans from prohormone convertase-2 knockout mice show α-cell hyperplasia and tumorigenesis with elevated α-cell neogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Variation

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Alleles

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

Targeted (1) 1 citation
Endonuclease-mediated (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Pcsk2 (e-PCR), detects polymorphism
- UniSTS:532491

M55669 (e-PCR)
- UniSTS:124956

AI839700 (e-PCR)
- UniSTS:164183

RH136607 (e-PCR)
- UniSTS:210587

RH94811 (e-PCR)
- UniSTS:120057

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables peptidase activity	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	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables serine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables serine-type endopeptidase activity	TAS Traceable Author Statement more info
enables serine-type peptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in enkephalin processing	IDA Inferred from Direct Assay more info	PubMed
involved_in insulin processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin processing	ISO Inferred from Sequence Orthology more info
involved_in islet amyloid polypeptide processing	ISO Inferred from Sequence Orthology more info
involved_in nervous system development	IEP Inferred from Expression Pattern more info	PubMed
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
acts_upstream_of_or_within peptide hormone processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptide hormone processing	ISO Inferred from Sequence Orthology more info
involved_in protein autoprocessing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular region	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
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	ISO Inferred from Sequence Orthology more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in perikaryon	ISO Inferred from Sequence Orthology more info
is_active_in secretory granule	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with secretory granule	ISO Inferred from Sequence Orthology more info
located_in secretory granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: neuroendocrine convertase 2

Names: KEX2-like endoprotease 2; NEC 2; prohormone convertase 2; proprotein convertase 2

NP_032818.1

EC 3.4.21.94

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_008792.4 → NP_032818.1 neuroendocrine convertase 2 precursor

See identical proteins and their annotated locations for NP_032818.1

Status: VALIDATED

Source sequence(s)

AK158598, AL807801, BC057348

Consensus CDS

CCDS16810.1

UniProtKB/Swiss-Prot

P21661, Q80WU1

UniProtKB/TrEMBL

Q3TYM6, Q547J8

Related

ENSMUSP00000028905.10, ENSMUST00000028905.10

Conserved Domains (4) summary

cd04059
Location:121 → 417

Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases

pfam00082
Location:157 → 434

Peptidase_S8; Subtilase family

pfam01483
Location:503 → 590

P_proprotein; Proprotein convertase P-domain

pfam16470
Location:32 → 108

S8_pro-domain; Peptidase S8 pro-domain