Pappa pregnancy-associated plasma protein A [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pappaprovided by MGI
Official Full Name: pregnancy-associated plasma protein Aprovided by MGI
Primary source: MGI:MGI:97479
See related: Ensembl:ENSMUSG00000028370 AllianceGenome:MGI:97479
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: PAG1; PAPP-A; IGFBP-4ase; 8430414N03Rik
Summary: Enables endopeptidase activity. Predicted to be involved in several processes, including protein catabolic process; proteolysis; and response to dexamethasone. Located in extracellular space. Is expressed in several structures, including central nervous system; genitourinary system; gut; limb; and paraxial mesenchyme. Human ortholog(s) of this gene implicated in myocardial infarction. Orthologous to human PAPPA (pappalysin 1). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Broad expression in testis adult (RPKM 2.1), subcutaneous fat pad adult (RPKM 0.8) and 18 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 C1; 4 34.14 cM

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (65041993..65276776)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (65124174..65357509)

Chromosome 4 - NC_000070.7 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: Mouse ENCODE transcriptome data 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?

Recapitulation of anti-aging phenotypes by global, but not by muscle-specific, deletion of PAPP-A in mice.
Title: Recapitulation of anti-aging phenotypes by global, but not by muscle-specific, deletion of PAPP-A in mice.
Brain-specific PAPP-A knock-out mice?
Title: Brain-specific PAPP-A knock-out mice?
Inhibition of longevity regulator PAPP-A modulates tissue homeostasis via restraint of mesenchymal stromal cells.
Title: Inhibition of longevity regulator PAPP-A modulates tissue homeostasis via restraint of mesenchymal stromal cells.
Suppression of PAPP-A mitigates atherosclerosis by mediating macrophage polarization via STAT3 signaling.
Title: Suppression of PAPP-A mitigates atherosclerosis by mediating macrophage polarization via STAT3 signaling.
PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans.
Title: PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans.
Genetic and Pharmacological Inhibition of PAPP-A Protects Against Visceral Obesity in Mice.
Title: Genetic and Pharmacological Inhibition of PAPP-A Protects Against Visceral Obesity in Mice.
This work provides a comprehensive characterization of the surfaceome of EWS, credentials PAPP-A as a highly differentially expressed therapeutic target, and discovers a novel link between IGF-1 signaling and immune evasion in cancer, thus implicating shared mechanisms of immune evasion between EWS and the placenta.
Title: Pregnancy-Associated Plasma Protein-A (PAPP-A) in Ewing Sarcoma: Role in Tumor Growth and Immune Evasion.
Inducible knockdown of PAPP-A gene expression in adult female mice extends life span.
Title: Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.
Intrinsic mitochondrial oxidative capacity was significantly increased in skeletal muscle of aged PAPP-A KO compared to WT mice. Moreover, 18-month-old PAPP-A KO mice exhibited significantly enhanced endurance running on a treadmill. Thus, PAPP-A deficiency in mice is associated with indices of healthy skeletal muscle function with age.
Title: Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice.
Snell, GHKRO, and PAPPA-KO mice express high levels of two proteins involved in DNA repair, O-6-methylguanine-DNA methyltransferase (MGMT) and N-myc downstream-regulated gene 1 (NDRG1).
Title: mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Variation

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Alleles

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

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

B.seq (e-PCR), detects polymorphism
- UniSTS:141145

D4Mcg10 (e-PCR), detects polymorphism
- UniSTS:142458

D4Nds9 (e-PCR), detects polymorphism
- UniSTS:142481

Pappa (e-PCR), detects polymorphism
- UniSTS:525978

Pappa (e-PCR), detects polymorphism
- UniSTS:546525

MHAa35a11.seq (e-PCR)
- UniSTS:125154

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metalloendopeptidase activity	ISO Inferred from Sequence Orthology more info
enables metallopeptidase activity	IEA Inferred from Electronic Annotation more info
enables metallopeptidase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in response to dexamethasone	IEA Inferred from Electronic Annotation more info
involved_in response to dexamethasone	ISO Inferred from Sequence Orthology more info
involved_in response to follicle-stimulating hormone	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular region	ISO Inferred from Sequence Orthology more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: pappalysin-1

Names: IGF-dependent IGFBP-4 protease; insulin-like growth factor-dependent IGF-binding protein 4 protease

NP_067337.1

EC 3.4.24.79

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_021362.2 → NP_067337.1 pappalysin-1 precursor

See identical proteins and their annotated locations for NP_067337.1

Status: VALIDATED

Source sequence(s)

AL691454, AL691491

Consensus CDS

CCDS18267.1

UniProtKB/Swiss-Prot

Q80VW3, Q80YY1, Q8K423, Q8R4K7, Q8R4K8, Q9ES06, Q9JK57

Related

ENSMUSP00000081545.4, ENSMUST00000084501.4

Conserved Domains (6) summary

cd00033
Location:1343 → 1418

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

smart00004
Location:1544 → 1580

NL; Domain found in Notch and Lin-12

TIGR02232
Location:941 → 980

myxo_disulf_rpt; Myxococcus cysteine-rich repeat

smart00560
Location:114 → 263

LamGL; LamG-like jellyroll fold domain

cd04275
Location:421 → 657

ZnMc_pappalysin_like; Zinc-dependent metalloprotease, pappalysin_like subfamily. The pregnancy-associated plasma protein A (PAPP-A or pappalysin-1) cleaves insulin-like growth factor-binding proteins 4 and 5, thereby promoting cell growth by releasing bound growth factor. ...

pfam00084
Location:1412 → 1468

Sushi; Sushi repeat (SCR repeat)