Pappa2 pappalysin 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pappa2provided by MGI
Official Full Name: pappalysin 2provided by MGI
Primary source: MGI:MGI:3051647
See related: Ensembl:ENSMUSG00000073530 AllianceGenome:MGI:3051647
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: PLAC3; Pappe; PAPP-A2
Summary: Predicted to enable metalloendopeptidase activity. Acts upstream of or within bone morphogenesis. Predicted to be located in apical plasma membrane and cytosol. Is expressed in several structures, including alimentary system; bone; genitourinary system; nervous system; and retina layer. Orthologous to human PAPPA2 (pappalysin 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Restricted expression toward placenta adult (RPKM 69.9) See more
Orthologs: human all
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Genomic context

Location:: 1 H1; 1 68.49 cM

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (158539297..158788019, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (158711727..158960451, complement)

Chromosome 1 - NC_000067.7 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

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?

Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors.
Title: Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors.
Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency.
Title: Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency.
Downregulation of PAPP-A2 expression or upregulation of IGFBP-5 expression can reduce collagen synthesis and cartilage proliferation. PAPP-A2 may be involved in the development of the hip joint by interfering in the fibrous and cartilaginous metabolism via IGF pathway-associated proteins pathway.
Title: Abnormal expression of Pappa2 gene may indirectly affect mouse hip development through the IGF signaling pathway.
Pappa2 mutation led to significant reductions in body length, body weight, and relative lean mass in mice. Micro-CT analyses of Pappa2 knock-in femurs from adult mice showed inhibited periosteal bone expansion leading to more slender bones in both male and female mice. Furthermore, in the Pappa2 knock-in mice, insulin resistance correlated with decreased serum free IGF-I and increased intact IGFBP-3 concentrations.
Title: Low IGF-I Bioavailability Impairs Growth and Glucose Metabolism in a Mouse Model of Human PAPPA2 p.Ala1033Val Mutation.
Pappa2 deletion is associated with bone resorption.
Title: Pappa2 deletion has sex- and age-specific effects on bone in mice.
This review evaluates the current data concerning PAPP-A2 function, and particularly the effect of PAPP-A2 mutation on growth.
Title: PAPP-A2 a new key regulator of growth.
Locally-produced Pappa2 in osteoblasts, epiphysis, and metaphysis, is required for normal postnatal bone growth.
Title: PAPP-A2 expression by osteoblasts is required for normal postnatal growth in mice.
Despite a dramatic disruption of the balance between circulating IGF-I, IGFBP-3 and -5, we found no effects of Pappa2 deletion on glucose metabolism, weight gain or adiposity on a high-fat diet.
Title: Pappa2 deletion alters IGFBPs but has little effect on glucose disposal or adiposity.
Pappa2 deletion had no effect on female reproduction and subtle effects on male fertility.
Title: Pappa2 deletion in mice affects male but not female fertility.
Pappa2 is responsible for the effects of the previously-identified QTL, demonstrating that natural variation in the Pappa2 gene contributes to variation in postnatal growth in mice
Title: Pregnancy associated plasma protein A2 (PAPP-A2) affects bone size and shape and contributes to natural variation in postnatal growth in mice.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

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

Chemically induced (ENU) (5)
Endonuclease-mediated (2)
Targeted (3) 1 citation

General gene information

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Markers

Pappa2 (e-PCR), detects polymorphism
- UniSTS:547283

Pappa2 (e-PCR), detects polymorphism
- UniSTS:546526

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
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	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within bone morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within proteolysis	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: pappalysin-2

Names: placenta-specific 3; pregnancy-associated plasma preproprotein-A2; pregnancy-associated plasma protein-E

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_001085376.3 → NP_001078845.1 pappalysin-2 precursor

See identical proteins and their annotated locations for NP_001078845.1

Status: VALIDATED

Source sequence(s)

AC115116, AC158910, AC162173

Consensus CDS

CCDS48409.1

UniProtKB/TrEMBL

E9PZ87

Related

ENSMUSP00000124022.3, ENSMUST00000159861.9

Conserved Domains (6) summary

smart00004
Location:1720 → 1756

NL; Domain found in Notch and Lin-12

TIGR02232
Location:1113 → 1152

myxo_disulf_rpt; Myxococcus cysteine-rich repeat

cd04275
Location:635 → 832

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:1523 → 1586

Sushi; Sushi repeat (SCR repeat)

pfam13385
Location:283 → 440

Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily

cl02419
Location:586 → 613

Notch; LNR 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_000067.7 Reference GRCm39 C57BL/6J

Range

158539297..158788019 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006496824.5 → XP_006496887.1 pappalysin-2 isoform X1

See identical proteins and their annotated locations for XP_006496887.1

UniProtKB/TrEMBL

E9PZ87

Conserved Domains (6) summary

smart00004
Location:1720 → 1756

NL; Domain found in Notch and Lin-12

TIGR02232
Location:1113 → 1152

myxo_disulf_rpt; Myxococcus cysteine-rich repeat

cd04275
Location:635 → 832

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:1523 → 1586

Sushi; Sushi repeat (SCR repeat)

pfam13385
Location:283 → 440

Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily

cl02419
Location:586 → 613

Notch; LNR domain
XM_036164644.1 → XP_036020537.1 pappalysin-2 isoform X1

UniProtKB/TrEMBL

E9PZ87

Conserved Domains (6) summary

smart00004
Location:1720 → 1756

NL; Domain found in Notch and Lin-12

TIGR02232
Location:1113 → 1152

myxo_disulf_rpt; Myxococcus cysteine-rich repeat

cd04275
Location:635 → 832

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:1523 → 1586

Sushi; Sushi repeat (SCR repeat)

pfam13385
Location:283 → 440

Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily

cl02419
Location:586 → 613

Notch; LNR domain