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Pappa2 pappalysin 2 [ Mus musculus (house mouse) ]

Gene ID: 23850, updated on 28-Oct-2024

Summary

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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. Predicted to be active in extracellular space. Is expressed in several structures, including alimentary system; genitourinary system; long bone; nervous system; and retina layer. Orthologous to human PAPPA2 (pappalysin 2). [provided by Alliance of Genome Resources, Oct 2024]
Expression
Restricted expression toward placenta adult (RPKM 69.9) See more
Orthologs
human all
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Genomic context

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See Pappa2 in Genome Data Viewer
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_000067.7Genomic Context describing neighboring genes Neighboring gene VISTA enhancer mm1369 Neighboring gene bone morphogenic protein/retinoic acid inducible neural-specific 2 Neighboring gene astrotactin 1 Neighboring gene STARR-seq mESC enhancer starr_02777 Neighboring gene predicted gene, 37679 Neighboring gene microRNA 488 Neighboring gene STARR-seq mESC enhancer starr_02778 Neighboring gene predicted gene, 53639 Neighboring gene STARR-seq mESC enhancer starr_02779 Neighboring gene STARR-seq mESC enhancer starr_02780 Neighboring gene RIKEN cDNA 1600012P17 gene Neighboring gene STARR-seq mESC enhancer starr_02781 Neighboring gene STARR-seq mESC enhancer starr_02782 Neighboring gene predicted gene, 39687

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Low IGF-I Bioavailability Impairs Growth and Glucose Metabolism in a Mouse Model of Human PAPPA2 p.Ala1033Val Mutation. Fujimoto M, et al. Endocrinology, 2019 Jun 1. PMID 30977789, Free PMC Article
  2. Pappa2 deletion has sex- and age-specific effects on bone in mice. Christians JK, et al. Growth Horm IGF Res, 2019 Feb. PMID 30445407
  3. Pappa2 deletion in mice affects male but not female fertility. Christians JK, et al. Reprod Biol Endocrinol, 2015 Sep 29. PMID 26416573, Free PMC Article
  4. PAPP-A2 expression by osteoblasts is required for normal postnatal growth in mice. Amiri N, et al. Growth Horm IGF Res, 2015 Dec. PMID 26385171
  5. Pappa2 deletion alters IGFBPs but has little effect on glucose disposal or adiposity. Christians JK, et al. Growth Horm IGF Res, 2015 Oct. PMID 26164771

See all (37) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Pappa2 deletion is associated with bone resorption.
    Title: Pappa2 deletion has sex- and age-specific effects on bone in mice.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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

Homology

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)

  1. 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

  1. NC_000067.7 Reference GRCm39 C57BL/6J

    Range
    158539297..158788019 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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
Nucleotide Protein Strain
Heading Accession and Version

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