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    PAPPA2 pappalysin 2 [ Homo sapiens (human) ]

    Gene ID: 60676, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PAPPA2provided by HGNC
    Official Full Name
    pappalysin 2provided by HGNC
    Primary source
    HGNC:HGNC:14615
    See related
    Ensembl:ENSG00000116183 MIM:619485; AllianceGenome:HGNC:14615
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SSDA; PAPPE; PLAC3; PAPP-E; PAPP-A2
    Summary
    This gene encodes a member of the pappalysin family of metzincin metalloproteinases. The encoded protein cleaves insulin-like growth factor-binding protein 5 and is thought to be a local regulator of insulin-like growth factor (IGF) bioavailability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]
    Expression
    Biased expression in placenta (RPKM 23.7), kidney (RPKM 2.2) and 1 other tissue See more
    Orthologs
    mouse all
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    Genomic context

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    See PAPPA2 in Genome Data Viewer
    Location:
    1q25.2
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (176463175..176845601)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (175818447..176200273)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (176432311..176814737)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene zinc finger AN1-type containing 1 pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:176282688-176283193 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1571 Neighboring gene mortality factor 4 like 1 pseudogene 7 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:176525984-176527183 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1572 Neighboring gene PTP4A1 pseudogene 7 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:176694898-176695118 Neighboring gene NANOG hESC enhancer GRCh37_chr1:176702698-176703199 Neighboring gene MPRA-validated peak474 silencer Neighboring gene GATA motif-containing MPRA enhancer 65 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:176873029-176873530 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:176873531-176874030 Neighboring gene astrotactin 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:177013479-177014043 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:177017656-177018356 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:177029877-177031076 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:177034489-177035123 Neighboring gene microRNA 488 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr1:177139732-177140321 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:177140322-177140910 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:177150672-177151233 Neighboring gene uncharacterized LOC105371625 Neighboring gene BMP/retinoic acid inducible neural specific 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:177224616-177225815

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. The potential role of pregnancy-associated plasma protein-A2 in angiogenesis and development of preeclampsia. Chen X, et al. Hypertens Res, 2019 Jul. PMID 30816319
    2. Differential expression of human placental PAPP-A2 over gestation and in preeclampsia. Kramer AW, et al. Placenta, 2016 Jan. PMID 26748159, Free PMC Article
    3. Pregnancy associated plasma protein-A2: a novel biomarker for Down syndrome. Munnangi S, et al. Placenta, 2014 Nov. PMID 25154785, Free PMC Article
    4. Expression of PAPPA2 in human fetomaternal interface and involvement in trophoblast invasion and migration. Wang HY, et al. Genet Mol Res, 2016 Jul 25. PMID 27525857
    5. A replication study for the association of rs726252 in PAPPA2 with developmental dysplasia of the hip in Chinese Han population. Shi D, et al. Biomed Res Int, 2014. PMID 24672801, Free PMC Article

    See all (54) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype.
      Title: Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype.
    2. Short stature with low insulin-like growth factor 1 availability due to pregnancy-associated plasma protein A2 deficiency in a Saudi family.
      Title: Short stature with low insulin-like growth factor 1 availability due to pregnancy-associated plasma protein A2 deficiency in a Saudi family.
    3. Genetic Study of IL6, GDF5 and PAPPA2 in Association with Developmental Dysplasia of the Hip.
      Title: Genetic Study of IL6, GDF5 and PAPPA2 in Association with Developmental Dysplasia of the Hip.
    4. Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women.
      Title: Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women.
    5. Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.
      Title: Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.
    6. Disorders caused by genetic defects associated with GH-dependent genes: PAPPA2 defects.
      Title: Disorders caused by genetic defects associated with GH-dependent genes: PAPPA2 defects.
    7. 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.
    8. PAPP-A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia.
      Title: PAPP-A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia.
    9. Uteroplacental Ischemia Is Associated with Increased PAPP-A2.
      Title: Uteroplacental Ischemia Is Associated with Increased PAPP-A2.
    10. The potential role of pregnancy-associated plasma protein-A2 in angiogenesis and development of preeclampsia.
      Title: The potential role of pregnancy-associated plasma protein-A2 in angiogenesis and development of preeclampsia.
    Submit: New GeneRIF Correction See all GeneRIFs (36)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Short stature, Dauber-Argente type
    MedGen: C5561968 OMIM: 619489 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
    EBI GWAS Catalog
    Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.
    EBI GWAS Catalog
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metalloendopeptidase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloendopeptidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables metallopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in bone morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    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
    		  
    involved_in proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell growth NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in response to salt stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in apical plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    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 E1

    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.

    Genomic

    1. NG_023390.2 RefSeqGene

      Range
      5002..387428
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_020318.3 → NP_064714.2  pappalysin-2 isoform 1 precursor

      See identical proteins and their annotated locations for NP_064714.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AF311940, AF342989, AL031290, BC062665
      Consensus CDS
      CCDS41438.1
      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
      Related
      ENSP00000356634.3, ENST00000367662.5
      Conserved Domains (7) summary
      cd00033
      Location:1525 → 1591
      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:1722 → 1758
      NL; Domain found in Notch and Lin-12
      TIGR02232
      Location:1112 → 1151
      myxo_disulf_rpt; Myxococcus cysteine-rich repeat
      cd04275
      Location:634 → 831
      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:1467 → 1521
      Sushi; Sushi repeat (SCR repeat)
      pfam13385
      Location:282 → 433
      Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
      cl02419
      Location:585 → 612
      Notch; LNR domain

    2. NM_021936.3 → NP_068755.2  pappalysin-2 isoform 2 precursor

      See identical proteins and their annotated locations for NP_068755.2

      Status: REVIEWED

      Description
      Transcript Variant: # This Variant: This variant (2) differs in the 3' UTR and has multiple coding region differences, compared to variant 1. The resulting protein (isoform 2) has a distinct C-terminus and is shorter than isoform 1.
      Source sequence(s)
      AL139282, AL596254, BC062665, BC117195
      Consensus CDS
      CCDS41439.1
      UniProtKB/Swiss-Prot
      Q9BXP8
      Related
      ENSP00000356633.3, ENST00000367661.7
      Conserved Domains (3) summary
      smart00004
      Location:585 → 612
      NL; Domain found in Notch and Lin-12
      pfam13385
      Location:282 → 433
      Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
      cl00064
      Location:634 → 811
      ZnMc; Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major branches, the astacin-like proteases and the adamalysin/reprolysin-like proteases. Both branches have wide phylogenetic distribution, and contain sub-families, which ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      176463175..176845601
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047427180.1 → XP_047283136.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

    2. XM_017002024.2 → XP_016857513.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
      Conserved Domains (7) summary
      cd00033
      Location:1525 → 1591
      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:1722 → 1758
      NL; Domain found in Notch and Lin-12
      TIGR02232
      Location:1112 → 1151
      myxo_disulf_rpt; Myxococcus cysteine-rich repeat
      cd04275
      Location:634 → 831
      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:1467 → 1521
      Sushi; Sushi repeat (SCR repeat)
      pfam13385
      Location:282 → 433
      Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
      cl02419
      Location:585 → 612
      Notch; LNR domain

    3. XM_017002023.2 → XP_016857512.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
      Conserved Domains (7) summary
      cd00033
      Location:1525 → 1591
      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:1722 → 1758
      NL; Domain found in Notch and Lin-12
      TIGR02232
      Location:1112 → 1151
      myxo_disulf_rpt; Myxococcus cysteine-rich repeat
      cd04275
      Location:634 → 831
      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:1467 → 1521
      Sushi; Sushi repeat (SCR repeat)
      pfam13385
      Location:282 → 433
      Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
      cl02419
      Location:585 → 612
      Notch; LNR domain

    4. XM_011509857.1 → XP_011508159.1  pappalysin-2 isoform X1

      See identical proteins and their annotated locations for XP_011508159.1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
      Conserved Domains (7) summary
      cd00033
      Location:1525 → 1591
      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:1722 → 1758
      NL; Domain found in Notch and Lin-12
      TIGR02232
      Location:1112 → 1151
      myxo_disulf_rpt; Myxococcus cysteine-rich repeat
      cd04275
      Location:634 → 831
      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:1467 → 1521
      Sushi; Sushi repeat (SCR repeat)
      pfam13385
      Location:282 → 433
      Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
      cl02419
      Location:585 → 612
      Notch; LNR domain

    5. XM_005245422.4 → XP_005245479.1  pappalysin-2 isoform X1

      See identical proteins and their annotated locations for XP_005245479.1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
      Conserved Domains (7) summary
      cd00033
      Location:1525 → 1591
      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:1722 → 1758
      NL; Domain found in Notch and Lin-12
      TIGR02232
      Location:1112 → 1151
      myxo_disulf_rpt; Myxococcus cysteine-rich repeat
      cd04275
      Location:634 → 831
      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:1467 → 1521
      Sushi; Sushi repeat (SCR repeat)
      pfam13385
      Location:282 → 433
      Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
      cl02419
      Location:585 → 612
      Notch; LNR domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      175818447..176200273
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054338079.1 → XP_054194054.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

    2. XM_054338081.1 → XP_054194056.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

    3. XM_054338082.1 → XP_054194057.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

    4. XM_054338080.1 → XP_054194055.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

    5. XM_054338083.1 → XP_054194058.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

    6. XM_054338085.1 → XP_054194060.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

    7. XM_054338084.1 → XP_054194059.1  pappalysin-2 isoform X1

      UniProtKB/Swiss-Prot
      A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BXP8.4 GenPept UniProtKB/Swiss-Prot:Q9BXP8

    Gene LinkOut

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