PAPPA2 (pappalysin 2)

Gene

• Entrez ID: 60676
• Gene name: Pappalysin 2
• Gene symbol: PAPPA2
• Synonyms (NCBI Gene): PAPP-A2, PAPP-E, PAPPE, PLAC3, SSDA
• Chromosome: 1
• Chromosome location: 1q25.2
• 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. Alter

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1213089	hsa-miR-186	CLIP-seq
MIRT1213090	hsa-miR-3133	CLIP-seq
MIRT1213091	hsa-miR-4252	CLIP-seq
MIRT1213092	hsa-miR-1228	CLIP-seq
MIRT1213093	hsa-miR-188-3p	CLIP-seq
MIRT1213094	hsa-miR-4267	CLIP-seq
MIRT1213095	hsa-miR-4640-5p	CLIP-seq
MIRT1213096	hsa-miR-4726-5p	CLIP-seq
MIRT1213097	hsa-miR-532-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001558	Process	Regulation of cell growth	NAS	11264294
GO:0004222	Function	Metalloendopeptidase activity	EXP	11513734
GO:0004222	Function	Metalloendopeptidase activity	IBA
GO:0004222	Function	Metalloendopeptidase activity	IEA
GO:0004222	Function	Metalloendopeptidase activity	TAS
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0006508	Process	Proteolysis	IBA
GO:0006508	Process	Proteolysis	IDA	11264294
GO:0006508	Process	Proteolysis	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IBA
GO:0008233	Function	Peptidase activity	IEA
GO:0008237	Function	Metallopeptidase activity	IDA	11264294
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0008270	Function	Zinc ion binding	NAS	11264294
GO:0009651	Process	Response to salt stress	IEA
GO:0016324	Component	Apical plasma membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0060349	Process	Bone morphogenesis	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145

Other IDs

• MIM: 619485
• HGNC: 14615
• e!Ensembl: ENSG00000116183

Protein

• UniProt ID: Q9BXP8
• Protein name: Pappalysin-2 (EC 3.4.24.-) (Pregnancy-associated plasma protein A2) (PAPP-A2) (Pregnancy-associated plasma protein E1) (PAPP-E)
• Protein function: Metalloproteinase which specifically cleaves insulin-like growth factor binding protein (IGFBP)-5 at the '163-Ser-|-Lys-164' bond. Shows limited proteolysis toward IGFBP-3.
• PDB: 8SL1
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13385	Laminin_G_3	270 → 437		Domain
  PF00066	Notch	584 → 613	LNR domain	Domain
  PF05572	Peptidase_M43	669 → 831	Pregnancy-associated plasma protein-A	Family
  PF00084	Sushi	1464 → 1521	Sushi repeat (SCR repeat)	Domain
  PF00084	Sushi	1525 → 1590	Sushi repeat (SCR repeat)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed abundantly in placenta, and non-pregnant mammary gland with low expression in the kidney, fetal brain and pancreas. {ECO:0000269|PubMed:11264294, ECO:0000269|PubMed:11597188}.
• Sequence:

  MMCLKILRISLAILAGWALCSANSELGWTRKKSLVEREHLNQVLLEGERCWLGAKVRRPR
  ASPQHHLFGVYPSRAGNYLRPYPVGEQEIHHTGRSKPDTEGNAVSLVPPDLTENPAGLRG
  AVEEPAAPWVGDSPIGQSELLGDDDAYLGNQRSKESLGEAGIQKGSAMAATTTTAIFTTL
  NEPKPETQRRGWAKSRQRRQVWKRRAEDGQGDSGISSHFQPWPKHSLKHRVKKSPPEESN
  QNGGEGSYREAETFNSQVGLPILYFSGRRERLLLRPEVLAEIPREAFTVEAWVKPEGGQN
  NPAIIAGVFDNCSHTVSDKGWALGIRSGKDKGKRDARFFFSLCTDRVKKATILISHSRYQ
  PGTWTHVAATYDGRHMALYVDGTQVASSLDQSGPLNSPFMASCRSLLLGGDSSEDGHYFR
  GHLGTLVFWSTALPQSHFQHSSQHSSGEEEATDLVLTASFEPVNTEWVPFRDEKYPRLEV
  LQGFEPEPEILSPLQPPLCGQTVCDNVELISQYNGYWPLRGEKVIRYQVVNICDDEGLNP
  IVSEEQIRLQHEALNEAFSRYNISWQLSVHQVHNSTLRHRVVLVNCEPSKIGNDHCDPEC
  EHPLTGYDGGDCRLQGRCYSWNRRDGLCHVECNNMLNDFDDGDCCDPQVADVRKTCFDPD
  SPKRAYMSVKELKEALQLNSTHFLNIYFASSVREDLAGAATWPWDKDAVTHLGGIVLSPA
  YYGMPGHTDTMIHEVGHVLGLYHVFKGVSERESCNDPCKETVPSMETGDLCADTAPTPKS
  ELCREPEPTSDTCGFTRFPGAPFTNYMSYTDDNCTDNFTPNQVARMHCYLDLVYQQWTES
  RKPTPIPIPPMVIGQTNKSLTIHWLPPISGVVYDRASGSLCGACTEDGTFRQYVHTASSR
  RVCDSSGYWTPEEAVGPPDVDQPCEPSLQAWSPEVHLYHMNMTVPCPTEGCSLELLFQHP
  VQADTLTLWVTSFFMESSQVLFDTEILLENKESVHLGPLDTFCDIPLTIKLHVDGKVSGV
  KVYTFDERIEIDAALLTSQPHSPLCSGCRPVRYQVLRDPPFASGLPVVVTHSHRKFTDVE
  VTPGQMYQYQVLAEAGGELGEASPPLNHIHGAPYCGDGKVSERLGEECDDGDLVSGDGCS
  KVCELEEGFNCVGEPSLCYMYEGDGICEPFERKTSIVDCGIYTPKGYLDQWATRAYSSHE
  DKKKCPVSLVTGEPHSLICTSYHPDLPNHRPLTGWFPCVASENETQDDRSEQPEGSLKKE
  DEVWLKVCFNRPGEARAIFIFLTTDGLVPGEHQQPTVTLYLTDVRGSNHSLGTYGLSCQH
  NPLIINVTHHQNVLFHHTTSVLLNFSSPRVGISAVALRTSSRIGLSAPSNCISEDEGQNH
  QGQSCIHRPCGKQDSCPSLLLDHADVVNCTSIGPGLMKCAITCQRGFALQASSGQYIRPM
  QKEILLTCSSGHWDQNVSCLPVDCGVPDPSLVNYANFSCSEGTKFLKRCSISCVPPAKLQ
  GLSPWLTCLEDGLWSLPEVYCKLECDAPPIILNANLLLPHCLQDNHDVGTICKYECKPGY
  YVAESAEGKVRNKLLKIQCLEGGIWEQGSCIPVVCEPPPPVFEGMYECTNGFSLDSQCVL
  NCNQEREKLPILCTKEGLWTQEFKLCENLQGECPPPPSELNSVEYKCEQGYGIGAVCSPL
  CVIPPSDPVMLPENITADTLEHWMEPVKVQSIVCTGRRQWHPDPVLVHCIQSCEPFQADG
  WCDTINNRAYCHYDGGDCCSSTLSSKKVIPFAADCDLDECTCRDPKAEENQ

• Sequence length: 1791

Pathways

Reactome:

Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Short stature, Dauber-Argente type	Pathogenic	rs2102651720, rs2102818589, rs2102813590	RCV001568412 RCV001568413 RCV001568414	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTISM SPECTRUM DISORDER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EBV-positive nodal T- and NK-cell lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PAPPA2-related disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia Hemolytic	Hemolytic anemia	Pubtator	21496272	Associate	★☆☆☆☆ Found in Text Mining only
Brachydactyly type A2	Brachydactyly	Pubtator	34358737	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	37962678	Associate	★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	GWASDB_DG	22941190		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	37214090	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Dysplasia Of The Hip	Developmental dysplasia of the hip	BEFREE	22037112, 24672801, 30915115, 31168749		★☆☆☆☆ Found in Text Mining only
Developmental Dysplasia of the Hip	Developmental dysplasia of the hip	Pubtator	22037112, 24672801	Associate	★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down syndrome	Pubtator	25154785	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	26902202, 29280739, 29653372		★☆☆☆☆ Found in Text Mining only
Eclampsia	Eclampsia	BEFREE	18805800, 23484525		★☆☆☆☆ Found in Text Mining only
Gastritis	Gastritis	Pubtator	37962678	Stimulate	★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	26902202, 27648969, 34358737	Associate	★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin Disease	BEFREE	28854436		★☆☆☆☆ Found in Text Mining only
Huntington Disease	Huntington Disease	BEFREE	28854436		★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	21496272	Stimulate	★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24069199		★☆☆☆☆ Found in Text Mining only
Melanoma Cutaneous Malignant	Melanoma	Pubtator	35811392	Associate	★☆☆☆☆ Found in Text Mining only
Micropenis	Micropenis	BEFREE	30840065		★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	BEFREE	30840065		★☆☆☆☆ Found in Text Mining only
Precocious Puberty	Precocious puberty	BEFREE	29293544		★☆☆☆☆ Found in Text Mining only