PAPPA (pappalysin 1)

Gene

• Entrez ID: 5069
• Gene name: Pappalysin 1
• Gene symbol: PAPPA
• Synonyms: ASBABP2, DIPLA1, IGFBP-4ase, PAPA, PAPP-A, PAPPA1
• Chromosome: 9
• Chromosome location: 9q33.1
• Summary: This gene encodes a secreted metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs). Following IGFBP cleavage, insulin growth factors dissociate from IGFBPs and bind to IGF receptors, resulting in activation of the IGF pathway. The encoded protein plays a role in bone formation, inflammation, wound healing and female fertility. Enhanced expression of this protein is associated with diabetic nephropathy in human patients and this protein may promote tumor invasion and growth in various human cancers. [provided by RefSeq, Aug 2017]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT025857	hsa-miR-7-5p	Microarray	19073608
MIRT029988	hsa-miR-26b-5p	Microarray	19088304
MIRT437513	hsa-miR-490-3p	ChIP-seq, ELISA, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23821525
MIRT438677	hsa-miR-214-3p	Immunohistochemistry, Immunoprecipitaion, Luciferase reporter assay, qRT-PCR, Western blot	23929716
MIRT446694	hsa-miR-1273f	PAR-CLIP	22100165
MIRT446695	hsa-miR-4708-5p	PAR-CLIP	22100165
MIRT446696	hsa-miR-6088	PAR-CLIP	22100165
MIRT446697	hsa-miR-4770	PAR-CLIP	22100165
MIRT446698	hsa-miR-143-3p	PAR-CLIP	22100165
MIRT707980	hsa-miR-190a-3p	HITS-CLIP	21572407
MIRT707981	hsa-miR-4789-5p	HITS-CLIP	21572407
MIRT707982	hsa-miR-3941	HITS-CLIP	21572407
MIRT707983	hsa-miR-5011-5p	HITS-CLIP	21572407
MIRT707984	hsa-miR-4789-3p	HITS-CLIP	21572407
MIRT707985	hsa-miR-603	HITS-CLIP	21572407
MIRT707986	hsa-miR-8485	HITS-CLIP	21572407
MIRT707987	hsa-miR-362-3p	HITS-CLIP	21572407
MIRT707988	hsa-miR-329-3p	HITS-CLIP	21572407
MIRT735495	hsa-miR-141-3p	Luciferase reporter assay, qRT-PCR, Western blot	26823756

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004222	Function	Metalloendopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	7685339, 12421832
GO:0005576	Component	Extracellular region	IDA	10077652
GO:0005576	Component	Extracellular region	NAS	10913121
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IEA
GO:0006508	Process	Proteolysis	IEA
GO:0007565	Process	Female pregnancy	NAS	10077652, 10913121
GO:0008237	Function	Metallopeptidase activity	IDA	10077652
GO:0008237	Function	Metallopeptidase activity	NAS	10913121
GO:0008270	Function	Zinc ion binding	NAS	10077652, 10913121
GO:0032354	Process	Response to follicle-stimulating hormone	IEA
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0051384	Process	Response to glucocorticoid	IEA

Other IDs

• MIM: 176385
• HGNC: 8602
• e!Ensembl: ENSG00000182752

Protein

• UniProt ID: Q13219
• Protein name: Pappalysin-1 (EC 3.4.24.79) (Insulin-like growth factor-dependent IGF-binding protein 4 protease) (IGF-dependent IGFBP-4 protease) (IGFBP-4ase) (Pregnancy-associated plasma protein A) (PAPP-A)
• Protein function: Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by the presence of IGF.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13385	Laminin_G_3	100 → 269		Domain
  PF05572	Peptidase_M43	499 → 660	Pregnancy-associated plasma protein-A	Family
  PF00084	Sushi	1280 → 1342	Sushi repeat (SCR repeat)	Domain
  PF00084	Sushi	1346 → 1412	Sushi repeat (SCR repeat)	Domain
  PF00084	Sushi	1415 → 1471	Sushi repeat (SCR repeat)	Domain

• Sequence:

  MRLWSWVLHLGLLSAALGCGLAERPRRARRDPRAGRPPRPAAGPATCATRAARGRRASPP
  PPPPPGGAWEAVRVPRRRQQREARGATEEPSPPSRALYFSGRGEQLRLRADLELPRDAFT
  LQVWLRAEGGQRSPAVITGLYDKCSYISRDRGWVVGIHTISDQDNKDPRYFFSLKTDRAR
  QVTTINAHRSYLPGQWVYLAATYDGQFMKLYVNGAQVATSGEQVGGIFSPLTQKCKVLML
  GGSALNHNYRGYIEHFSLWKVARTQREILSDMETHGAHTALPQLLLQENWDNVKHAWSPM
  KDGSSPKVEFSNAHGFLLDTSLEPPLCGQTLCDNTEVIASYNQLSSFRQPKVVRYRVVNL
  YEDDHKNPTVTREQVDFQHHQLAEAFKQYNISWELDVLEVSNSSLRRRLILANCDISKIG
  DENCDPECNHTLTGHDGGDCRHLRHPAFVKKQHNGVCDMDCNYERFNFDGGECCDPEITN
  VTQTCFDPDSPHRAYLDVNELKNILKLDGSTHLNIFFAKSSEEELAGVATWPWDKEALMH
  LGGIVLNPSFYGMPGHTHTMIHEIGHSLGLYHVFRGISEIQSCSDPCMETEPSFETGDLC
  NDTNPAPKHKSCGDPGPGNDTCGFHSFFNTPYNNFMSYADDDCTDSFTPNQVARMHCYLD
  LVYQGWQPSRKPAPVALAPQVLGHTTDSVTLEWFPPIDGHFFERELGSACHLCLEGRILV
  QYASNASSPMPCSPSGHWSPREAEGHPDVEQPCKSSVRTWSPNSAVNPHTVPPACPEPQG
  CYLELEFLYPLVPESLTIWVTFVSTDWDSSGAVNDIKLLAVSGKNISLGPQNVFCDVPLT
  IRLWDVGEEVYGIQIYTLDEHLEIDAAMLTSTADTPLCLQCKPLKYKVVRDPPLQMDVAS
  ILHLNRKFVDMDLNLGSVYQYWVITISGTEESEPSPAVTYIHGSGYCGDGIIQKDQGEQC
  DDMNKINGDGCSLFCRQEVSFNCIDEPSRCYFHDGDGVCEEFEQKTSIKDCGVYTPQGFL
  DQWASNASVSHQDQQCPGWVIIGQPAASQVCRTKVIDLSEGISQHAWYPCTISYPYSQLA
  QTTFWLRAYFSQPMVAAAVIVHLVTDGTYYGDQKQETISVQLLDTKDQSHDLGLHVLSCR
  NNPLIIPVVHDLSQPFYHSQAVRVSFSSPLVAISGVALRSFDNFDPVTLSSCQRGETYSP
  AEQSCVHFACEKTDCPELAVENASLNCSSSDRYHGAQCTVSCRTGYVLQIRRDDELIKSQ
  TGPSVTVTCTEGKWNKQVACEPVDCSIPDHHQVYAASFSCPEGTTFGSQCSFQCRHPAQL
  KGNNSLLTCMEDGLWSFPEALCELMCLAPPPVPNADLQTARCRENKHKVGSFCKYKCKPG
  YHVPGSSRKSKKRAFKTQCTQDGSWQEGACVPVTCDPPPPKFHGLYQCTNGFQFNSECRI
  KCEDSDASQGLGSNVIHCRKDGTWNGSFHVCQEMQGQCSVPNELNSNLKLQCPDGYAIGS
  ECATSCLDHNSESIILPMNVTVRDIPHWLNPTRVERVVCTAGLKWYPHPALIHCVKGCEP
  FMGDNYCDAINNRAFCNYDGGDCCTSTVKTKKVTPFPMSCDLQGDCACRDPQAQEHSRKD
  LRGYSHG

• Sequence length: 1627

Pathways

Reactome:

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

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	11586954
Myocardial infarction	Myocardial Infarction	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	11586954

Unknown
Disease name	Disease term	dbSNP ID	References
Coronary syndrome	Acute Coronary Syndrome	rs4986893	11586954
Endometriosis	Endometriosis	rs1800629, rs-1, rs1143634	21063030
Coronary arteriosclerosis	Coronary Arteriosclerosis		11586954
Endometrioma	Endometrioma		21063030
Intermediate coronary syndrome	Angina, Unstable		11586954
Subfertility	Subfertility, Female		20130263