pappalysin-1 (pregnancy-associated plasma protein-A, PAPP-A, insulin-like growth factor-dependent IGF-binding protein 4 protease, IGF-dependent IGFBP-4 protease, IGFBP-4ase, PAPPA)

Function: 1) metalloproteinase 2) specifically cleaves IGFBP-4 & IGFBP-5, resulting in release of bound IGF 3) cleavage of IGFBP-4 is enhanced by IGF cleavage of IGFBP-5 is inhibited by IGF (slight) 4) cleavage of the 135-Met-|-Lys-136 bond in IGFBP4 & 143-Ser-|-Lys-144 bond in IGFBP-5 5) inhibited by complexation with the proform of PRG2 6) induction by 8-bromoadenosine-3',5'-phosphate Cofactor: binds 1 Zn⁺² per subunit Structure: 1) homodimer; disulfide-linked - in pregnancy serum, predominantly found as a disulfide- linked 2:2 heterotetramer with proform of PRG2 2) belongs to the peptidase M43B family. - contains 5 Sushi domains (CCP/SCR domains) Compartment: secreted Expression: - expressed in placenta > other tissues - X cells in septa & anchoring villi - syncytiotrophoblasts in chorionic villi - expressed in kidney, myometrium, endometrium, ovaries, breast, prostate, bone marrow, colon, fibroblasts, osteoblasts - present in serum & placenta during pregnancy - levels increase throughout pregnancy

General

glycoprotein metalloprotease secreted protein

Properties

SIZE: MW = 181 kD entity length = 1628 aa COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-22} arginine-rich region {24-83} MOTIF: arginine residue (SEVERAL) cysteine residue {C145} MODIFICATION: cysteine residue {C236} cysteine residue {C236} MODIFICATION: cysteine residue {C145} Metalloprotease {273-584} MOTIF: cysteine residue {C328} MODIFICATION: cysteine residue {C623} cysteine residue {C333} MODIFICATION: cysteine residue {C658} N-glycosylation site {N391} N-glycosylation site {N403} cysteine residue {C415} MODIFICATION: cysteine residue {C429} cysteine residue {C425} MODIFICATION: cysteine residue {C441} cysteine residue {C429} MODIFICATION: cysteine residue {C415} N-glycosylation site {N430} cysteine residue {C441} MODIFICATION: cysteine residue {C425} cysteine residue {C458} MODIFICATION: cysteine residue {C474} cysteine residue {C462} MODIFICATION: cysteine residue {C51 IN PRG2 PROFORM} cysteine residue {C474} MODIFICATION: cysteine residue {C458} cysteine residue {C475} MODIFICATION: cysteine residue {C486} N-glycosylation site {N481} cysteine residue {C486} MODIFICATION: cysteine residue {C475} Zn+2-binding site SITE: 563-563 glutamate residue {E564} Zn+2-binding site SITE: 567-567 Zn+2-binding site SITE: 573-573 cysteine residue {C584} MODIFICATION: cysteine residue {C601} cysteine residue {C588} MODIFICATION: cysteine residue {C613} cysteine residue {C601} MODIFICATION: cysteine residue {C584} N-glycosylation site {N602} cysteine residue {C613} MODIFICATION: cysteine residue {C588} N-glycosylation site {N620} cysteine residue {C623} MODIFICATION: cysteine residue {C328} cysteine residue {C658} MODIFICATION: cysteine residue {C333} cysteine residue {C711} MODIFICATION: cysteine residue {C879} cysteine residue {C714} MODIFICATION: cysteine residue {C882} N-glycosylation site {N726} cysteine residue {C733} MODIFICATION: cysteine residue {C169 IN PRG2 PROFORM} cysteine residue {C754} MODIFICATION: cysteine residue {C836} cysteine residue {C776} MODIFICATION: cysteine residue {C782} cysteine residue {C782} MODIFICATION: cysteine residue {C776} N-glycosylation site {N826} cysteine residue {C836} MODIFICATION: cysteine residue {C754} cysteine residue {C879} MODIFICATION: cysteine residue {C711} cysteine residue {C882} MODIFICATION: cysteine residue {C714} cysteine residue {C948} MODIFICATION: cysteine residue {C976} cysteine residue {C961} MODIFICATION: cysteine residue {C972} cysteine residue {C972} MODIFICATION: cysteine residue {C961} cysteine residue {C976} MODIFICATION: cysteine residue {C948} cysteine residue {C984} MODIFICATION: cysteine residue {C991} cysteine residue {C991} MODIFICATION: cysteine residue {C984} cysteine residue {C1000} MODIFICATION: cysteine residue {C1012} cysteine residue {C1012} MODIFICATION: cysteine residue {C1000} N-glycosylation site {N1027} cysteine residue {C1037} MODIFICATION: cysteine residue {C1071} cysteine residue {C1052} MODIFICATION: cysteine residue {C1140} cysteine residue {C1071} MODIFICATION: cysteine residue {C1037} cysteine residue {C1140} MODIFICATION: cysteine residue {C1052} cysteine residue {C1193} MODIFICATION: cysteine residue {C1206} cysteine residue {C1206} MODIFICATION: cysteine residue {C1193} cysteine residue {C1211} MODIFICATION: cysteine residue {C-INTERCHAIN} Sushi domain {1214-1283} MOTIF: cysteine residue {C1216} MODIFICATION: cysteine residue {C1270} N-glycosylation site {N1223} N-glycosylation site {N1227} cysteine residue {C1228} MODIFICATION: cysteine residue {C1239} cysteine residue {C1239} MODIFICATION: cysteine residue {C1228} cysteine residue {C1243} MODIFICATION: cysteine residue {C1281} cysteine residue {C1270} MODIFICATION: cysteine residue {C1216} cysteine residue {C1281} MODIFICATION: cysteine residue {C1243} Sushi domain {1284-1345} MOTIF: cysteine residue {C1286} MODIFICATION: cysteine residue {C1330} cysteine residue {C1301} MODIFICATION: cysteine residue {C1311} cysteine residue {C1311} MODIFICATION: cysteine residue {C1301} cysteine residue {C1315} MODIFICATION: cysteine residue {C1343} N-glycosylation site {N1324} cysteine residue {C1330} MODIFICATION: cysteine residue {C1286} cysteine residue {C1343} MODIFICATION: cysteine residue {C1315} Sushi domain {1346-1413} MOTIF: cysteine residue {C1347} MODIFICATION: cysteine residue {C1400} cysteine residue {C1363} MODIFICATION: cysteine residue {C1374} cysteine residue {C1374} MODIFICATION: cysteine residue {C1363} cysteine residue {C1378} MODIFICATION: cysteine residue {C1411} cysteine residue {C1400} MODIFICATION: cysteine residue {C1347} cysteine residue {C1411} MODIFICATION: cysteine residue {C1378} Sushi domain {1414-1474} MOTIF: cysteine residue {C1416} MODIFICATION: cysteine residue {C1459} cysteine residue {C1429} MODIFICATION: cysteine residue {C1439} cysteine residue {C1439} MODIFICATION: cysteine residue {C1429} cysteine residue {C1443} MODIFICATION: cysteine residue {C1472} cysteine residue {C1459} MODIFICATION: cysteine residue {C1416} N-glycosylation site {N1466} cysteine residue {C1472} MODIFICATION: cysteine residue {C1443} Sushi domain {1477-1557} MOTIF: cysteine residue {C1479} MODIFICATION: cysteine residue {C1540} cysteine residue {C1493} MODIFICATION: cysteine residue {C1503} cysteine residue {C1503} MODIFICATION: cysteine residue {C1493} cysteine residue {C1507} MODIFICATION: cysteine residue {C1555} N-glycosylation site {N1520} cysteine residue {C1540} MODIFICATION: cysteine residue {C1479} cysteine residue {C1555} MODIFICATION: cysteine residue {C1507} cysteine residue {C1559} MODIFICATION: cysteine residue {C1577} cysteine residue {C1577} MODIFICATION: cysteine residue {C1559}

Database Correlations

OMIM 176385 UniProt Q13219 PFAM correlations ENZYME 3.4.24.79

References

UniProt :accession Q13219