| IED ID | IndEnz0002006598 |
| Enzyme Type ID | protease006598 |
| 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 |
| Gene Name | PAPPA |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MRLWSWVLHLGLLSAALGCGLAERPRRARRDPRAGRPPRPAAGPATCATRAARGRRASPPPPPPPGGAWEAVRVPRRRQQREARGATEEPSPPSRALYFSGRGEQLRLRADLELPRDAFTLQVWLRAEGGQRSPAVITGLYDKCSYISRDRGWVVGIHTISDQDNKDPRYFFSLKTDRARQVTTINAHRSYLPGQWVYLAATYDGQFMKLYVNGAQVATSGEQVGGIFSPLTQKCKVLMLGGSALNHNYRGYIEHFSLWKVARTQREILSDMETHGAHTALPQLLLQENWDNVKHAWSPMKDGSSPKVEFSNAHGFLLDTSLEPPLCGQTLCDNTEVIASYNQLSSFRQPKVVRYRVVNLYEDDHKNPTVTREQVDFQHHQLAEAFKQYNISWELDVLEVSNSSLRRRLILANCDISKIGDENCDPECNHTLTGHDGGDCRHLRHPAFVKKQHNGVCDMDCNYERFNFDGGECCDPEITNVTQTCFDPDSPHRAYLDVNELKNILKLDGSTHLNIFFAKSSEEELAGVATWPWDKEALMHLGGIVLNPSFYGMPGHTHTMIHEIGHSLGLYHVFRGISEIQSCSDPCMETEPSFETGDLCNDTNPAPKHKSCGDPGPGNDTCGFHSFFNTPYNNFMSYADDDCTDSFTPNQVARMHCYLDLVYQGWQPSRKPAPVALAPQVLGHTTDSVTLEWFPPIDGHFFERELGSACHLCLEGRILVQYASNASSPMPCSPSGHWSPREAEGHPDVEQPCKSSVRTWSPNSAVNPHTVPPACPEPQGCYLELEFLYPLVPESLTIWVTFVSTDWDSSGAVNDIKLLAVSGKNISLGPQNVFCDVPLTIRLWDVGEEVYGIQIYTLDEHLEIDAAMLTSTADTPLCLQCKPLKYKVVRDPPLQMDVASILHLNRKFVDMDLNLGSVYQYWVITISGTEESEPSPAVTYIHGSGYCGDGIIQKDQGEQCDDMNKINGDGCSLFCRQEVSFNCIDEPSRCYFHDGDGVCEEFEQKTSIKDCGVYTPQGFLDQWASNASVSHQDQQCPGWVIIGQPAASQVCRTKVIDLSEGISQHAWYPCTISYPYSQLAQTTFWLRAYFSQPMVAAAVIVHLVTDGTYYGDQKQETISVQLLDTKDQSHDLGLHVLSCRNNPLIIPVVHDLSQPFYHSQAVRVSFSSPLVAISGVALRSFDNFDPVTLSSCQRGETYSPAEQSCVHFACEKTDCPELAVENASLNCSSSDRYHGAQCTVSCRTGYVLQIRRDDELIKSQTGPSVTVTCTEGKWNKQVACEPVDCSIPDHHQVYAASFSCPEGTTFGSQCSFQCRHPAQLKGNNSLLTCMEDGLWSFPEALCELMCLAPPPVPNADLQTARCRENKHKVGSFCKYKCKPGYHVPGSSRKSKKRAFKTQCTQDGSWQEGACVPVTCDPPPPKFHGLYQCTNGFQFNSECRIKCEDSDASQGLGSNVIHCRKDGTWNGSFHVCQEMQGQCSVPNELNSNLKLQCPDGYAIGSECATSCLDHNSESIILPMNVTVRDIPHWLNPTRVERVVCTAGLKWYPHPALIHCVKGCEPFMGDNYCDAINNRAFCNYDGGDCCTSTVKTKKVTPFPMSCDLQGDCACRDPQAQEHSRKDLRGYSHG |
| Enzyme Length | 1627 |
| Uniprot Accession Number | Q13219 |
| Absorption | |
| Active Site | ACT_SITE 563; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by complexation with the proform of PRG2. {ECO:0000269|PubMed:10913121}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Cleavage of the 135-Met-|-Lys-136 bond in insulin-like growth factor binding protein (IGFBP)-4, and the 143-Ser-|-Lys-144 bond in IGFBP-5.; EC=3.4.24.79; |
| DNA Binding | |
| EC Number | 3.4.24.79 |
| Enzyme Function | 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. {ECO:0000269|PubMed:10077652, ECO:0000269|PubMed:10913121, ECO:0000269|PubMed:11522292}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (1); Disulfide bond (39); Domain (5); Frameshift (1); Glycosylation (14); Metal binding (3); Natural variant (4); Propeptide (1); Region (3); Sequence conflict (4); Signal peptide (1) |
| Keywords | Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Metal-binding;Metalloprotease;Protease;Reference proteome;Repeat;Secreted;Signal;Sushi;Zinc;Zymogen |
| Interact With | P13727 |
| Induction | INDUCTION: By 8-bromoadenosine-3',5'-phosphate. {ECO:0000269|PubMed:8620868}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10077652}. |
| Modified Residue | |
| Post Translational Modification | PTM: There appear to be no free sulfhydryl groups. |
| Signal Peptide | SIGNAL 1..22; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10898936; 11158056; 11264294; 11606061; 11788658; 11897673; 11914564; 12087395; 12213189; 12241545; 12370176; 12379487; 12414897; 12466191; 12524241; 12817760; 12904166; 12970325; 14530192; 14657012; 14705967; 14988014; 15146551; 15174051; 15231748; 15262980; 15305104; 15647258; 15754336; 15919757; 16086443; 16115888; 16388849; 16963045; 17047378; 17145752; 17177834; 17223728; 17237617; 17249697; 17312271; 17314100; 17437322; 17509577; 17516846; 17565927; 17700210; 17714879; 17936662; 18089325; 18267116; 18279673; 18295168; 18377765; 18391950; 18434323; 18552658; 18789800; 18805800; 18855223; 18925584; 19003798; 19106261; 19246276; 19304869; 19318028; 19328196; 19365167; 19646567; 19781342; 19842139; 19842999; 19862778; 20087924; 20148724; 20379614; 20388505; 20472761; 20509148; 20515576; 20583170; 20716560; 20734665; 20865665; 21093861; 21111564; 21290395; 21324404; 21360554; 21427871; 21557695; 21631965; 21717483; 21753069; 21779191; 21781597; 21986593; 22015022; 22123284; 22148978; 22365285; 22367671; 22377654; 22395770; 22630333; 22644835; 22709655; 22783577; 22836155; 22940118; 22954283; 23010598; 23152806; 23169786; 23461814; 23569011; 23642968; 23654313; 23756051; 23795618; 23795813; 23821525; 23880622; 23881937; 23891063; 23891271; 24060054; 24069146; 24099568; 24107527; 24151105; 24155168; 24171308; 24188108; 24201068; 24226752; 24226839; 24227626; 24312907; 24338604; 24395628; 24667032; 24743523; 24786703; 24817938; 24931331; 24940710; 25016703; 25108075; 25139218; 25159705; 25238218; 25316741; 25395363; 25468445; 25543334; 25596909; 25633269; 25639820; 25720282; 25773764; 25845987; 25858516; 26020769; 26122709; 26214492; 26223809; 26297643; 26336825; 26362726; 26520690; 26697810; 26773241; 26823756; 26874357; 26951623; 26983002; 27007282; 27090654; 27125092; 27793387; 27809366; 27809614; 28323969; 28381225; 28514830; 28537443; 28606451; 28655969; 28675948; 28706275; 28791822; 29144175; 29532882; 29587776; 29674192; 29712555; 29758559; 29973962; 30340109; 30371129; 30487186; 31046834; 31138428; 31177175; 31401027; 31631239; 31670029; 32292079; 32459893; 32470448; 32500475; 32569826; 32684596; 32746916; 32792532; 33239385; 33388371; 33561324; 33979553; 34329446; 34469009; |
| Motif | |
| Gene Encoded By | |
| Mass | 180,973 |
| Kinetics | |
| Metal Binding | METAL 562; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095; METAL 566; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095; METAL 572; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.79; |