Pappalysin-1

Name	Pappalysin-1
Synonyms	3.4.24.79 IGF-dependent IGFBP-4 protease IGFBP-4ase Insulin-like growth factor-dependent IGF-binding protein 4 protease PAPP-A Pregnancy-associated plasma protein A
Gene Name	PAPPA
Organism	Human
Amino acid sequence	>lcl\|BSEQ0049775\|Pappalysin-1 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
Number of residues	None
Molecular Weight	180971.11
Theoretical pI	None
GO Classification	Functions zinc ion binding metallopeptidase activity metalloendopeptidase activity Processes cellular protein metabolic process response to glucocorticoid female pregnancy response to follicle-stimulating hormone Components extracellular region extracellular space
General 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.
Specific Function	Metalloendopeptidase activity
Transmembrane Regions
GenBank Protein ID
UniProtKB ID	Q13219
UniProtKB Entry Name
Cellular Location	Secreted
Gene sequence	>lcl\|BSEQ0049776\|Pappalysin-1 (PAPPA) ATGCGGCTCTGGAGTTGGGTGCTGCACCTGGGGCTGCTGAGCGCCGCGCTGGGCTGCGGG CTGGCCGAGCGTCCCCGCCGGGCCCGGAGAGACCCGCGGGCCGGCCGACCCCCGCGCCCC GCCGCCGGCCCGGCCACCTGCGCCACCCGGGCGGCCCGCGGCCGCCGCGCCTCGCCGCCG CCGCCGCCGCCGCCGGGCGGTGCCTGGGAAGCCGTGCGCGTCCCCCGGCGGCGGCAGCAG CGGGAGGCGAGGGGCGCCACCGAGGAGCCGAGCCCGCCGAGCCGGGCGCTCTATTTCAGC GGGCGAGGCGAGCAGCTGCGCCTCCGGGCCGACCTCGAGCTGCCCCGGGACGCGTTCACG CTGCAAGTGTGGCTGCGAGCGGAGGGGGGCCAGAGGTCTCCGGCAGTGATCACAGGGCTG TATGACAAATGTTCTTATATCTCACGTGACCGAGGATGGGTCGTGGGCATTCACACCATC AGTGACCAAGACAACAAAGACCCACGCTACTTTTTCTCCTTGAAGACAGACCGAGCCCGG CAAGTGACCACCATCAATGCCCACCGCAGCTACCTCCCAGGCCAGTGGGTATACCTAGCT GCCACCTATGATGGGCAGTTCATGAAGCTCTATGTGAATGGTGCCCAGGTGGCCACCTCT GGGGAACAAGTGGGTGGCATATTCAGCCCACTGACCCAGAAGTGCAAAGTGCTCATGTTA GGGGGCAGTGCCCTGAATCACAACTACCGGGGCTACATCGAGCACTTCAGTCTGTGGAAG GTGGCCAGGACTCAGCGGGAGATACTGTCTGACATGGAAACCCATGGCGCCCACACTGCT CTACCTCAGCTCCTCCTCCAGGAGAACTGGGACAATGTGAAGCATGCCTGGTCCCCCATG AAGGATGGCAGCAGCCCCAAAGTGGAATTCAGCAATGCCCACGGCTTTCTGCTGGACACG AGTCTGGAGCCTCCTCTGTGCGGACAGACATTGTGTGACAACACAGAGGTCATTGCCAGC TACAATCAGCTCTCAAGTTTCCGCCAGCCCAAGGTGGTGCGCTACCGCGTGGTCAACCTC TATGAAGATGATCATAAGAACCCGACGGTGACGCGCGAGCAGGTGGACTTCCAGCACCAT CAGCTGGCTGAGGCCTTCAAGCAATACAACATCTCCTGGGAGCTGGACGTGCTGGAGGTG AGCAACTCCTCCCTTCGCCGCCGCCTCATCCTGGCCAACTGTGACATCAGCAAGATTGGG GATGAGAACTGTGACCCCGAGTGCAACCACACGCTGACGGGCCACGACGGCGGGGATTGC CGCCACCTGCGCCACCCTGCCTTCGTGAAGAAGCAGCACAACGGGGTGTGTGACATGGAC TGCAACTATGAACGGTTCAACTTTGATGGTGGAGAGTGCTGTGACCCTGAAATCACCAAT GTCACTCAGACTTGCTTTGACCCCGACTCTCCACACAGAGCCTACTTGGATGTTAATGAG CTGAAGAACATTCTTAAATTGGATGGATCAACACATCTCAATATTTTCTTTGCAAAATCC TCAGAGGAGGAGTTGGCAGGAGTAGCAACTTGGCCATGGGACAAGGAGGCCCTGATGCAC TTAGGTGGCATTGTCTTGAACCCATCTTTCTATGGCATGCCTGGGCACACCCACACCATG ATCCATGAGATTGGTCACAGCCTGGGCCTCTATCACGTCTTCCGAGGCATCTCAGAAATC CAGTCCTGCAGTGACCCCTGCATGGAGACAGAGCCCTCCTTCGAGACTGGAGACCTCTGC AATGATACCAACCCAGCCCCTAAACACAAGTCCTGTGGTGACCCAGGGCCAGGAAATGAC ACCTGTGGCTTTCATAGCTTCTTCAACACTCCTTACAACAACTTCATGAGCTATGCAGAT GACGACTGTACGGACTCCTTCACGCCCAATCAAGTCGCCAGAATGCACTGTTACCTGGAC CTGGTCTACCAGGGCTGGCAGCCCTCCAGGAAACCAGCGCCTGTTGCCCTCGCCCCCCAA GTTCTGGGCCACACAACGGACTCTGTGACACTGGAGTGGTTCCCACCTATAGATGGCCAT TTCTTTGAAAGAGAATTGGGATCAGCATGTCATCTTTGCCTGGAAGGGAGAATCCTGGTG CAGTATGCTTCCAACGCTTCCTCCCCAATGCCCTGCAGCCCATCAGGACACTGGAGCCCT CGTGAAGCAGAAGGTCATCCTGATGTTGAACAGCCCTGTAAGTCCAGTGTCCGCACCTGG AGCCCAAATTCAGCTGTCAACCCACACACGGTTCCTCCAGCCTGCCCTGAGCCTCAAGGC TGCTACCTCGAGCTGGAGTTCCTCTACCCCTTGGTCCCTGAGTCTCTGACCATTTGGGTG ACCTTTGTCTCCACTGACTGGGACTCTAGTGGAGCTGTCAATGACATCAAACTGTTGGCT GTCAGTGGGAAGAACATCTCCCTGGGTCCTCAGAATGTCTTCTGTGATGTCCCACTGACC ATCAGACTCTGGGACGTGGGCGAGGAGGTGTATGGCATCCAAATCTACACGCTGGATGAG CACCTGGAGATCGATGCTGCCATGTTGACCTCCACTGCAGACACCCCACTCTGTCTACAG TGTAAGCCCCTGAAGTATAAGGTGGTCCGGGACCCTCCTCTCCAGATGGATGTGGCCTCC ATCCTACATCTCAATAGGAAATTCGTAGACATGGATCTAAATCTTGGCAGTGTGTACCAG TATTGGGTCATAACTATTTCAGGAACTGAAGAGAGTGAGCCATCACCTGCTGTCACATAC ATCCATGGAAGTGGGTACTGTGGCGATGGCATTATACAAAAAGACCAAGGTGAACAATGC GACGACATGAATAAGATCAATGGTGATGGCTGCTCCCTTTTCTGCCGACAAGAAGTCTCC TTCAATTGTATTGATGAACCCAGCCGGTGCTATTTCCATGATGGTGATGGGGTATGTGAG GAGTTTGAACAAAAAACCAGCATTAAGGACTGTGGTGTCTACACGCCCCAGGGATTCCTG GATCAGTGGGCATCCAATGCTTCAGTATCTCATCAAGACCAGCAATGCCCAGGCTGGGTC ATCATCGGACAGCCAGCAGCATCCCAGGTGTGTCGAACCAAGGTGATAGATCTCAGTGAA GGCATTTCCCAGCATGCCTGGTACCCTTGCACCATCAGCTACCCATATTCCCAGCTGGCT CAGACCACTTTTTGGCTCCGGGCGTATTTTTCTCAACCAATGGTTGCCGCAGCTGTCATT GTCCACCTGGTGACGGATGGGACATATTATGGGGACCAAAAGCAGGAGACCATCAGCGTG CAGCTGCTTGATACCAAAGATCAGAGCCACGATCTAGGCCTCCATGTCCTGAGCTGCAGG AACAATCCCCTGATTATCCCTGTGGTCCATGACCTCAGCCAGCCCTTCTACCACAGCCAG GCGGTACGTGTGAGCTTCAGTTCGCCCCTGGTCGCCATCTCGGGGGTGGCCCTCCGTTCC TTCGACAACTTTGACCCCGTCACCCTGAGCAGCTGCCAGAGAGGGGAGACCTACAGCCCT GCCGAGCAGAGCTGCGTGCACTTCGCATGTGAGAAAACTGACTGTCCAGAGCTGGCTGTG GAGAATGCTTCTCTCAATTGCTCCAGCAGCGACCGCTACCACGGTGCCCAGTGTACTGTG AGCTGCCGGACAGGCTACGTGCTCCAGATACGGCGGGATGATGAGCTGATCAAGAGCCAG ACGGGACCCAGCGTCACAGTGACCTGTACAGAGGGCAAGTGGAATAAGCAGGTGGCCTGT GAGCCAGTCGACTGCAGCATCCCAGATCACCATCAAGTCTATGCTGCCTCCTTCTCCTGC CCTGAGGGCACCACCTTTGGCAGTCAATGTTCCTTCCAGTGCCGTCACCCTGCACAATTG AAAGGCAACAACAGCCTCCTGACCTGCATGGAGGATGGGCTGTGGTCCTTCCCAGAGGCC CTGTGTGAGCTCATGTGCCTCGCTCCACCCCCTGTGCCCAATGCAGACCTCCAGACCGCC CGGTGCCGAGAGAATAAGCACAAGGTGGGCTCCTTCTGCAAATACAAATGCAAGCCTGGA TACCATGTGCCTGGATCCTCTCGGAAGTCAAAGAAACGGGCCTTCAAGACTCAGTGTACC CAGGATGGCAGCTGGCAGGAGGGAGCTTGTGTTCCTGTGACCTGTGACCCACCTCCACCA AAATTCCATGGGCTCTACCAGTGTACTAATGGCTTCCAGTTCAACAGTGAGTGTAGGATC AAGTGTGAAGACAGTGATGCCTCCCAGGGACTTGGGAGCAATGTCATTCATTGCCGGAAA GATGGCACCTGGAACGGCTCCTTCCATGTCTGCCAGGAGATGCAAGGCCAGTGCTCGGTT CCAAACGAGCTCAACAGCAACCTCAAACTGCAGTGCCCTGATGGCTATGCCATAGGGTCG GAGTGTGCCACCTCGTGCCTGGACCACAACAGCGAGTCCATCATCCTGCCAATGAACGTG ACCGTGCGTGACATCCCCCACTGGCTGAACCCCACACGGGTAGAGAGAGTTGTCTGCACT GCTGGTCTCAAGTGGTATCCTCACCCTGCTCTGATTCACTGTGTCAAAGGCTGTGAGCCC TTCATGGGAGACAATTATTGTGATGCCATCAACAACCGAGCCTTTTGCAACTATGACGGT GGGGATTGCTGCACCTCCACAGTGAAGACCAAAAAGGTCACCCCATTCCCTATGTCCTGT GATCTACAAGGTGACTGTGCTTGTCGGGACCCCCAGGCCCAAGAACACAGCCGGAAAGAC CTCCGGGGATACAGCCATGGCTAA
GenBank Gene ID
GeneCard ID	None
GenAtlas ID
HGNC ID
Chromosome Location	9
Locus	9q33.1
References	Haaning J, Oxvig C, Overgaard MT, Ebbesen P, Kristensen T, Sottrup-Jensen L: Complete cDNA sequence of the preproform of human pregnancy-associated plasma protein-A. Evidence for expression in the brain and induction by cAMP. Eur J Biochem. 1996 Apr 1;237(1):159-63. 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[15164053 ] Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [15489334 ] Kristensen T, Oxvig C, Sand O, Moller NP, Sottrup-Jensen L: Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA. Biochemistry. 1994 Feb 15;33(6):1592-8. [7508748 ] Oxvig C, Sand O, Kristensen T, Gleich GJ, Sottrup-Jensen L: Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein. J Biol Chem. 1993 Jun 15;268(17):12243-6. [7685339 ] Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L, Oxvig C: Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment. J Biol Chem. 2003 Jan 24;278(4):2106-17. Epub 2002 Nov 5. [12421832 ] Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, Yates JR 3rd, Conover CA: The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3149-53. [10077652 ] Overgaard MT, Haaning J, Boldt HB, Olsen IM, Laursen LS, Christiansen M, Gleich GJ, Sottrup-Jensen L, Conover CA, Oxvig C: Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor. J Biol Chem. 2000 Oct 6;275(40):31128-33. [10913121 ] Bonno M, Oxvig C, Kephart GM, Wagner JM, Kristensen T, Sottrup-Jensen L, Gleich GJ: Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta. Lab Invest. 1994 Oct;71(4):560-6. [7526035 ] Overgaard MT, Oxvig C, Christiansen M, Lawrence JB, Conover CA, Gleich GJ, Sottrup-Jensen L, Haaning J: Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonreproductive tissues. Biol Reprod. 1999 Oct;61(4):1083-9. [10491647 ] Oxvig C, Haaning J, Kristensen L, Wagner JM, Rubin I, Stigbrand T, Gleich GJ, Sottrup-Jensen L: Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma. J Biol Chem. 1995 Jun 9;270(23):13645-51. [7539791 ] Laursen LS, Overgaard MT, Soe R, Boldt HB, Sottrup-Jensen L, Giudice LC, Conover CA, Oxvig C: Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth factor binding protein (IGFBP)-5 independent of IGF: implications for the mechanism of IGFBP-4 proteolysis by PAPP-A. FEBS Lett. 2001 Aug 24;504(1-2):36-40. [11522292 ] Frosk P, Weiler T, Nylen E, Sudha T, Greenberg CR, Morgan K, Fujiwara TM, Wrogemann K: Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. Am J Hum Genet. 2002 Mar;70(3):663-72. Epub 2002 Jan 29. [11822024 ]

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