Pappalysin-1

Details

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
Humans
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
1627
Molecular Weight
180971.11
Theoretical pI
Not Available
GO Classification
Functions
metalloendopeptidase activity / metallopeptidase activity / zinc ion binding
Processes
cellular protein metabolic process / female pregnancy / response to follicle-stimulating hormone / response to glucocorticoid
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
Pfam Domain Function
Transmembrane Regions
Not Available
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
Chromosome Location
9
Locus
9q33.1
External Identifiers
ResourceLink
UniProtKB IDQ13219
UniProtKB Entry NamePAPP1_HUMAN
HGNC IDHGNC:8602
General References
  1. 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. [Article]
  2. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  3. 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. [Article]
  4. 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. [Article]
  5. 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. [Article]
  6. 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. [Article]
  7. 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. [Article]
  8. 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. [Article]
  9. 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. [Article]
  10. 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. [Article]
  11. 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. [Article]
  12. 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. [Article]
  13. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12695Phenethyl IsothiocyanateinvestigationalunknownDetails