Hmdb loader

Showing Protein Proactivator polypeptide (HMDBP01673)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 41 metabolites
Identification
HMDB Protein ID HMDBP01673
Secondary Accession Numbers
  • 7010
Name Proactivator polypeptide
Synonyms
  1. A1 activator
  2. CSAct
  3. Cerebroside sulfate activator
  4. Co-beta-glucosidase
  5. Component C
  6. Dispersin
  7. Glucosylceramidase activator
  8. Protein A
  9. Protein C
  10. SAP-1
  11. SAP-2
  12. Saposin-A
  13. Saposin-B
  14. Saposin-B-Val
  15. Saposin-C
  16. Saposin-D
  17. Sphingolipid activator protein 1
  18. Sphingolipid activator protein 2
  19. Sulfatide/GM1 activator
Gene Name PSAP
Protein Type Enzyme
Biological Properties
General Function Involved in lipid metabolic process
Specific Function Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12)
Pathways Not Available
Reactions Not Available
GO Classification
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
vacuole
lytic vacuole
lysosome
Process
metabolic process
sphingolipid metabolic process
membrane lipid metabolic process
primary metabolic process
lipid metabolic process
cellular lipid metabolic process
Cellular Location
  1. Lysosome
Gene Properties
Chromosome Location Chromosome:1
Locus 10q21-q22
SNPs PSAP
Gene Sequence 
>1575 bp
ATGTACGCCCTCTTCCTCCTGGCCAGCCTCCTGGGCGCGGCTCTAGCCGGCCCGGTCCTT
GGACTGAAAGAATGCACCAGGGGCTCGGCAGTGTGGTGCCAGAATGTGAAGACGGCGTCC
GACTGCGGGGCAGTGAAGCACTGCCTGCAGACCGTTTGGAACAAGCCAACAGTGAAATCC
CTTCCCTGCGACATATGCAAAGACGTTGTCACCGCAGCTGGTGATATGCTGAAGGACAAT
GCCACTGAGGAGGAGATCCTTGTTTACTTGGAGAAGACCTGTGACTGGCTTCCGAAACCG
AACATGTCTGCTTCATGCAAGGAGATAGTGGACTCCTACCTCCCTGTCATCCTGGACATC
ATTAAAGGAGAAATGAGCCGTCCTGGGGAGGTGTGCTCTGCTCTCAACCTCTGCGAGTCT
CTCCAGAAGCACCTAGCAGAGCTGAATCACCAGAAGCAGCTGGAGTCCAATAAGATCCCA
GAGCTGGACATGACTGAGGTGGTGGCCCCCTTCATGGCCAACATCCCTCTCCTCCTCTAC
CCTCAGGACGGCCCCCGCAGCAAGCCCCAGCCAAAGGATAATGGGGACGTTTGCCAGGAC
TGCATTCAGATGGTGACTGACATCCAGACTGCTGTACGGACCAACTCCACCTTTGTCCAG
GCCTTGGTGGAACATGTCAAGGAGGAGTGTGACCGCCTGGGCCCTGGCATGGCCGACATA
TGCAAGAACTATATCAGCCAGTATTCTGAAATTGCTATCCAGATGATGATGCACATGCAA
CCCAAGGAGATCTGTGCGCTGGTTGGGTTCTGTGATGAGGTGAAAGAGATGCCCATGCAG
ACTCTGGTCCCCGCCAAAGTGGCCTCCAAGAATGTCATCCCTGCCCTGGAACTGGTGGAG
CCCATTAAGAAGCACGAGGTCCCAGCAAAGTCTGATGTTTACTGTGAGGTGTGTGAATTC
CTGGTGAAGGAGGTGACCAAGCTGATTGACAACAACAAGACTGAGAAAGAAATACTCGAC
GCTTTTGACAAAATGTGCTCGAAGCTGCCGAAGTCCCTGTCGGAAGAGTGCCAGGAGGTG
GTGGACACGTACGGCAGCTCCATCCTGTCCATCCTGCTGGAGGAGGTCAGCCCTGAGCTG
GTGTGCAGCATGCTGCACCTCTGCTCTGGCACGCGGCTGCCTGCACTGACCGTTCACGTG
ACTCAGCCAAAGGACGGTGGCTTCTGCGAAGTGTGCAAGAAGCTGGTGGGTTATTTGGAT
CGCAACCTGGAGAAAAACAGCACCAAGCAGGAGATCCTGGCTGCTCTTGAGAAAGGCTGC
AGCTTCCTGCCAGACCCTTACCAGAAGCAGTGTGATCAGTTTGTGGCAGAGTACGAGCCC
GTGCTGATCGAGATCCTGGTGGAGGTGATGGATCCTTCCTTCGTGTGCTTGAAAATTGGA
GCCTGCCCCTCGGCCCATAAGCCCTTGTTGGGAACTGAGAAGTGTATATGGGGCCCAAGC
TACTGGTGCCAGAACACAGAGACAGCAGCCCAGTGCAATGCTGTCGAGCATTGCAAACGC
CATGTGTGGAACTAG
Protein Properties
Number of Residues 524
Molecular Weight 58112.1
Theoretical pI 4.82
Pfam Domain Function
Signals
  • 1-16
Transmembrane Regions
  • None
Protein Sequence 
>Proactivator polypeptide
MYALFLLASLLGAALAGPVLGLKECTRGSAVWCQNVKTASDCGAVKHCLQTVWNKPTVKS
LPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDI
IKGEMSRPGEVCSALNLCESLQKHLAELNHQKQLESNKIPELDMTEVVAPFMANIPLLLY
PQDGPRSKPQPKDNGDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADI
CKNYISQYSEIAIQMMMHMQPKEICALVGFCDEVKEMPMQTLVPAKVASKNVIPALELVE
PIKKHEVPAKSDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEV
VDTYGSSILSILLEEVSPELVCSMLHLCSGTRLPALTVHVTQPKDGGFCEVCKKLVGYLD
RNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIG
ACPSAHKPLLGTEKCIWGPSYWCQNTETAAQCNAVEHCKRHVWN
GenBank ID Protein 16306656
UniProtKB/Swiss-Prot ID P07602
UniProtKB/Swiss-Prot Entry Name SAP_HUMAN
PDB IDs
GenBank Gene ID BC001503
GeneCard ID PSAP
GenAtlas ID PSAP
HGNC ID HGNC:9498
References
General References
  1. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218 ]
  2. 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. [PubMed:15489334 ]
  3. Gieselmann V, Zlotogora J, Harris A, Wenger DA, Morris CP: Molecular genetics of metachromatic leukodystrophy. Hum Mutat. 1994;4(4):233-42. [PubMed:7866401 ]
  4. Rorman EG, Grabowski GA: Molecular cloning of a human co-beta-glucosidase cDNA: evidence that four sphingolipid hydrolase activator proteins are encoded by single genes in humans and rats. Genomics. 1989 Oct;5(3):486-92. [PubMed:2515150 ]
  5. Nakano T, Sandhoff K, Stumper J, Christomanou H, Suzuki K: Structure of full-length cDNA coding for sulfatide activator, a Co-beta-glucosidase and two other homologous proteins: two alternate forms of the sulfatide activator. J Biochem. 1989 Feb;105(2):152-4. [PubMed:2498298 ]
  6. O'Brien JS, Kretz KA, Dewji N, Wenger DA, Esch F, Fluharty AL: Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus. Science. 1988 Aug 26;241(4869):1098-101. [PubMed:2842863 ]
  7. Rorman EG, Scheinker V, Grabowski GA: Structure and evolution of the human prosaposin chromosomal gene. Genomics. 1992 Jun;13(2):312-8. [PubMed:1612590 ]
  8. Hiraiwa M, O'Brien JS, Kishimoto Y, Galdzicka M, Fluharty AL, Ginns EI, Martin BM: Isolation, characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins). Arch Biochem Biophys. 1993 Jul;304(1):110-6. [PubMed:8323276 ]
  9. Kondoh K, Hineno T, Sano A, Kakimoto Y: Isolation and characterization of prosaposin from human milk. Biochem Biophys Res Commun. 1991 Nov 27;181(1):286-92. [PubMed:1958198 ]
  10. Holtschmidt H, Sandhoff K, Furst W, Kwon HY, Schnabel D, Suzuki K: The organization of the gene for the human cerebroside sulfate activator protein. FEBS Lett. 1991 Mar 25;280(2):267-70. [PubMed:2013321 ]
  11. Morimoto S, Martin BM, Yamamoto Y, Kretz KA, O'Brien JS, Kishimoto Y: Saposin A: second cerebrosidase activator protein. Proc Natl Acad Sci U S A. 1989 May;86(9):3389-93. [PubMed:2717620 ]
  12. Tyynela J, Palmer DN, Baumann M, Haltia M: Storage of saposins A and D in infantile neuronal ceroid-lipofuscinosis. FEBS Lett. 1993 Sep 6;330(1):8-12. [PubMed:8370464 ]
  13. Dewji NN, Wenger DA, O'Brien JS: Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8652-6. [PubMed:2825202 ]
  14. Dewji N, Wenger D, Fujibayashi S, Donoviel M, Esch F, Hill F, O'Brien JS: Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the sulfatide sulfatase activator. Biochem Biophys Res Commun. 1986 Jan 29;134(2):989-94. [PubMed:2868718 ]
  15. Kleinschmidt T, Christomanou H, Braunitzer G: Complete amino-acid sequence of the naturally occurring A2 activator protein for enzymic sphingomyelin degradation: identity to the sulfatide activator protein (SAP-1). Biol Chem Hoppe Seyler. 1988 Dec;369(12):1361-5. [PubMed:3242555 ]
  16. Furst W, Schubert J, Machleidt W, Meyer HE, Sandhoff K: The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein. Eur J Biochem. 1990 Sep 24;192(3):709-14. [PubMed:2209618 ]
  17. Kleinschmidt T, Christomanou H, Braunitzer G: Complete amino-acid sequence and carbohydrate content of the naturally occurring glucosylceramide activator protein (A1 activator) absent from a new human Gaucher disease variant. Biol Chem Hoppe Seyler. 1987 Dec;368(12):1571-8. [PubMed:3442600 ]
  18. Morimoto S, Martin BM, Kishimoto Y, O'Brien JS: Saposin D: a sphingomyelinase activator. Biochem Biophys Res Commun. 1988 Oct 14;156(1):403-10. [PubMed:2845979 ]
  19. Furst W, Machleidt W, Sandhoff K: The precursor of sulfatide activator protein is processed to three different proteins. Biol Chem Hoppe Seyler. 1988 May;369(5):317-28. [PubMed:3048308 ]
  20. Fluharty AL, Lombardo C, Louis A, Stevens RL, Whitelegge J, Waring AJ, To T, Fluharty CB, Faull KF: Preparation of the cerebroside sulfate activator (CSAct or saposin B) from human urine. Mol Genet Metab. 1999 Nov;68(3):391-403. [PubMed:10562467 ]
  21. Vaccaro AM, Salvioli R, Barca A, Tatti M, Ciaffoni F, Maras B, Siciliano R, Zappacosta F, Amoresano A, Pucci P: Structural analysis of saposin C and B. Complete localization of disulfide bridges. J Biol Chem. 1995 Apr 28;270(17):9953-60. [PubMed:7730378 ]
  22. Faull KF, Johnson J, Kim MJ, To T, Whitelegge JP, Stevens RL, Fluharty CB, Fluharty AL: Structure of the asparagine-linked sugar chains of porcine kidney and human urine cerebroside sulfate activator protein. J Mass Spectrom. 2000 Dec;35(12):1416-24. [PubMed:11180632 ]
  23. Tatti M, Salvioli R, Ciaffoni F, Pucci P, Andolfo A, Amoresano A, Vaccaro AM: Structural and membrane-binding properties of saposin D. Eur J Biochem. 1999 Jul;263(2):486-94. [PubMed:10406958 ]
  24. Ahn VE, Faull KF, Whitelegge JP, Higginson J, Fluharty AL, Prive GG: Expression, purification, crystallization, and preliminary X-ray analysis of recombinant human saposin B. Protein Expr Purif. 2003 Jan;27(1):186-93. [PubMed:12510003 ]
  25. Faull KF, Whitelegge JP, Higginson J, To T, Johnson J, Krutchinsky AN, Standing KG, Waring AJ, Stevens RL, Fluharty CB, Fluharty AL: Cerebroside sulfate activator protein (Saposin B): chromatographic and electrospray mass spectrometric properties. J Mass Spectrom. 1999 Oct;34(10):1040-54. [PubMed:10510427 ]
  26. Ahn VE, Faull KF, Whitelegge JP, Fluharty AL, Prive GG: Crystal structure of saposin B reveals a dimeric shell for lipid binding. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):38-43. Epub 2002 Dec 23. [PubMed:12518053 ]
  27. Rafi MA, Zhang XL, DeGala G, Wenger DA: Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy. Biochem Biophys Res Commun. 1990 Jan 30;166(2):1017-23. [PubMed:2302219 ]
  28. Kretz KA, Carson GS, Morimoto S, Kishimoto Y, Fluharty AL, O'Brien JS: Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2541-4. [PubMed:2320574 ]
  29. Holtschmidt H, Sandhoff K, Kwon HY, Harzer K, Nakano T, Suzuki K: Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease. J Biol Chem. 1991 Apr 25;266(12):7556-60. [PubMed:2019586 ]
  30. Schnabel D, Schroder M, Furst W, Klein A, Hurwitz R, Zenk T, Weber J, Harzer K, Paton BC, Poulos A, et al.: Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene. J Biol Chem. 1992 Feb 15;267(5):3312-5. [PubMed:1371116 ]
  31. Schnabel D, Schroder M, Sandhoff K: Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease. FEBS Lett. 1991 Jun 17;284(1):57-9. [PubMed:2060627 ]
  32. Regis S, Filocamo M, Corsolini F, Caroli F, Keulemans JL, van Diggelen OP, Gatti R: An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity. Eur J Hum Genet. 1999 Feb-Mar;7(2):125-30. [PubMed:10196694 ]
  33. Wrobe D, Henseler M, Huettler S, Pascual Pascual SI, Chabas A, Sandhoff K: A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD). J Inherit Metab Dis. 2000 Feb;23(1):63-76. [PubMed:10682309 ]
  34. Hulkova H, Cervenkova M, Ledvinova J, Tochackova M, Hrebicek M, Poupetova H, Befekadu A, Berna L, Paton BC, Harzer K, Boor A, Smid F, Elleder M: A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation. Hum Mol Genet. 2001 Apr 15;10(9):927-40. [PubMed:11309366 ]
  35. Spiegel R, Bach G, Sury V, Mengistu G, Meidan B, Shalev S, Shneor Y, Mandel H, Zeigler M: A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans. Mol Genet Metab. 2005 Feb;84(2):160-6. [PubMed:15773042 ]
  36. Tylki-Szymanska A, Czartoryska B, Vanier MT, Poorthuis BJ, Groener JA, Lugowska A, Millat G, Vaccaro AM, Jurkiewicz E: Non-neuronopathic Gaucher disease due to saposin C deficiency. Clin Genet. 2007 Dec;72(6):538-42. Epub 2007 Oct 7. [PubMed:17919309 ]