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1.C.35.2.1
Cerebroside sulfate activator protein, CSAP or prosaposin (PSAP, GLBA, SAP1) of 524 aas. Saposin A, B, C and D are derived from prosaposin by proteolysis. Saposin-A and C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase and galactosylceramide by beta-galactosylceramidase. Saposin-C apparently acts by combining with the enzyme and acidic lipids to form an activated complex, rather than by solubilizing the substrate. Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A, GM1 gangliosides by β-galactosidase and globotriaosylceramide by α-galactosidase A. Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases. Saposin-D is a specific sphingomyelin phosphodiesterase activator. Prosaposin behaves as a myelinotrophic and neurotrophic factor; these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling (Hiraiwa et al. 1999).

Accession Number:P07602
Protein Name:SAP aka CSAP aka PSAP
Length:524
Molecular Weight:58113.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Lysosome1
Substrate small molecules

Cross database links:

Genevestigator: P07602
eggNOG: prNOG19449
DIP: DIP-29803N
RefSeq: NP_001035930.1    NP_001035931.1    NP_002769.1   
Entrez Gene ID: 5660   
Pfam: PF02199    PF05184    PF03489   
Drugbank: Drugbank Link   
OMIM: 176801  gene
249900  phenotype
610539  phenotype
611721  phenotype
611722  phenotype
KEGG: hsa:5660   

Gene Ontology

GO:0005615 C:extracellular space
GO:0005794 C:Golgi apparatus
GO:0016021 C:integral to membrane
GO:0043202 C:lysosomal lumen
GO:0008047 F:enzyme activator activity
GO:0008289 F:lipid binding
GO:0006687 P:glycosphingolipid metabolic process
GO:0006869 P:lipid transport

References (36)

[1] “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.”  Rorman E.G.et.al.   2515150
[2] “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.”  Nakano T.et.al.   2498298
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus.”  O'Brien J.S.et.al.   2842863
[5] “Structure and evolution of the human prosaposin chromosomal gene.”  Rorman E.G.et.al.   1612590
[6] “Isolation, characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins).”  Hiraiwa M.et.al.   8323276
[7] “Isolation and characterization of prosaposin from human milk.”  Kondoh K.et.al.   1958198
[8] “The organization of the gene for the human cerebroside sulfate activator protein.”  Holtschmidt H.et.al.   2013321
[9] “Saposin A: second cerebrosidase activator protein.”  Morimoto S.et.al.   2717620
[10] “Storage of saposins A and D in infantile neuronal ceroid-lipofuscinosis.”  Tyynela J.et.al.   8370464
[11] “Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor.”  Dewji N.N.et.al.   2825202
[12] “Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the sulfatide sulfatase activator.”  Dewji N.N.et.al.   2868718
[13] “Complete amino-acid sequence of the naturally occurring A2 activator protein for enzymic sphingomyelin degradation: identity to the sulfatide activator protein (SAP-1).”  Kleinschmidt T.et.al.   3242555
[14] “The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein.”  Furst W.et.al.   2209618
[15] “Complete amino-acid sequence and carbohydrate content of the naturally occurring glucosylceramide activator protein (A1 activator) absent from a new human Gaucher disease variant.”  Kleinschmidt T.et.al.   3442600
[16] “Saposin D: a sphingomyelinase activator.”  Morimoto S.et.al.   2845979
[17] “The precursor of sulfatide activator protein is processed to three different proteins.”  Furst W.et.al.   3048308
[18] “Preparation of the cerebroside sulfate activator (CSAct or saposin B) from human urine.”  Fluharty A.L.et.al.   10562467
[19] “Structural analysis of saposin C and B. Complete localization of disulfide bridges.”  Vaccaro A.M.et.al.   7730378
[20] “Structure of the asparagine-linked sugar chains of porcine kidney and human urine cerebroside sulfate activator protein.”  Faull K.F.et.al.   11180632
[21] “Structural and membrane-binding properties of saposin D.”  Tatti M.et.al.   10406958
[22] “Expression, purification, crystallization, and preliminary X-ray analysis of recombinant human saposin B.”  Ahn V.E.et.al.   12510003
[23] “Cerebroside sulfate activator protein (Saposin B): chromatographic and electrospray mass spectrometric properties.”  Faull K.F.et.al.   10510427
[24] “Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.”  Chen R.et.al.   19159218
[25] “Crystal structure of saposin B reveals a dimeric shell for lipid binding.”  Ahn V.E.et.al.   12518053
[26] “Molecular genetics of metachromatic leukodystrophy.”  Gieselmann V.et.al.   7866401
[27] “Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy.”  Rafi M.A.et.al.   2302219
[28] “Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect.”  Kretz K.A.et.al.   2320574
[29] “Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease.”  Holtschmidt H.et.al.   2019586
[30] “Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene.”  Schnabel D.et.al.   1371116
[31] “Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease.”  Schnabel D.et.al.   2060627
[32] “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.”  Regis S.et.al.   10196694
[33] “A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD).”  Wrobe D.et.al.   10682309
[34] “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.”  Hulkova H.et.al.   11309366
[35] “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.”  Spiegel R.et.al.   15773042
[36] “Non-neuronopathic Gaucher disease due to saposin C deficiency.”  Tylki-Szymanska A.et.al.   17919309
Structure:
1M12   1N69   1SN6   2DOB   2GTG   2QYP   2R0R   2R1Q   2RB3   2Z9A   [...more]

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FASTA formatted sequence
1:	MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ TVWNKPTVKS 
61:	LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP NMSASCKEIV DSYLPVILDI 
121:	IKGEMSRPGE VCSALNLCES LQKHLAELNH QKQLESNKIP ELDMTEVVAP FMANIPLLLY 
181:	PQDGPRSKPQ PKDNGDVCQD CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI 
241:	CKNYISQYSE IAIQMMMHMQ PKEICALVGF CDEVKEMPMQ TLVPAKVASK NVIPALELVE 
301:	PIKKHEVPAK SDVYCEVCEF LVKEVTKLID NNKTEKEILD AFDKMCSKLP KSLSEECQEV 
361:	VDTYGSSILS ILLEEVSPEL VCSMLHLCSG TRLPALTVHV TQPKDGGFCE VCKKLVGYLD 
421:	RNLEKNSTKQ EILAALEKGC SFLPDPYQKQ CDQFVAEYEP VLIEILVEVM DPSFVCLKIG 
481:	ACPSAHKPLL GTEKCIWGPS YWCQNTETAA QCNAVEHCKR HVWN