ID SAP_HUMAN Reviewed; 524 AA.
AC P07602; P07292; P15793; P78538; P78541; P78546; P78547; P78558;
AC Q53Y86; Q6IBQ6; Q92739; Q92740; Q92741; Q92742;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 2.
DT 01-MAY-2013, entry version 171.
DE RecName: Full=Proactivator polypeptide;
DE Contains:
DE RecName: Full=Saposin-A;
DE AltName: Full=Protein A;
DE Contains:
DE RecName: Full=Saposin-B-Val;
DE Contains:
DE RecName: Full=Saposin-B;
DE AltName: Full=Cerebroside sulfate activator;
DE Short=CSAct;
DE AltName: Full=Dispersin;
DE AltName: Full=Sphingolipid activator protein 1;
DE Short=SAP-1;
DE AltName: Full=Sulfatide/GM1 activator;
DE Contains:
DE RecName: Full=Saposin-C;
DE AltName: Full=A1 activator;
DE AltName: Full=Co-beta-glucosidase;
DE AltName: Full=Glucosylceramidase activator;
DE AltName: Full=Sphingolipid activator protein 2;
DE Short=SAP-2;
DE Contains:
DE RecName: Full=Saposin-D;
DE AltName: Full=Component C;
DE AltName: Full=Protein C;
DE Flags: Precursor;
GN Name=PSAP; Synonyms=GLBA, SAP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2515150; DOI=10.1016/0888-7543(89)90014-1;
RA Rorman E.G., Grabowski G.A.;
RT "Molecular cloning of a human co-beta-glucosidase cDNA: evidence that
RT four sphingolipid hydrolase activator proteins are encoded by single
RT genes in humans and rats.";
RL Genomics 5:486-492(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2498298;
RA Nakano T., Sandhoff K., Stuemper J., Christomanou H., Suzuki K.;
RT "Structure of full-length cDNA coding for sulfatide activator, a Co-
RT beta-glucosidase and two other homologous proteins: two alternate
RT forms of the sulfatide activator.";
RL J. Biochem. 105:152-154(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SAP-MU-0).
RC TISSUE=Brain, Eye, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-524.
RX PubMed=2842863; DOI=10.1126/science.2842863;
RA O'Brien J.S., Kretz K.A., Dewji N., Wenger D.A., Esch F.,
RA Fluharty A.L.;
RT "Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by
RT same genetic locus.";
RL Science 241:1098-1101(1988).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-524.
RX PubMed=1612590; DOI=10.1016/0888-7543(92)90247-P;
RA Rorman E.G., Scheinker V., Grabowski G.A.;
RT "Structure and evolution of the human prosaposin chromosomal gene.";
RL Genomics 13:312-318(1992).
RN [10]
RP PROTEIN SEQUENCE OF 17-24; 165-172; 180-189 AND 298-302.
RX PubMed=8323276; DOI=10.1006/abbi.1993.1328;
RA Hiraiwa M., O'Brien J.S., Kishimoto Y., Galdzicka M., Fluharty A.L.,
RA Ginns E.I., Martin B.M.;
RT "Isolation, characterization, and proteolysis of human prosaposin, the
RT precursor of saposins (sphingolipid activator proteins).";
RL Arch. Biochem. Biophys. 304:110-116(1993).
RN [11]
RP PROTEIN SEQUENCE OF 17-26.
RC TISSUE=Milk;
RX PubMed=1958198; DOI=10.1016/S0006-291X(05)81415-9;
RA Kondoh K., Hineno T., Sano A., Kakimoto Y.;
RT "Isolation and characterization of prosaposin from human milk.";
RL Biochem. Biophys. Res. Commun. 181:286-292(1991).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 59-125 AND 304-513.
RC TISSUE=Brain;
RX PubMed=2013321; DOI=10.1016/0014-5793(91)80308-P;
RA Holtschmidt H., Sandhoff K., Fuerst W., Kwon H.Y., Schnabel D.,
RA Suzuki K.;
RT "The organization of the gene for the human cerebroside sulfate
RT activator protein.";
RL FEBS Lett. 280:267-270(1991).
RN [13]
RP PROTEIN SEQUENCE OF 60-142.
RX PubMed=2717620; DOI=10.1073/pnas.86.9.3389;
RA Morimoto S., Martin B.M., Yamamoto Y., Kretz K.A., O'Brien J.S.,
RA Kishimoto Y.;
RT "Saposin A: second cerebrosidase activator protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:3389-3393(1989).
RN [14]
RP PROTEIN SEQUENCE OF 62-84 AND 410-431.
RX PubMed=8370464; DOI=10.1016/0014-5793(93)80908-D;
RA Tyynela J., Palmer D.N., Baumann M., Haltia M.;
RT "Storage of saposins A and D in infantile neuronal ceroid-
RT lipofuscinosis.";
RL FEBS Lett. 330:8-12(1993).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 164-524.
RX PubMed=2825202; DOI=10.1073/pnas.84.23.8652;
RA Dewji N.N., Wenger D.A., O'Brien J.S.;
RT "Nucleotide sequence of cloned cDNA for human sphingolipid activator
RT protein 1 precursor.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8652-8656(1987).
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 195-263.
RX PubMed=2868718; DOI=10.1016/S0006-291X(86)80518-6;
RA Dewji N.N., Wenger D.A., Fujibayashi S., Donoviel M., Esch F.,
RA Hill F., O'Brien J.S.;
RT "Molecular cloning of the sphingolipid activator protein-1 (SAP-1),
RT the sulfatide sulfatase activator.";
RL Biochem. Biophys. Res. Commun. 134:989-994(1986).
RN [17]
RP PROTEIN SEQUENCE OF 195-274.
RX PubMed=3242555;
RA Kleinschmidt T., Christomanou H., Braunitzer G.;
RT "Complete amino-acid sequence of the naturally occurring A2 activator
RT protein for enzymic sphingomyelin degradation: identity to the
RT sulfatide activator protein (SAP-1).";
RL Biol. Chem. Hoppe-Seyler 369:1361-1365(1988).
RN [18]
RP PROTEIN SEQUENCE OF 195-274.
RC TISSUE=Kidney;
RX PubMed=2209618; DOI=10.1111/j.1432-1033.1990.tb19280.x;
RA Furst W., Schubert J., Machleidt W., Meyer H.E., Sandhoff K.;
RT "The complete amino-acid sequences of human ganglioside GM2 activator
RT protein and cerebroside sulfate activator protein.";
RL Eur. J. Biochem. 192:709-714(1990).
RN [19]
RP PROTEIN SEQUENCE OF 311-390.
RX PubMed=3442600;
RA Kleinschmidt T., Christomanou H., Braunitzer G.;
RT "Complete amino-acid sequence and carbohydrate content of the
RT naturally occurring glucosylceramide activator protein (A1 activator)
RT absent from a new human Gaucher disease variant.";
RL Biol. Chem. Hoppe-Seyler 368:1571-1578(1987).
RN [20]
RP PROTEIN SEQUENCE OF 405-484.
RX PubMed=2845979; DOI=10.1016/S0006-291X(88)80855-6;
RA Morimoto S., Martin B.M., Kishimoto Y., O'Brien J.S.;
RT "Saposin D: a sphingomyelinase activator.";
RL Biochem. Biophys. Res. Commun. 156:403-410(1988).
RN [21]
RP PROTEIN SEQUENCE OF 407-484.
RX PubMed=3048308;
RA Furst W., Machleidt W., Sandhoff K.;
RT "The precursor of sulfatide activator protein is processed to three
RT different proteins.";
RL Biol. Chem. Hoppe-Seyler 369:317-328(1988).
RN [22]
RP PARTIAL PROTEIN SEQUENCE (SAPOSIN-B), AND STRUCTURE OF CARBOHYDRATES.
RC TISSUE=Urine;
RX PubMed=10562467; DOI=10.1006/mgme.1999.2900;
RA Fluharty A.L., Lombardo C., Louis A., Stevens R.L., Whitelegge J.P.,
RA Waring A.J., To T., Fluharty C.B., Faull K.F.;
RT "Preparation of the cerebroside sulfate activator (CSAct or saposin B)
RT from human urine.";
RL Mol. Genet. Metab. 68:391-403(1999).
RN [23]
RP DISULFIDE BONDS IN SAPOSINS-B AND C, AND MASS SPECTROMETRY.
RX PubMed=7730378; DOI=10.1074/jbc.270.17.9953;
RA Vaccaro A.M., Salvioli R., Barca A., Tatti M., Ciaffoni F., Maras B.,
RA Siciliano R., Zappacosta F., Amoresano A., Pucci P.;
RT "Structural analysis of saposin C and B. Complete localization of
RT disulfide bridges.";
RL J. Biol. Chem. 270:9953-9960(1995).
RN [24]
RP STRUCTURE OF CARBOHYDRATE ON ASN-215.
RX PubMed=11180632;
RX DOI=10.1002/1096-9888(200012)35:12<1416::AID-JMS75>3.0.CO;2-K;
RA Faull K.F., Johnson J., Kim M.J., To T., Whitelegge J.P.,
RA Stevens R.L., Fluharty C.B., Fluharty A.L.;
RT "Structure of the asparagine-linked sugar chains of porcine kidney and
RT human urine cerebroside sulfate activator protein.";
RL J. Mass Spectrom. 35:1416-1424(2000).
RN [25]
RP DISULFIDE BONDS IN SAPOSIN-D.
RX PubMed=10406958; DOI=10.1046/j.1432-1327.1999.00521.x;
RA Tatti M., Salvioli R., Ciaffoni F., Pucci P., Andolfo A.,
RA Amoresano A., Vaccaro A.M.;
RT "Structural and membrane-binding properties of saposin D.";
RL Eur. J. Biochem. 263:486-494(1999).
RN [26]
RP DISULFIDE BONDS IN SAPOSIN-B.
RX PubMed=12510003; DOI=10.1016/S1046-5928(02)00597-1;
RA Ahn V.E., Faull K.F., Whitelegge J.P., Higginson J., Fluharty A.L.,
RA Prive G.G.;
RT "Expression, purification, crystallization, and preliminary X-ray
RT analysis of recombinant human saposin B.";
RL Protein Expr. Purif. 27:186-193(2003).
RN [27]
RP MASS SPECTROMETRY.
RC TISSUE=Urine;
RX PubMed=10510427;
RX DOI=10.1002/(SICI)1096-9888(199910)34:10<1040::AID-JMS863>3.0.CO;2-X;
RA Faull K.F., Whitelegge J.P., Higginson J., To T., Johnson J.,
RA Krutchinsky A.N., Standing K.G., Waring A.J., Stevens R.L.,
RA Fluharty C.B., Fluharty A.L.;
RT "Cerebroside sulfate activator protein (Saposin B): chromatographic
RT and electrospray mass spectrometric properties.";
RL J. Mass Spectrom. 34:1040-1054(1999).
RN [28]
RP GLYCOSYLATION AT ASN-80; ASN-101; ASN-215; ASN-332 AND ASN-426.
RX PubMed=19167329; DOI=10.1016/j.cell.2008.11.047;
RA Ruiz-Canada C., Kelleher D.J., Gilmore R.;
RT "Cotranslational and posttranslational N-glycosylation of polypeptides
RT by distinct mammalian OST isoforms.";
RL Cell 136:272-283(2009).
RN [29]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-80; ASN-101; ASN-332 AND
RP ASN-426, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 195-273, AND MUTAGENESIS OF
RP ILE-240.
RX PubMed=12518053; DOI=10.1073/pnas.0136947100;
RA Ahn V.E., Faull K.F., Whitelegge J.P., Fluharty A.L., Prive G.G.;
RT "Crystal structure of saposin B reveals a dimeric shell for lipid
RT binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:38-43(2003).
RN [32]
RP REVIEW ON MLD-SAPB VARIANTS.
RX PubMed=7866401; DOI=10.1002/humu.1380040402;
RA Gieselmann V., Zlotogora J., Harris A., Wenger D.A., Morris C.P.;
RT "Molecular genetics of metachromatic leukodystrophy.";
RL Hum. Mutat. 4:233-242(1994).
RN [33]
RP VARIANT MLD-SAPB ILE-217.
RX PubMed=2302219; DOI=10.1016/0006-291X(90)90912-7;
RA Rafi M.A., Zhang X.-L., Degala G., Wenger D.A.;
RT "Detection of a point mutation in sphingolipid activator protein-1
RT mRNA in patients with a variant form of metachromatic
RT leukodystrophy.";
RL Biochem. Biophys. Res. Commun. 166:1017-1023(1990).
RN [34]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT MLD-SAPB ILE-217.
RX PubMed=2320574; DOI=10.1073/pnas.87.7.2541;
RA Kretz K.A., Carson G.S., Morimoto S., Kishimoto Y., Fluharty A.L.,
RA O'Brien J.S.;
RT "Characterization of a mutation in a family with saposin B deficiency:
RT a glycosylation site defect.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2541-2544(1990).
RN [35]
RP VARIANT MLD-SAPB SER-241, NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE
RP SPLICING.
RX PubMed=2019586;
RA Holtschmidt H., Sandhoff K., Kwon H.Y., Harzer K., Nakano T.,
RA Suzuki K.;
RT "Sulfatide activator protein. Alternative splicing that generates
RT three mRNAs and a newly found mutation responsible for a clinical
RT disease.";
RL J. Biol. Chem. 266:7556-7560(1991).
RN [36]
RP INVOLVEMENT IN CSAPD.
RX PubMed=1371116;
RA Schnabel D., Schroder M., Furst W., Klein A., Hurwitz R., Zenk T.,
RA Weber J., Harzer K., Paton B.C., Poulos A., Suzuki K., Sandhoff K.;
RT "Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is
RT caused by a mutation in the initiation codon of their common gene.";
RL J. Biol. Chem. 267:3312-3315(1992).
RN [37]
RP VARIANT AGD PHE-388.
RX PubMed=2060627; DOI=10.1016/0014-5793(91)80760-Z;
RA Schnabel D., Schroeder M., Sandhoff K.;
RT "Mutation in the sphingolipid activator protein 2 in a patient with a
RT variant of Gaucher disease.";
RL FEBS Lett. 284:57-59(1991).
RN [38]
RP VARIANT MLD-SAPB LYS-215.
RX PubMed=10196694; DOI=10.1038/sj.ejhg.5200266;
RA Regis S., Filocamo M., Corsolini F., Caroli F., Keulemans J.L.M.,
RA van Diggelen O.P., Gatti R.;
RT "An Asn > Lys substitution in saposin B involving a conserved amino
RT acidic residue and leading to the loss of the single N-glycosylation
RT site in a patient with metachromatic leukodystrophy and normal
RT arylsulphatase A activity.";
RL Eur. J. Hum. Genet. 7:125-130(1999).
RN [39]
RP VARIANT MLD-SAPB HIS-215, AND CHARACTERIZATION OF VARIANT MLD-SAPB
RP HIS-215.
RX PubMed=10682309; DOI=10.1023/A:1005603014401;
RA Wrobe D., Henseler M., Huettler S., Pascual Pascual S.I., Chabas A.,
RA Sandhoff K.;
RT "A non-glycosylated and functionally deficient mutant (N215H) of the
RT sphingolipid activator protein B (SAP-B) in a novel case of
RT metachromatic leukodystrophy (MLD).";
RL J. Inherit. Metab. Dis. 23:63-76(2000).
RN [40]
RP INVOLVEMENT IN CSAPD.
RX PubMed=11309366; DOI=10.1093/hmg/10.9.927;
RA Hulkova H., Cervenkova M., Ledvinova J., Tochackova M., Hrebicek M.,
RA Poupetova H., Befekadu A., Berna L., Paton B.C., Harzer K., Boor A.,
RA Smid F., Elleder M.;
RT "A novel mutation in the coding region of the prosaposin gene leads to
RT a complete deficiency of prosaposin and saposins, and is associated
RT with a complex sphingolipidosis dominated by lactosylceramide
RT accumulation.";
RL Hum. Mol. Genet. 10:927-940(2001).
RN [41]
RP VARIANT AKRD VAL-70 DEL.
RX PubMed=15773042; DOI=10.1016/j.ymgme.2004.10.004;
RA Spiegel R., Bach G., Sury V., Mengistu G., Meidan B., Shalev S.,
RA Shneor Y., Mandel H., Zeigler M.;
RT "A mutation in the saposin A coding region of the prosaposin gene in
RT an infant presenting as Krabbe disease: first report of saposin A
RT deficiency in humans.";
RL Mol. Genet. Metab. 84:160-166(2005).
RN [42]
RP VARIANT AGD PRO-349.
RX PubMed=17919309; DOI=10.1111/j.1399-0004.2007.00899.x;
RA Tylki-Szymanska A., Czartoryska B., Vanier M.T., Poorthuis B.J.,
RA Groener J.A., Lugowska A., Millat G., Vaccaro A.M., Jurkiewicz E.;
RT "Non-neuronopathic Gaucher disease due to saposin C deficiency.";
RL Clin. Genet. 72:538-542(2007).
CC -!- FUNCTION: The lysosomal degradation of sphingolipids takes place
CC by the sequential action of specific hydrolases. Some of these
CC enzymes require specific low-molecular mass, non-enzymic proteins:
CC the sphingolipids activator proteins (coproteins).
CC -!- FUNCTION: Saposin-A and saposin-C stimulate the hydrolysis of
CC glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and
CC galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46).
CC Saposin-C apparently acts by combining with the enzyme and acidic
CC lipid to form an activated complex, rather than by solubilizing
CC the substrate.
CC -!- FUNCTION: Saposin-B stimulates the hydrolysis of galacto-
CC cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1
CC gangliosides by beta-galactosidase (EC 3.2.1.23) and
CC globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22).
CC Saposin-B forms a solubilizing complex with the substrates of the
CC sphingolipid hydrolases.
CC -!- FUNCTION: Saposin-D is a specific sphingomyelin phosphodiesterase
CC activator (EC 3.1.4.12).
CC -!- SUBUNIT: Saposin-B is a homodimer.
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=Sap-mu-0;
CC IsoId=P07602-1; Sequence=Displayed;
CC Name=Sap-mu-6;
CC IsoId=P07602-2; Sequence=VSP_006014;
CC Name=Sap-mu-9;
CC IsoId=P07602-3; Sequence=VSP_006015;
CC -!- PTM: This precursor is proteolytically processed to 4 small
CC peptides, which are similar to each other and are sphingolipid
CC hydrolase activator proteins.
CC -!- PTM: N-linked glycans show a high degree of microheterogeneity.
CC -!- PTM: The one residue extended Saposin-B-Val is only found in 5% of
CC the chains.
CC -!- DISEASE: Combined saposin deficiency (CSAPD) [MIM:611721]: Due to
CC absence of all saposins, leading to a fatal storage disorder with
CC hepatosplenomegaly and severe neurological involvement. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Leukodystrophy metachromatic due to saposin-B deficiency
CC (MLD-SAPB) [MIM:249900]: An atypical form of metachromatic
CC leukodystrophy. It is characterized by tissue accumulation of
CC cerebroside-3-sulfate, demyelination, periventricular white matter
CC abnormalities, peripheral neuropathy. Additional neurological
CC features include dysarthria, ataxic gait, psychomotr regression,
CC seizures, cognitive decline and spastic quadriparesis. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Gaucher disease, atypical, due to saposin C deficiency
CC (AGD) [MIM:610539]: A disease characterized by marked
CC glucosylceramide accumulation in the spleen without having a
CC deficiency of glucosylceramide-beta glucosidase characteristic of
CC classic Gaucher disease. Gaucher disease is a lysosomal storage
CC disorder characterized by skeletal deterioration,
CC hepatosplenomegaly, and organ dysfunction. There are several
CC subtypes based on the presence and severity of neurological
CC involvement. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- DISEASE: Krabbe disease, atypical, due to saposin A deficiency
CC (AKRD) [MIM:611722]: A disorder of galactosylceramide metabolism.
CC Clinical features include neurologic regression around age 3
CC months, loss of spontaneous movements, hyporeflexia, generalized
CC brain atrophy, and diffuse white matter dysmyelination. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Note=Defects in PSAP saposin-D region are found in a
CC variant of Tay-Sachs disease (GM2-gangliosidosis).
CC -!- MISCELLANEOUS: Saposin-B co-purifies with 1 molecule of
CC phosphatidylethanolamine.
CC -!- SIMILARITY: Contains 2 saposin A-type domains.
CC -!- SIMILARITY: Contains 4 saposin B-type domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PSAPID42980ch10q22.html";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PSAP";
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DR EMBL; J03077; AAA52560.1; -; mRNA.
DR EMBL; D00422; BAA00321.1; -; mRNA.
DR EMBL; BT006849; AAP35495.1; -; mRNA.
DR EMBL; CR456746; CAG33027.1; -; mRNA.
DR EMBL; AL731541; CAI40837.1; -; Genomic_DNA.
DR EMBL; AC073370; CAI40837.1; JOINED; Genomic_DNA.
DR EMBL; CH471083; EAW54437.1; -; Genomic_DNA.
DR EMBL; BC001503; AAH01503.1; -; mRNA.
DR EMBL; BC004275; AAH04275.1; -; mRNA.
DR EMBL; BC007612; AAH07612.1; -; mRNA.
DR EMBL; M86181; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X57107; CAA40391.1; -; Genomic_DNA.
DR EMBL; X57108; CAA40392.1; -; Genomic_DNA.
DR EMBL; M12710; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; J03015; AAB59494.1; -; mRNA.
DR EMBL; M32221; AAA60303.1; -; mRNA.
DR EMBL; M60257; AAA36595.1; -; mRNA.
DR EMBL; M60258; AAA36596.1; -; mRNA.
DR EMBL; M60255; AAA36594.1; -; mRNA.
DR IPI; IPI00012503; -.
DR IPI; IPI00219825; -.
DR IPI; IPI00744835; -.
DR PIR; JX0061; SAHUP.
DR RefSeq; NP_001035930.1; NM_001042465.1.
DR RefSeq; NP_001035931.1; NM_001042466.1.
DR RefSeq; NP_002769.1; NM_002778.2.
DR UniGene; Hs.523004; -.
DR PDB; 1M12; NMR; -; A=311-390.
DR PDB; 1N69; X-ray; 2.20 A; A/B/C=195-273.
DR PDB; 1SN6; NMR; -; A=311-390.
DR PDB; 2DOB; X-ray; 2.00 A; A=60-140.
DR PDB; 2GTG; X-ray; 2.40 A; A=311-391.
DR PDB; 2QYP; X-ray; 2.45 A; A/B=311-392.
DR PDB; 2R0R; X-ray; 2.50 A; A/B=407-484.
DR PDB; 2R1Q; X-ray; 2.50 A; A=407-484.
DR PDB; 2RB3; X-ray; 2.10 A; A/B/C/D=407-484.
DR PDB; 2Z9A; X-ray; 2.50 A; A/B=311-389.
DR PDB; 3BQP; X-ray; 1.30 A; A/B=405-484.
DR PDB; 3BQQ; X-ray; 2.00 A; A/B/C/D=405-484.
DR PDB; 4DDJ; X-ray; 1.90 A; A=60-140.
DR PDBsum; 1M12; -.
DR PDBsum; 1N69; -.
DR PDBsum; 1SN6; -.
DR PDBsum; 2DOB; -.
DR PDBsum; 2GTG; -.
DR PDBsum; 2QYP; -.
DR PDBsum; 2R0R; -.
DR PDBsum; 2R1Q; -.
DR PDBsum; 2RB3; -.
DR PDBsum; 2Z9A; -.
DR PDBsum; 3BQP; -.
DR PDBsum; 3BQQ; -.
DR PDBsum; 4DDJ; -.
DR ProteinModelPortal; P07602; -.
DR DIP; DIP-29803N; -.
DR IntAct; P07602; 10.
DR MINT; MINT-1193270; -.
DR TCDB; 1.C.35.2.1; amoebapore family.
DR GlycoSuiteDB; P07602; -.
DR PhosphoSite; P07602; -.
DR DMDM; 134218; -.
DR PaxDb; P07602; -.
DR PRIDE; P07602; -.
DR DNASU; 5660; -.
DR Ensembl; ENST00000394936; ENSP00000378394; ENSG00000197746.
DR GeneID; 5660; -.
DR KEGG; hsa:5660; -.
DR UCSC; uc001jsm.3; human.
DR CTD; 5660; -.
DR GeneCards; GC10M073576; -.
DR HGNC; HGNC:9498; PSAP.
DR HPA; CAB004647; -.
DR HPA; HPA004426; -.
DR MIM; 176801; gene.
DR MIM; 249900; phenotype.
DR MIM; 610539; phenotype.
DR MIM; 611721; phenotype.
DR MIM; 611722; phenotype.
DR neXtProt; NX_P07602; -.
DR Orphanet; 139406; Encephalopathy due to prosaposin deficiency.
DR Orphanet; 512; Metachromatic leukodystrophy.
DR PharmGKB; PA33845; -.
DR eggNOG; NOG269151; -.
DR HOVERGEN; HBG002617; -.
DR KO; K12382; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; PSAP; human.
DR EvolutionaryTrace; P07602; -.
DR GenomeRNAi; 5660; -.
DR NextBio; 21992; -.
DR ArrayExpress; P07602; -.
DR Bgee; P07602; -.
DR CleanEx; HS_PSAP; -.
DR Genevestigator; P07602; -.
DR GermOnline; ENSG00000197746; Homo sapiens.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016021; C:integral to membrane; TAS:ProtInc.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Compara.
DR GO; GO:0008047; F:enzyme activator activity; TAS:ProtInc.
DR GO; GO:0008289; F:lipid binding; TAS:ProtInc.
DR GO; GO:0071310; P:cellular response to organic substance; IEA:Compara.
DR GO; GO:0060742; P:epithelial cell differentiation involved in prostate gland development; IEA:Compara.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:0006869; P:lipid transport; TAS:ProtInc.
DR GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0060736; P:prostate gland growth; IEA:Compara.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IEA:Compara.
DR GO; GO:0043408; P:regulation of MAPK cascade; IEA:Compara.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 1.10.225.10; -; 4.
DR InterPro; IPR003119; SapA.
DR InterPro; IPR007856; SapB_1.
DR InterPro; IPR008138; SapB_2.
DR InterPro; IPR008373; Saposin.
DR InterPro; IPR011001; Saposin-like.
DR InterPro; IPR021165; Saposin_chordata.
DR InterPro; IPR008139; SaposinB.
DR Pfam; PF02199; SapA; 2.
DR Pfam; PF05184; SapB_1; 4.
DR Pfam; PF03489; SapB_2; 4.
DR PIRSF; PIRSF002431; Saposin; 1.
DR PRINTS; PR01797; SAPOSIN.
DR SMART; SM00162; SAPA; 2.
DR SMART; SM00741; SapB; 4.
DR SUPFAM; SSF47862; Saposin_like; 4.
DR PROSITE; PS51110; SAP_A; 2.
DR PROSITE; PS50015; SAP_B; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Disease mutation; Disulfide bond;
KW Gangliosidosis; Gaucher disease; Glycoprotein; Leukodystrophy;
KW Lipid metabolism; Lysosome; Metachromatic leukodystrophy;
KW Reference proteome; Repeat; Signal; Sphingolipid metabolism.
FT SIGNAL 1 16
FT PROPEP 17 58
FT /FTId=PRO_0000031616.
FT CHAIN 60 142 Saposin-A.
FT /FTId=PRO_0000031617.
FT PROPEP 144 194
FT /FTId=PRO_0000031618.
FT CHAIN 195 274 Saposin-B-Val.
FT /FTId=PRO_0000031619.
FT CHAIN 195 273 Saposin-B.
FT /FTId=PRO_0000031620.
FT PROPEP 276 309
FT /FTId=PRO_0000031621.
FT CHAIN 311 391 Saposin-C.
FT /FTId=PRO_0000031622.
FT PROPEP 393 403
FT /FTId=PRO_0000031623.
FT CHAIN 405 486 Saposin-D.
FT /FTId=PRO_0000031624.
FT PROPEP 488 524
FT /FTId=PRO_0000031625.
FT DOMAIN 18 58 Saposin A-type 1.
FT DOMAIN 59 142 Saposin B-type 1.
FT DOMAIN 194 275 Saposin B-type 2.
FT DOMAIN 311 392 Saposin B-type 3.
FT DOMAIN 405 486 Saposin B-type 4.
FT DOMAIN 488 524 Saposin A-type 2.
FT SITE 215 215 Not glycosylated; in variant MLD-SAPB
FT Ile-217.
FT CARBOHYD 80 80 N-linked (GlcNAc...).
FT CARBOHYD 101 101 N-linked (GlcNAc...).
FT CARBOHYD 215 215 N-linked (GlcNAc...) (complex).
FT /FTId=CAR_000176.
FT CARBOHYD 332 332 N-linked (GlcNAc...).
FT CARBOHYD 426 426 N-linked (GlcNAc...).
FT DISULFID 63 138
FT DISULFID 66 132
FT DISULFID 94 106
FT DISULFID 198 271
FT DISULFID 201 265
FT DISULFID 230 241
FT DISULFID 315 388
FT DISULFID 318 382
FT DISULFID 346 357
FT DISULFID 409 482
FT DISULFID 412 476
FT DISULFID 440 451
FT VAR_SEQ 259 259 M -> MDQ (in isoform Sap-mu-6).
FT /FTId=VSP_006014.
FT VAR_SEQ 260 260 Q -> QDQQ (in isoform Sap-mu-9).
FT /FTId=VSP_006015.
FT VARIANT 70 70 Missing (in AKRD).
FT /FTId=VAR_042440.
FT VARIANT 215 215 N -> H (in MLD-SAPB; reduces the
FT intracellular activity of the protein
FT significantly).
FT /FTId=VAR_031823.
FT VARIANT 215 215 N -> K (in MLD-SAPB).
FT /FTId=VAR_031899.
FT VARIANT 217 217 T -> I (in MLD-SAPB; juvenile; affects
FT glycosylation at N-215).
FT /FTId=VAR_006943.
FT VARIANT 241 241 C -> S (in MLD-SAPB; severe;
FT dbSNP:rs1130793).
FT /FTId=VAR_006944.
FT VARIANT 349 349 L -> P (in AGD).
FT /FTId=VAR_042441.
FT VARIANT 388 388 C -> F (in AGD).
FT /FTId=VAR_006945.
FT MUTAGEN 240 240 I->C: Strongly decreases stimulation of
FT cerebroside sulfate hydrolysis.
FT CONFLICT 369 369 L -> P (in Ref. 4; CAG33027).
FT HELIX 61 78
FT HELIX 82 94
FT STRAND 97 99
FT HELIX 101 125
FT HELIX 128 134
FT HELIX 196 214
FT HELIX 218 229
FT HELIX 230 233
FT HELIX 237 256
FT HELIX 261 267
FT HELIX 314 330
FT HELIX 335 345
FT HELIX 346 348
FT HELIX 351 373
FT HELIX 378 384
FT TURN 386 388
FT HELIX 409 422
FT HELIX 429 439
FT HELIX 440 442
FT HELIX 445 447
FT HELIX 448 466
FT HELIX 472 478
SQ SEQUENCE 524 AA; 58113 MW; 71977F7A8C9E1533 CRC64;
MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ TVWNKPTVKS
LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP NMSASCKEIV DSYLPVILDI
IKGEMSRPGE VCSALNLCES LQKHLAELNH QKQLESNKIP ELDMTEVVAP FMANIPLLLY
PQDGPRSKPQ PKDNGDVCQD CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI
CKNYISQYSE IAIQMMMHMQ PKEICALVGF CDEVKEMPMQ TLVPAKVASK NVIPALELVE
PIKKHEVPAK SDVYCEVCEF LVKEVTKLID NNKTEKEILD AFDKMCSKLP KSLSEECQEV
VDTYGSSILS ILLEEVSPEL VCSMLHLCSG TRLPALTVHV TQPKDGGFCE VCKKLVGYLD
RNLEKNSTKQ EILAALEKGC SFLPDPYQKQ CDQFVAEYEP VLIEILVEVM DPSFVCLKIG
ACPSAHKPLL GTEKCIWGPS YWCQNTETAA QCNAVEHCKR HVWN
//
