SAP_HUMAN
ID SAP_HUMAN Reviewed; 524 AA.
AC P07602; P07292; P15793; P78538; P78541; P78546; P78547; P78558; Q53Y86;
AC Q6IBQ6; Q92739; Q92740; Q92741; Q92742;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 2.
DT 03-AUG-2022, entry version 251.
DE RecName: Full=Prosaposin;
DE AltName: 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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 four
RT sphingolipid hydrolase activator proteins are encoded by single genes in
RT humans and rats.";
RL Genomics 5:486-492(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2498298; DOI=10.1093/oxfordjournals.jbchem.a122629;
RA Nakano T., Sandhoff K., Stuemper J., Christomanou H., Suzuki K.;
RT "Structure of full-length cDNA coding for sulfatide activator, a Co-beta-
RT glucosidase and two other homologous proteins: two alternate forms of the
RT 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 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., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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., Fluharty A.L.;
RT "Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same
RT 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 AND 165-172.
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., Suzuki K.;
RT "The organization of the gene for the human cerebroside sulfate activator
RT 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-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., Hill F.,
RA O'Brien J.S.;
RT "Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the
RT sulfatide sulfatase activator.";
RL Biochem. Biophys. Res. Commun. 134:989-994(1986).
RN [17]
RP PROTEIN SEQUENCE OF 195-274.
RX PubMed=3242555; DOI=10.1515/bchm3.1988.369.2.1361;
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 sulfatide
RT 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; DOI=10.1515/bchm3.1987.368.2.1571;
RA Kleinschmidt T., Christomanou H., Braunitzer G.;
RT "Complete amino-acid sequence and carbohydrate content of the naturally
RT occurring glucosylceramide activator protein (A1 activator) absent from a
RT 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; DOI=10.1515/bchm3.1988.369.1.317;
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) from
RT human urine.";
RL Mol. Genet. Metab. 68:391-403(1999).
RN [23]
RP DISULFIDE BONDS IN SAPOSINS-B AND C, AND IDENTIFICATION BY MASS
RP 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 disulfide
RT bridges.";
RL J. Biol. Chem. 270:9953-9960(1995).
RN [24]
RP FUNCTION.
RX PubMed=10383054;
RX DOI=10.1002/(sici)1098-1136(199906)26:4<353::aid-glia9>3.0.co;2-g;
RA Hiraiwa M., Campana W.M., Mizisin A.P., Mohiuddin L., O'Brien J.S.;
RT "Prosaposin: a myelinotrophic protein that promotes expression of myelin
RT constituents and is secreted after nerve injury.";
RL Glia 26:353-360(1999).
RN [25]
RP IDENTIFICATION BY 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., Fluharty C.B.,
RA Fluharty A.L.;
RT "Cerebroside sulfate activator protein (Saposin B): chromatographic and
RT electrospray mass spectrometric properties.";
RL J. Mass Spectrom. 34:1040-1054(1999).
RN [26]
RP GLYCOSYLATION AT ASN-215, AND 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., Stevens R.L.,
RA 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 [27]
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., Amoresano A.,
RA Vaccaro A.M.;
RT "Structural and membrane-binding properties of saposin D.";
RL Eur. J. Biochem. 263:486-494(1999).
RN [28]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SORT1.
RX PubMed=14657016; DOI=10.1093/emboj/cdg629;
RA Lefrancois S., Zeng J., Hassan A.J., Canuel M., Morales C.R.;
RT "The lysosomal trafficking of sphingolipid activator proteins (SAPs) is
RT mediated by sortilin.";
RL EMBO J. 22:6430-6437(2003).
RN [29]
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 analysis
RT of recombinant human saposin B.";
RL Protein Expr. Purif. 27:186-193(2003).
RN [30]
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 by
RT distinct mammalian OST isoforms.";
RL Cell 136:272-283(2009).
RN [31]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-80; ASN-101; ASN-332 AND
RP ASN-426.
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 multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [32]
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., Buerckstuemmer T.,
RA 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 [33]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=21835174; DOI=10.1016/j.yexcr.2011.07.017;
RA Yuan L., Morales C.R.;
RT "Prosaposin sorting is mediated by oligomerization.";
RL Exp. Cell Res. 317:2456-2467(2011).
RN [34]
RP INTERACTION WITH SORT1, AND SUBCELLULAR LOCATION.
RX PubMed=22431521; DOI=10.1128/mcb.06726-11;
RA Mamo A., Jules F., Dumaresq-Doiron K., Costantino S., Lefrancois S.;
RT "The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal
RT sorting.";
RL Mol. Cell. Biol. 32:1855-1866(2012).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [36]
RP INTERACTION WITH GRN.
RX PubMed=26370502; DOI=10.1083/jcb.201502029;
RA Zhou X., Sun L., Bastos de Oliveira F., Qi X., Brown W.J., Smolka M.B.,
RA Sun Y., Hu F.;
RT "Prosaposin facilitates sortilin-independent lysosomal trafficking of
RT progranulin.";
RL J. Cell Biol. 210:991-1002(2015).
RN [37]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER ALA-16, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [38]
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 [39]
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 [40]
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 mRNA in
RT patients with a variant form of metachromatic leukodystrophy.";
RL Biochem. Biophys. Res. Commun. 166:1017-1023(1990).
RN [41]
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: a
RT glycosylation site defect.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2541-2544(1990).
RN [42]
RP VARIANT MLD-SAPB SER-241, NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE
RP SPLICING.
RX PubMed=2019586; DOI=10.1016/s0021-9258(20)89483-6;
RA Holtschmidt H., Sandhoff K., Kwon H.Y., Harzer K., Nakano T., Suzuki K.;
RT "Sulfatide activator protein. Alternative splicing that generates three
RT mRNAs and a newly found mutation responsible for a clinical disease.";
RL J. Biol. Chem. 266:7556-7560(1991).
RN [43]
RP INVOLVEMENT IN CSAPD.
RX PubMed=1371116; DOI=10.1016/s0021-9258(19)50733-5;
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 [44]
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 [45]
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 acidic
RT residue and leading to the loss of the single N-glycosylation site in a
RT patient with metachromatic leukodystrophy and normal arylsulphatase A
RT activity.";
RL Eur. J. Hum. Genet. 7:125-130(1999).
RN [46]
RP VARIANT MLD-SAPB HIS-215, AND CHARACTERIZATION OF VARIANT MLD-SAPB 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 metachromatic
RT leukodystrophy (MLD).";
RL J. Inherit. Metab. Dis. 23:63-76(2000).
RN [47]
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 a
RT complete deficiency of prosaposin and saposins, and is associated with a
RT complex sphingolipidosis dominated by lactosylceramide accumulation.";
RL Hum. Mol. Genet. 10:927-940(2001).
RN [48]
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., Shneor Y.,
RA Mandel H., Zeigler M.;
RT "A mutation in the saposin A coding region of the prosaposin gene in an
RT infant presenting as Krabbe disease: first report of saposin A deficiency
RT in humans.";
RL Mol. Genet. Metab. 84:160-166(2005).
RN [49]
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).
RN [50]
RP INVOLVEMENT IN PARK24, VARIANTS PARK24 TYR-412 AND PRO-453, AND
RP CHARACTERIZATION OF VARIANTS PARK24 TYR-412 AND PRO-453.
RX PubMed=32201884; DOI=10.1093/brain/awaa064;
RA Oji Y., Hatano T., Ueno S.I., Funayama M., Ishikawa K.I., Okuzumi A.,
RA Noda S., Sato S., Satake W., Toda T., Li Y., Hino-Takai T., Kakuta S.,
RA Tsunemi T., Yoshino H., Nishioka K., Hattori T., Mizutani Y., Mutoh T.,
RA Yokochi F., Ichinose Y., Koh K., Shindo K., Takiyama Y., Hamaguchi T.,
RA Yamada M., Farrer M.J., Uchiyama Y., Akamatsu W., Wu Y.R., Matsuda J.,
RA Hattori N.;
RT "Variants in saposin D domain of prosaposin gene linked to Parkinson's
RT disease.";
RL Brain 143:1190-1205(2020).
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). Saposin-
CC C apparently acts by combining with the enzyme and acidic lipid to form
CC an activated complex, rather than by solubilizing the substrate.
CC -!- FUNCTION: Saposin-B stimulates the hydrolysis of galacto-cerebroside
CC sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-
CC galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-
CC galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex
CC with the substrates of the sphingolipid hydrolases.
CC -!- FUNCTION: Saposin-D is a specific sphingomyelin phosphodiesterase
CC activator (EC 3.1.4.12).
CC -!- FUNCTION: [Prosaposin]: Behaves as a myelinotrophic and neurotrophic
CC factor, these effects are mediated by its G-protein-coupled receptors,
CC GPR37 and GPR37L1, undergoing ligand-mediated internalization followed
CC by ERK phosphorylation signaling. {ECO:0000250|UniProtKB:Q61207,
CC ECO:0000269|PubMed:10383054}.
CC -!- FUNCTION: Saposins are specific low-molecular mass non-enzymic
CC proteins, they participate in the lysosomal degradation of
CC sphingolipids, which takes place by the sequential action of specific
CC hydrolases.
CC -!- SUBUNIT: Saposin-B is a homodimer. Prosaposin exists as a roughly half-
CC half mixture of monomers and disulfide-linked dimers (PubMed:10406958,
CC PubMed:12510003, PubMed:7730378, PubMed:21835174). Monomeric prosaposin
CC interacts (via C-terminus) with sortilin/SORT1, the interaction is
CC required for targeting to lysosomes (PubMed:14657016, PubMed:22431521).
CC Interacts with GRN; facilitates lysosomal delivery of progranulin from
CC the extracellular space and the biosynthetic pathway (PubMed:26370502).
CC {ECO:0000269|PubMed:10406958, ECO:0000269|PubMed:12510003,
CC ECO:0000269|PubMed:14657016, ECO:0000269|PubMed:21835174,
CC ECO:0000269|PubMed:22431521, ECO:0000269|PubMed:26370502,
CC ECO:0000269|PubMed:7730378}.
CC -!- INTERACTION:
CC P07602; P05067: APP; NbExp=3; IntAct=EBI-716699, EBI-77613;
CC P07602; Q92624: APPBP2; NbExp=3; IntAct=EBI-716699, EBI-743771;
CC P07602; P31944: CASP14; NbExp=3; IntAct=EBI-716699, EBI-2510738;
CC P07602; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-716699, EBI-9087876;
CC P07602; P28799: GRN; NbExp=5; IntAct=EBI-716699, EBI-747754;
CC P07602; P07948: LYN; NbExp=3; IntAct=EBI-716699, EBI-79452;
CC P07602; P50542-3: PEX5; NbExp=3; IntAct=EBI-716699, EBI-12181987;
CC P07602; O96006: ZBED1; NbExp=4; IntAct=EBI-716699, EBI-740037;
CC P07602-1; P07602-1: PSAP; NbExp=5; IntAct=EBI-10635648, EBI-10635648;
CC P07602-1; P55072: VCP; NbExp=3; IntAct=EBI-10635648, EBI-355164;
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:14657016,
CC ECO:0000269|PubMed:21835174, ECO:0000269|PubMed:22431521}.
CC -!- SUBCELLULAR LOCATION: [Prosaposin]: Secreted
CC {ECO:0000250|UniProtKB:Q61207}. Note=Secreted as a fully glycosylated
CC 70 kDa protein composed of complex glycans.
CC {ECO:0000250|UniProtKB:Q61207}.
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: The lysosomal 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 {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19167329}.
CC -!- PTM: The one residue extended Saposin-B-Val is only found in 5% of the
CC 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.
CC {ECO:0000269|PubMed:11309366, ECO:0000269|PubMed:1371116}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Metachromatic leukodystrophy due to saposin-B deficiency (MLD-
CC SAPB) [MIM:249900]: An atypical form of metachromatic leukodystrophy.
CC It is characterized by tissue accumulation of cerebroside-3-sulfate,
CC demyelination, periventricular white matter abnormalities, peripheral
CC neuropathy. Additional neurological features include dysarthria, ataxic
CC gait, psychomotor regression, seizures, cognitive decline and spastic
CC quadriparesis. {ECO:0000269|PubMed:10196694,
CC ECO:0000269|PubMed:10682309, ECO:0000269|PubMed:2019586,
CC ECO:0000269|PubMed:2302219, ECO:0000269|PubMed:2320574}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Gaucher disease, atypical, due to saposin C deficiency (AGD)
CC [MIM:610539]: A disease characterized by marked glucosylceramide
CC accumulation in the spleen without having a deficiency of
CC glucosylceramide-beta glucosidase characteristic of classic Gaucher
CC disease. Gaucher disease is a lysosomal storage disorder characterized
CC by skeletal deterioration, hepatosplenomegaly, and organ dysfunction.
CC There are several subtypes based on the presence and severity of
CC neurological involvement. {ECO:0000269|PubMed:17919309,
CC ECO:0000269|PubMed:2060627}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Krabbe disease, atypical, due to saposin A deficiency (AKRD)
CC [MIM:611722]: A disorder of galactosylceramide metabolism. Clinical
CC features include neurologic regression around age 3 months, loss of
CC spontaneous movements, hyporeflexia, generalized brain atrophy, and
CC diffuse white matter dysmyelination. {ECO:0000269|PubMed:15773042}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Note=Defects in PSAP saposin-D region are found in a variant
CC of Tay-Sachs disease (GM2-gangliosidosis).
CC -!- DISEASE: Parkinson disease 24, autosomal dominant (PARK24)
CC [MIM:619491]: An autosomal dominant form of Parkinson disease, a
CC complex neurodegenerative disorder characterized by bradykinesia,
CC resting tremor, muscular rigidity and postural instability, as well as
CC by a clinically significant response to treatment with levodopa. The
CC pathology involves the loss of dopaminergic neurons in the substantia
CC nigra and the presence of Lewy bodies (intraneuronal accumulations of
CC aggregated proteins), in surviving neurons in various areas of the
CC brain. PARK24 shows incomplete penetrance.
CC {ECO:0000269|PubMed:32201884}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Saposin-B co-purifies with 1 molecule of
CC phosphatidylethanolamine.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PSAPID42980ch10q22.html";
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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; AC073370; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731541; -; NOT_ANNOTATED_CDS; 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 CCDS; CCDS7311.1; -. [P07602-1]
DR PIR; JX0061; SAHUP.
DR RefSeq; NP_001035930.1; NM_001042465.2. [P07602-3]
DR RefSeq; NP_001035931.1; NM_001042466.2. [P07602-2]
DR RefSeq; NP_002769.1; NM_002778.3. [P07602-1]
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 PDB; 4UEX; X-ray; 1.80 A; A/B=60-142.
DR PDB; 4V2O; X-ray; 2.13 A; A/B/C=195-273.
DR PDB; 6SLR; X-ray; 2.38 A; A/B/C=195-272.
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 PDBsum; 4UEX; -.
DR PDBsum; 4V2O; -.
DR PDBsum; 6SLR; -.
DR AlphaFoldDB; P07602; -.
DR SASBDB; P07602; -.
DR SMR; P07602; -.
DR BioGRID; 111639; 83.
DR CORUM; P07602; -.
DR DIP; DIP-29803N; -.
DR IntAct; P07602; 113.
DR MINT; P07602; -.
DR STRING; 9606.ENSP00000378394; -.
DR BindingDB; P07602; -.
DR ChEMBL; CHEMBL3580523; -.
DR DrugBank; DB01966; Di-Stearoyl-3-Sn-Phosphatidylethanolamine.
DR TCDB; 1.C.35.2.1; the amoebapore (amoebapore) family.
DR GlyConnect; 1645; 140 N-Linked glycans (6 sites), 2 O-Linked glycans (3 sites).
DR GlyGen; P07602; 16 sites, 165 N-linked glycans (7 sites), 3 O-linked glycans (8 sites).
DR iPTMnet; P07602; -.
DR MetOSite; P07602; -.
DR PhosphoSitePlus; P07602; -.
DR BioMuta; PSAP; -.
DR DMDM; 134218; -.
DR EPD; P07602; -.
DR jPOST; P07602; -.
DR MassIVE; P07602; -.
DR MaxQB; P07602; -.
DR PaxDb; P07602; -.
DR PeptideAtlas; P07602; -.
DR PRIDE; P07602; -.
DR ProteomicsDB; 52019; -. [P07602-1]
DR ProteomicsDB; 52020; -. [P07602-2]
DR ProteomicsDB; 52021; -. [P07602-3]
DR TopDownProteomics; P07602-1; -. [P07602-1]
DR Antibodypedia; 1388; 498 antibodies from 35 providers.
DR DNASU; 5660; -.
DR Ensembl; ENST00000394936.8; ENSP00000378394.3; ENSG00000197746.15. [P07602-1]
DR GeneID; 5660; -.
DR KEGG; hsa:5660; -.
DR MANE-Select; ENST00000394936.8; ENSP00000378394.3; NM_002778.4; NP_002769.1.
DR UCSC; uc001jsm.4; human. [P07602-1]
DR CTD; 5660; -.
DR DisGeNET; 5660; -.
DR GeneCards; PSAP; -.
DR HGNC; HGNC:9498; PSAP.
DR HPA; ENSG00000197746; Low tissue specificity.
DR MalaCards; PSAP; -.
DR MIM; 176801; gene.
DR MIM; 249900; phenotype.
DR MIM; 610539; phenotype.
DR MIM; 611721; phenotype.
DR MIM; 611722; phenotype.
DR MIM; 619491; phenotype.
DR neXtProt; NX_P07602; -.
DR OpenTargets; ENSG00000197746; -.
DR Orphanet; 309252; Atypical Gaucher disease due to saposin C deficiency.
DR Orphanet; 139406; Encephalopathy due to prosaposin deficiency.
DR Orphanet; 206436; Infantile Krabbe disease.
DR Orphanet; 309271; Metachromatic leukodystrophy, adult form.
DR Orphanet; 309263; Metachromatic leukodystrophy, juvenile form.
DR Orphanet; 309256; Metachromatic leukodystrophy, late infantile form.
DR PharmGKB; PA33845; -.
DR VEuPathDB; HostDB:ENSG00000197746; -.
DR eggNOG; KOG1340; Eukaryota.
DR GeneTree; ENSGT00940000156695; -.
DR HOGENOM; CLU_033757_0_0_1; -.
DR InParanoid; P07602; -.
DR OrthoDB; 865505at2759; -.
DR PhylomeDB; P07602; -.
DR TreeFam; TF316942; -.
DR PathwayCommons; P07602; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P07602; -.
DR BioGRID-ORCS; 5660; 19 hits in 1087 CRISPR screens.
DR ChiTaRS; PSAP; human.
DR EvolutionaryTrace; P07602; -.
DR GeneWiki; Prosaposin; -.
DR GenomeRNAi; 5660; -.
DR Pharos; P07602; Tbio.
DR PRO; PR:P07602; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P07602; protein.
DR Bgee; ENSG00000197746; Expressed in monocyte and 209 other tissues.
DR ExpressionAtlas; P07602; baseline and differential.
DR Genevisible; P07602; HS.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:CAFA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008047; F:enzyme activator activity; TAS:ProtInc.
DR GO; GO:1905573; F:ganglioside GM1 binding; IDA:CAFA.
DR GO; GO:1905574; F:ganglioside GM2 binding; IDA:CAFA.
DR GO; GO:1905575; F:ganglioside GM3 binding; IDA:CAFA.
DR GO; GO:1905577; F:ganglioside GP1c binding; IDA:CAFA.
DR GO; GO:1905576; F:ganglioside GT1b binding; IDA:CAFA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005543; F:phospholipid binding; IDA:CAFA.
DR GO; GO:0002020; F:protease binding; IPI:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0097110; F:scaffold protein binding; IPI:ARUK-UCL.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0060742; P:epithelial cell differentiation involved in prostate gland development; IBA:GO_Central.
DR GO; GO:1905572; P:ganglioside GM1 transport to membrane; IDA:CAFA.
DR GO; GO:0007041; P:lysosomal transport; IDA:UniProtKB.
DR GO; GO:1903771; P:positive regulation of beta-galactosidase activity; IDA:CAFA.
DR GO; GO:0060736; P:prostate gland growth; IBA:GO_Central.
DR GO; GO:0010506; P:regulation of autophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IBA:GO_Central.
DR GO; GO:0006665; P:sphingolipid metabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR003119; SAP_A.
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_dom.
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; SSF47862; 4.
DR PROSITE; PS51110; SAP_A; 2.
DR PROSITE; PS50015; SAP_B; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Disulfide bond; Gangliosidosis; Gaucher disease;
KW Glycoprotein; Leukodystrophy; Lipid metabolism; Lysosome;
KW Metachromatic leukodystrophy; Neurodegeneration; Parkinson disease;
KW Parkinsonism; Reference proteome; Repeat; Secreted; Signal;
KW Sphingolipid metabolism.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:1958198,
FT ECO:0000269|PubMed:8323276, ECO:0007744|PubMed:25944712"
FT CHAIN 17..524
FT /note="Prosaposin"
FT /evidence="ECO:0000269|PubMed:8323276"
FT /id="PRO_0000424774"
FT PROPEP 17..59
FT /evidence="ECO:0000305"
FT /id="PRO_0000031616"
FT CHAIN 60..142
FT /note="Saposin-A"
FT /evidence="ECO:0000269|PubMed:2717620"
FT /id="PRO_0000031617"
FT PROPEP 143..194
FT /evidence="ECO:0000305"
FT /id="PRO_0000031618"
FT CHAIN 195..274
FT /note="Saposin-B-Val"
FT /evidence="ECO:0000269|PubMed:2209618,
FT ECO:0000269|PubMed:3242555"
FT /id="PRO_0000031619"
FT CHAIN 195..273
FT /note="Saposin-B"
FT /evidence="ECO:0000269|PubMed:2209618"
FT /id="PRO_0000031620"
FT PROPEP 275..310
FT /evidence="ECO:0000305"
FT /id="PRO_0000031621"
FT CHAIN 311..390
FT /note="Saposin-C"
FT /evidence="ECO:0000269|PubMed:3442600"
FT /id="PRO_0000031622"
FT PROPEP 393..404
FT /evidence="ECO:0000305"
FT /id="PRO_0000031623"
FT CHAIN 405..486
FT /note="Saposin-D"
FT /evidence="ECO:0000269|PubMed:2845979"
FT /id="PRO_0000031624"
FT PROPEP 487..524
FT /evidence="ECO:0000305"
FT /id="PRO_0000031625"
FT DOMAIN 18..58
FT /note="Saposin A-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00414"
FT DOMAIN 59..142
FT /note="Saposin B-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DOMAIN 194..275
FT /note="Saposin B-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DOMAIN 311..392
FT /note="Saposin B-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DOMAIN 405..486
FT /note="Saposin B-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DOMAIN 488..524
FT /note="Saposin A-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00414"
FT SITE 215
FT /note="Not glycosylated; in variant MLD-SAPB Ile-217"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19167329,
FT ECO:0000269|PubMed:2842863"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19167329,
FT ECO:0000269|PubMed:2842863"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:11180632, ECO:0000269|PubMed:19167329"
FT /id="CAR_000176"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19167329"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19167329"
FT DISULFID 63..138
FT /evidence="ECO:0000305|PubMed:2717620"
FT DISULFID 66..132
FT /evidence="ECO:0000305|PubMed:2717620"
FT DISULFID 94..106
FT /evidence="ECO:0000305|PubMed:2717620"
FT DISULFID 198..271
FT /evidence="ECO:0000269|PubMed:12510003"
FT DISULFID 201..265
FT /evidence="ECO:0000269|PubMed:12510003"
FT DISULFID 230..241
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:7730378"
FT DISULFID 315..388
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:7730378"
FT DISULFID 318..382
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:7730378"
FT DISULFID 346..357
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415,
FT ECO:0000269|PubMed:7730378"
FT DISULFID 409..482
FT /evidence="ECO:0000269|PubMed:10406958"
FT DISULFID 412..476
FT /evidence="ECO:0000269|PubMed:10406958"
FT DISULFID 440..451
FT /evidence="ECO:0000269|PubMed:10406958"
FT VAR_SEQ 259
FT /note="M -> MDQ (in isoform Sap-mu-6)"
FT /evidence="ECO:0000305"
FT /id="VSP_006014"
FT VAR_SEQ 260
FT /note="Q -> QDQQ (in isoform Sap-mu-9)"
FT /evidence="ECO:0000305"
FT /id="VSP_006015"
FT VARIANT 70
FT /note="Missing (in AKRD)"
FT /evidence="ECO:0000269|PubMed:15773042"
FT /id="VAR_042440"
FT VARIANT 215
FT /note="N -> H (in MLD-SAPB; reduces the intracellular
FT activity of the protein significantly; dbSNP:rs121918107)"
FT /evidence="ECO:0000269|PubMed:10682309"
FT /id="VAR_031823"
FT VARIANT 215
FT /note="N -> K (in MLD-SAPB; dbSNP:rs770171865)"
FT /evidence="ECO:0000269|PubMed:10196694"
FT /id="VAR_031899"
FT VARIANT 217
FT /note="T -> I (in MLD-SAPB; juvenile; affects glycosylation
FT at N-215; dbSNP:rs121918103)"
FT /evidence="ECO:0000269|PubMed:2302219,
FT ECO:0000269|PubMed:2320574"
FT /id="VAR_006943"
FT VARIANT 241
FT /note="C -> S (in MLD-SAPB; severe; dbSNP:rs121918104)"
FT /evidence="ECO:0000269|PubMed:2019586"
FT /id="VAR_006944"
FT VARIANT 349
FT /note="L -> P (in AGD; dbSNP:rs121918110)"
FT /evidence="ECO:0000269|PubMed:17919309"
FT /id="VAR_042441"
FT VARIANT 388
FT /note="C -> F (in AGD)"
FT /evidence="ECO:0000269|PubMed:2060627"
FT /id="VAR_006945"
FT VARIANT 412
FT /note="C -> Y (in PARK24; associated with disease
FT susceptibility; affects the intracellular trafficking,
FT resulting in endoplasmic reticulum retention; affects the
FT intracellular trafficking, resulting in endoplasmic
FT reticulum retention; cells carrying this variant show
FT accumulation of autophagic vacuoles, impaired autophagic
FT flux and alpha-synuclein/SNCA aggregation)"
FT /evidence="ECO:0000269|PubMed:32201884"
FT /id="VAR_086130"
FT VARIANT 453
FT /note="Q -> P (in PARK24; associated with disease
FT susceptibility; affects the intracellular trafficking,
FT resulting in endoplasmic reticulum retention; cells
FT carrying this variant show accumulation of autophagic
FT vacuoles, impaired autophagic flux and alpha-synuclein/SNCA
FT aggregation)"
FT /evidence="ECO:0000269|PubMed:32201884"
FT /id="VAR_086131"
FT MUTAGEN 240
FT /note="I->C: Strongly decreases stimulation of cerebroside
FT sulfate hydrolysis."
FT /evidence="ECO:0000269|PubMed:12518053"
FT CONFLICT 369
FT /note="L -> P (in Ref. 4; CAG33027)"
FT /evidence="ECO:0000305"
FT HELIX 61..78
FT /evidence="ECO:0007829|PDB:4UEX"
FT HELIX 83..96
FT /evidence="ECO:0007829|PDB:4UEX"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:4UEX"
FT HELIX 100..122
FT /evidence="ECO:0007829|PDB:4UEX"
FT HELIX 128..134
FT /evidence="ECO:0007829|PDB:4UEX"
FT HELIX 196..214
FT /evidence="ECO:0007829|PDB:4V2O"
FT HELIX 218..229
FT /evidence="ECO:0007829|PDB:4V2O"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:4V2O"
FT HELIX 237..257
FT /evidence="ECO:0007829|PDB:4V2O"
FT HELIX 261..267
FT /evidence="ECO:0007829|PDB:4V2O"
FT HELIX 314..330
FT /evidence="ECO:0007829|PDB:2GTG"
FT HELIX 335..345
FT /evidence="ECO:0007829|PDB:2GTG"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:1M12"
FT HELIX 351..373
FT /evidence="ECO:0007829|PDB:2GTG"
FT HELIX 378..384
FT /evidence="ECO:0007829|PDB:2GTG"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:1SN6"
FT HELIX 409..422
FT /evidence="ECO:0007829|PDB:3BQP"
FT HELIX 429..439
FT /evidence="ECO:0007829|PDB:3BQP"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:3BQP"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:3BQP"
FT HELIX 448..466
FT /evidence="ECO:0007829|PDB:3BQP"
FT HELIX 472..478
FT /evidence="ECO:0007829|PDB:3BQP"
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
