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 27-MAR-2024, entry version 260. 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>3.3.co;2-7; 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 MLDSAPB 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 MLDSAPB 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 MLDSAPB 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 MLDSAPB 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 PSAPD. 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 GDSAPC 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 MLDSAPB 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 MLDSAPB HIS-215, AND CHARACTERIZATION OF VARIANT MLDSAPB 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 PSAPD. 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 KRBSAPA 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 GDSAPC 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 (PSAPD) [MIM:611721]: An autosomal CC recessive storage disorder characterized by hepatosplenomegaly and CC severe neurologic disease, due to absence of all saposins. PSAPD has a CC fatal outcome in infancy. {ECO:0000269|PubMed:11309366, CC ECO:0000269|PubMed:1371116}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Metachromatic leukodystrophy due to saposin B deficiency CC (MLDSAPB) [MIM:249900]: A form of metachromatic leukodystrophy CC biochemically characterized by tissue accumulation of cerebroside-3- CC sulfate, saposin B deficiency, and normal arylsulfatase A activity. CC Clinical manifestations include periventricular white matter CC abnormalities, demyelination, and peripheral neuropathy. Additional CC neurological features include dysarthria, ataxic gait, psychomotor CC regression, seizures, cognitive decline and spastic quadriparesis. CC {ECO:0000269|PubMed:10196694, ECO:0000269|PubMed:10682309, CC ECO:0000269|PubMed:2019586, ECO:0000269|PubMed:2302219, CC ECO:0000269|PubMed:2320574}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Gaucher disease, atypical, due to saposin C deficiency CC (GDSAPC) [MIM:610539]: A disease characterized by marked CC glucosylceramide accumulation in the spleen without having a deficiency CC of 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 CC (KRBSAPA) [MIM:611722]: An autosomal recessive disorder of CC galactosylceramide metabolism. Clinical features include neurologic CC regression around age 3 months, loss of spontaneous movements, CC hyporeflexia, generalized brain atrophy, and diffuse white matter CC dysmyelination. {ECO:0000269|PubMed:15773042}. Note=The disease is CC caused by variants affecting the gene represented 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="https://atlasgeneticsoncology.org/gene/42980/PSAP"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8EQU; EM; 2.80 A; C/F=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 PDBsum; 4UEX; -. DR PDBsum; 4V2O; -. DR PDBsum; 6SLR; -. DR PDBsum; 8EQU; -. DR AlphaFoldDB; P07602; -. DR EMDB; EMD-28546; -. DR SASBDB; P07602; -. DR SMR; P07602; -. DR BioGRID; 111639; 118. DR CORUM; P07602; -. DR DIP; DIP-29803N; -. DR IntAct; P07602; 116. 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 GlyCosmos; P07602; 14 sites, 167 glycans. DR GlyGen; P07602; 22 sites, 167 N-linked glycans (7 sites), 4 O-linked glycans (15 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; 9606-ENSP00000378394; -. DR PeptideAtlas; P07602; -. DR PRIDE; P07602; -. DR ProteomicsDB; 52019; -. [P07602-1] DR ProteomicsDB; 52020; -. [P07602-2] DR ProteomicsDB; 52021; -. [P07602-3] DR Pumba; P07602; -. DR TopDownProteomics; P07602-1; -. [P07602-1] DR Antibodypedia; 1388; 561 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 AGR; HGNC:9498; -. 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; 7299at2759; -. DR PhylomeDB; P07602; -. DR TreeFam; TF316942; -. DR PathwayCommons; P07602; -. DR Reactome; R-HSA-114608; Platelet degranulation. 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 Reactome; R-HSA-9840310; Glycosphingolipid catabolism. DR SignaLink; P07602; -. DR BioGRID-ORCS; 5660; 21 hits in 1170 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 211 other cell types or tissues. DR ExpressionAtlas; P07602; baseline and differential. 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 Gene3D; 1.10.225.10; Saposin-like; 4. 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 PANTHER; PTHR11480:SF36; PROSAPOSIN; 1. DR PANTHER; PTHR11480; SAPOSIN-RELATED; 1. DR Pfam; PF02199; SapA; 2. DR Pfam; PF05184; SapB_1; 3. 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; 4. DR PROSITE; PS51110; SAP_A; 2. DR PROSITE; PS50015; SAP_B; 4. DR Genevisible; P07602; HS. 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 MLDSAPB 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 KRBSAPA)" FT /evidence="ECO:0000269|PubMed:15773042" FT /id="VAR_042440" FT VARIANT 215 FT /note="N -> H (in MLDSAPB; 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 MLDSAPB; dbSNP:rs770171865)" FT /evidence="ECO:0000269|PubMed:10196694" FT /id="VAR_031899" FT VARIANT 217 FT /note="T -> I (in MLDSAPB; 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 MLDSAPB; severe; dbSNP:rs121918104)" FT /evidence="ECO:0000269|PubMed:2019586" FT /id="VAR_006944" FT VARIANT 349 FT /note="L -> P (in GDSAPC; dbSNP:rs121918110)" FT /evidence="ECO:0000269|PubMed:17919309" FT /id="VAR_042441" FT VARIANT 388 FT /note="C -> F (in GDSAPC)" 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 //