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P07602 (SAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 182. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prosaposin
Alternative name(s):
Proactivator polypeptide

Cleaved into the following 5 chains:

  1. Saposin-A
    Alternative name(s):
    Protein A
  2. Saposin-B-Val
  3. Saposin-B
    Alternative name(s):
    Cerebroside sulfate activator
    Short name=CSAct
    Dispersin
    Sphingolipid activator protein 1
    Short name=SAP-1
    Sulfatide/GM1 activator
  4. Saposin-C
    Alternative name(s):
    A1 activator
    Co-beta-glucosidase
    Glucosylceramidase activator
    Sphingolipid activator protein 2
    Short name=SAP-2
  5. Saposin-D
    Alternative name(s):
    Component C
    Protein C
Gene names
Name:PSAP
Synonyms:GLBA, SAP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate. Ref.24 Ref.34

Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases. Ref.24 Ref.34

Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12). Ref.24 Ref.34

Prosaposin: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling. Ref.24 Ref.34

Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases. Ref.24 Ref.34

Subunit structure

Saposin-B is a homodimer. Prosaposin exists as a roughly half-half mixture of monomers and disulfide-linked dimers. Monomeric prosaposin interacts (via C-terminus) with sortilin/SORT1, the interaction is required for targeting to lysosomes. Ref.23 Ref.27 Ref.28 Ref.29 Ref.33

Subcellular location

Lysosome Ref.28 Ref.33 Ref.34.

Prosaposin: Secreted. Note: Secreted as a fully glycosylated 70 kDa protein composed of complex glycans. Ref.28 Ref.33 Ref.34

Post-translational modification

The lysosomal precursor is proteolytically processed to 4 small peptides, which are similar to each other and are sphingolipid hydrolase activator proteins.

N-linked glycans show a high degree of microheterogeneity.

The one residue extended Saposin-B-Val is only found in 5% of the chains.

Involvement in disease

Combined saposin deficiency (CSAPD) [MIM:611721]: Due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.40 Ref.44

Leukodystrophy metachromatic due to saposin-B deficiency (MLD-SAPB) [MIM:249900]: An atypical form of metachromatic leukodystrophy. It is characterized by tissue accumulation of cerebroside-3-sulfate, demyelination, periventricular white matter abnormalities, peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotor regression, seizures, cognitive decline and spastic quadriparesis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.38 Ref.39 Ref.42 Ref.43

Gaucher disease, atypical, due to saposin C deficiency (AGD) [MIM:610539]: A disease characterized by marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease. Gaucher disease is a lysosomal storage disorder characterized by skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.41 Ref.46

Krabbe disease, atypical, due to saposin A deficiency (AKRD) [MIM:611722]: A disorder of galactosylceramide metabolism. Clinical features include neurologic regression around age 3 months, loss of spontaneous movements, hyporeflexia, generalized brain atrophy, and diffuse white matter dysmyelination.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.45

Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).

Miscellaneous

Saposin-B co-purifies with 1 molecule of phosphatidylethanolamine.

Sequence similarities

Contains 2 saposin A-type domains.

Contains 4 saposin B-type domains.

Ontologies

Keywords
   Biological processLipid metabolism
Sphingolipid metabolism
   Cellular componentLysosome
Secreted
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Gangliosidosis
Gaucher disease
Leukodystrophy
Metachromatic leukodystrophy
   DomainRepeat
Signal
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

cellular response to organic substance

Inferred from electronic annotation. Source: Ensembl

epithelial cell differentiation involved in prostate gland development

Inferred from electronic annotation. Source: Ensembl

glycosphingolipid metabolic process

Traceable author statement. Source: Reactome

lipid transport

Traceable author statement PubMed 1454804. Source: ProtInc

platelet activation

Traceable author statement. Source: Reactome

platelet degranulation

Traceable author statement. Source: Reactome

positive regulation of catalytic activity

Traceable author statement Ref.13. Source: GOC

prostate gland growth

Inferred from electronic annotation. Source: Ensembl

regulation of MAPK cascade

Inferred from electronic annotation. Source: Ensembl

regulation of lipid metabolic process

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 20551380. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of membrane

Traceable author statement PubMed 1454804. Source: ProtInc

lysosomal lumen

Traceable author statement. Source: Reactome

lysosomal membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionenzyme activator activity

Traceable author statement Ref.13. Source: ProtInc

lipid binding

Traceable author statement PubMed 1454804. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform Sap-mu-0 (identifier: P07602-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Sap-mu-6 (identifier: P07602-2)

The sequence of this isoform differs from the canonical sequence as follows:
     259-259: M → MDQ
Isoform Sap-mu-9 (identifier: P07602-3)

The sequence of this isoform differs from the canonical sequence as follows:
     260-260: Q → QDQQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Ref.10 Ref.11
Chain17 – 524508Prosaposin
PRO_0000424774
Propeptide17 – 5842
PRO_0000031616
Chain60 – 14283Saposin-A
PRO_0000031617
Propeptide144 – 19451
PRO_0000031618
Chain195 – 27480Saposin-B-Val
PRO_0000031619
Chain195 – 27379Saposin-B
PRO_0000031620
Propeptide276 – 30934
PRO_0000031621
Chain311 – 39181Saposin-C
PRO_0000031622
Propeptide393 – 40311
PRO_0000031623
Chain405 – 48682Saposin-D
PRO_0000031624
Propeptide488 – 52437
PRO_0000031625

Regions

Domain18 – 5841Saposin A-type 1
Domain59 – 14284Saposin B-type 1
Domain194 – 27582Saposin B-type 2
Domain311 – 39282Saposin B-type 3
Domain405 – 48682Saposin B-type 4
Domain488 – 52437Saposin A-type 2

Sites

Site2151Not glycosylated; in variant MLD-SAPB Ile-217

Amino acid modifications

Glycosylation801N-linked (GlcNAc...) Ref.8 Ref.30 Ref.31
Glycosylation1011N-linked (GlcNAc...) Ref.8 Ref.30 Ref.31
Glycosylation2151N-linked (GlcNAc...) (complex) Ref.30
CAR_000176
Glycosylation3321N-linked (GlcNAc...) Ref.30 Ref.31
Glycosylation4261N-linked (GlcNAc...) Ref.30 Ref.31
Disulfide bond63 ↔ 138 Ref.23 Ref.27 Ref.29
Disulfide bond66 ↔ 132 Ref.23 Ref.27 Ref.29
Disulfide bond94 ↔ 106 Ref.23 Ref.27 Ref.29
Disulfide bond198 ↔ 271 Ref.23 Ref.27 Ref.29
Disulfide bond201 ↔ 265 Ref.23 Ref.27 Ref.29
Disulfide bond230 ↔ 241 Ref.23 Ref.27 Ref.29
Disulfide bond315 ↔ 388 Ref.23 Ref.27 Ref.29
Disulfide bond318 ↔ 382 Ref.23 Ref.27 Ref.29
Disulfide bond346 ↔ 357 Ref.23 Ref.27 Ref.29
Disulfide bond409 ↔ 482 Ref.23 Ref.27 Ref.29
Disulfide bond412 ↔ 476 Ref.23 Ref.27 Ref.29
Disulfide bond440 ↔ 451 Ref.23 Ref.27 Ref.29

Natural variations

Alternative sequence2591M → MDQ in isoform Sap-mu-6.
VSP_006014
Alternative sequence2601Q → QDQQ in isoform Sap-mu-9.
VSP_006015
Natural variant701Missing in AKRD. Ref.45
VAR_042440
Natural variant2151N → H in MLD-SAPB; reduces the intracellular activity of the protein significantly. Ref.43
VAR_031823
Natural variant2151N → K in MLD-SAPB. Ref.42
VAR_031899
Natural variant2171T → I in MLD-SAPB; juvenile; affects glycosylation at N-215. Ref.37 Ref.38
VAR_006943
Natural variant2411C → S in MLD-SAPB; severe. Ref.39
Corresponds to variant rs1130793 [ dbSNP | Ensembl ].
VAR_006944
Natural variant3491L → P in AGD. Ref.46
VAR_042441
Natural variant3881C → F in AGD. Ref.41
VAR_006945

Experimental info

Mutagenesis2401I → C: Strongly decreases stimulation of cerebroside sulfate hydrolysis. Ref.35
Sequence conflict3691L → P in CAG33027. Ref.4

Secondary structure

......................................... 524
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Sap-mu-0 [UniParc].

Last modified August 1, 1990. Version 2.
Checksum: 71977F7A8C9E1533

FASTA52458,113
        10         20         30         40         50         60 
MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ TVWNKPTVKS 

        70         80         90        100        110        120 
LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP NMSASCKEIV DSYLPVILDI 

       130        140        150        160        170        180 
IKGEMSRPGE VCSALNLCES LQKHLAELNH QKQLESNKIP ELDMTEVVAP FMANIPLLLY 

       190        200        210        220        230        240 
PQDGPRSKPQ PKDNGDVCQD CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI 

       250        260        270        280        290        300 
CKNYISQYSE IAIQMMMHMQ PKEICALVGF CDEVKEMPMQ TLVPAKVASK NVIPALELVE 

       310        320        330        340        350        360 
PIKKHEVPAK SDVYCEVCEF LVKEVTKLID NNKTEKEILD AFDKMCSKLP KSLSEECQEV 

       370        380        390        400        410        420 
VDTYGSSILS ILLEEVSPEL VCSMLHLCSG TRLPALTVHV TQPKDGGFCE VCKKLVGYLD 

       430        440        450        460        470        480 
RNLEKNSTKQ EILAALEKGC SFLPDPYQKQ CDQFVAEYEP VLIEILVEVM DPSFVCLKIG 

       490        500        510        520 
ACPSAHKPLL GTEKCIWGPS YWCQNTETAA QCNAVEHCKR HVWN 

« Hide

Isoform Sap-mu-6 [UniParc].

Checksum: 2A6E54624BA9D814
Show »

FASTA52658,356
Isoform Sap-mu-9 [UniParc].

Checksum: 293FBB7472D82BD0
Show »

FASTA52758,484

References

« Hide 'large scale' references
[1]"Molecular cloning of a human co-beta-glucosidase cDNA: evidence that four sphingolipid hydrolase activator proteins are encoded by single genes in humans and rats."
Rorman E.G., Grabowski G.A.
Genomics 5:486-492(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Structure of full-length cDNA coding for sulfatide activator, a Co-beta-glucosidase and two other homologous proteins: two alternate forms of the sulfatide activator."
Nakano T., Sandhoff K., Stuemper J., Christomanou H., Suzuki K.
J. Biochem. 105:152-154(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SAP-MU-0).
Tissue: Brain, Eye and Skin.
[8]"Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus."
O'Brien J.S., Kretz K.A., Dewji N., Wenger D.A., Esch F., Fluharty A.L.
Science 241:1098-1101(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-524.
[9]"Structure and evolution of the human prosaposin chromosomal gene."
Rorman E.G., Scheinker V., Grabowski G.A.
Genomics 13:312-318(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-524.
[10]"Isolation, characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins)."
Hiraiwa M., O'Brien J.S., Kishimoto Y., Galdzicka M., Fluharty A.L., Ginns E.I., Martin B.M.
Arch. Biochem. Biophys. 304:110-116(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 17-24; 165-172; 180-189 AND 298-302.
[11]"Isolation and characterization of prosaposin from human milk."
Kondoh K., Hineno T., Sano A., Kakimoto Y.
Biochem. Biophys. Res. Commun. 181:286-292(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 17-26.
Tissue: Milk.
[12]"The organization of the gene for the human cerebroside sulfate activator protein."
Holtschmidt H., Sandhoff K., Fuerst W., Kwon H.Y., Schnabel D., Suzuki K.
FEBS Lett. 280:267-270(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 59-125 AND 304-513.
Tissue: Brain.
[13]"Saposin A: second cerebrosidase activator protein."
Morimoto S., Martin B.M., Yamamoto Y., Kretz K.A., O'Brien J.S., Kishimoto Y.
Proc. Natl. Acad. Sci. U.S.A. 86:3389-3393(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 60-142.
[14]"Storage of saposins A and D in infantile neuronal ceroid-lipofuscinosis."
Tyynela J., Palmer D.N., Baumann M., Haltia M.
FEBS Lett. 330:8-12(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 62-84 AND 410-431.
[15]"Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor."
Dewji N.N., Wenger D.A., O'Brien J.S.
Proc. Natl. Acad. Sci. U.S.A. 84:8652-8656(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 164-524.
[16]"Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the sulfatide sulfatase activator."
Dewji N.N., Wenger D.A., Fujibayashi S., Donoviel M., Esch F., Hill F., O'Brien J.S.
Biochem. Biophys. Res. Commun. 134:989-994(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 195-263.
[17]"Complete amino-acid sequence of the naturally occurring A2 activator protein for enzymic sphingomyelin degradation: identity to the sulfatide activator protein (SAP-1)."
Kleinschmidt T., Christomanou H., Braunitzer G.
Biol. Chem. Hoppe-Seyler 369:1361-1365(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 195-274.
[18]"The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein."
Furst W., Schubert J., Machleidt W., Meyer H.E., Sandhoff K.
Eur. J. Biochem. 192:709-714(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 195-274.
Tissue: Kidney.
[19]"Complete amino-acid sequence and carbohydrate content of the naturally occurring glucosylceramide activator protein (A1 activator) absent from a new human Gaucher disease variant."
Kleinschmidt T., Christomanou H., Braunitzer G.
Biol. Chem. Hoppe-Seyler 368:1571-1578(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 311-390.
[20]"Saposin D: a sphingomyelinase activator."
Morimoto S., Martin B.M., Kishimoto Y., O'Brien J.S.
Biochem. Biophys. Res. Commun. 156:403-410(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 405-484.
[21]"The precursor of sulfatide activator protein is processed to three different proteins."
Furst W., Machleidt W., Sandhoff K.
Biol. Chem. Hoppe-Seyler 369:317-328(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 407-484.
[22]"Preparation of the cerebroside sulfate activator (CSAct or saposin B) from human urine."
Fluharty A.L., Lombardo C., Louis A., Stevens R.L., Whitelegge J.P., Waring A.J., To T., Fluharty C.B., Faull K.F.
Mol. Genet. Metab. 68:391-403(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE (SAPOSIN-B), STRUCTURE OF CARBOHYDRATES.
Tissue: Urine.
[23]"Structural analysis of saposin C and B. Complete localization of disulfide bridges."
Vaccaro A.M., Salvioli R., Barca A., Tatti M., Ciaffoni F., Maras B., Siciliano R., Zappacosta F., Amoresano A., Pucci P.
J. Biol. Chem. 270:9953-9960(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS IN SAPOSINS-B AND C, IDENTIFICATION BY MASS SPECTROMETRY.
[24]"Prosaposin: a myelinotrophic protein that promotes expression of myelin constituents and is secreted after nerve injury."
Hiraiwa M., Campana W.M., Mizisin A.P., Mohiuddin L., O'Brien J.S.
Glia 26:353-360(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[25]"Cerebroside sulfate activator protein (Saposin B): chromatographic and electrospray mass spectrometric properties."
Faull K.F., Whitelegge J.P., Higginson J., To T., Johnson J., Krutchinsky A.N., Standing K.G., Waring A.J., Stevens R.L., Fluharty C.B., Fluharty A.L.
J. Mass Spectrom. 34:1040-1054(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Urine.
[26]"Structure of the asparagine-linked sugar chains of porcine kidney and human urine cerebroside sulfate activator protein."
Faull K.F., Johnson J., Kim M.J., To T., Whitelegge J.P., Stevens R.L., Fluharty C.B., Fluharty A.L.
J. Mass Spectrom. 35:1416-1424(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF CARBOHYDRATE ON ASN-215.
[27]"Structural and membrane-binding properties of saposin D."
Tatti M., Salvioli R., Ciaffoni F., Pucci P., Andolfo A., Amoresano A., Vaccaro A.M.
Eur. J. Biochem. 263:486-494(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS IN SAPOSIN-D.
[28]"The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin."
Lefrancois S., Zeng J., Hassan A.J., Canuel M., Morales C.R.
EMBO J. 22:6430-6437(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SORT1.
[29]"Expression, purification, crystallization, and preliminary X-ray analysis of recombinant human saposin B."
Ahn V.E., Faull K.F., Whitelegge J.P., Higginson J., Fluharty A.L., Prive G.G.
Protein Expr. Purif. 27:186-193(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS IN SAPOSIN-B.
[30]"Cotranslational and posttranslational N-glycosylation of polypeptides by distinct mammalian OST isoforms."
Ruiz-Canada C., Kelleher D.J., Gilmore R.
Cell 136:272-283(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-80; ASN-101; ASN-215; ASN-332 AND ASN-426.
[31]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-80; ASN-101; ASN-332 AND ASN-426.
Tissue: Liver.
[32]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"Prosaposin sorting is mediated by oligomerization."
Yuan L., Morales C.R.
Exp. Cell Res. 317:2456-2467(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION.
[34]"GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin."
Meyer R.C., Giddens M.M., Schaefer S.A., Hall R.A.
Proc. Natl. Acad. Sci. U.S.A. 110:9529-9534(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[35]"Crystal structure of saposin B reveals a dimeric shell for lipid binding."
Ahn V.E., Faull K.F., Whitelegge J.P., Fluharty A.L., Prive G.G.
Proc. Natl. Acad. Sci. U.S.A. 100:38-43(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 195-273, MUTAGENESIS OF ILE-240.
[36]"Molecular genetics of metachromatic leukodystrophy."
Gieselmann V., Zlotogora J., Harris A., Wenger D.A., Morris C.P.
Hum. Mutat. 4:233-242(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON MLD-SAPB VARIANTS.
[37]"Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy."
Rafi M.A., Zhang X.-L., Degala G., Wenger D.A.
Biochem. Biophys. Res. Commun. 166:1017-1023(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD-SAPB ILE-217.
[38]"Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect."
Kretz K.A., Carson G.S., Morimoto S., Kishimoto Y., Fluharty A.L., O'Brien J.S.
Proc. Natl. Acad. Sci. U.S.A. 87:2541-2544(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MLD-SAPB ILE-217.
[39]"Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease."
Holtschmidt H., Sandhoff K., Kwon H.Y., Harzer K., Nakano T., Suzuki K.
J. Biol. Chem. 266:7556-7560(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD-SAPB SER-241, NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[40]"Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene."
Schnabel D., Schroder M., Furst W., Klein A., Hurwitz R., Zenk T., Weber J., Harzer K., Paton B.C., Poulos A., Suzuki K., Sandhoff K.
J. Biol. Chem. 267:3312-3315(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CSAPD.
[41]"Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease."
Schnabel D., Schroeder M., Sandhoff K.
FEBS Lett. 284:57-59(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AGD PHE-388.
[42]"An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity."
Regis S., Filocamo M., Corsolini F., Caroli F., Keulemans J.L.M., van Diggelen O.P., Gatti R.
Eur. J. Hum. Genet. 7:125-130(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD-SAPB LYS-215.
[43]"A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD)."
Wrobe D., Henseler M., Huettler S., Pascual Pascual S.I., Chabas A., Sandhoff K.
J. Inherit. Metab. Dis. 23:63-76(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MLD-SAPB HIS-215, CHARACTERIZATION OF VARIANT MLD-SAPB HIS-215.
[44]"A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation."
Hulkova H., Cervenkova M., Ledvinova J., Tochackova M., Hrebicek M., Poupetova H., Befekadu A., Berna L., Paton B.C., Harzer K., Boor A., Smid F., Elleder M.
Hum. Mol. Genet. 10:927-940(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CSAPD.
[45]"A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans."
Spiegel R., Bach G., Sury V., Mengistu G., Meidan B., Shalev S., Shneor Y., Mandel H., Zeigler M.
Mol. Genet. Metab. 84:160-166(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AKRD VAL-70 DEL.
[46]"Non-neuronopathic Gaucher disease due to saposin C deficiency."
Tylki-Szymanska A., Czartoryska B., Vanier M.T., Poorthuis B.J., Groener J.A., Lugowska A., Millat G., Vaccaro A.M., Jurkiewicz E.
Clin. Genet. 72:538-542(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AGD PRO-349.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03077 mRNA. Translation: AAA52560.1.
D00422 mRNA. Translation: BAA00321.1.
BT006849 mRNA. Translation: AAP35495.1.
CR456746 mRNA. Translation: CAG33027.1.
AL731541, AC073370 Genomic DNA. Translation: CAI40837.1.
CH471083 Genomic DNA. Translation: EAW54437.1.
BC001503 mRNA. Translation: AAH01503.1.
BC004275 mRNA. Translation: AAH04275.1.
BC007612 mRNA. Translation: AAH07612.1.
M86181 Genomic DNA. No translation available.
X57107 Genomic DNA. Translation: CAA40391.1.
X57108 Genomic DNA. Translation: CAA40392.1.
M12710 mRNA. No translation available.
J03015 mRNA. Translation: AAB59494.1.
M32221 mRNA. Translation: AAA60303.1.
M60257 mRNA. Translation: AAA36595.1.
M60258 mRNA. Translation: AAA36596.1.
M60255 mRNA. Translation: AAA36594.1.
PIRSAHUP. JX0061.
RefSeqNP_001035930.1. NM_001042465.1.
NP_001035931.1. NM_001042466.1.
NP_002769.1. NM_002778.2.
UniGeneHs.523004.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M12NMR-A311-390[»]
1N69X-ray2.20A/B/C195-273[»]
1SN6NMR-A311-390[»]
2DOBX-ray2.00A60-140[»]
2GTGX-ray2.40A311-391[»]
2QYPX-ray2.45A/B311-392[»]
2R0RX-ray2.50A/B407-484[»]
2R1QX-ray2.50A407-484[»]
2RB3X-ray2.10A/B/C/D407-484[»]
2Z9AX-ray2.50A/B311-389[»]
3BQPX-ray1.30A/B405-484[»]
3BQQX-ray2.00A/B/C/D405-484[»]
4DDJX-ray1.90A60-140[»]
DisProtDP00733.
ProteinModelPortalP07602.
SMRP07602. Positions 34-139, 195-272, 312-484.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111639. 42 interactions.
DIPDIP-29803N.
IntActP07602. 13 interactions.
MINTMINT-1193270.

Protein family/group databases

TCDB1.C.35.2.1. the amoebapore (amoebapore) family.

PTM databases

PhosphoSiteP07602.
UniCarbKBP07602.

Polymorphism databases

DMDM134218.

Proteomic databases

PaxDbP07602.
PRIDEP07602.

Protocols and materials databases

DNASU5660.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000394936; ENSP00000378394; ENSG00000197746. [P07602-1]
GeneID5660.
KEGGhsa:5660.
UCSCuc001jsm.3. human. [P07602-1]

Organism-specific databases

CTD5660.
GeneCardsGC10M073576.
HGNCHGNC:9498. PSAP.
HPACAB004647.
HPA004426.
MIM176801. gene.
249900. phenotype.
610539. phenotype.
611721. phenotype.
611722. phenotype.
neXtProtNX_P07602.
Orphanet309252. Atypical Gaucher disease due to saposin C deficiency.
139406. Encephalopathy due to prosaposin deficiency.
206436. Infantile Krabbe disease.
309271. Metachromatic leukodystrophy, adult form.
309263. Metachromatic leukodystrophy, juvenile form.
309256. Metachromatic leukodystrophy, late infantile form.
PharmGKBPA33845.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG269151.
HOVERGENHBG002617.
KOK12382.
OrthoDBEOG7ZSHSC.
PhylomeDBP07602.
TreeFamTF316942.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP07602.
BgeeP07602.
CleanExHS_PSAP.
GenevestigatorP07602.

Family and domain databases

Gene3D1.10.225.10. 4 hits.
InterProIPR003119. SapA.
IPR007856. SapB_1.
IPR008138. SapB_2.
IPR008373. Saposin.
IPR011001. Saposin-like.
IPR021165. Saposin_chordata.
IPR008139. SaposinB.
[Graphical view]
PfamPF02199. SapA. 2 hits.
PF05184. SapB_1. 4 hits.
PF03489. SapB_2. 4 hits.
[Graphical view]
PIRSFPIRSF002431. Saposin. 1 hit.
PRINTSPR01797. SAPOSIN.
SMARTSM00162. SAPA. 2 hits.
SM00741. SapB. 4 hits.
[Graphical view]
SUPFAMSSF47862. SSF47862. 4 hits.
PROSITEPS51110. SAP_A. 2 hits.
PS50015. SAP_B. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPSAP. human.
EvolutionaryTraceP07602.
GeneWikiProsaposin.
GenomeRNAi5660.
NextBio21992.
PROP07602.
SOURCESearch...

Entry information

Entry nameSAP_HUMAN
AccessionPrimary (citable) accession number: P07602
Secondary accession number(s): P07292 expand/collapse secondary AC list , P15793, P78538, P78541, P78546, P78547, P78558, Q53Y86, Q6IBQ6, Q92739, Q92740, Q92741, Q92742
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: August 1, 1990
Last modified: April 16, 2014
This is version 182 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM