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P07602

- SAP_HUMAN

UniProt

P07602 - SAP_HUMAN

Protein

Prosaposin

Gene

PSAP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 187 (01 Oct 2014)
      Sequence version 2 (01 Aug 1990)
      Previous versions | rss
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    Functioni

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei215 – 2151Not glycosylated; in variant MLD-SAPB Ile-217

    GO - Molecular functioni

    1. enzyme activator activity Source: ProtInc
    2. lipid binding Source: ProtInc
    3. protein binding Source: UniProt

    GO - Biological processi

    1. blood coagulation Source: Reactome
    2. cellular response to organic substance Source: Ensembl
    3. epithelial cell differentiation involved in prostate gland development Source: Ensembl
    4. glycosphingolipid metabolic process Source: Reactome
    5. lipid transport Source: ProtInc
    6. platelet activation Source: Reactome
    7. platelet degranulation Source: Reactome
    8. positive regulation of catalytic activity Source: GOC
    9. prostate gland growth Source: Ensembl
    10. regulation of lipid metabolic process Source: Ensembl
    11. regulation of MAPK cascade Source: Ensembl
    12. small molecule metabolic process Source: Reactome
    13. sphingolipid metabolic process Source: Reactome

    Keywords - Biological processi

    Lipid metabolism, Sphingolipid metabolism

    Enzyme and pathway databases

    ReactomeiREACT_116105. Glycosphingolipid metabolism.

    Protein family/group databases

    TCDBi1.C.35.2.1. the amoebapore (amoebapore) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prosaposin
    Alternative name(s):
    Proactivator polypeptide
    Cleaved into the following 5 chains:
    Alternative name(s):
    Protein A
    Alternative name(s):
    Cerebroside sulfate activator
    Short name:
    CSAct
    Dispersin
    Sphingolipid activator protein 1
    Short name:
    SAP-1
    Sulfatide/GM1 activator
    Alternative name(s):
    A1 activator
    Co-beta-glucosidase
    Glucosylceramidase activator
    Sphingolipid activator protein 2
    Short name:
    SAP-2
    Alternative name(s):
    Component C
    Protein C
    Gene namesi
    Name:PSAP
    Synonyms:GLBA, SAP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:9498. PSAP.

    Subcellular locationi

    Lysosome 3 Publications
    Chain Prosaposin : Secreted
    Note: Secreted as a fully glycosylated 70 kDa protein composed of complex glycans.

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. extracellular space Source: BHF-UCL
    3. extracellular vesicular exosome Source: UniProt
    4. integral component of membrane Source: ProtInc
    5. lysosomal lumen Source: Reactome
    6. lysosomal membrane Source: Reactome
    7. mitochondrion Source: Ensembl

    Keywords - Cellular componenti

    Lysosome, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Combined saposin deficiency (CSAPD) [MIM:611721]: Due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti215 – 2151N → H in MLD-SAPB; reduces the intracellular activity of the protein significantly. 1 Publication
    VAR_031823
    Natural varianti215 – 2151N → K in MLD-SAPB. 1 Publication
    VAR_031899
    Natural varianti217 – 2171T → I in MLD-SAPB; juvenile; affects glycosylation at N-215. 2 Publications
    VAR_006943
    Natural varianti241 – 2411C → S in MLD-SAPB; severe. 1 Publication
    Corresponds to variant rs1130793 [ dbSNP | Ensembl ].
    VAR_006944
    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti349 – 3491L → P in AGD. 1 Publication
    VAR_042441
    Natural varianti388 – 3881C → F in AGD. 1 Publication
    VAR_006945
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti70 – 701Missing in AKRD. 1 Publication
    VAR_042440
    Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi240 – 2401I → C: Strongly decreases stimulation of cerebroside sulfate hydrolysis. 1 Publication

    Keywords - Diseasei

    Disease mutation, Gangliosidosis, Gaucher disease, Leukodystrophy, Metachromatic leukodystrophy

    Organism-specific databases

    MIMi249900. phenotype.
    610539. phenotype.
    611721. phenotype.
    611722. phenotype.
    Orphaneti309252. 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.
    PharmGKBiPA33845.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 16162 PublicationsAdd
    BLAST
    Chaini17 – 524508ProsaposinPRO_0000424774Add
    BLAST
    Propeptidei17 – 5842PRO_0000031616Add
    BLAST
    Chaini60 – 14283Saposin-APRO_0000031617Add
    BLAST
    Propeptidei144 – 19451PRO_0000031618Add
    BLAST
    Chaini195 – 27480Saposin-B-ValPRO_0000031619Add
    BLAST
    Chaini195 – 27379Saposin-BPRO_0000031620Add
    BLAST
    Propeptidei276 – 30934PRO_0000031621Add
    BLAST
    Chaini311 – 39181Saposin-CPRO_0000031622Add
    BLAST
    Propeptidei393 – 40311PRO_0000031623Add
    BLAST
    Chaini405 – 48682Saposin-DPRO_0000031624Add
    BLAST
    Propeptidei488 – 52437PRO_0000031625Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi63 ↔ 138
    Disulfide bondi66 ↔ 132
    Glycosylationi80 – 801N-linked (GlcNAc...)3 PublicationsPROSITE-ProRule annotation
    Disulfide bondi94 ↔ 106
    Glycosylationi101 – 1011N-linked (GlcNAc...)3 PublicationsPROSITE-ProRule annotation
    Disulfide bondi198 ↔ 271
    Disulfide bondi201 ↔ 265
    Glycosylationi215 – 2151N-linked (GlcNAc...) (complex)1 PublicationPROSITE-ProRule annotationCAR_000176
    Disulfide bondi230 ↔ 2411 PublicationPROSITE-ProRule annotation
    Disulfide bondi315 ↔ 3881 PublicationPROSITE-ProRule annotation
    Disulfide bondi318 ↔ 3821 PublicationPROSITE-ProRule annotation
    Glycosylationi332 – 3321N-linked (GlcNAc...)2 PublicationsPROSITE-ProRule annotation
    Disulfide bondi346 ↔ 3571 PublicationPROSITE-ProRule annotation
    Disulfide bondi409 ↔ 482
    Disulfide bondi412 ↔ 476
    Glycosylationi426 – 4261N-linked (GlcNAc...)2 PublicationsPROSITE-ProRule annotation
    Disulfide bondi440 ↔ 451

    Post-translational modificationi

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

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiP07602.
    PaxDbiP07602.
    PRIDEiP07602.

    PTM databases

    PhosphoSiteiP07602.
    UniCarbKBiP07602.

    Expressioni

    Gene expression databases

    ArrayExpressiP07602.
    BgeeiP07602.
    CleanExiHS_PSAP.
    GenevestigatoriP07602.

    Organism-specific databases

    HPAiCAB004647.
    HPA004426.

    Interactioni

    Subunit structurei

    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.5 Publications

    Protein-protein interaction databases

    BioGridi111639. 42 interactions.
    DIPiDIP-29803N.
    IntActiP07602. 13 interactions.
    MINTiMINT-1193270.

    Structurei

    Secondary structure

    1
    524
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi61 – 7818
    Helixi82 – 9413
    Beta strandi97 – 993
    Helixi101 – 12525
    Helixi128 – 1347
    Helixi196 – 21419
    Helixi218 – 22912
    Helixi230 – 2334
    Helixi237 – 25620
    Helixi261 – 2677
    Helixi314 – 33017
    Helixi335 – 34511
    Helixi346 – 3483
    Helixi351 – 37323
    Helixi378 – 3847
    Turni386 – 3883
    Helixi409 – 42214
    Helixi429 – 43911
    Helixi440 – 4423
    Helixi445 – 4473
    Helixi448 – 46619
    Helixi472 – 4787

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    DisProtiDP00733.
    ProteinModelPortaliP07602.
    SMRiP07602. Positions 60-139, 195-272, 312-484.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP07602.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini18 – 5841Saposin A-type 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini59 – 14284Saposin B-type 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini194 – 27582Saposin B-type 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini311 – 39282Saposin B-type 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini405 – 48682Saposin B-type 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini488 – 52437Saposin A-type 2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 2 saposin A-type domains.PROSITE-ProRule annotation
    Contains 4 saposin B-type domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG269151.
    HOVERGENiHBG002617.
    KOiK12382.
    OrthoDBiEOG7ZSHSC.
    PhylomeDBiP07602.
    TreeFamiTF316942.

    Family and domain databases

    Gene3Di1.10.225.10. 4 hits.
    InterProiIPR003119. SapA.
    IPR007856. SapB_1.
    IPR008138. SapB_2.
    IPR008373. Saposin.
    IPR011001. Saposin-like.
    IPR021165. Saposin_chordata.
    IPR008139. SaposinB.
    [Graphical view]
    PfamiPF02199. SapA. 2 hits.
    PF05184. SapB_1. 4 hits.
    PF03489. SapB_2. 4 hits.
    [Graphical view]
    PIRSFiPIRSF002431. Saposin. 1 hit.
    PRINTSiPR01797. SAPOSIN.
    SMARTiSM00162. SAPA. 2 hits.
    SM00741. SapB. 4 hits.
    [Graphical view]
    SUPFAMiSSF47862. SSF47862. 4 hits.
    PROSITEiPS51110. SAP_A. 2 hits.
    PS50015. SAP_B. 4 hits.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform Sap-mu-0 (identifier: P07602-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ    50
    TVWNKPTVKS LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP 100
    NMSASCKEIV DSYLPVILDI IKGEMSRPGE VCSALNLCES LQKHLAELNH 150
    QKQLESNKIP ELDMTEVVAP FMANIPLLLY PQDGPRSKPQ PKDNGDVCQD 200
    CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI CKNYISQYSE 250
    IAIQMMMHMQ PKEICALVGF CDEVKEMPMQ TLVPAKVASK NVIPALELVE 300
    PIKKHEVPAK SDVYCEVCEF LVKEVTKLID NNKTEKEILD AFDKMCSKLP 350
    KSLSEECQEV VDTYGSSILS ILLEEVSPEL VCSMLHLCSG TRLPALTVHV 400
    TQPKDGGFCE VCKKLVGYLD RNLEKNSTKQ EILAALEKGC SFLPDPYQKQ 450
    CDQFVAEYEP VLIEILVEVM DPSFVCLKIG ACPSAHKPLL GTEKCIWGPS 500
    YWCQNTETAA QCNAVEHCKR HVWN 524
    Length:524
    Mass (Da):58,113
    Last modified:August 1, 1990 - v2
    Checksum:i71977F7A8C9E1533
    GO
    Isoform Sap-mu-6 (identifier: P07602-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         259-259: M → MDQ

    Show »
    Length:526
    Mass (Da):58,356
    Checksum:i2A6E54624BA9D814
    GO
    Isoform Sap-mu-9 (identifier: P07602-3) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:527
    Mass (Da):58,484
    Checksum:i293FBB7472D82BD0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti369 – 3691L → P in CAG33027. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti70 – 701Missing in AKRD. 1 Publication
    VAR_042440
    Natural varianti215 – 2151N → H in MLD-SAPB; reduces the intracellular activity of the protein significantly. 1 Publication
    VAR_031823
    Natural varianti215 – 2151N → K in MLD-SAPB. 1 Publication
    VAR_031899
    Natural varianti217 – 2171T → I in MLD-SAPB; juvenile; affects glycosylation at N-215. 2 Publications
    VAR_006943
    Natural varianti241 – 2411C → S in MLD-SAPB; severe. 1 Publication
    Corresponds to variant rs1130793 [ dbSNP | Ensembl ].
    VAR_006944
    Natural varianti349 – 3491L → P in AGD. 1 Publication
    VAR_042441
    Natural varianti388 – 3881C → F in AGD. 1 Publication
    VAR_006945

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei259 – 2591M → MDQ in isoform Sap-mu-6. CuratedVSP_006014
    Alternative sequencei260 – 2601Q → QDQQ in isoform Sap-mu-9. CuratedVSP_006015

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS7311.1. [P07602-1]
    PIRiJX0061. SAHUP.
    RefSeqiNP_001035930.1. NM_001042465.1. [P07602-3]
    NP_001035931.1. NM_001042466.1. [P07602-2]
    NP_002769.1. NM_002778.2. [P07602-1]
    UniGeneiHs.523004.

    Genome annotation databases

    EnsembliENST00000394936; ENSP00000378394; ENSG00000197746. [P07602-1]
    GeneIDi5660.
    KEGGihsa:5660.
    UCSCiuc001jsm.3. human. [P07602-1]

    Polymorphism databases

    DMDMi134218.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS7311.1. [P07602-1 ]
    PIRi JX0061. SAHUP.
    RefSeqi NP_001035930.1. NM_001042465.1. [P07602-3 ]
    NP_001035931.1. NM_001042466.1. [P07602-2 ]
    NP_002769.1. NM_002778.2. [P07602-1 ]
    UniGenei Hs.523004.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1M12 NMR - A 311-390 [» ]
    1N69 X-ray 2.20 A/B/C 195-273 [» ]
    1SN6 NMR - A 311-390 [» ]
    2DOB X-ray 2.00 A 60-140 [» ]
    2GTG X-ray 2.40 A 311-391 [» ]
    2QYP X-ray 2.45 A/B 311-392 [» ]
    2R0R X-ray 2.50 A/B 407-484 [» ]
    2R1Q X-ray 2.50 A 407-484 [» ]
    2RB3 X-ray 2.10 A/B/C/D 407-484 [» ]
    2Z9A X-ray 2.50 A/B 311-389 [» ]
    3BQP X-ray 1.30 A/B 405-484 [» ]
    3BQQ X-ray 2.00 A/B/C/D 405-484 [» ]
    4DDJ X-ray 1.90 A 60-140 [» ]
    DisProti DP00733.
    ProteinModelPortali P07602.
    SMRi P07602. Positions 60-139, 195-272, 312-484.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111639. 42 interactions.
    DIPi DIP-29803N.
    IntActi P07602. 13 interactions.
    MINTi MINT-1193270.

    Protein family/group databases

    TCDBi 1.C.35.2.1. the amoebapore (amoebapore) family.

    PTM databases

    PhosphoSitei P07602.
    UniCarbKBi P07602.

    Polymorphism databases

    DMDMi 134218.

    Proteomic databases

    MaxQBi P07602.
    PaxDbi P07602.
    PRIDEi P07602.

    Protocols and materials databases

    DNASUi 5660.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000394936 ; ENSP00000378394 ; ENSG00000197746 . [P07602-1 ]
    GeneIDi 5660.
    KEGGi hsa:5660.
    UCSCi uc001jsm.3. human. [P07602-1 ]

    Organism-specific databases

    CTDi 5660.
    GeneCardsi GC10M073576.
    HGNCi HGNC:9498. PSAP.
    HPAi CAB004647.
    HPA004426.
    MIMi 176801. gene.
    249900. phenotype.
    610539. phenotype.
    611721. phenotype.
    611722. phenotype.
    neXtProti NX_P07602.
    Orphaneti 309252. 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.
    PharmGKBi PA33845.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG269151.
    HOVERGENi HBG002617.
    KOi K12382.
    OrthoDBi EOG7ZSHSC.
    PhylomeDBi P07602.
    TreeFami TF316942.

    Enzyme and pathway databases

    Reactomei REACT_116105. Glycosphingolipid metabolism.

    Miscellaneous databases

    ChiTaRSi PSAP. human.
    EvolutionaryTracei P07602.
    GeneWikii Prosaposin.
    GenomeRNAii 5660.
    NextBioi 21992.
    PROi P07602.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P07602.
    Bgeei P07602.
    CleanExi HS_PSAP.
    Genevestigatori P07602.

    Family and domain databases

    Gene3Di 1.10.225.10. 4 hits.
    InterProi IPR003119. SapA.
    IPR007856. SapB_1.
    IPR008138. SapB_2.
    IPR008373. Saposin.
    IPR011001. Saposin-like.
    IPR021165. Saposin_chordata.
    IPR008139. SaposinB.
    [Graphical view ]
    Pfami PF02199. SapA. 2 hits.
    PF05184. SapB_1. 4 hits.
    PF03489. SapB_2. 4 hits.
    [Graphical view ]
    PIRSFi PIRSF002431. Saposin. 1 hit.
    PRINTSi PR01797. SAPOSIN.
    SMARTi SM00162. SAPA. 2 hits.
    SM00741. SapB. 4 hits.
    [Graphical view ]
    SUPFAMi SSF47862. SSF47862. 4 hits.
    PROSITEi PS51110. SAP_A. 2 hits.
    PS50015. SAP_B. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. 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. 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. 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. 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. Cited for: VARIANT AGD PRO-349.

    Entry informationi

    Entry nameiSAP_HUMAN
    AccessioniPrimary (citable) accession number: P07602
    Secondary accession number(s): P07292
    , P15793, P78538, P78541, P78546, P78547, P78558, Q53Y86, Q6IBQ6, Q92739, Q92740, Q92741, Q92742
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1988
    Last sequence update: August 1, 1990
    Last modified: October 1, 2014
    This is version 187 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3