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    PSAP prosaposin [ Homo sapiens ]

    Gene ID: 5660, updated on 12-May-2012
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    Summary

    Official Symbol
    PSAPprovided by HGNC
    Official Full Name
    prosaposinprovided by HGNC
    Primary source
    HGNC:9498
    See related
    Ensembl:ENSG00000197746; HPRD:01460; MIM:176801; Vega:OTTHUMG00000018429
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GLBA; SAP1; FLJ00245; MGC110993
    Summary
    This gene encodes a highly conserved glycoprotein which is a precursor for 4 cleavage products: saposins A, B, C, and D. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities. Mutations in this gene have been associated with Gaucher disease, Tay-Sachs disease, and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    10q21-q22
    Sequence :
    Chromosome: 10; NC_000010.10 (73576055..73611082, complement)
    See PSAP in Epigenomics, MapViewer

    Chromosome 10 - NC_000010.10Genomic Context describing neighboring genes Neighboring gene cadherin-related 23 Neighboring gene chromosome 10 open reading frame 105 Neighboring gene chromosome 10 open reading frame 54 Neighboring gene RNA, U7 small nuclear 38 pseudogene Neighboring gene carbohydrate (chondroitin 6) sulfotransferase 3 Neighboring gene sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 2

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. The interaction of the second Kunitz-type domain (KD2) of TFPI-2 with a novel interaction partner, prosaposin, mediates the inhibition of the invasion and migration of human fibrosarcoma cells. Xu C, et al. Biochem J, 2012 Jan 15. PMID 21943334.
    2. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    3. A directed protein interaction network for investigating intracellular signal transduction. Vinayagam A, et al. Sci Signal, 2011 Sep 6. PMID 21900206.
    4. Protein oligomerization mediated by the transmembrane carboxyl terminal domain of Bcl-XL. Ospina A, et al. FEBS Lett, 2011 Oct 3. PMID 21856303.
    5. Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery. Pawar H, et al. Cancer Biol Ther, 2011 Sep 15. PMID 21743296.

    See all (91) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. PSAP is a novel TFPI-2-interacting protein and that the binding sites are the KD2 of TFPI-2 and the C-terminus of PSAP.
      Title: The interaction of the second Kunitz-type domain (KD2) of TFPI-2 with a novel interaction partner, prosaposin, mediates the inhibition of the invasion and migration of human fibrosarcoma cells.
    2. novel esophageal squamous cell carcinoma marker PSAP was identified by mass spectrometry and immunohistochemical analysis
      Title: Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery.
    3. Data suggest that the transmembrane domain of Bcl-XL could be involved in protein oligomerization, shown here with presenilin-1 associated protein.
      Title: Protein oligomerization mediated by the transmembrane carboxyl terminal domain of Bcl-XL.
    4. PSAP is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells.
      Title: The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
    5. saposin C caused stimulation of androgen receptor expression and activity by associations with Src kinases
      Title: Associations of saposin C, Src, and androgen receptor upregulate the expression and function of androgen receptor in human prostate cancer cells.
    6. Saposin B(Sap B) is not a limiting factor of the coupled Sap B-arylsulfatase A reaction in mouse kidney cells even if sulfatide has accumulated to unphysiologically high levels
      Title: Saposin B-dependent reconstitution of arylsulfatase A activity in vitro and in cell culture models of metachromatic leukodystrophy.
    7. The biological properties of cells from four recently described Gaucher disease patients carrying mutations in the Sap C domain of the PSAP gene have been characterized.
      Title: Saposin C mutations in Gaucher disease patients resulting in lysosomal lipid accumulation, saposin C deficiency, but normal prosaposin processing and sorting.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. PSAP is involved in prostate cancer invasion.
      Title: Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion, migration, and invasion.
    10. Prosaposin functions in a paracrine and endocrine fashion by stimulating the expression of thrombospondin-1 (Tsp-1) in fibroblasts present in both primary tumors and distant organs, doing so in a p53-dependent manner.
      Title: Prosaposin inhibits tumor metastasis via paracrine and endocrine stimulation of stromal p53 and Tsp-1.
    Submit: New GeneRIF Correction See all (33)
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    Phenotypes

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Combined SAP deficiency

    Gaucher disease, atypical

    Krabbe disease, atypical

    Metachromatic leukodystrophy due to SAP-b deficiency

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_002769.1 NP_036236.1 BACE1    BIND  PubMed BACE1 interacts with PSAP (prosaposin). This interaction was modelled on a demonstrated interaction between mouse BACE1 and human prosaposin. 
    P07602 P56817 BACE1    HPRD  PubMed  
    P07602 P38398 BRCA1    HPRD  PubMed  
    P07602 P29016 CD1B    HPRD  PubMed  
    P07602 Q9NYQ6 CELSR1    HPRD  PubMed  
    P07602 Q7L5N1 COPS6    HPRD  PubMed  
    P07602 P07339 CTSD    HPRD  PubMed  
    P07602 P04062 GBA    HPRD  PubMed  
    P07602 Q9ULX9 MAFF    HPRD  PubMed  
    P07602 P07602 PSAP    HPRD  PubMed  
    P07602 Q15796 SMAD2    HPRD  PubMed  
    P07602 O15198 SMAD9    HPRD  PubMed  
    P07602 O96006 ZBED1    HPRD  PubMed  
    BioGRID:111639 BioGRID:114981 CELSR1    BioGRID  PubMed Two-hybrid 
    BioGRID:111639 BioGRID:116176 COPS6    BioGRID  PubMed Two-hybrid 
    BioGRID:111639 BioGRID:107889 CTSD    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:111639 BioGRID:117264 MAFF    BioGRID  PubMed Two-hybrid 
    BioGRID:111639 BioGRID:111639 PSAP    BioGRID  PubMed Co-crystal Structure 
    BioGRID:111639 BioGRID:127591 SGK223    BioGRID  PubMed Two-hybrid 
    BioGRID:111639 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111639 BioGRID:113185 UBE3A    BioGRID  PubMed Two-hybrid 
    BioGRID:111639 BioGRID:1205545 nef    BioGRID  PubMed Co-fractionation 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Glycosphingolipid metabolism, organism-specific biosystem (from REACTOME)
      Glycosphingolipid metabolism, organism-specific biosystemThe steps involved in the synthesis of glycosphingolipids (sphingolipids with one or more sugars attached) are annotated here (Gault et al. 2010).
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Lysosome, organism-specific biosystem (from KEGG)
      Lysosome, organism-specific biosystemLysosomes are membrane-delimited organelles in animal cells serving as the cell's main digestive compartment to which all sorts of macromolecules are delivered for degradation. They contain more than...
    • Lysosome, conserved biosystem (from KEGG)
      Lysosome, conserved biosystemLysosomes are membrane-delimited organelles in animal cells serving as the cell's main digestive compartment to which all sorts of macromolecules are delivered for degradation. They contain more than...
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
      Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
    • Platelet degranulation, organism-specific biosystem (from REACTOME)
      Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
    • Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
      Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
    • Sphingolipid metabolism, organism-specific biosystem (from REACTOME)
      Sphingolipid metabolism, organism-specific biosystemSphingolipids are derivatives of long chain sphingoid bases such as sphingosine (trans-1,3-dihydroxy 2-amino-4-octadecene), an 18-carbon unsaturated amino alcohol which is the most abundant sphingoid...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enzyme activator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    lipid binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    blood coagulation TAS
    Traceable Author Statement
    more info
    		  
    glycosphingolipid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    lipid transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    platelet activation TAS
    Traceable Author Statement
    more info
    		  
    platelet degranulation TAS
    Traceable Author Statement
    more info
    		  
    positive regulation of catalytic activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    small molecule metabolic process TAS
    Traceable Author Statement
    more info
    		  
    sphingolipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    sphingolipid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
    		  
    extracellular space IDA
    Inferred from Direct Assay
    more info
    		  
    extracellular space ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    integral to membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    lysosomal lumen TAS
    Traceable Author Statement
    more info
    		  
    lysosomal membrane TAS
    Traceable Author Statement
    more info
    		  
    lysosome IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    proactivator polypeptide
    Names
    proactivator polypeptide
    sphingolipid activator protein-1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009301.1 RefSeqGene

      Range
      5001..40028
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001042465.1 → NP_001035930.1  proactivator polypeptide isoform b preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (b).
      Source sequence(s)
      AC073370, BC004275, D00422
      UniProtKB/Swiss-Prot
      P07602
      Conserved Domains (4) summary
      pfam03489
      Location:238 – 274
      Blast Score: 106
      SapB_2; Saposin-like type B, region 2
      pfam05184
      Location:315 – 353
      Blast Score: 123
      SapB_1; Saposin-like type B, region 1
      smart00741
      Location:411 – 485
      Blast Score: 191
      SapB; Saposin (B) Domains
      cl02494
      Location:494 – 527
      Blast Score: 181
      SapA; Saposin A-type domain

    2. NM_001042466.1 → NP_001035931.1  proactivator polypeptide isoform c preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice site in the coding region, compared to variant 2, resulting in a shorter protein (isoform c), compared to isoform b.
      Source sequence(s)
      AC073370, BC004275, D00422
      UniProtKB/Swiss-Prot
      P07602
      Conserved Domains (4) summary
      pfam03489
      Location:238 – 273
      Blast Score: 104
      SapB_2; Saposin-like type B, region 2
      pfam05184
      Location:314 – 352
      Blast Score: 124
      SapB_1; Saposin-like type B, region 1
      smart00741
      Location:410 – 484
      Blast Score: 191
      SapB; Saposin (B) Domains
      cl02494
      Location:493 – 526
      Blast Score: 181
      SapA; Saposin A-type domain

    3. NM_002778.2 → NP_002769.1  proactivator polypeptide isoform a preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) lacks an exon in the coding region, compared to variant 2, resulting in a shorter protein (isoform a), compared to isoform b.
      Source sequence(s)
      AC073370, BC004275
      Consensus CDS
      CCDS7311.1
      UniProtKB/Swiss-Prot
      P07602
      Related
      ENSP00000378394, OTTHUMP00000019776, ENST00000394936, OTTHUMT00000048553
      Conserved Domains (4) summary
      pfam03489
      Location:238 – 271
      Blast Score: 105
      SapB_2; Saposin-like type B, region 2
      pfam05184
      Location:312 – 350
      Blast Score: 124
      SapB_1; Saposin-like type B, region 1
      smart00741
      Location:408 – 482
      Blast Score: 192
      SapB; Saposin (B) Domains
      cl02494
      Location:491 – 524
      Blast Score: 181
      SapA; Saposin A-type domain

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000010.10 Reference GRCh37.p5 Primary Assembly

      Range
      73576055..73611082, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000142.1 Alternate HuRef

      Range
      67569822..67604837, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC073370.7 (2000..19841) None
    genomic AF057307.2 AAC64921.2
    genomic AF307850.1 AAG31635.1
    genomic AL731541.6 CAI40836.1
      CAI40837.1
    genomic CH471083.1 EAW54436.1
      EAW54437.1
      EAW54438.1
    genomic M86181.1 None
    genomic X57107.1 CAA40391.1
    genomic X57108.1 CAA40392.1
    mRNA AB209776.1 BAD93013.1
    mRNA AK057878.1 None
    mRNA AK129790.1 None
    mRNA AK223290.1 BAD97010.1
    mRNA AK293672.1 BAG57116.1
    mRNA AK299184.1 BAG61229.1
    mRNA AK307721.1 None
    mRNA BC001503.2 AAH01503.1
    mRNA BC004275.1 AAH04275.1
    mRNA BC007612.1 AAH07612.1
    mRNA BC091483.1 AAH91483.1
    mRNA BT006849.1 AAP35495.1
    mRNA CR456746.1 CAG33027.1
    mRNA D00422.1 BAA00321.1
    mRNA J03015.1 AAB59494.1
    mRNA J03077.1 AAA52560.1
    mRNA M12710.1 None
    mRNA M32221.1 AAA60303.1
    mRNA M60255.1 AAA36594.1
    mRNA M60257.1 AAA36595.1
    mRNA M60258.1 AAA36596.1
    mRNA M81355.1 None
    other-genetic DQ893009.2 ABM83935.1
    other-genetic DQ896255.2 ABM87254.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75905 GenPept UniProtKB/TrEMBL:O75905
    P07602.2 GenPept UniProtKB/Swiss-Prot:P07602
    Q53FJ5 GenPept UniProtKB/TrEMBL:Q53FJ5
    Q59EN5 GenPept UniProtKB/TrEMBL:Q59EN5
    Q5BJH1 GenPept UniProtKB/TrEMBL:Q5BJH1
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
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