PSAP prosaposin [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSAPprovided by HGNC
Official Full Name: prosaposinprovided by HGNC
Primary source: HGNC:HGNC:9498
See related: Ensembl:ENSG00000197746 MIM:176801; AllianceGenome:HGNC:9498
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; SAP2; PSAPD; PARK24
Summary: This gene encodes a highly conserved preproprotein that is proteolytically processed to generate four main cleavage products including 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 and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
Annotation information: Note: PSAP (Gene ID: 5660) and MTCH1 (Gene ID: 23787) share the PSAP symbol/alias in common. PSAP is a widely used alternative name for mitochondrial carrier 1 (MTCH1), which can be confused with the official symbol for PSAP (prosaposin, GeneID 5660). [01 Jun 2018]
Expression: Ubiquitous expression in spleen (RPKM 523.6), gall bladder (RPKM 491.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q22.1

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (71816298..71851251, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (72687031..72721975, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (73576055..73611008, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Meta-analysis of the association of prosaposin polymorphisms rs4747203 and rs885828 with risk of Parkinson's disease.
Title: Meta-analysis of the association of prosaposin polymorphisms rs4747203 and rs885828 with risk of Parkinson's disease.
Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape.
Title: Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape.
Single-cell RNA-sequencing analysis reveals enhanced non-canonical neurotrophic factor signaling in the subacute phase of traumatic brain injury.
Title: Single-cell RNA-sequencing analysis reveals enhanced non-canonical neurotrophic factor signaling in the subacute phase of traumatic brain injury.
Prosaposin, tumor-secreted protein, promotes pancreatic cancer progression by decreasing tumor-infiltrating lymphocytes.
Title: Prosaposin, tumor-secreted protein, promotes pancreatic cancer progression by decreasing tumor-infiltrating lymphocytes.
Efficient progranulin exit from the ER requires its interaction with prosaposin, a Surf4 cargo.
Title: Efficient progranulin exit from the ER requires its interaction with prosaposin, a Surf4 cargo.
Loss of Lysosomal Proteins Progranulin and Prosaposin Associated with Increased Neurofibrillary Tangle Development in Alzheimer Disease.
Title: Loss of Lysosomal Proteins Progranulin and Prosaposin Associated with Increased Neurofibrillary Tangle Development in Alzheimer Disease.
Genetic Analysis of Prosaposin, the Lysosomal Storage Disorder Gene in Parkinson's Disease.
Title: Genetic Analysis of Prosaposin, the Lysosomal Storage Disorder Gene in Parkinson's Disease.
PSAP intronic variants around saposin D domain and Parkinson's disease.
Title: PSAP intronic variants around saposin D domain and Parkinson's disease.
Glucosylsphingosine but not Saposin C, is the target antigen in Gaucher disease-associated gammopathy.
Title: Glucosylsphingosine but not Saposin C, is the target antigen in Gaucher disease-associated gammopathy.
Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer's disease and aged brains: increased levels correlate with neuropathology.
Title: Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer's disease and aged brains: increased levels correlate with neuropathology.

Submit: New GeneRIF Correction See all GeneRIFs (63)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Combined PSAP deficiency MedGen: C2673635 OMIM: 611721 GeneReviews: Not available	Compare labs
Gaucher disease due to saposin C deficiency MedGen: C1864651 OMIM: 610539 GeneReviews: Not available	Compare labs
Krabbe disease due to saposin A deficiency MedGen: C2673266 OMIM: 611722 GeneReviews: Not available	Compare labs
Parkinson disease 24, autosomal dominant, susceptibility to MedGen: C5561969 OMIM: 619491 GeneReviews: Not available	Compare labs
Sphingolipid activator protein 1 deficiency MedGen: C0268262 OMIM: 249900 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Rank-based genome-wide analysis reveals the association of ryanodine receptor-2 gene variants with childhood asthma among human populations. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH68874 (e-PCR)
- UniSTS:67082

D10S1299E (e-PCR)
- UniSTS:151332

D10S1301E (e-PCR)
- UniSTS:151334

D10S1303E (e-PCR)
- UniSTS:151336

RH121750 (e-PCR)
- UniSTS:134494

RH11184 (e-PCR)
- UniSTS:2675

STS-J03077 (e-PCR)
- UniSTS:22397

RH41802 (e-PCR)
- UniSTS:35986

D10S2162 (e-PCR)
- UniSTS:47851

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables enzyme activator activity	TAS Traceable Author Statement more info	PubMed
enables ganglioside GM1 binding	IDA Inferred from Direct Assay more info	PubMed
enables ganglioside GM2 binding	IDA Inferred from Direct Assay more info	PubMed
enables ganglioside GM3 binding	IDA Inferred from Direct Assay more info	PubMed
enables ganglioside GP1c binding	IDA Inferred from Direct Assay more info	PubMed
enables ganglioside GT1b binding	IDA Inferred from Direct Assay more info	PubMed
enables phospholipid binding	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in epithelial cell differentiation involved in prostate gland development	IBA Inferred from Biological aspect of Ancestor more info
involved_in ganglioside GM1 transport to membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in lysosomal transport	IDA Inferred from Direct Assay more info	PubMed
involved_in lysosomal transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of beta-galactosidase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in prostate gland growth	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of autophagy	TAS Traceable Author Statement more info	PubMed
involved_in regulation of lipid metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in sphingolipid metabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in azurophil granule membrane	TAS Traceable Author Statement more info
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal lumen	TAS Traceable Author Statement more info
located_in lysosomal membrane	TAS Traceable Author Statement more info
is_active_in lysosome	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: prosaposin

Names: precursor of saposins; proactivator polypeptide; saposin-A; saposin-B; saposin-C; saposin-D; sphingolipid activator protein-1; sphingolipid activator protein-2

NCBI Reference Sequences (RefSeq)

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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

NG_009301.1 RefSeqGene

Range

5075..40028

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001042465.3 → NP_001035930.1 prosaposin isoform b preproprotein

See identical proteins and their annotated locations for NP_001035930.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (b).

Source sequence(s)

BC004275, D00422, DC420206

UniProtKB/TrEMBL

Q59EN5

Conserved Domains (4) summary

smart00162
Location:21 → 54

SAPA; Saposin/surfactant protein-B A-type DOMAIN

smart00741
Location:318 → 391

SapB; Saposin (B) Domains

pfam03489
Location:360 → 391

SapB_2; Saposin-like type B, region 2

pfam05184
Location:63 → 97

SapB_1; Saposin-like type B, region 1
NM_001042466.3 → NP_001035931.1 prosaposin 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)

BC004275, D00422, DC420206

UniProtKB/TrEMBL

Q53FJ5

Conserved Domains (4) summary

smart00162
Location:21 → 54

SAPA; Saposin/surfactant protein-B A-type DOMAIN

smart00741
Location:317 → 390

SapB; Saposin (B) Domains

pfam03489
Location:359 → 390

SapB_2; Saposin-like type B, region 2

pfam05184
Location:63 → 97

SapB_1; Saposin-like type B, region 1
NM_002778.4 → NP_002769.1 prosaposin isoform a preproprotein

See identical proteins and their annotated locations for NP_002769.1

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)

BC004275, DC420206

Consensus CDS

CCDS7311.1

UniProtKB/Swiss-Prot

P07292, P07602, P15793, P78538, P78541, P78546, P78547, P78558, Q53Y86, Q6IBQ6, Q92739, Q92740, Q92741, Q92742

UniProtKB/TrEMBL

Q53FJ5

Related

ENSP00000378394.3, ENST00000394936.8

Conserved Domains (3) summary

smart00162
Location:21 → 54

SAPA; Saposin/surfactant protein-B A-type DOMAIN

smart00741
Location:315 → 388

SapB; Saposin (B) Domains

pfam02199
Location:492 → 524

SapA; Saposin A-type domain