PSAP

Protein identityUniProt · HPA

UniProt accession

P07602

Gene

PSAP

Ensembl

ENSG00000197746

Chromosome

10

Canonical length

524 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters

Subcellular location

Vesicles

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

524 residues, UniProt reviewed canonical sequence.

>P07602|PSAP
     1  MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ TVWNKPTVKS
    61  LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP NMSASCKEIV DSYLPVILDI
   121  IKGEMSRPGE VCSALNLCES LQKHLAELNH QKQLESNKIP ELDMTEVVAP FMANIPLLLY
   181  PQDGPRSKPQ PKDNGDVCQD CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI
   241  CKNYISQYSE IAIQMMMHMQ PKEICALVGF CDEVKEMPMQ TLVPAKVASK NVIPALELVE
   301  PIKKHEVPAK SDVYCEVCEF LVKEVTKLID NNKTEKEILD AFDKMCSKLP KSLSEECQEV
   361  VDTYGSSILS ILLEEVSPEL VCSMLHLCSG TRLPALTVHV TQPKDGGFCE VCKKLVGYLD
   421  RNLEKNSTKQ EILAALEKGC SFLPDPYQKQ CDQFVAEYEP VLIEILVEVM DPSFVCLKIG
   481  ACPSAHKPLL GTEKCIWGPS YWCQNTETAA QCNAVEHCKR HVWN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PSAP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

1,612 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PSAP.

Disease | AllUniProt

Conditions PSAP is implicated in, by any mechanism.

• Combined saposin deficiency (PSAPD) MIM:611721
• Metachromatic leukodystrophy due to saposin B deficiency (MLDSAPB) MIM:249900
• Gaucher disease, atypical, due to saposin C deficiency (GDSAPC) MIM:610539
• Krabbe disease, atypical, due to saposin A deficiency (KRBSAPA) MIM:611722
• Parkinson disease 24, autosomal dominant (PARK24) MIM:619491

Disease | GeneticClinVar

95 pathogenic / likely-pathogenic of 996 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Sphingolipid activator protein 1 deficiency
• Metachromatic leukodystrophy
• Combined PSAP deficiency
• Parkinson disease 24, autosomal dominant, susceptibility to
• Gaucher disease due to saposin C deficiency

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.28

gnomAD pLI

0.99

gnomAD missense Z

-0.52

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• epithelial cell differentiation involved in prostate gland development
• gene expression
• lysosomal transport
• prostate gland growth
• regulation of autophagy
• regulation of lipid metabolic process
• sphingolipid metabolic process
• ganglioside GM1 transport to membrane

Molecular functions

• enzyme activator activity
• ganglioside GM1 binding
• ganglioside GT1b binding
• identical protein binding
• phospholipid binding
• protease binding
• protein homodimerization activity
• scaffold protein binding
• ganglioside GM2 binding
• ganglioside GM3 binding
• ganglioside GP1c binding

Cellular components

• azurophil granule membrane
• extracellular exosome
• extracellular region
• extracellular space
• late endosome
• lysosomal lumen
• lysosomal membrane
• lysosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Saposin A-type domain
• Saposin-like type B, region 1
• Saposin B type, region 2
• Saposin B type domain
• Saposin
• Saposin-like
• Saposin, chordata
• Sphingolipid Activators and Surfactant Proteins
• Saposin A-type domain
• Saposin-like type B, region 2
• Saposin-like type B, region 1

KeywordsUniProt

• Disulfide bond
• Gangliosidosis
• Gaucher disease
• Glycoprotein
• Leukodystrophy
• Lipid metabolism
• Lysosome
• Metachromatic leukodystrophy
• Neurodegeneration
• Parkinson disease
• Parkinsonism
• Repeat
• Secreted
• Signal
• Sphingolipid metabolism

InteractionsUniProt · HPA

Protein binding partners of PSAP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GRN
• SORT1
• ZBED1