UniProt functional annotation for P15309



	UniProt functional annotation for P15309

UniProt code: P15309.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins (PubMed:10506173, PubMed:15280042, PubMed:20498373, PubMed:9584846). Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma (PubMed:10506173, PubMed:15280042). {ECO:0000269|PubMed:10506173, ECO:0000269|PubMed:15280042, ECO:0000269|PubMed:20498373, ECO:0000269|PubMed:9584846}.

Function: [Isoform 2]: Tyrosine phosphatase that acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling (PubMed:20498373). In addition to its tyrosine phosphatase activity has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor (By similarity). {ECO:0000250|UniProtKB:Q8CE08, ECO:0000269|PubMed:20498373}.

Function: [PAPf39]: (Microbial infection) Forms amyloid beta-sheet fibrils in semen. These fibrils, termed SEVI (semen-derived enhancer of viral infection) capture HIV virions, attach them to target cells and enhance infection (PubMed:18083097, PubMed:19451623, PubMed:19897482). SEVI amyloid fibrils are degraded by polyphenol epigallocatechin-3- gallate (EGCG), a constituent of green tea (PubMed:19451623). Target cell attachment and enhancement of HIV infection is inhibited by surfen (PubMed:19897482). Also similarly boosts XMRV (xenotropic murine leukemia virus-related virus) infection (PubMed:19403677). {ECO:0000269|PubMed:18083097, ECO:0000269|PubMed:19403677, ECO:0000269|PubMed:19451623, ECO:0000269|PubMed:19897482}.

Catalytic activity: Reaction=a phosphate monoester + H2O = an alcohol + phosphate; Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.2; Evidence={ECO:0000269|PubMed:10506173, ECO:0000269|PubMed:15280042, ECO:0000269|PubMed:9584846};

Catalytic activity: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z- octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:39835, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:74544, ChEBI:CHEBI:75757; Evidence={ECO:0000269|PubMed:10506173}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39836; Evidence={ECO:0000305|PubMed:10506173};

Catalytic activity: Reaction=a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + phosphate; Xref=Rhea:RHEA:12484, ChEBI:CHEBI:15377, ChEBI:CHEBI:18254, ChEBI:CHEBI:43474, ChEBI:CHEBI:58043; EC=3.1.3.5; Evidence={ECO:0000250|UniProtKB:Q8CE08};

Catalytic activity: Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000269|PubMed:20498373};

Activity regulation: Phosphatase activity inhibited by L(+)-tartrate, and by its derivative, alpha-benzylaminobenzylphosphonic acid. {ECO:0000269|PubMed:9584846}.

Subunit: Homodimer; dimer formation is required for phosphatase activity. {ECO:0000250|UniProtKB:P20646}.

Subcellular location: [Isoform 1]: Secreted {ECO:0000305|PubMed:17638863}.

Subcellular location: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:17638863, ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:20498373}; Single-pass type I membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:17638863, ECO:0000269|PubMed:17897319}; Single-pass type I membrane protein {ECO:0000255}. Nucleus {ECO:0000269|PubMed:20498373}. Cytoplasm, cytosol {ECO:0000269|PubMed:20498373}. Note=Appears to shuttle between the cell membrane and intracellular vesicles. Colocalizes with FLOT1 at cell membrane and in intracellular vesicles (PubMed:17638863). Colocalizes with LAMP2 on the lysosome membrane (PubMed:17897319). {ECO:0000269|PubMed:17638863, ECO:0000269|PubMed:17897319}.

Tissue specificity: Highly expressed in the prostate, restricted to glandular and ductal epithelial cells. Also expressed in bladder, kidney, pancreas, lung, cervix, testis and ovary. Weak expression in a subset of pancreatic islet cells, squamous epithelia, the pilosebaceous unit, colonic neuroendocrine cells and skin adnexal structures. Low expression in prostate carcinoma cells and tissues. {ECO:0000269|PubMed:17638863, ECO:0000269|PubMed:21487525}.

Tissue specificity: [Isoform 2]: Widely expressed. Expressed in the sarcolemma of skeletal muscle. {ECO:0000269|PubMed:17638863}.

Ptm: N-glycosylated. High mannose content, partially sialylated and fucosylated biantennary complex. Also fucosylated with partially sialylated triantennary complex oligosaccharides. {ECO:0000269|PubMed:10639192, ECO:0000269|PubMed:12525165}.

Ptm: Proteolytically cleaved in seminal fluid to produce several peptides. Peptide PAPf39, the most prominent, forms amyloid beta-sheet fibrils, SEVI (semen-derived enhancer of viral infection). {ECO:0000269|PubMed:18083097}.

Miscellaneous: Has been used as a diagnostic tool for staging metastatic prostatic cancer.

Similarity: Belongs to the histidine acid phosphatase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins (PubMed:10506173, PubMed:15280042, PubMed:20498373, PubMed:9584846). Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma (PubMed:10506173, PubMed:15280042). {ECO:0000269\|PubMed:10506173, ECO:0000269\|PubMed:15280042, ECO:0000269\|PubMed:20498373, ECO:0000269\|PubMed:9584846}.



Function:		[Isoform 2]: Tyrosine phosphatase that acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling (PubMed:20498373). In addition to its tyrosine phosphatase activity has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor (By similarity). {ECO:0000250\|UniProtKB:Q8CE08, ECO:0000269\|PubMed:20498373}.



Function:		[PAPf39]: (Microbial infection) Forms amyloid beta-sheet fibrils in semen. These fibrils, termed SEVI (semen-derived enhancer of viral infection) capture HIV virions, attach them to target cells and enhance infection (PubMed:18083097, PubMed:19451623, PubMed:19897482). SEVI amyloid fibrils are degraded by polyphenol epigallocatechin-3- gallate (EGCG), a constituent of green tea (PubMed:19451623). Target cell attachment and enhancement of HIV infection is inhibited by surfen (PubMed:19897482). Also similarly boosts XMRV (xenotropic murine leukemia virus-related virus) infection (PubMed:19403677). {ECO:0000269\|PubMed:18083097, ECO:0000269\|PubMed:19403677, ECO:0000269\|PubMed:19451623, ECO:0000269\|PubMed:19897482}.


Catalytic activity:		Reaction=a phosphate monoester + H2O = an alcohol + phosphate; Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.2; Evidence={ECO:0000269\|PubMed:10506173, ECO:0000269\|PubMed:15280042, ECO:0000269\|PubMed:9584846};
Catalytic activity:		Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z- octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:39835, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:74544, ChEBI:CHEBI:75757; Evidence={ECO:0000269\|PubMed:10506173}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39836; Evidence={ECO:0000305\|PubMed:10506173};
Catalytic activity:		Reaction=a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + phosphate; Xref=Rhea:RHEA:12484, ChEBI:CHEBI:15377, ChEBI:CHEBI:18254, ChEBI:CHEBI:43474, ChEBI:CHEBI:58043; EC=3.1.3.5; Evidence={ECO:0000250\|UniProtKB:Q8CE08};
Catalytic activity:		Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000269\|PubMed:20498373};
Activity regulation:		Phosphatase activity inhibited by L(+)-tartrate, and by its derivative, alpha-benzylaminobenzylphosphonic acid. {ECO:0000269\|PubMed:9584846}.
Subunit:		Homodimer; dimer formation is required for phosphatase activity. {ECO:0000250\|UniProtKB:P20646}.
Subcellular location:		[Isoform 1]: Secreted {ECO:0000305\|PubMed:17638863}.
Subcellular location:		[Isoform 2]: Cell membrane {ECO:0000269\|PubMed:17638863, ECO:0000269\|PubMed:17897319, ECO:0000269\|PubMed:20498373}; Single-pass type I membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269\|PubMed:17638863, ECO:0000269\|PubMed:17897319}; Single-pass type I membrane protein {ECO:0000255}. Nucleus {ECO:0000269\|PubMed:20498373}. Cytoplasm, cytosol {ECO:0000269\|PubMed:20498373}. Note=Appears to shuttle between the cell membrane and intracellular vesicles. Colocalizes with FLOT1 at cell membrane and in intracellular vesicles (PubMed:17638863). Colocalizes with LAMP2 on the lysosome membrane (PubMed:17897319). {ECO:0000269\|PubMed:17638863, ECO:0000269\|PubMed:17897319}.
Tissue specificity:		Highly expressed in the prostate, restricted to glandular and ductal epithelial cells. Also expressed in bladder, kidney, pancreas, lung, cervix, testis and ovary. Weak expression in a subset of pancreatic islet cells, squamous epithelia, the pilosebaceous unit, colonic neuroendocrine cells and skin adnexal structures. Low expression in prostate carcinoma cells and tissues. {ECO:0000269\|PubMed:17638863, ECO:0000269\|PubMed:21487525}.
Tissue specificity:		[Isoform 2]: Widely expressed. Expressed in the sarcolemma of skeletal muscle. {ECO:0000269\|PubMed:17638863}.
Ptm:		N-glycosylated. High mannose content, partially sialylated and fucosylated biantennary complex. Also fucosylated with partially sialylated triantennary complex oligosaccharides. {ECO:0000269\|PubMed:10639192, ECO:0000269\|PubMed:12525165}.
Ptm:		Proteolytically cleaved in seminal fluid to produce several peptides. Peptide PAPf39, the most prominent, forms amyloid beta-sheet fibrils, SEVI (semen-derived enhancer of viral infection). {ECO:0000269\|PubMed:18083097}.
Miscellaneous:		Has been used as a diagnostic tool for staging metastatic prostatic cancer.
Similarity:		Belongs to the histidine acid phosphatase family. {ECO:0000305}.