UniProt functional annotation for P18031



	UniProt functional annotation for P18031

UniProt code: P18031.

Organism: Homo sapiens (Human).

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

Function: Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c- src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}.

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:0000255|PROSITE- ProRule:PRU10044};

Subunit: Interacts with EPHA3 (phosphorylated); dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts with MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139}.

Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:1739967, ECO:0000269|PubMed:21135139}; Peripheral membrane protein {ECO:0000269|PubMed:1739967, ECO:0000269|PubMed:21135139}; Cytoplasmic side {ECO:0000269|PubMed:1739967, ECO:0000269|PubMed:21135139}. Note=Interacts with EPHA3 at the cell membrane.

Tissue specificity: Expressed in keratinocytes (at protein level). {ECO:0000269|PubMed:29043977}.

Ptm: Oxidized on Cys-215; the Cys-SOH formed in response to redox signaling reacts with the alpha-amido of the following residue to form a sulfenamide cross-link, triggering a conformational change that inhibits substrate binding and activity. The active site can be restored by reduction. {ECO:0000269|PubMed:12802338, ECO:0000269|PubMed:12802339}.

Ptm: Ser-50 is the major site of phosphorylation as compared to Ser-242 and Ser-243. Activated by phosphorylation at Ser-50. {ECO:0000269|PubMed:10480872, ECO:0000269|PubMed:11579209, ECO:0000269|PubMed:8491187, ECO:0000269|PubMed:9355745}.

Ptm: S-nitrosylation of Cys-215 inactivates the enzyme activity. {ECO:0000269|PubMed:22169477}.

Ptm: Sulfhydration at Cys-215 following endoplasmic reticulum stress inactivates the enzyme activity, promoting EIF2AK3/PERK activity.

Similarity: Belongs to the protein-tyrosine phosphatase family. Non- receptor class 1 subfamily. {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:		Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c- src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269\|PubMed:18819921, ECO:0000269\|PubMed:21135139, ECO:0000269\|PubMed:22169477}.


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:0000255\|PROSITE- ProRule:PRU10044};
Subunit:		Interacts with EPHA3 (phosphorylated); dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts with MET. {ECO:0000269\|PubMed:18819921, ECO:0000269\|PubMed:21135139}.
Subcellular location:		Endoplasmic reticulum membrane {ECO:0000269\|PubMed:1739967, ECO:0000269\|PubMed:21135139}; Peripheral membrane protein {ECO:0000269\|PubMed:1739967, ECO:0000269\|PubMed:21135139}; Cytoplasmic side {ECO:0000269\|PubMed:1739967, ECO:0000269\|PubMed:21135139}. Note=Interacts with EPHA3 at the cell membrane.
Tissue specificity:		Expressed in keratinocytes (at protein level). {ECO:0000269\|PubMed:29043977}.
Ptm:		Oxidized on Cys-215; the Cys-SOH formed in response to redox signaling reacts with the alpha-amido of the following residue to form a sulfenamide cross-link, triggering a conformational change that inhibits substrate binding and activity. The active site can be restored by reduction. {ECO:0000269\|PubMed:12802338, ECO:0000269\|PubMed:12802339}.
Ptm:		Ser-50 is the major site of phosphorylation as compared to Ser-242 and Ser-243. Activated by phosphorylation at Ser-50. {ECO:0000269\|PubMed:10480872, ECO:0000269\|PubMed:11579209, ECO:0000269\|PubMed:8491187, ECO:0000269\|PubMed:9355745}.
Ptm:		S-nitrosylation of Cys-215 inactivates the enzyme activity. {ECO:0000269\|PubMed:22169477}.
Ptm:		Sulfhydration at Cys-215 following endoplasmic reticulum stress inactivates the enzyme activity, promoting EIF2AK3/PERK activity.
Similarity:		Belongs to the protein-tyrosine phosphatase family. Non- receptor class 1 subfamily. {ECO:0000305}.