UniProt functional annotation for P23458



	UniProt functional annotation for P23458

UniProt code: P23458.

Organism: Homo sapiens (Human).

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

Function: Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:7615558). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:7615558}.

Catalytic activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:1848670, ECO:0000269|PubMed:7615558};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305|PubMed:7615558}; Note=Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely to be the in vivo cofactor. {ECO:0000305|PubMed:7615558};

Subunit: Interacts with IL31RA (PubMed:15194700). Interacts with IFNAR2 (PubMed:7759950). Interacts with IFNGR1 (PubMed:7615558). Interacts with JAKMIP1 (PubMed:15277531). Interacts with SHB (PubMed:12200137). Interacts (via N-terminus) with IL2RB and IL10RA (via its cytoplasmic domain) (PubMed:12133952). Interacts with FER (By similarity). {ECO:0000250|UniProtKB:P52332, ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:12200137, ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:15277531, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7759950}.

Subcellular location: Endomembrane system; Peripheral membrane protein. Note=Wholly intracellular, possibly membrane associated.

Tissue specificity: Expressed at higher levels in primary colon tumors than in normal colon tissue. The expression level in metastatic colon tumors is comparable to the expression level in normal colon tissue. {ECO:0000269|PubMed:7896447}.

Domain: Possesses two phosphotransferase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for domain 1. {ECO:0000250}.

Domain: The FERM domain mediates interaction with JAKMIP1.

Ptm: Autophosphorylated (PubMed:7615558). Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558). Dephosphorylation of Tyr-1034 and Tyr-1035 by PTPN2 negatively regulates cytokine-mediated signaling (PubMed:11909529). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:7615558}.

Ptm: Ubiquitinated by RNF125; leading to its degradation by the proteasome. {ECO:0000269|PubMed:26027934}.

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.

Sequence caution: Sequence=AAA36527.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAA36527.1; Type=Frameshift; Evidence={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 kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:7615558). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). {ECO:0000269\|PubMed:11909529, ECO:0000269\|PubMed:7615558}.


Catalytic activity:		Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; Evidence={ECO:0000255\|PROSITE-ProRule:PRU10028, ECO:0000269\|PubMed:1848670, ECO:0000269\|PubMed:7615558};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305\|PubMed:7615558}; Note=Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely to be the in vivo cofactor. {ECO:0000305\|PubMed:7615558};
Subunit:		Interacts with IL31RA (PubMed:15194700). Interacts with IFNAR2 (PubMed:7759950). Interacts with IFNGR1 (PubMed:7615558). Interacts with JAKMIP1 (PubMed:15277531). Interacts with SHB (PubMed:12200137). Interacts (via N-terminus) with IL2RB and IL10RA (via its cytoplasmic domain) (PubMed:12133952). Interacts with FER (By similarity). {ECO:0000250\|UniProtKB:P52332, ECO:0000269\|PubMed:12133952, ECO:0000269\|PubMed:12200137, ECO:0000269\|PubMed:15194700, ECO:0000269\|PubMed:15277531, ECO:0000269\|PubMed:7615558, ECO:0000269\|PubMed:7759950}.
Subcellular location:		Endomembrane system; Peripheral membrane protein. Note=Wholly intracellular, possibly membrane associated.
Tissue specificity:		Expressed at higher levels in primary colon tumors than in normal colon tissue. The expression level in metastatic colon tumors is comparable to the expression level in normal colon tissue. {ECO:0000269\|PubMed:7896447}.
Domain:		Possesses two phosphotransferase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for domain 1. {ECO:0000250}.
Domain:		The FERM domain mediates interaction with JAKMIP1.
Ptm:		Autophosphorylated (PubMed:7615558). Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558). Dephosphorylation of Tyr-1034 and Tyr-1035 by PTPN2 negatively regulates cytokine-mediated signaling (PubMed:11909529). {ECO:0000269\|PubMed:11909529, ECO:0000269\|PubMed:7615558}.
Ptm:		Ubiquitinated by RNF125; leading to its degradation by the proteasome. {ECO:0000269\|PubMed:26027934}.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Sequence caution:		Sequence=AAA36527.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAA36527.1; Type=Frameshift; Evidence={ECO:0000305};