UniProt functional annotation for Q13526



	UniProt functional annotation for Q13526

UniProt code: Q13526.

Organism: Homo sapiens (Human).

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

Function: Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs (PubMed:21497122, PubMed:23623683, PubMed:29686383). By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes (PubMed:21497122, PubMed:22033920, PubMed:23623683). Displays a preference for acidic residues located N-terminally to the proline bond to be isomerized. Regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Down-regulates kinase activity of BTK (PubMed:16644721). Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation (PubMed:15664191). Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner (PubMed:17828269). Acts as a regulator of JNK cascade by binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation: degradation of FBXW7 leads to subsequent stabilization of JUN (PubMed:22608923). May facilitate the ubiquitination and proteasomal degradation of RBBP8/CtIP through CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:23623683, PubMed:27561354). Upon IL33-induced lung inflammation, catalyzes cis-trans isomerization of phosphorylated IRAK3/IRAK-M, inducing IRAK3 stabilization, nuclear translocation and expression of pro-inflammatory genes in dendritic cells (PubMed:29686383). {ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:16644721, ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:21497122, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:27561354, ECO:0000269|PubMed:29686383}.

Catalytic activity: Reaction=[protein]-peptidylproline (omega=180) = [protein]- peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269|PubMed:21497122, ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:29686383};

Subunit: Interacts with STIL (By similarity). Interacts with KIF20B (PubMed:11470801). Interacts with NEK6 (PubMed:16476580). Interacts (via WW domain) with PRKX (PubMed:19367327). Interacts with BTK (PubMed:16644721). Interacts (via PpiC domain) with DAPK1 (PubMed:21497122). Interacts with the phosphorylated form of RAF1 (PubMed:15664191). Interacts (via WW domain) with ATCAY; upon NGF stimulation (PubMed:18628984). Interacts with PML (isoform PML-4) (PubMed:22033920). Interacts with BCL6 (PubMed:17828269). Interacts with FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (PubMed:22608923). Directly interacts with RBBP8/CtIP; this interaction depends upon RBBP8 phosphorylation (PubMed:23623683). Interacts (via WW domain) with IRAK3/IRAK-M (when phosphorylated at 'Ser-110') in response to IL33- mediated (but not TLR4 ligand LPS) dendritic cell stimulation (PubMed:29686383). {ECO:0000250|UniProtKB:Q9QUR7, ECO:0000269|PubMed:11470801, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:16476580, ECO:0000269|PubMed:16644721, ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:18628984, ECO:0000269|PubMed:19367327, ECO:0000269|PubMed:21497122, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:29686383}.

Subcellular location: Nucleus {ECO:0000269|PubMed:16476580, ECO:0000269|PubMed:23623683}. Nucleus speckle {ECO:0000269|PubMed:21497122}. Cytoplasm {ECO:0000269|PubMed:21497122}. Note=Colocalizes with NEK6 in the nucleus (PubMed:16476580). Mainly localized in the nucleus but phosphorylation at Ser-71 by DAPK1 results in inhibition of its nuclear localization (PubMed:21497122). {ECO:0000269|PubMed:16476580}.

Tissue specificity: Expressed in immune cells in the lung (at protein level) (PubMed:29686383). The phosphorylated form at Ser-71 is expressed in normal breast tissue cells but not in breast cancer cells. {ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:21497122, ECO:0000269|PubMed:29686383}.

Domain: The WW domain is required for the interaction with STIL and KIF20B.

Ptm: Phosphorylation at Ser-71 by DAPK1 results in inhibition of its catalytic activity, nuclear localization, and its ability to induce centrosome amplification, chromosome instability and cell transformation (PubMed:21497122). Ser-71 is dephosphorylated upon IL33- stimulation of dendritic cells (By similarity). {ECO:0000250|UniProtKB:Q9QUR7, ECO:0000269|PubMed:21497122}.

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:		Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs (PubMed:21497122, PubMed:23623683, PubMed:29686383). By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes (PubMed:21497122, PubMed:22033920, PubMed:23623683). Displays a preference for acidic residues located N-terminally to the proline bond to be isomerized. Regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Down-regulates kinase activity of BTK (PubMed:16644721). Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation (PubMed:15664191). Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner (PubMed:17828269). Acts as a regulator of JNK cascade by binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation: degradation of FBXW7 leads to subsequent stabilization of JUN (PubMed:22608923). May facilitate the ubiquitination and proteasomal degradation of RBBP8/CtIP through CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:23623683, PubMed:27561354). Upon IL33-induced lung inflammation, catalyzes cis-trans isomerization of phosphorylated IRAK3/IRAK-M, inducing IRAK3 stabilization, nuclear translocation and expression of pro-inflammatory genes in dendritic cells (PubMed:29686383). {ECO:0000269\|PubMed:15664191, ECO:0000269\|PubMed:16644721, ECO:0000269\|PubMed:17828269, ECO:0000269\|PubMed:21497122, ECO:0000269\|PubMed:22033920, ECO:0000269\|PubMed:22608923, ECO:0000269\|PubMed:23623683, ECO:0000269\|PubMed:27561354, ECO:0000269\|PubMed:29686383}.


Catalytic activity:		Reaction=[protein]-peptidylproline (omega=180) = [protein]- peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269\|PubMed:21497122, ECO:0000269\|PubMed:23623683, ECO:0000269\|PubMed:29686383};
Subunit:		Interacts with STIL (By similarity). Interacts with KIF20B (PubMed:11470801). Interacts with NEK6 (PubMed:16476580). Interacts (via WW domain) with PRKX (PubMed:19367327). Interacts with BTK (PubMed:16644721). Interacts (via PpiC domain) with DAPK1 (PubMed:21497122). Interacts with the phosphorylated form of RAF1 (PubMed:15664191). Interacts (via WW domain) with ATCAY; upon NGF stimulation (PubMed:18628984). Interacts with PML (isoform PML-4) (PubMed:22033920). Interacts with BCL6 (PubMed:17828269). Interacts with FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (PubMed:22608923). Directly interacts with RBBP8/CtIP; this interaction depends upon RBBP8 phosphorylation (PubMed:23623683). Interacts (via WW domain) with IRAK3/IRAK-M (when phosphorylated at 'Ser-110') in response to IL33- mediated (but not TLR4 ligand LPS) dendritic cell stimulation (PubMed:29686383). {ECO:0000250\|UniProtKB:Q9QUR7, ECO:0000269\|PubMed:11470801, ECO:0000269\|PubMed:15664191, ECO:0000269\|PubMed:16476580, ECO:0000269\|PubMed:16644721, ECO:0000269\|PubMed:17828269, ECO:0000269\|PubMed:18628984, ECO:0000269\|PubMed:19367327, ECO:0000269\|PubMed:21497122, ECO:0000269\|PubMed:22033920, ECO:0000269\|PubMed:22608923, ECO:0000269\|PubMed:23623683, ECO:0000269\|PubMed:29686383}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:16476580, ECO:0000269\|PubMed:23623683}. Nucleus speckle {ECO:0000269\|PubMed:21497122}. Cytoplasm {ECO:0000269\|PubMed:21497122}. Note=Colocalizes with NEK6 in the nucleus (PubMed:16476580). Mainly localized in the nucleus but phosphorylation at Ser-71 by DAPK1 results in inhibition of its nuclear localization (PubMed:21497122). {ECO:0000269\|PubMed:16476580}.
Tissue specificity:		Expressed in immune cells in the lung (at protein level) (PubMed:29686383). The phosphorylated form at Ser-71 is expressed in normal breast tissue cells but not in breast cancer cells. {ECO:0000269\|PubMed:17828269, ECO:0000269\|PubMed:21497122, ECO:0000269\|PubMed:29686383}.
Domain:		The WW domain is required for the interaction with STIL and KIF20B.
Ptm:		Phosphorylation at Ser-71 by DAPK1 results in inhibition of its catalytic activity, nuclear localization, and its ability to induce centrosome amplification, chromosome instability and cell transformation (PubMed:21497122). Ser-71 is dephosphorylated upon IL33- stimulation of dendritic cells (By similarity). {ECO:0000250\|UniProtKB:Q9QUR7, ECO:0000269\|PubMed:21497122}.