Protein: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (EC 5.2.1.8) (Peptidyl-prolyl cis-trans isomerase Pin1) (PPIase Pin1) (Rotamase Pin1) (Q13526)
Organism: Homo sapiens (Human)
Function: Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs. By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes. 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. 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. Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner. 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. 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). 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.
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}.
Sequence: MADEEKLPPGWEKRMSRSSGRVYYFNHITNASQWERPSGNSSSGGKNGQGEPARVRCSHLLVKHSQSRRPSSWRQEKITRTKEEALELINGYIQKIKSGEEDFESLASQFSDCSSAKARGDLGAFSRGQMQKPFEDASFALRTGEMSGPVFTDSGIHIILRTE
InterPro domains: - IPR001202: WW domain (domain) [5-39]
- IPR046357: Peptidyl-prolyl cis-trans isomerase domain superfamily (homologous_superfamily) [45-163]
- IPR000297: Peptidyl-prolyl cis-trans isomerase, PpiC-type (domain) [52-163]
- IPR036020: WW domain superfamily (homologous_superfamily) [2-39]
- IPR051370: Peptidyl-prolyl cis-trans isomerase Pin1 (family) [4-163]
- IPR023058: Peptidyl-prolyl cis-trans isomerase, PpiC-type, conserved site (conserved_site) [103-123]
Interaction partners: - Interferon regulatory factor 3
- Homeodomain-interacting protein kinase 2
- Cellular tumor antigen p53
- DNA-directed RNA polymerase II subunit RPB1
- 14-3-3 protein sigma
- Myc proto-oncogene protein
- Protein PML
- Serine/threonine-protein kinase PLK1
- Neutrophil cytosol factor 1
- Neutrophil cytosol factor 4
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016853 (isomerase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016859 (cis-trans isomerase activity), GO:0031072 (heat shock protein binding), GO:0003755 (peptidyl-prolyl cis-trans isomerase activity), GO:0051879 (Hsp90 protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0044238 (primary metabolic process), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0006807 (nitrogen compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0019538 (protein metabolic process), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0044248 (cellular catabolic process), GO:0009057 (macromolecule catabolic process), GO:1901565 (organonitrogen compound catabolic process), GO:0006508 (proteolysis), GO:0044265 (cellular macromolecule catabolic process), GO:0030163 (protein catabolic process), GO:0043632 (modification-dependent macromolecule catabolic process), GO:0051603 (proteolysis involved in protein catabolic process), GO:0019941 (modification-dependent protein catabolic process), GO:0006511 (ubiquitin-dependent protein catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)