Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1

Details

Name
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
Synonyms
  • 5.2.1.8
  • Peptidyl-prolyl cis-trans isomerase Pin1
  • PPIase Pin1
  • Rotamase Pin1
Gene Name
PIN1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0017209|Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
MADEEKLPPGWEKRMSRSSGRVYYFNHITNASQWERPSGNSSSGGKNGQGEPARVRCSHL
LVKHSQSRRPSSWRQEKITRTKEEALELINGYIQKIKSGEEDFESLASQFSDCSSAKARG
DLGAFSRGQMQKPFEDASFALRTGEMSGPVFTDSGIHIILRTE
Number of residues
163
Molecular Weight
18243.13
Theoretical pI
9.18
GO Classification
Functions
GTPase activating protein binding / mitogen-activated protein kinase kinase binding / peptidyl-prolyl cis-trans isomerase activity / phosphoserine binding / phosphothreonine binding
Processes
cell cycle / cytokine-mediated signaling pathway / innate immune response / negative regulation of cell motility / negative regulation of ERK1 and ERK2 cascade / negative regulation of neuron apoptotic process / negative regulation of transforming growth factor beta receptor signaling pathway / negative regulation of type I interferon production / positive regulation of cell growth involved in cardiac muscle cell development / positive regulation of GTPase activity / positive regulation of neuron apoptotic process / positive regulation of protein dephosphorylation / positive regulation of protein phosphorylation / positive regulation of ubiquitin-protein transferase activity / protein peptidyl-prolyl isomerization / regulation of cytokinesis / regulation of mitotic nuclear division / regulation of pathway-restricted SMAD protein phosphorylation
Components
cytosol / midbody / mitochondrion / neuron projection / nuclear speck / nucleoplasm / nucleus
General Function
Phosphothreonine binding
Specific Function
Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs in a subset of proteins, resulting in conformational changes in the proteins (PubMed:21497122, PubMed:22033920). Displays a preference for an acidic residue N-terminal to the isomerized proline bond. 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).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0017210|Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)
ATGGCGGACGAGGAGAAGCTGCCGCCCGGCTGGGAGAAGCGCATGAGCCGCAGCTCAGGC
CGAGTGTACTACTTCAACCACATCACTAACGCCAGCCAGTGGGAGCGGCCCAGCGGCAAC
AGCAGCAGTGGTGGCAAAAACGGGCAGGGGGAGCCTGCCAGGGTCCGCTGCTCGCACCTG
CTGGTGAAGCACAGCCAGTCACGGCGGCCCTCGTCCTGGCGGCAGGAGAAGATCACCCGG
ACCAAGGAGGAGGCCCTGGAGCTGATCAACGGCTACATCCAGAAGATCAAGTCGGGAGAG
GAGGACTTTGAGTCTCTGGCCTCACAGTTCAGCGACTGCAGCTCAGCCAAGGCCAGGGGA
GACCTGGGTGCCTTCAGCAGAGGTCAGATGCAGAAGCCATTTGAAGACGCCTCGTTTGCG
CTGCGGACGGGGGAGATGAGCGGGCCCGTGTTCACGGATTCCGGCATCCACATCATCCTC
CGCACTGAGTGA
Chromosome Location
19
Locus
19p13
External Identifiers
ResourceLink
UniProtKB IDQ13526
UniProtKB Entry NamePIN1_HUMAN
GenBank Protein ID1332710
GenBank Gene IDU49070
HGNC IDHGNC:8988
General References
  1. Lu KP, Hanes SD, Hunter T: A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature. 1996 Apr 11;380(6574):544-7. [Article]
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  4. Kamimoto T, Zama T, Aoki R, Muro Y, Hagiwara M: Identification of a novel kinesin-related protein, KRMP1, as a target for mitotic peptidyl-prolyl isomerase Pin1. J Biol Chem. 2001 Oct 5;276(40):37520-8. Epub 2001 Jul 24. [Article]
  5. Dougherty MK, Muller J, Ritt DA, Zhou M, Zhou XZ, Copeland TD, Conrads TP, Veenstra TD, Lu KP, Morrison DK: Regulation of Raf-1 by direct feedback phosphorylation. Mol Cell. 2005 Jan 21;17(2):215-24. [Article]
  6. Chen J, Li L, Zhang Y, Yang H, Wei Y, Zhang L, Liu X, Yu L: Interaction of Pin1 with Nek6 and characterization of their expression correlation in Chinese hepatocellular carcinoma patients. Biochem Biophys Res Commun. 2006 Mar 24;341(4):1059-65. Epub 2006 Jan 25. [Article]
  7. Yu L, Mohamed AJ, Vargas L, Berglof A, Finn G, Lu KP, Smith CI: Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1. J Biol Chem. 2006 Jun 30;281(26):18201-7. Epub 2006 Apr 27. [Article]
  8. Phan RT, Saito M, Kitagawa Y, Means AR, Dalla-Favera R: Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells. Nat Immunol. 2007 Oct;8(10):1132-9. Epub 2007 Sep 9. [Article]
  9. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [Article]
  10. Buschdorf JP, Chew LL, Soh UJ, Liou YC, Low BC: Nerve growth factor stimulates interaction of Cayman ataxia protein BNIP-H/Caytaxin with peptidyl-prolyl isomerase Pin1 in differentiating neurons. PLoS One. 2008 Jul 16;3(7):e2686. doi: 10.1371/journal.pone.0002686. [Article]
  11. Li X, Hyink DP, Radbill B, Sudol M, Zhang H, Zheleznova NN, Wilson PD: Protein kinase-X interacts with Pin-1 and Polycystin-1 during mouse kidney development. Kidney Int. 2009 Jul;76(1):54-62. doi: 10.1038/ki.2009.95. Epub 2009 Apr 15. [Article]
  12. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  13. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  14. Lim JH, Liu Y, Reineke E, Kao HY: Mitogen-activated protein kinase extracellular signal-regulated kinase 2 phosphorylates and promotes Pin1 protein-dependent promyelocytic leukemia protein turnover. J Biol Chem. 2011 Dec 30;286(52):44403-11. doi: 10.1074/jbc.M111.289512. Epub 2011 Oct 27. [Article]
  15. Lee TH, Chen CH, Suizu F, Huang P, Schiene-Fischer C, Daum S, Zhang YJ, Goate A, Chen RH, Zhou XZ, Lu KP: Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. Mol Cell. 2011 Apr 22;42(2):147-59. doi: 10.1016/j.molcel.2011.03.005. Epub 2011 Apr 14. [Article]
  16. Min SH, Lau AW, Lee TH, Inuzuka H, Wei S, Huang P, Shaik S, Lee DY, Finn G, Balastik M, Chen CH, Luo M, Tron AE, Decaprio JA, Zhou XZ, Wei W, Lu KP: Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Mol Cell. 2012 Jun 29;46(6):771-83. doi: 10.1016/j.molcel.2012.04.012. Epub 2012 May 17. [Article]
  17. Ranganathan R, Lu KP, Hunter T, Noel JP: Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent. Cell. 1997 Jun 13;89(6):875-86. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB068673,6,9,12,15,18-HEXAOXAICOSANEexperimentalunknownDetails
DB01766Beta-(2-Naphthyl)-AlanineexperimentalunknownDetails