Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
Details
- Name
- Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
- Kind
- protein
- Synonyms
- 5.2.1.8
- Peptidyl-prolyl cis-trans isomerase Pin1
- PPIase Pin1
- Rotamase Pin1
- Gene Name
- PIN1
- UniProtKB Entry
- Q13526Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- 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
- Functionsbeta-catenin binding / cis-trans isomerase activity / cytoskeletal motor activity / phosphoprotein binding / phosphoserine residue binding / phosphothreonine residue binding / tau protein binding / ubiquitin ligase activator activityProcessesnegative regulation of amyloid-beta formation / negative regulation of protein binding / negative regulation of protein catabolic process / negative regulation of SMAD protein signal transduction / neuron differentiation / positive regulation of canonical Wnt signaling pathway / positive regulation of protein binding / positive regulation of transcription by RNA polymerase II / protein stabilization / regulation of gene expression / regulation of protein localization to nucleus / regulation of protein phosphorylation / regulation of protein stability / response to hypoxia / synapse organizationComponentsciliary basal body / cytoplasm / glutamatergic synapse / postsynaptic cytosol
- General 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)
- Specific Function
- Beta-catenin binding
- Pfam Domain Function
- Signal Regions
- Not Available
- 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
- 19p13.2
- External Identifiers
Resource Link UniProtKB ID Q13526 UniProtKB Entry Name PIN1_HUMAN GenBank Protein ID 1332710 GenBank Gene ID U49070 GeneCard ID PIN1 HGNC ID HGNC:8988 PDB ID(s) 1F8A, 1I6C, 1I8G, 1I8H, 1NMV, 1NMW, 1PIN, 1ZCN, 2F21, 2ITK, 2KBU, 2KCF, 2LB3, 2M8I, 2M8J, 2M9E, 2M9F, 2M9I, 2M9J, 2N1O, 2Q5A, 2RUC, 2RUD, 2RUQ, 2RUR, 2XP3, 2XP4, 2XP5, 2XP6, 2XP7, 2XP8, 2XP9, 2XPA, 2XPB, 2ZQS, 2ZQT, 2ZQU, 2ZQV, 2ZR4, 2ZR5, 2ZR6, 3I6C, 3IK8, 3IKD, 3IKG, 3JYJ, 3KAB, 3KAC, 3KAD, 3KAF, 3KAG, 3KAH, 3KAI, 3KCE, 3NTP, 3ODK, 3OOB, 3TC5, 3TCZ, 3TDB, 3WH0, 4GWT, 4GWV, 4QIB, 4TNS, 4TYO, 4U84, 4U85, 4U86, 5B3W, 5B3X, 5B3Y, 5B3Z, 5BMY, 5GPH, 5UY9, 5VTI, 5VTJ, 5VTK, 6DUN, 6O33, 6O34, 6SVC, 6SVE, 6SVH, 6VAJ, 7AOG, 7AXN, 7AYF, 7AZ1, 7AZ2, 7BDP, 7BDT, 7BDY, 7BFW, 7BG3, 7BGQ, 7BGR, 7BGV, 7BGW, 7EFJ, 7EFX, 7EKV, 7F0M, 7NIF, 7NIG, 7NJ6, 7NJ8, 7NJA, 7NRK, 7NRL, 7OQ9, 7OQA, 7SA5, 7SUQ, 7SUR, 8C2G, 8C3C KEGG ID hsa:5300 IUPHAR/Guide To Pharmacology ID 3171 NCBI Gene ID 5300 - General References
- 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]
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details 3,6,9,12,15,18-HEXAOXAICOSANE experimental yes target inhibitor Details Beta-(2-Naphthyl)-Alanine experimental yes target inhibitor Details