NameSerine/threonine-protein kinase pim-1
Synonyms
  • 2.7.11.1
Gene NamePIM1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002541|Serine/threonine-protein kinase pim-1
MPHEPHEPLTPPFSALPDPAGAPSRRQSRQRPQLSSDSPSAFRASRSHSRNATRSHSHSH
SPRHSLRHSPGSGSCGSSSGHRPCADILEVGMLLSKINSLAHLRAAPCNDLHATKLAPGK
EKEPLESQYQVGPLLGSGGFGSVYSGIRVSDNLPVAIKHVEKDRISDWGELPNGTRVPME
VVLLKKVSSGFSGVIRLLDWFERPDSFVLILERPEPVQDLFDFITERGALQEELARSFFW
QVLEAVRHCHNCGVLHRDIKDENILIDLNRGELKLIDFGSGALLKDTVYTDFDGTRVYSP
PEWIRYHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIRW
CLALRPSDRPTFEEIQNHPWMQDVLLPQETAEIHLHSLSPGPSK
Number of residues404
Molecular Weight45411.905
Theoretical pI7.01
GO Classification
Functions
  • ribosomal small subunit binding
  • ATP binding
  • protein serine/threonine kinase activity
  • transcription factor binding
  • manganese ion binding
Processes
  • hyaluronan metabolic process
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
  • regulation of mitotic cell cycle
  • cell cycle
  • cell proliferation
  • apoptotic process
  • negative regulation of apoptotic process
  • protein phosphorylation
  • multicellular organismal development
  • protein autophosphorylation
  • negative regulation of sequence-specific DNA binding transcription factor activity
  • vitamin D receptor signaling pathway
Components
  • cytoplasm
  • nucleus
  • plasma membrane
General FunctionTranscription factor binding
Specific FunctionProto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID387022
UniProtKB IDP11309
UniProtKB Entry NamePIM1_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0010889|Serine/threonine-protein kinase pim-1 (PIM1)
CTGCCGCACGAGCCCCACGAGCCGCTCACCCCGCCGTTCTCAGCGCTGCCCGACCCCGCT
GGCGCGCCCTCCCGCCGCCAGTCCCGGCAGCGCCCTCAGTTGTCCTCCGACTCGCCCTCG
GCCTTCCGCGCCAGCCGCAGCCACAGCCGCAACGCCACCCGCAGCCACAGCCACAGCCAC
AGCCCCAGGCATAGCCTTCGGCACAGCCCCGGCTCCGGCTCCTGCGGCAGCTCCTCTGGG
CACCGTCCCTGCGCCGACATCCTGGAGGTTGGGATGCTCTTGTCCAAAATCAACTCGCTT
GCCCACCTGCGCGCCGCGCCCTGCAACGACCTGCACGCCACCAAGCTGGCGCCCGGCAAG
GAGAAGGAGCCCCTGGAGTCGCAGTACCAGGTGGGCCCGCTACTGGGCAGCGGCGGCTTC
GGCTCGGTCTACTCAGGCATCCGCGTCTCCGACAACTTGCCGGTGGCCATCAAACACGTG
GAGAAGGACCGGATTTCCGACTGGGGAGAGCTGCCTAATGGCACTCGAGTGCCCATGGAA
GTGGTCCTGCTGAAGAAGGTGAGCTCGGGTTTCTCCGGCGTCATTAGGCTCCTGGACTGG
TTCGAGAGGCCCGACAGTTTCGTCCTGATCCTGGAGAGGCCCGAGCCGGTGCAAGATCTC
TTCGACTTCATCACGGAAAGGGGAGCCCTGCAAGAGGAGCTGGCCCGCAGCTTCTTCTGG
CAGGTGCTGGAGGCCGTGCGGCACTGCCACAACTGCGGGGTGCTCCACCGCGACATCAAG
GACGAAAACATCCTTATCGACCTCAATCGCGGCGAGCTCAAGCTCATCGACTTCGGGTCG
GGGGCGCTGCTCAAGGACACCGTCTACACGGACTTCGATGGGACCCGAGTGTATAGCCCT
CCAGAGTGGATCCGCTACCATCGCTACCATGGCAGGTCGGCGGCAGTCTGGTCCCTGGGG
ATCCTGCTGTATGATATGGTGTGTGGAGATATTCCTTTCGAGCATGACGAAGAGATCATC
AGGGGCCAGGTTTTCTTCAGGCAGAGGGTCTCTTCAGAATGTCAGCATCTCATTAGATGG
TGCTTGGCCCTGAGACCATCAGATAGGCCAACCTTCGAAGAAATCCAGAACCATCCATGG
ATGCAAGATGTTCTCCTGCCCCAGGAAACTGCTGAGATCCACCTCCACAGCCTGTCGCCG
GGGCCCAGCAAATAG
GenBank Gene IDM27903
GeneCard IDNot Available
GenAtlas IDPIM1
HGNC IDHGNC:8986
Chromosome Location6
Locus6p21.2
References
  1. Reeves R, Spies GA, Kiefer M, Barr PJ, Power M: Primary structure of the putative human oncogene, pim-1. Gene. 1990 Jun 15;90(2):303-7. 2205533
  2. Zakut-Houri R, Hazum S, Givol D, Telerman A: The cDNA sequence and gene analysis of the human pim oncogene. Gene. 1987;54(1):105-11. 3475233
  3. Domen J, Von Lindern M, Hermans A, Breuer M, Grosveld G, Berns A: Comparison of the human and mouse PIM-1 cDNAs: nucleotide sequence and immunological identification of the in vitro synthesized PIM-1 protein. Oncogene Res. 1987 Jun;1(1):103-12. 3329709
  4. Meeker TC, Nagarajan L, ar-Rushdi A, Croce CM: Cloning and characterization of the human PIM-1 gene: a putative oncogene related to the protein kinases. J Cell Biochem. 1987 Oct;35(2):105-12. 3429489
  5. Xie Y, Xu K, Dai B, Guo Z, Jiang T, Chen H, Qiu Y: The 44 kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs. Oncogene. 2006 Jan 5;25(1):70-8. 16186805
  6. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. 14574404
  7. 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. 15489334
  8. Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Kuppers R, Dalla-Favera R: Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature. 2001 Jul 19;412(6844):341-6. 11460166
  9. Telerman A, Amson R, Zakut-Houri R, Givol D: Identification of the human pim-1 gene product as a 33-kilodalton cytoplasmic protein with tyrosine kinase activity. Mol Cell Biol. 1988 Apr;8(4):1498-503. 2837645
  10. Saris CJ, Domen J, Berns A: The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG. EMBO J. 1991 Mar;10(3):655-64. 1825810
  11. Koike N, Maita H, Taira T, Ariga H, Iguchi-Ariga SM: Identification of heterochromatin protein 1 (HP1) as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional repression function of HP1(1). FEBS Lett. 2000 Feb 4;467(1):17-21. 10664448
  12. Wang Z, Bhattacharya N, Mixter PF, Wei W, Sedivy J, Magnuson NS: Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase. Biochim Biophys Acta. 2002 Dec 16;1593(1):45-55. 12431783
  13. Ionov Y, Le X, Tunquist BJ, Sweetenham J, Sachs T, Ryder J, Johnson T, Lilly MB, Kraft AS: Pim-1 protein kinase is nuclear in Burkitt's lymphoma: nuclear localization is necessary for its biologic effects. Anticancer Res. 2003 Jan-Feb;23(1A):167-78. 12680209
  14. Losman JA, Chen XP, Vuong BQ, Fay S, Rothman PB: Protein phosphatase 2A regulates the stability of Pim protein kinases. J Biol Chem. 2003 Feb 14;278(7):4800-5. Epub 2002 Dec 6. 12473674
  15. Stout BA, Bates ME, Liu LY, Farrington NN, Bertics PJ: IL-5 and granulocyte-macrophage colony-stimulating factor activate STAT3 and STAT5 and promote Pim-1 and cyclin D3 protein expression in human eosinophils. J Immunol. 2004 Nov 15;173(10):6409-17. 15528381
  16. Shay KP, Wang Z, Xing PX, McKenzie IF, Magnuson NS: Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway. Mol Cancer Res. 2005 Mar;3(3):170-81. 15798097
  17. Bachmann M, Kosan C, Xing PX, Montenarh M, Hoffmann I, Moroy T: The oncogenic serine/threonine kinase Pim-1 directly phosphorylates and activates the G2/M specific phosphatase Cdc25C. Int J Biochem Cell Biol. 2006 Mar;38(3):430-43. Epub 2005 Nov 8. 16356754
  18. Morishita D, Katayama R, Sekimizu K, Tsuruo T, Fujita N: Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. Cancer Res. 2008 Jul 1;68(13):5076-85. doi: 10.1158/0008-5472.CAN-08-0634. 18593906
  19. Gu JJ, Wang Z, Reeves R, Magnuson NS: PIM1 phosphorylates and negatively regulates ASK1-mediated apoptosis. Oncogene. 2009 Dec 3;28(48):4261-71. doi: 10.1038/onc.2009.276. Epub 2009 Sep 14. 19749799
  20. Jacobs MD, Black J, Futer O, Swenson L, Hare B, Fleming M, Saxena K: Pim-1 ligand-bound structures reveal the mechanism of serine/threonine kinase inhibition by LY294002. J Biol Chem. 2005 Apr 8;280(14):13728-34. Epub 2005 Jan 17. 15657054
  21. Qian KC, Wang L, Hickey ER, Studts J, Barringer K, Peng C, Kronkaitis A, Li J, White A, Mische S, Farmer B: Structural basis of constitutive activity and a unique nucleotide binding mode of human Pim-1 kinase. J Biol Chem. 2005 Feb 18;280(7):6130-7. Epub 2004 Nov 3. 15525646
  22. Kumar A, Mandiyan V, Suzuki Y, Zhang C, Rice J, Tsai J, Artis DR, Ibrahim P, Bremer R: Crystal structures of proto-oncogene kinase Pim1: a target of aberrant somatic hypermutations in diffuse large cell lymphoma. J Mol Biol. 2005 Apr 22;348(1):183-93. 15808862
  23. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846