Serine/threonine-protein kinase pim-1

Details

Name
Serine/threonine-protein kinase pim-1
Synonyms
  • 2.7.11.1
Gene Name
PIM1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002541|Serine/threonine-protein kinase pim-1 MPHEPHEPLTPPFSALPDPAGAPSRRQSRQRPQLSSDSPSAFRASRSHSRNATRSHSHSH SPRHSLRHSPGSGSCGSSSGHRPCADILEVGMLLSKINSLAHLRAAPCNDLHATKLAPGK EKEPLESQYQVGPLLGSGGFGSVYSGIRVSDNLPVAIKHVEKDRISDWGELPNGTRVPME VVLLKKVSSGFSGVIRLLDWFERPDSFVLILERPEPVQDLFDFITERGALQEELARSFFW QVLEAVRHCHNCGVLHRDIKDENILIDLNRGELKLIDFGSGALLKDTVYTDFDGTRVYSP PEWIRYHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIRW CLALRPSDRPTFEEIQNHPWMQDVLLPQETAEIHLHSLSPGPSK
Number of residues
404
分子量
45411.905
Theoretical pI
7.01
GO Classification
Functions
ATP binding/manganese ion binding/protein serine/threonine kinase activity/ribosomal small subunit binding/transcription factor binding
Processes
apoptotic process/cell cycle/cell proliferation/hyaluronan metabolic process/multicellular organismal development/negative regulation of apoptotic process/negative regulation of sequence-specific DNA binding transcription factor activity/positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle/protein autophosphorylation/protein phosphorylation/regulation of mitotic cell cycle/vitamin D receptor signaling pathway
Components
cytoplasm/nucleus/plasma membrane
General Function
Transcription factor binding
Specific Function
原癌基因与丝氨酸/苏氨酸激酶活动ty 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 Regions
Not Available
Cellular Location
Cytoplasm
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
Chromosome Location
6
Locus
6p21.2
External Identifiers
Resource Link
UniProtKB ID P11309
UniProtKB Entry Name PIM1_HUMAN
GenBank Protein ID 387022
GenBank Gene ID M27903
GenAtlas ID PIM1
HGNC ID HGNC:8986
General References
  1. Reeves R,间谍GA,基弗米,巴尔PJ,电力M:公关imary structure of the putative human oncogene, pim-1. Gene. 1990 Jun 15;90(2):303-7. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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  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. [Article]
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  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. [Article]
  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. [Article]
  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. [Article]
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Drug Relations

Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details
DB01754 3,4-Dihydroxy-1-Methylquinolin-2(1h)-One experimental unknown Details
DB02010 Staurosporine experimental unknown Details
DB02656 LY-294002 experimental unknown Details
DB03366 Imidazole experimental, investigational unknown Details
DB03650 (3e)-3-[(4-Hydroxyphenyl)Imino]-1h-Indol-2(3h)-One experimental unknown Details
DB03777 Bisindolylmaleimide I experimental unknown Details
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester experimental unknown Details
DB04522 Dexfosfoserine experimental unknown Details
DB04530 S,S-(2-Hydroxyethyl)Thiocysteine experimental unknown Details
DB04715 IMIDAZOPYRIDAZIN 1 experimental unknown Details
DB07151 4-(4-hydroxy-3-methylphenyl)-6-phenylpyrimidin-2(5H)-one experimental unknown Details
DB07524 N-phenyl-1H-pyrrolo[2,3-b]pyridin-3-amine experimental unknown Details
DB08022 (2S)-1,3-benzothiazol-2-yl{2-[(2-pyridin-3-ylethyl)amino]pyrimidin-4-yl}ethanenitrile experimental unknown Details
DB07242 (4R)-7,8-dichloro-1',9-dimethyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrile experimental unknown Details
DB08166 (4R)-7-chloro-9-methyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrile experimental unknown Details
DB08230 Tricetin experimental unknown Details
DB04216 Quercetin experimental, investigational unknown Details
DB08705 6-(5-BROMO-2-HYDROXYPHENYL)-2-OXO-4-PHENYL-1,2-DIHYDROPYRIDINE-3-CARBONITRILE experimental unknown Details
DB08707 4-[3-(4-chlorophenyl)-2,1-benzisoxazol-5-yl]pyrimidin-2-amine experimental unknown Details
DB08708 N-cyclohexyl-3-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[4,3-b]pyridazin-6-amine experimental unknown Details
DB08709 2,3-diphenyl-1H-indole-7-carboxylic acid experimental unknown Details
DB12010 Fostamatinib approved, investigational unknown inhibitor Details