ID   PIM1_HUMAN              Reviewed;         404 AA.
AC   P11309-2;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2018, sequence version 4.
DT   27-MAR-2024, entry version 255.
DE   RecName: Full=Isoform 2 of Serine/threonine-protein kinase pim-1;
DE            EC=2.7.11.1 {ECO:0000269|PubMed:15525646, ECO:0000269|PubMed:15657054, ECO:0000269|PubMed:15808862, ECO:0000269|PubMed:31548394};
GN   Name=PIM1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX   PubMed=2205533; DOI=10.1016/0378-1119(90)90195-w;
RA   Reeves R., Spies G.A., Kiefer M., Barr P.J., Power M.;
RT   "Primary structure of the putative human oncogene, pim-1.";
RL   Gene 90:303-307(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=3475233; DOI=10.1016/0378-1119(87)90352-0;
RA   Zakut-Houri R., Hazum S., Givol D., Telerman A.;
RT   "The cDNA sequence and gene analysis of the human pim oncogene.";
RL   Gene 54:105-111(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=3329709;
RA   Domen J., von Lindern M., Hermans A., Breuer M., Grosveld G., Berns A.;
RT   "Comparison of the human and mouse PIM-1 cDNAs: nucleotide sequence and
RT   immunological identification of the in vitro synthesized PIM-1 protein.";
RL   Oncogene Res. 1:103-112(1987).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=3429489; DOI=10.1002/jcb.240350204;
RA   Meeker T.C., Nagarajan L., Ar-Rushdi A., Croce C.M.;
RT   "Cloning and characterization of the human PIM-1 gene: a putative oncogene
RT   related to the protein kinases.";
RL   J. Cell. Biochem. 35:105-112(1987).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE INITIATION, TISSUE
RP   SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH BMX.
RX   PubMed=16186805; DOI=10.1038/sj.onc.1209058;
RA   Xie Y., Xu K., Dai B., Guo Z., Jiang T., Chen H., Qiu Y.;
RT   "The 44 kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX
RT   and protects human prostate cancer cells from apoptosis induced by
RT   chemotherapeutic drugs.";
RL   Oncogene 25:70-78(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-202 (ISOFORM 1).
RX   PubMed=11460166; DOI=10.1038/35085588;
RA   Pasqualucci L., Neumeister P., Goossens T., Nanjangud G., Chaganti R.S.K.,
RA   Kuppers R., Dalla-Favera R.;
RT   "Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell
RT   lymphomas.";
RL   Nature 412:341-346(2001).
RN   [10]
RP   CHARACTERIZATION.
RX   PubMed=2837645; DOI=10.1128/mcb.8.4.1498-1503.1988;
RA   Telerman A., Amson R., Zakut-Houri R., Givol D.;
RT   "Identification of the human pim-1 gene product as a 33-kilodalton
RT   cytoplasmic protein with tyrosine kinase activity.";
RL   Mol. Cell. Biol. 8:1498-1503(1988).
RN   [11]
RP   FUNCTION, AND ALTERNATIVE INITIATION.
RX   PubMed=1825810; DOI=10.1002/j.1460-2075.1991.tb07994.x;
RA   Saris C.J., Domen J., Berns A.;
RT   "The pim-1 oncogene encodes two related protein-serine/threonine kinases by
RT   alternative initiation at AUG and CUG.";
RL   EMBO J. 10:655-664(1991).
RN   [12]
RP   FUNCTION IN PHOSPHORYLATION OF CBX3.
RX   PubMed=10664448; DOI=10.1016/s0014-5793(00)01105-4;
RA   Koike N., Maita H., Taira T., Ariga H., Iguchi-Ariga S.M.M.;
RT   "Identification of heterochromatin protein 1 (HP1) as a phosphorylation
RT   target by Pim-1 kinase and the effect of phosphorylation on the
RT   transcriptional repression function of HP1.";
RL   FEBS Lett. 467:17-21(2000).
RN   [13]
RP   SUBCELLULAR LOCATION, AND FUNCTION IN PHOSPHORYLATION OF CDKN1A.
RX   PubMed=12431783; DOI=10.1016/s0167-4889(02)00347-6;
RA   Wang Z., Bhattacharya N., Mixter P.F., Wei W., Sedivy J., Magnuson N.S.;
RT   "Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1
RT   kinase.";
RL   Biochim. Biophys. Acta 1593:45-55(2002).
RN   [14]
RP   SUBCELLULAR LOCATION.
RX   PubMed=12680209;
RA   Ionov Y., Le X., Tunquist B.J., Sweetenham J., Sachs T., Ryder J.,
RA   Johnson T., Lilly M.B., Kraft A.S.;
RT   "Pim-1 protein kinase is nuclear in Burkitt's lymphoma: nuclear
RT   localization is necessary for its biologic effects.";
RL   Anticancer Res. 23:167-178(2003).
RN   [15]
RP   PHOSPHORYLATION, AND UBIQUITINATION.
RX   PubMed=12473674; DOI=10.1074/jbc.m208246200;
RA   Losman J.A., Chen X.P., Vuong B.Q., Fay S., Rothman P.B.;
RT   "Protein phosphatase 2A regulates the stability of Pim protein kinases.";
RL   J. Biol. Chem. 278:4800-4805(2003).
RN   [16]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=15528381; DOI=10.4049/jimmunol.173.10.6409;
RA   Stout B.A., Bates M.E., Liu L.Y., Farrington N.N., Bertics P.J.;
RT   "IL-5 and granulocyte-macrophage colony-stimulating factor activate STAT3
RT   and STAT5 and promote Pim-1 and cyclin D3 protein expression in human
RT   eosinophils.";
RL   J. Immunol. 173:6409-6417(2004).
RN   [17]
RP   UBIQUITINATION, INTERACTION WITH HSP90AA1 AND HSP70, AND INDUCTION.
RX   PubMed=15798097; DOI=10.1158/1541-7786.mcr-04-0192;
RA   Shay K.P., Wang Z., Xing P.X., McKenzie I.F., Magnuson N.S.;
RT   "Pim-1 kinase stability is regulated by heat shock proteins and the
RT   ubiquitin-proteasome pathway.";
RL   Mol. Cancer Res. 3:170-181(2005).
RN   [18]
RP   FUNCTION IN PHOSPHORYLATION OF CDC25C, AND INTERACTION WITH CDC25C.
RX   PubMed=16356754; DOI=10.1016/j.biocel.2005.10.010;
RA   Bachmann M., Kosan C., Xing P.X., Montenarh M., Hoffmann I., Moroy T.;
RT   "The oncogenic serine/threonine kinase Pim-1 directly phosphorylates and
RT   activates the G2/M specific phosphatase Cdc25C.";
RL   Int. J. Biochem. Cell Biol. 38:430-443(2006).
RN   [19]
RP   FUNCTION IN CELL CYCLE PROGRESSION, AND PHOSPHORYLATION OF CDKN1B AND
RP   FOXO3.
RX   PubMed=18593906; DOI=10.1158/0008-5472.can-08-0634;
RA   Morishita D., Katayama R., Sekimizu K., Tsuruo T., Fujita N.;
RT   "Pim kinases promote cell cycle progression by phosphorylating and down-
RT   regulating p27Kip1 at the transcriptional and posttranscriptional levels.";
RL   Cancer Res. 68:5076-5085(2008).
RN   [20]
RP   FUNCTION.
RX   PubMed=18056989; DOI=10.1074/jbc.m707773200;
RA   Xie Y., Xu K., Linn D.E., Yang X., Guo Z., Shimelis H., Nakanishi T.,
RA   Ross D.D., Chen H., Fazli L., Gleave M.E., Qiu Y.;
RT   "The 44-kDa Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its
RT   multimerization and drug-resistant activity in human prostate cancer
RT   cells.";
RL   J. Biol. Chem. 283:3349-3356(2008).
RN   [21]
RP   FUNCTION IN PHOSPHORYLATION OF MAP3K5.
RX   PubMed=19749799; DOI=10.1038/onc.2009.276;
RA   Gu J.J., Wang Z., Reeves R., Magnuson N.S.;
RT   "PIM1 phosphorylates and negatively regulates ASK1-mediated apoptosis.";
RL   Oncogene 28:4261-4271(2009).
RN   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [23]
RP   INTERACTION WITH EPSTEIN-BARR VIRUS EBNA6 (MICROBIAL INFECTION).
RX   PubMed=25121590; DOI=10.1371/journal.ppat.1004304;
RA   Banerjee S., Lu J., Cai Q., Sun Z., Jha H.C., Robertson E.S.;
RT   "EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to
RT   promote B-cell proliferation.";
RL   PLoS Pathog. 10:E1004304-E1004304(2014).
RN   [24]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=31548394; DOI=10.1073/pnas.1904774116;
RA   Padi S.K.R., Singh N., Bearss J.J., Olive V., Song J.H., Cardo-Vila M.,
RA   Kraft A.S., Okumura K.;
RT   "Phosphorylation of DEPDC5, a component of the GATOR1 complex, releases
RT   inhibition of mTORC1 and promotes tumor growth.";
RL   Proc. Natl. Acad. Sci. U.S.A. 116:20505-20510(2019).
RN   [25]
RP   FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND MUTAGENESIS OF PRO-81.
RX   PubMed=37797010; DOI=10.1126/science.adg2253;
RA   Fisch D., Pfleiderer M.M., Anastasakou E., Mackie G.M., Wendt F., Liu X.,
RA   Clough B., Lara-Reyna S., Encheva V., Snijders A.P., Bando H., Yamamoto M.,
RA   Beggs A.D., Mercer J., Shenoy A.R., Wollscheid B., Maslowski K.M.,
RA   Galej W.P., Frickel E.M.;
RT   "PIM1 controls GBP1 activity to limit self-damage and to guard against
RT   pathogen infection.";
RL   Science 382:eadg2253-eadg2253(2023).
RN   [26]
RP   X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 33-305 IN COMPLEXES WITH
RP   ADENOSINE AND INHIBITORS STAUROSPORINE AND LY294002, CATALYTIC ACTIVITY,
RP   COFACTOR, ACTIVITY REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP   PHOSPHORYLATION AT SER-8; THR-23; SER-98 AND SER-261.
RX   PubMed=15657054; DOI=10.1074/jbc.m413155200;
RA   Jacobs M.D., Black J., Futer O., Swenson L., Hare B., Fleming M.,
RA   Saxena K.;
RT   "Pim-1 ligand-bound structures reveal the mechanism of serine/threonine
RT   kinase inhibition by LY294002.";
RL   J. Biol. Chem. 280:13728-13734(2005).
RN   [27]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 14-313 OF APOPROTEIN AND IN
RP   COMPLEX WITH AMP-PNP, CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY
RP   REGULATION.
RX   PubMed=15525646; DOI=10.1074/jbc.m409123200;
RA   Qian K.C., Wang L., Hickey E.R., Studts J., Barringer K., Peng C.,
RA   Kronkaitis A., Li J., White A., Mische S., Farmer B.;
RT   "Structural basis of constitutive activity and a unique nucleotide binding
RT   mode of human Pim-1 kinase.";
RL   J. Biol. Chem. 280:6130-6137(2005).
RN   [28]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 29-313 OF APOPROTEIN AND IN
RP   COMPLEXES WITH AMP-PNP AND INHIBITORS, PARTIAL PROTEIN SEQUENCE, CATALYTIC
RP   ACTIVITY, ACTIVITY REGULATION, COFACTOR, AND MUTAGENESIS OF HIS-68; PRO-81;
RP   ASN-82 AND LEU-193.
RX   PubMed=15808862; DOI=10.1016/j.jmb.2005.02.039;
RA   Kumar A., Mandiyan V., Suzuki Y., Zhang C., Rice J., Tsai J., Artis D.R.,
RA   Ibrahim P., Bremer R.;
RT   "Crystal structures of proto-oncogene kinase Pim1: a target of aberrant
RT   somatic hypermutations in diffuse large cell lymphoma.";
RL   J. Mol. Biol. 348:183-193(2005).
RN   [29]
RP   VARIANTS [LARGE SCALE ANALYSIS] HIS-53; GLN-124; LYS-135 AND ASP-142.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- SUBUNIT: Isoform 2, but not isoform 1, binds BMX.
CC       {ECO:0000269|PubMed:16186805}.
CC   -!- INTERACTION:
CC       P11309-2; Q9UNQ0: ABCG2; NbExp=5; IntAct=EBI-1018633, EBI-1569435;
CC       P11309-2; P51813: BMX; NbExp=6; IntAct=EBI-1018633, EBI-696657;
CC       P11309-2; P17252: PRKCA; NbExp=2; IntAct=EBI-1018633, EBI-1383528;
CC   -!- SUBCELLULAR LOCATION: Cell membrane.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=1; Synonyms=Pim-1 {ECO:0000303|PubMed:18056989};
CC         IsoId=P11309-1; Sequence=Displayed;
CC       Name=2; Synonyms=Pim-1L {ECO:0000303|PubMed:18056989};
CC         IsoId=P11309-2; Sequence=VSP_059829;
CC   -!- MISCELLANEOUS: Initiates from CTG codon. {ECO:0000269|PubMed:16186805,
CC       ECO:0000269|PubMed:1825810}.
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DR   RefSeq; NP_001230115.1; NM_001243186.1.
DR   ProteomicsDB; 52742; -.
DR   Proteomes; UP000005640; Chromosome 6.
PE   1: Evidence at protein level;
SQ   SEQUENCE   404 AA;  45412 MW;  18C421B7CFF87818 CRC64;
     MPHEPHEPLT PPFSALPDPA GAPSRRQSRQ RPQLSSDSPS AFRASRSHSR NATRSHSHSH
     SPRHSLRHSP GSGSCGSSSG HRPCADILEV GMLLSKINSL AHLRAAPCND LHATKLAPGK
     EKEPLESQYQ VGPLLGSGGF GSVYSGIRVS DNLPVAIKHV EKDRISDWGE LPNGTRVPME
     VVLLKKVSSG FSGVIRLLDW FERPDSFVLI LERPEPVQDL FDFITERGAL QEELARSFFW
     QVLEAVRHCH NCGVLHRDIK DENILIDLNR GELKLIDFGS GALLKDTVYT DFDGTRVYSP
     PEWIRYHRYH GRSAAVWSLG ILLYDMVCGD IPFEHDEEII RGQVFFRQRV SSECQHLIRW
     CLALRPSDRP TFEEIQNHPW MQDVLLPQET AEIHLHSLSP GPSK
//