PIM3_HUMAN
ID PIM3_HUMAN Reviewed; 326 AA.
AC Q86V86; A5D8X8; A8K7J0; B1B0P0; Q68BM2;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Serine/threonine-protein kinase pim-3;
DE EC=2.7.11.1;
GN Name=PIM3;
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 [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=15540201; DOI=10.1002/ijc.20719;
RA Fujii C., Nakamoto Y., Lu P., Tsuneyama K., Popivanova B.K., Kaneko S.,
RA Mukaida N.;
RT "Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular
RT carcinoma development and its role in the proliferation of human hepatoma
RT cell lines.";
RL Int. J. Cancer 114:209-218(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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 [5]
RP IDENTIFICATION FROM ESTS.
RX PubMed=12798037; DOI=10.1016/s1476-9271(02)00095-6;
RA Chichester C., Nikitin F., Ravarini J.-C., Lisacek F.;
RT "Consistency checks for characterizing protein forms.";
RL Comput. Biol. Chem. 27:29-35(2003).
RN [6]
RP INTERACTION WITH PPP2CA, 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 [7]
RP FUNCTION IN PHOSPHORYLATION OF BAD, AND TISSUE SPECIFICITY.
RX PubMed=16818649; DOI=10.1158/0008-5472.can-05-4272;
RA Li Y.Y., Popivanova B.K., Nagai Y., Ishikura H., Fujii C., Mukaida N.;
RT "Pim-3, a proto-oncogene with serine/threonine kinase activity, is
RT aberrantly expressed in human pancreatic cancer and phosphorylates bad to
RT block bad-mediated apoptosis in human pancreatic cancer cell lines.";
RL Cancer Res. 66:6741-6747(2006).
RN [8]
RP FUNCTION, INTERACTION WITH BAD, AND TISSUE SPECIFICITY.
RX PubMed=17270021; DOI=10.1111/j.1349-7006.2007.00390.x;
RA Popivanova B.K., Li Y.Y., Zheng H., Omura K., Fujii C., Tsuneyama K.,
RA Mukaida N.;
RT "Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly
RT expressed in human colon cancer cells and can prevent Bad-mediated
RT apoptosis.";
RL Cancer Sci. 98:321-328(2007).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF CDKN1B.
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 [10]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=17876606; DOI=10.1007/s00432-007-0310-1;
RA Zheng H.C., Tsuneyama K., Takahashi H., Miwa S., Sugiyama T.,
RA Popivanova B.K., Fujii C., Nomoto K., Mukaida N., Takano Y.;
RT "Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma
RT sequence and cancer progression.";
RL J. Cancer Res. Clin. Oncol. 134:481-488(2008).
CC -!- FUNCTION: Proto-oncogene with serine/threonine kinase activity that can
CC prevent apoptosis, promote cell survival and protein translation. May
CC contribute to tumorigenesis through: the delivery of survival signaling
CC through phosphorylation of BAD which induces release of the anti-
CC apoptotic protein Bcl-X(L), the regulation of cell cycle progression,
CC protein synthesis and by regulation of MYC transcriptional activity.
CC Additionally to this role on tumorigenesis, can also negatively
CC regulate insulin secretion by inhibiting the activation of MAPK1/3
CC (ERK1/2), through SOCS6. Involved also in the control of energy
CC metabolism and regulation of AMPK activity in modulating MYC and
CC PPARGC1A protein levels and cell growth. {ECO:0000269|PubMed:15540201,
CC ECO:0000269|PubMed:16818649, ECO:0000269|PubMed:17270021,
CC ECO:0000269|PubMed:17876606, ECO:0000269|PubMed:18593906}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Interacts with BAD. Interacts with PPP2CA; this interaction
CC promotes dephosphorylation of PIM3, ubiquitination and proteasomal
CC degradation. Interacts with SOCS6 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17876606}.
CC -!- TISSUE SPECIFICITY: Detected in various tissues, including the heart,
CC brain, lung, kidney, spleen, placenta, skeletal muscle, and peripheral
CC blood leukocytes. Not found or barely expressed in the normal adult
CC endoderm-derived organs such as colon, thymus, liver, or small
CC intestine. However, expression is augmented in premalignant and
CC malignant lesions of these organs. {ECO:0000269|PubMed:15540201,
CC ECO:0000269|PubMed:16818649, ECO:0000269|PubMed:17270021}.
CC -!- PTM: Ubiquitinated, leading to proteasomal degradation.
CC {ECO:0000269|PubMed:12473674}.
CC -!- PTM: Phosphorylated. Interaction with PPP2CA promotes
CC dephosphorylation. {ECO:0000269|PubMed:12473674}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. PIM subfamily. {ECO:0000305}.
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DR EMBL; AB114795; BAD42438.1; -; mRNA.
DR EMBL; AK292005; BAF84694.1; -; mRNA.
DR EMBL; CR536608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX539320; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC052239; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC141855; AAI41856.1; -; mRNA.
DR CCDS; CCDS33678.1; -.
DR RefSeq; NP_001001852.2; NM_001001852.3.
DR AlphaFoldDB; Q86V86; -.
DR SMR; Q86V86; -.
DR BioGRID; 136104; 3.
DR IntAct; Q86V86; 57.
DR MINT; Q86V86; -.
DR STRING; 9606.ENSP00000353824; -.
DR BindingDB; Q86V86; -.
DR ChEMBL; CHEMBL5407; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q86V86; -.
DR GuidetoPHARMACOLOGY; 2160; -.
DR GlyGen; Q86V86; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86V86; -.
DR PhosphoSitePlus; Q86V86; -.
DR BioMuta; PIM3; -.
DR DMDM; 215274221; -.
DR MassIVE; Q86V86; -.
DR MaxQB; Q86V86; -.
DR PaxDb; Q86V86; -.
DR PeptideAtlas; Q86V86; -.
DR PRIDE; Q86V86; -.
DR ProteomicsDB; 69976; -.
DR Antibodypedia; 28269; 163 antibodies from 24 providers.
DR DNASU; 415116; -.
DR Ensembl; ENST00000360612.5; ENSP00000353824.4; ENSG00000198355.5.
DR GeneID; 415116; -.
DR KEGG; hsa:415116; -.
DR MANE-Select; ENST00000360612.5; ENSP00000353824.4; NM_001001852.4; NP_001001852.2.
DR UCSC; uc003bjb.4; human.
DR CTD; 415116; -.
DR DisGeNET; 415116; -.
DR GeneCards; PIM3; -.
DR HGNC; HGNC:19310; PIM3.
DR HPA; ENSG00000198355; Low tissue specificity.
DR MIM; 610580; gene.
DR neXtProt; NX_Q86V86; -.
DR OpenTargets; ENSG00000198355; -.
DR PharmGKB; PA134980758; -.
DR VEuPathDB; HostDB:ENSG00000198355; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000153394; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q86V86; -.
DR OMA; WGTINGT; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q86V86; -.
DR TreeFam; TF320810; -.
DR PathwayCommons; Q86V86; -.
DR SignaLink; Q86V86; -.
DR SIGNOR; Q86V86; -.
DR BioGRID-ORCS; 415116; 31 hits in 1112 CRISPR screens.
DR ChiTaRS; PIM3; human.
DR GenomeRNAi; 415116; -.
DR Pharos; Q86V86; Tchem.
DR PRO; PR:Q86V86; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q86V86; protein.
DR Bgee; ENSG00000198355; Expressed in olfactory segment of nasal mucosa and 93 other tissues.
DR Genevisible; Q86V86; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017348; PIM1/2/3.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF037993; STPK_Pim-1; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Apoptosis; ATP-binding; Cell cycle; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..326
FT /note="Serine/threonine-protein kinase pim-3"
FT /id="PRO_0000086533"
FT DOMAIN 40..293
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 170
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 46..54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CONFLICT 37
FT /note="E -> K (in Ref. 4; AAI41856)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="V -> A (in Ref. 1; BAD42438, 2; BAF84694 and 4;
FT AAI41856)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 326 AA; 35891 MW; 41FDEFAC4367A162 CRC64;
MLLSKFGSLA HLCGPGGVDH LPVKILQPAK ADKESFEKAY QVGAVLGSGG FGTVYAGSRI
ADGLPVAVKH VVKERVTEWG SLGGATVPLE VVLLRKVGAA GGARGVIRLL DWFERPDGFL
LVLERPEPAQ DLFDFITERG ALDEPLARRF FAQVLAAVRH CHSCGVVHRD IKDENLLVDL
RSGELKLIDF GSGALLKDTV YTDFDGTRVY SPPEWIRYHR YHGRSATVWS LGVLLYDMVC
GDIPFEQDEE ILRGRLLFRR RVSPECQQLI RWCLSLRPSE RPSLDQIAAH PWMLGADGGV
PESCDLRLCT LDPDDVASTT SSSESL
