Q86V86 (PIM3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase pim-3
EC=2.7.11.1

Gene names

Name:

PIM3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	326 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with BAD. Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM3, ubiquitination and proteasomal degradation. Interacts with SOCS6 By similarity. Ref.6 Ref.8
Subcellular location	Cytoplasm Ref.10.
Tissue specificity	Detected in various tissues, including the heart, brain, lung, kidney, spleen, placenta, skeletal muscle, and peripheral blood leukocytes. Not found or barely expressed in the normal adult endoderm-derived organs such as colon, thymus, liver, or small intestine. However, expression is augmented in premalignant and malignant lesions of these organs. Ref.1 Ref.7 Ref.8
Post-translational modification	Ubiquitinated, leading to proteasomal degradation. Ref.6 Phosphorylated. Interaction with PPP2CA promotes dephosphorylation. Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle
Cellular component	Cytoplasm
Disease	Proto-oncogene
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW histone phosphorylation Inferred from electronic annotation. Source: Ensembl negative regulation of apoptotic process Inferred from mutant phenotype Ref.8. Source: UniProtKB negative regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from electronic annotation. Source: Ensembl regulation of mitotic cell cycle Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 326	326	Serine/threonine-protein kinase pim-3		PRO_0000086533
Regions
	Domain	40 – 293	254	Protein kinase
	Nucleotide binding	46 – 54	9	ATP By similarity
Sites
	Active site	170	1	Proton acceptor By similarity
	Binding site	69	1	ATP By similarity
Experimental info
	Sequence conflict	37	1	E → K in AAI41856. Ref.4
	Sequence conflict	300	1	V → A in BAD42438. Ref.1
	Sequence conflict	300	1	V → A in BAF84694. Ref.2
	Sequence conflict	300	1	V → A in AAI41856. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q86V86 [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 41FDEFAC4367A162	FASTA	326	35,891
	10 20 30 40 50 60 MLLSKFGSLA HLCGPGGVDH LPVKILQPAK ADKESFEKAY QVGAVLGSGG FGTVYAGSRI 70 80 90 100 110 120 ADGLPVAVKH VVKERVTEWG SLGGATVPLE VVLLRKVGAA GGARGVIRLL DWFERPDGFL 130 140 150 160 170 180 LVLERPEPAQ DLFDFITERG ALDEPLARRF FAQVLAAVRH CHSCGVVHRD IKDENLLVDL 190 200 210 220 230 240 RSGELKLIDF GSGALLKDTV YTDFDGTRVY SPPEWIRYHR YHGRSATVWS LGVLLYDMVC 250 260 270 280 290 300 GDIPFEQDEE ILRGRLLFRR RVSPECQQLI RWCLSLRPSE RPSLDQIAAH PWMLGADGGV 310 320 PESCDLRLCT LDPDDVASTT SSSESL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines." Fujii C., Nakamoto Y., Lu P., Tsuneyama K., Popivanova B.K., Kaneko S., Mukaida N. Int. J. Cancer 114:209-218(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Small intestine.
[3]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph.
[5]	"Consistency checks for characterizing protein forms." Chichester C., Nikitin F., Ravarini J.-C., Lisacek F. Comput. Biol. Chem. 27:29-35(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION FROM ESTS.
[6]	"Protein phosphatase 2A regulates the stability of Pim protein kinases." Losman J.A., Chen X.P., Vuong B.Q., Fay S., Rothman P.B. J. Biol. Chem. 278:4800-4805(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPP2CA, PHOSPHORYLATION, UBIQUITINATION.
[7]	"Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines." Li Y.Y., Popivanova B.K., Nagai Y., Ishikura H., Fujii C., Mukaida N. Cancer Res. 66:6741-6747(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF BAD, TISSUE SPECIFICITY.
[8]	"Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis." Popivanova B.K., Li Y.Y., Zheng H., Omura K., Fujii C., Tsuneyama K., Mukaida N. Cancer Sci. 98:321-328(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BAD, TISSUE SPECIFICITY.
[9]	"Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels." Morishita D., Katayama R., Sekimizu K., Tsuruo T., Fujita N. Cancer Res. 68:5076-5085(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CDKN1B.
[10]	"Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression." Zheng H.C., Tsuneyama K., Takahashi H., Miwa S., Sugiyama T., Popivanova B.K., Fujii C., Nomoto K., Mukaida N., Takano Y. J. Cancer Res. Clin. Oncol. 134:481-488(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB114795 mRNA. Translation: BAD42438.1. AK292005 mRNA. Translation: BAF84694.1. CR536608, BX539320 Genomic DNA. Translation: CAO03523.1. BX539320, CR536608 Genomic DNA. Translation: CAO03581.1. BC052239 mRNA. No translation available. BC141855 mRNA. Translation: AAI41856.1.
RefSeq	NP_001001852.2. NM_001001852.3.
UniGene	Hs.530381.
3D structure databases
ProteinModelPortal	Q86V86.
SMR	Q86V86. Positions 40-293.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	136104. 2 interactions.
IntAct	Q86V86. 2 interactions.
MINT	MINT-6823599.
STRING	9606.ENSP00000353824.
Chemistry
BindingDB	Q86V86.
ChEMBL	CHEMBL5407.
GuidetoPHARMACOLOGY	2160.
PTM databases
PhosphoSite	Q86V86.
Polymorphism databases
DMDM	215274221.
Proteomic databases
PaxDb	Q86V86.
PRIDE	Q86V86.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360612; ENSP00000353824; ENSG00000198355.
GeneID	415116.
KEGG	hsa:415116.
UCSC	uc003bjb.3. human.
Organism-specific databases
CTD	415116.
GeneCards	GC22P050354.
H-InvDB	HIX0203204.
HGNC	HGNC:19310. PIM3.
MIM	610580. gene.
neXtProt	NX_Q86V86.
PharmGKB	PA134980758.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000231357.
HOVERGEN	HBG106681.
InParanoid	Q86V86.
KO	K08807.
OMA	RVTEWGT.
OrthoDB	EOG7NW6B0.
TreeFam	TF320810.
Enzyme and pathway databases
SignaLink	Q86V86.
Gene expression databases
Bgee	Q86V86.
CleanEx	HS_PIM3.
Genevestigator	Q86V86.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. SSF56112. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PIM3. human.
GenomeRNAi	415116.
NextBio	108679.
PRO	Q86V86.
SOURCE	Search...

Entry information

Entry name

PIM3_HUMAN

Accession

Primary (citable) accession number: Q86V86
Secondary accession number(s): A5D8X8 , A8K7J0, B1B0P0, Q68BM2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 21, 2003
Last sequence update:	November 25, 2008
Last modified:	February 19, 2014
This is version 104 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.