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Q9P1W9 (PIM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase pim-2

EC=2.7.11.1
Alternative name(s):
Pim-2h
Gene names
Name:PIM2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length311 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression, the regulation of cap-dependent protein translation and through survival signaling by phosphorylation of a pro-apoptotic protein, BAD. Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase transcriptional activity. The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner and in parallel to the PI3K-Akt pathway. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Promotes cell survival in response to a variety of proliferative signals via positive regulation of the I-kappa-B kinase/NF-kappa-B cascade; this process requires phosphorylation of MAP3K8/COT. Isoform 1is less active in this respect. Promotes growth factor-independent proliferation by phosphorylation of cell cycle factors such as CDKN1A and CDKN1B. Involved in the positive regulation of chondrocyte survival and autophagy in the epiphyseal growth plate. Ref.7 Ref.8 Ref.9

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Interacts with MYC By similarity.

Tissue specificity

Highly expressed in hematopoietic tissues, in leukemic and lymphoma cell lines, testis, small intestine, colon and colorectal adenocarcinoma cells. Weakly expressed in normal liver, but highly expressed in hepatocellular carcinoma tissues. Ref.8

Induction

Down-regulated in response to enterovirus 71 (EV71) infection. Ref.6

Post-translational modification

Autophosphorylated By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAC78506.1 differs from that shown. Reason: Frameshift at position 293.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
   Coding sequence diversityPolymorphism
   DiseaseProto-oncogene
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from direct assay Ref.9. Source: UniProtKB

apoptotic mitochondrial changes

Inferred from electronic annotation. Source: Ensembl

cell proliferation

Traceable author statement Ref.1. Source: ProtInc

male meiosis

Traceable author statement Ref.1. Source: ProtInc

negative regulation of apoptotic process

Inferred from direct assay Ref.8. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay Ref.9. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of autophagy

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.7. Source: UniProtKB

protein stabilization

Inferred from mutant phenotype Ref.9. Source: UniProtKB

response to virus

Inferred from expression pattern Ref.6. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein serine/threonine kinase activity

Inferred from direct assay Ref.7. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 311311Serine/threonine-protein kinase pim-2
PRO_0000086532

Regions

Domain32 – 286255Protein kinase
Nucleotide binding38 – 469ATP By similarity

Sites

Active site1631Proton acceptor By similarity
Binding site611ATP By similarity

Natural variations

Natural variant1381G → D. Ref.11
Corresponds to variant rs35044770 [ dbSNP | Ensembl ].
VAR_041008
Natural variant2801I → V. Ref.11
Corresponds to variant rs35208542 [ dbSNP | Ensembl ].
VAR_041009

Experimental info

Sequence conflict661N → Y in BAF83620. Ref.2

Secondary structure

............................................. 311
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9P1W9 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 160E56C368C67A69

FASTA31134,190
        10         20         30         40         50         60 
MLTKPLQGPP APPGTPTPPP GGKDREAFEA EYRLGPLLGK GGFGTVFAGH RLTDRLQVAI 

        70         80         90        100        110        120 
KVIPRNRVLG WSPLSDSVTC PLEVALLWKV GAGGGHPGVI RLLDWFETQE GFMLVLERPL 

       130        140        150        160        170        180 
PAQDLFDYIT EKGPLGEGPS RCFFGQVVAA IQHCHSRGVV HRDIKDENIL IDLRRGCAKL 

       190        200        210        220        230        240 
IDFGSGALLH DEPYTDFDGT RVYSPPEWIS RHQYHALPAT VWSLGILLYD MVCGDIPFER 

       250        260        270        280        290        300 
DQEILEAELH FPAHVSPDCC ALIRRCLAPK PSSRPSLEEI LLDPWMQTPA EDVPLNPSKG 

       310 
GPAPLAWSLL P 

« Hide

References

« Hide 'large scale' references
[1]"The human Pim-2 proto-oncogene and its testicular expression."
Baytel D., Shalom S., Madgar I., Weissenberg R., Don J.
Biochim. Biophys. Acta 1442:274-285(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Testis.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Genomic organization of the human UDP-galactose transporter gene."
Ishida N., Miura N., Yamauchi M., Kawakita M.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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: Uterus.
[6]"Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection."
Leong W.F., Chow V.T.
Cell. Microbiol. 8:565-580(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, IDENTIFICATION BY MASS SPECTROMETRY.
[7]"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.
[8]"Serine/threonine kinase Pim-2 promotes liver tumorigenesis induction through mediating survival and preventing apoptosis of liver cell."
Gong J., Wang J., Ren K., Liu C., Li B., Shi Y.
J. Surg. Res. 153:17-22(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[9]"Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells."
Wang Z., Zhang Y., Gu J.J., Davitt C., Reeves R., Magnuson N.S.
Int. J. Biochem. Cell Biol. 42:1030-1038(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CDKN1A.
[10]"Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor."
Bullock A.N., Russo S., Amos A., Pagano N., Bregman H., Debreczeni J.E., Lee W.H., von Delft F., Meggers E., Knapp S.
PLoS ONE 4:E7112-E7112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH RUTHENIUM-PYRIDOCARBAZOLE-1.
[11]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-138 AND VAL-280.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U77735 mRNA. Translation: AAC78506.1. Frameshift.
AK290931 mRNA. Translation: BAF83620.1.
AB042425 Genomic DNA. Translation: BAA95613.1.
AF207550 Genomic DNA. No translation available.
BC018111 mRNA. Translation: AAH18111.1.
RefSeqNP_006866.2. NM_006875.3.
UniGeneHs.727148.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IWIX-ray2.80A/B1-311[»]
ProteinModelPortalQ9P1W9.
SMRQ9P1W9. Positions 32-288.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116228. 9 interactions.
IntActQ9P1W9. 9 interactions.
MINTMINT-1432143.
STRING9606.ENSP00000365692.

Chemistry

BindingDBQ9P1W9.
ChEMBLCHEMBL4523.
GuidetoPHARMACOLOGY2159.

PTM databases

PhosphoSiteQ9P1W9.

Polymorphism databases

DMDM20139243.

Proteomic databases

PaxDbQ9P1W9.
PRIDEQ9P1W9.

Protocols and materials databases

DNASU11040.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000376509; ENSP00000365692; ENSG00000102096.
ENST00000601083; ENSP00000469116; ENSG00000267878.
GeneID11040.
KEGGhsa:11040.
UCSCuc004dls.3. human.

Organism-specific databases

CTD11040.
GeneCardsGC0XM048770.
HGNCHGNC:8987. PIM2.
HPAHPA000285.
MIM300295. gene.
neXtProtNX_Q9P1W9.
PharmGKBPA33319.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000231357.
HOVERGENHBG106681.
InParanoidQ9P1W9.
KOK08806.
OMAQEGFMLV.
PhylomeDBQ9P1W9.
TreeFamTF320810.

Enzyme and pathway databases

SignaLinkQ9P1W9.

Gene expression databases

ArrayExpressQ9P1W9.
BgeeQ9P1W9.
CleanExHS_PIM2.
GenevestigatorQ9P1W9.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPIM2. human.
EvolutionaryTraceQ9P1W9.
GeneWikiPIM2_(gene).
GenomeRNAi11040.
NextBio41955.
PROQ9P1W9.
SOURCESearch...

Entry information

Entry namePIM2_HUMAN
AccessionPrimary (citable) accession number: Q9P1W9
Secondary accession number(s): A8K4G6, Q99739
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM