Reviewed, UniProtKB/Swiss-Prot P11309 (PIM1_HUMAN)

Names and origin

Protein names

Recommended name:
    Proto-oncogene serine/threonine-protein kinase Pim-1
    EC=2.7.11.1

Gene names

Name:

PIM1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	404 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a role in signal transduction in blood cells. Contributes to both cell proliferation and survival and thus provide a selective advantage in tumorigenesis. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Manganese.
Subunit structure	Binds to RP9. Isoform 2 is isolated as a monomer whereas isoform 1 complexes with other proteins. Isoform 1, but not isoform 2, binds BMX.
Subcellular location	Isoform 2: Cytoplasm. Nucleus. Isoform 1: Cell membrane.
Tissue specificity	Expressed primarily in cells of the hematopoietic and germline lineages. Isoform 1 and isoform 2 are both expressed in prostate cancer cell lines.
Induction	Strongly induced in leukocytes by the JAK/STAT pathway in response to cytokines.
Post-translational modification	Autophosphorylated on both serine/threonine and tyrosine residues.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative initiation Polymorphism
Disease	Proto-oncogene
Ligand	ATP-binding Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell proliferation Ref.5 Inferred from direct assay. Source: UniProtKB multicellular organismal development Traceable author statement. Source: ProtInc negative regulation of apoptosis Ref.5 Inferred from direct assay. Source: UniProtKB protein amino acid phosphorylation Ref.9 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.9 Inferred from direct assay. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Ref.9 Inferred from direct assay. Source: UniProtKB manganese ion binding Ref.9 Inferred from direct assay. Source: UniProtKB protein binding Ref.5 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.9 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABCG2	Q9UNQ0	7	EBI-1018629,EBI-1569435
BMX	P51813	2	EBI-696621,EBI-696657

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform 1 (identifier: P11309-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P11309-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-91: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 404

404

Proto-oncogene serine/threonine-protein kinase Pim-1

PRO_0000043349

Regions

Domain

129 – 381

253

Protein kinase

Nucleotide binding

135 – 143

9

ATP By similarity

Sites

Active site

258

1

Proton acceptor By similarity

Binding site

158

1

ATP By similarity

Natural variations

Alternative sequence

1 – 91

91

Missing in isoform 2.

VSP_016530

Natural variant

144

1

Y → H in a colorectal adenocarcinoma sample; somatic mutation.

VAR_041004

Natural variant

215

1

E → Q

VAR_041005

Natural variant

226

1

E → K

VAR_041006

Natural variant

233

1

E → D

VAR_041007

Experimental info

Sequence conflict

106 – 107

2

AP → RA in AAA60089. Ref.2

Secondary structure

1

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404

Helix Strand Turn

Details...

Turn

126 – 128

3

Beta strand

129 – 140

12

Beta strand

142 – 148

7

Turn

149 – 151

3

Beta strand

154 – 161

8

Turn

162 – 164

3

Beta strand

168 – 170

3

Beta strand

176 – 178

3

Helix

179 – 187

9

Beta strand

197 – 202

6

Beta strand

204 – 212

9

Beta strand

215 – 219

5

Helix

220 – 227

8

Helix

232 – 251

20

Helix

261 – 263

3

Beta strand

264 – 267

4

Turn

268 – 271

4

Beta strand

272 – 275

4

Helix

296 – 298

3

Helix

301 – 306

6

Helix

311 – 328

18

Helix

336 – 341

6

Helix

352 – 361

10

Helix

366 – 368

3

Helix

372 – 377

6

Helix

379 – 381

3

Helix

387 – 394

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 6, 2005. Version 3. Checksum: 18C421B7CFF87818	FASTA	404	45,412
	10 20 30 40 50 60 MPHEPHEPLT PPFSALPDPA GAPSRRQSRQ RPQLSSDSPS AFRASRSHSR NATRSHSHSH 70 80 90 100 110 120 SPRHSLRHSP GSGSCGSSSG HRPCADILEV GMLLSKINSL AHLRAAPCND LHATKLAPGK 130 140 150 160 170 180 EKEPLESQYQ VGPLLGSGGF GSVYSGIRVS DNLPVAIKHV EKDRISDWGE LPNGTRVPME 190 200 210 220 230 240 VVLLKKVSSG FSGVIRLLDW FERPDSFVLI LERPEPVQDL FDFITERGAL QEELARSFFW 250 260 270 280 290 300 QVLEAVRHCH NCGVLHRDIK DENILIDLNR GELKLIDFGS GALLKDTVYT DFDGTRVYSP 310 320 330 340 350 360 PEWIRYHRYH GRSAAVWSLG ILLYDMVCGD IPFEHDEEII RGQVFFRQRV SSECQHLIRW 370 380 390 400 CLALRPSDRP TFEEIQNHPW MQDVLLPQET AEIHLHSLSP GPSK
	Isoform 2 [UniParc]. Checksum: 35BA76D3668E69A3		313	35,686
	10 20 30 40 50 60 MLLSKINSLA HLRAAPCNDL HATKLAPGKE KEPLESQYQV GPLLGSGGFG SVYSGIRVSD 70 80 90 100 110 120 NLPVAIKHVE KDRISDWGEL PNGTRVPMEV VLLKKVSSGF SGVIRLLDWF ERPDSFVLIL 130 140 150 160 170 180 ERPEPVQDLF DFITERGALQ EELARSFFWQ VLEAVRHCHN CGVLHRDIKD ENILIDLNRG 190 200 210 220 230 240 ELKLIDFGSG ALLKDTVYTD FDGTRVYSPP EWIRYHRYHG RSAAVWSLGI LLYDMVCGDI 250 260 270 280 290 300 PFEHDEEIIR GQVFFRQRVS SECQHLIRWC LALRPSDRPT FEEIQNHPWM QDVLLPQETA 310 EIHLHSLSPG PSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of the putative human oncogene, pim-1." Reeves R., Spies G.A., Kiefer M., Barr P.J., Power M. Gene 90:303-307(1990) [PubMed: 2205533] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
[2]	"The cDNA sequence and gene analysis of the human pim oncogene." Zakut-Houri R., Hazum S., Givol D., Telerman A. Gene 54:105-111(1987) [PubMed: 3475233] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"Comparison of the human and mouse PIM-1 cDNAs: nucleotide sequence and immunological identification of the in vitro synthesized PIM-1 protein." Domen J., von Lindern M., Hermans A., Breuer M., Grosveld G., Berns A. Oncogene Res. 1:103-112(1987) [PubMed: 3329709] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Cloning and characterization of the human PIM-1 gene: a putative oncogene related to the protein kinases." Meeker T.C., Nagarajan L., Ar-Rushdi A., Croce C.M. J. Cell. Biochem. 35:105-112(1987) [PubMed: 3429489] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"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." Xie Y., Xu K., Dai B., Guo Z., Jiang T., Chen H., Qiu Y. Oncogene 25:70-78(2006) [PubMed: 16186805] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE INITIATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH BMX.
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Kidney.
[7]	"Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas." Pasqualucci L., Neumeister P., Goossens T., Nanjangud G., Chaganti R.S.K., Kuppers R., Dalla-Favera R. Nature 412:341-346(2001) [PubMed: 11460166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 92-293 (ISOFORM 2).
[8]	"Identification of the human pim-1 gene product as a 33-kilodalton cytoplasmic protein with tyrosine kinase activity." Telerman A., Amson R., Zakut-Houri R., Givol D. Mol. Cell. Biol. 8:1498-1503(1988) [PubMed: 2837645] [Abstract] Cited for: CHARACTERIZATION.
[9]	"The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG." Saris C.J., Domen J., Berns A. EMBO J. 10:655-664(1991) [PubMed: 1825810] [Abstract] Cited for: FUNCTION.
[10]	"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." Koike N., Maita H., Taira T., Ariga H., Iguchi-Ariga S.M.M. FEBS Lett. 467:17-21(2000) [PubMed: 10664448] [Abstract] Cited for: FUNCTION.
[11]	"Pim-1 protein kinase is nuclear in Burkitt's lymphoma: nuclear localization is necessary for its biologic effects." Ionov Y., Le X., Tunquist B.J., Sweetenham J., Sachs T., Ryder J., Johnson T., Lilly M.B., Kraft A.S. Anticancer Res. 23:167-178(2003) [PubMed: 12680209] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"IL-5 and granulocyte-macrophage colony-stimulating factor activate STAT3 and STAT5 and promote Pim-1 and cyclin D3 protein expression in human eosinophils." Stout B.A., Bates M.E., Liu L.Y., Farrington N.N., Bertics P.J. J. Immunol. 173:6409-6417(2004) [PubMed: 15528381] [Abstract] Cited for: FUNCTION, INDUCTION.
[13]	"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. , 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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-144; GLN-215; LYS-226 AND ASP-233.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

M27903 Genomic DNA. Translation: AAA60090.1.
M16750 mRNA. Translation: AAA60089.1.
M54915 mRNA. Translation: AAA36447.1.
M24779 mRNA. Translation: AAA81553.1.
DQ022562 mRNA. Translation: AAY87461.1.
BC020224 mRNA. Translation: AAH20224.1.
AF386792 Genomic DNA. Translation: AAK70871.1.

PIR

TVHUP1. JU0327.

UniGene

Hs.81170

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XQZ	X-ray	2.10	A	105-404	[»]
1XR1	X-ray	2.10	A	105-404	[»]
1XWS	X-ray	1.80	A	92-404	[»]
1YHS	X-ray	2.15	A	124-396	[»]
1YI3	X-ray	2.50	A	124-396	[»]
1YI4	X-ray	2.40	A	124-396	[»]
1YWV	X-ray	2.00	A	120-404	[»]
1YXS	X-ray	2.20	A	120-404	[»]
1YXT	X-ray	2.00	A	120-404	[»]
1YXU	X-ray	2.24	A/B/C/D	120-404	[»]
1YXV	X-ray	2.00	A	120-404	[»]
1YXX	X-ray	2.00	A	120-404	[»]
2BIK	X-ray	1.80	B	92-404	[»]
2BIL	X-ray	2.55	B	92-404	[»]
2BZH	X-ray	1.90	B	92-404	[»]
2BZI	X-ray	1.90	B	92-404	[»]
2BZJ	X-ray	2.05	A	92-404	[»]
2BZK	X-ray	2.45	B	92-404	[»]
2C3I	X-ray	1.90	B	92-404	[»]
2J2I	X-ray	1.90	B	92-403	[»]
2O3P	X-ray	2.24	A	120-404	[»]
2O63	X-ray	2.00	A	120-404	[»]
2O64	X-ray	2.44	A	120-404	[»]
2O65	X-ray	2.85	A	120-404	[»]
2OI4	X-ray	2.20	X	92-404	[»]
3BWF	X-ray	2.35	A	92-404	[»]
3C4E	X-ray	1.98	A/B/C/D	124-396	[»]

DisProt

DP00322.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11309.

PTM databases