CPLM-003905

Genbank Nucleotide ID

Serine/threonine-protein kinase pim-1

Protein Synonyms/Alias

Homo sapiens (Human)

Position	Peptide	Type	References
96	EVGMLLSKINSLAHL	ubiquitination	[1, 2]
122	KLAPGKEKEPLESQY	ubiquitination	[3]
158	DNLPVAIKHVEKDRI	ubiquitination	[3, 4, 5]
260	GVLHRDIKDENILID	ubiquitination	[5]
274	DLNRGELKLIDFGSG	ubiquitination	[4]
285	FGSGALLKDTVYTDF	ubiquitination	[3, 4, 5, 6]

[1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[6] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]

Functional Description

Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl- X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post- translational levels. Phosphorylation of CDKN1B,induces 14-3-3- proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.

DOMAIN 129 381 Protein kinase.
NP_BIND 135 143 ATP (By similarity).
ACT_SITE 258 258 Proton acceptor (By similarity).
BINDING 158 158 ATP.
BINDING 212 212 ATP; via carbonyl oxygen.
BINDING 219 219 ATP.
MOD_RES 99 99 Phosphoserine.
MOD_RES 114 114 Phosphothreonine.
MOD_RES 189 189 Phosphoserine.
MOD_RES 352 352 Phosphoserine.

3D-structure; Alternative initiation; Apoptosis; ATP-binding; Cell cycle; Cell membrane; Complete proteome; Cytoplasm; Direct protein sequencing; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO:0005524; F:ATP binding; IDA:UniProtKB.
GO:0030145; F:manganese ion binding; IDA:UniProtKB.
GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
GO:0043024; F:ribosomal small subunit binding; IPI:UniProtKB.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO:0008283; P:cell proliferation; IDA:UniProtKB.
GO:0007275; P:multicellular organismal development; TAS:ProtInc.
GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IDA:UniProtKB.
GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.

IPR011009; Kinase-like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR002290; Ser/Thr_dual-sp_kinase_dom.
IPR008271; Ser/Thr_kinase_AS.
IPR017348; Ser/Thr_kinase_Pim-1.

PS00107; PROTEIN_KINASE_ATP
PS50011; PROTEIN_KINASE_DOM
PS00108; PROTEIN_KINASE_ST