CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-003906
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase pim-1 
Protein Synonyms/Alias
  
Gene Name
 PIM1 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
31KLAPGKEKEPLESQYubiquitination[1]
67DNLPVAIKHVEKDRIubiquitination[1]
Reference
 [1] 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] 
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. 
Sequence Annotation
 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.  
Keyword
 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. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 404 AA 
Protein Sequence
MLLSKINSLA HLRAAPCNDL HATKLAPGKE KEPLESQYQV GPLLGSGGFG SVYSGIRVSD 60
NLPVAIKHVE KDRISDWGEL PNGTRVPMEV VLLKKVSSGF SGVIRLLDWF ERPDSFVLIL 120
ERPEPVQDLF DFITERGALQ EELARSFFWQ VLEAVRHCHN CGVLHRDIKD ENILIDLNRG 180
ELKLIDFGSG ALLKDTVYTD FDGTRVYSPP EWIRYHRYHG RSAAVWSLGI LLYDMVCGDI 240
PFEHDEEIIR GQVFFRQRVS SECQHLIRWC LALRPSDRPT FEEIQNHPWM QDVLLPQETA 300
EIHLHSLSPG PSK 313 
Gene Ontology
 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. 
Interpro
 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. 
Pfam
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS