P11309

Background

Protein Name
Serine/threonine-protein kinase pim-1
Gene Name
PIM1
Organism
Homo sapiens

Annotations

Function
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.

Mapping Statistics

Site Maximum Consensus Site Population Minimum Consensus Site Population Median Consensus Site Population
MT3 29 2 12.0
ATP 27 1 11.0
MPP 16 4 10.0
DFG 19 1 11.0
EDI 20 10 16.0
CMP 15 2 8.0
PDIG 21 2 6.0
DRS 16 2 9.0
LBP 10 2 4.0
AAS 17 8 15.0

Mapping Results

PDB ID Maximum Consensus Site Population
MT3 site ATP site MPP site PIF site DFG site EDI site CMP site PDIG site DRS site PMP site LBP site AAS site DEF site
Total Druggable Structures per Site 32 80 1 0 14 91 0 17 6 0 0 2 0
4MBI 0 16 0 0 11 16 9 6 3 0 4 0 0
4K1B 0 16 0 0 8 16 6 16 15 0 6 0 0
4K18 0 16 0 0 17 16 13 6 15 0 0 0 0
4WSY 3 18 0 0 14 16 11 15 12 0 0 0 0
4MBL 12 20 0 0 11 20 7 16 0 0 2 0 0
2OI4 8 18 0 0 5 16 0 19 4 0 0 0 0
3QF9 19 19 0 0 9 17 0 2 13 0 0 0 0
1YXS 3 16 0 0 18 16 9 10 3 0 0 0 0
AFP11309 9 16 16 0 16 0 0 15 0 0 0 0 0
5DWR 0 17 0 0 15 17 8 15 10 0 4 0 0
4LMU 0 12 0 0 10 17 10 6 13 0 2 0 0
1YHS 14 16 0 0 10 17 10 15 0 0 0 0 0
4MTA 25 15 0 0 14 17 11 0 13 0 2 0 0
2XJ1 12 19 0 0 9 18 0 12 11 0 2 0 0
1YXU 23 12 0 0 13 18 10 9 12 0 5 0 0
5EOL 10 17 0 0 14 17 7 4 12 0 0 0 0
1YXV 25 12 0 0 15 10 7 6 14 0 0 0 0
3VC4 5 22 0 0 16 17 5 10 10 0 7 0 0
5C1Q 0 17 0 0 12 14 3 11 6 0 0 0 0
3UMW 25 14 0 0 3 17 6 5 12 0 5 0 0
4RC2 0 17 0 0 15 16 11 6 5 0 2 0 0
4WRS 28 14 0 0 15 16 8 16 10 0 2 0 0
4TY1 0 14 0 0 14 17 4 20 6 0 0 0 0
4RPV 12 17 0 0 14 14 13 12 10 0 5 0 0
3VBQ 15 8 0 0 9 19 11 5 0 0 2 0 0
4LM5 0 16 0 0 18 16 11 15 10 0 2 0 0
3WE8 8 22 0 0 9 16 14 14 0 0 0 0 0
3VBY 22 16 0 0 11 17 0 3 16 0 0 0 0
5IIS 22 19 0 0 10 17 3 3 11 0 0 0 0
3JY0 0 17 0 0 13 16 12 15 16 0 0 0 0
4K0Y 8 16 0 0 12 16 8 5 14 0 2 0 0
4JX3 0 25 0 0 14 15 9 11 14 0 0 0 0
3BGQ 23 17 0 0 4 17 10 16 13 0 0 0 0
2BZH 10 17 0 0 5 16 14 21 0 0 3 0 0
4WT6 23 19 0 0 11 16 0 14 15 0 3 0 0
4IAA 0 21 0 0 15 17 0 19 0 0 2 0 0
2O65 0 27 0 0 12 16 6 2 2 0 7 17 0
3DCV 0 17 0 0 6 17 10 4 0 0 10 0 0
3CY2 9 9 0 0 16 17 3 0 0 0 7 0 0
1YWV 13 15 0 0 16 16 11 3 0 0 0 0 0
4BZO 25 19 0 0 10 17 7 8 14 0 6 0 0
4RBL 0 20 0 0 11 16 5 8 8 0 0 0 0
2XJ2 25 13 0 0 12 16 6 15 7 0 7 0 0
2BIK 0 16 0 0 5 16 0 6 3 0 0 0 0
2J2I 29 15 0 0 7 16 9 12 0 0 3 0 0
2BZJ 0 13 0 0 4 17 13 10 0 0 0 0 0
3C4E 23 17 0 0 15 18 13 13 15 0 6 0 0
5DHJ 0 17 0 0 14 15 10 10 14 0 2 0 0
4A7C 23 25 0 0 10 20 8 2 6 0 10 13 0
1YXT 0 17 0 0 16 17 8 17 11 0 3 0 0
4ENY 14 18 0 0 4 17 7 4 0 0 3 0 0
3T9I 0 26 0 0 3 17 2 3 13 0 4 0 0
3BGZ 12 18 0 0 16 16 3 17 0 0 0 0 0
2XIZ 9 20 0 0 15 15 0 14 14 0 7 0 0
4N6Z 23 16 0 0 10 15 5 3 15 0 0 0 0
4RC4 11 17 0 0 10 16 5 13 4 0 7 0 0
1YI3 19 14 0 0 9 16 2 19 12 0 6 0 0
4I41 0 16 0 0 15 18 6 14 0 0 0 0 0
5DGZ 0 19 0 0 11 17 8 18 12 0 4 0 0
3VBX 8 14 0 0 19 19 12 3 9 0 5 0 0
1XQZ 0 13 0 0 10 16 15 14 11 0 2 0 0
4XHK 10 13 0 0 11 15 3 6 15 0 5 0 0
3R02 9 21 0 0 14 17 14 3 12 0 5 0 0
3VBT 13 14 0 0 8 17 3 4 13 0 6 0 0
4N6Y 0 16 0 0 8 16 0 6 13 0 10 0 0
3CY3 21 14 0 0 10 17 15 0 3 0 7 0 0
4ALV 14 21 0 0 12 15 0 4 16 0 0 0 0
2O3P 16 21 0 0 5 17 7 7 13 0 4 0 0
5DIA 0 18 0 0 13 17 8 7 9 0 4 0 0
3R04 7 20 0 0 12 17 8 5 0 0 5 0 0
1XR1 12 16 0 0 14 17 11 12 13 0 2 0 0
2O64 25 16 0 0 9 17 0 5 14 0 6 16 0
1YI4 20 22 0 0 8 17 0 4 13 0 9 0 0
4MED 0 16 0 0 14 16 7 13 0 0 0 0 0
3BGP 11 20 0 0 0 17 3 3 15 0 0 0 0
2BIL 0 17 0 0 4 16 9 0 13 0 3 0 0
2XIX 5 25 0 0 15 17 0 16 11 0 4 0 0
3JYA 8 25 0 0 9 15 3 4 0 0 4 0 0
4ENX 14 16 0 0 5 18 13 4 12 0 3 0 0
3A99 16 16 0 0 12 15 13 2 10 0 3 15 0
1YXX 5 18 0 0 12 15 4 15 14 0 0 0 0
2XIY 5 11 0 0 13 16 2 8 13 0 0 0 0
3BWF 0 14 0 0 6 18 14 3 3 0 2 0 0
3UMX 0 21 0 0 6 16 0 17 13 0 9 0 0
4ALW 0 14 0 0 19 17 8 10 0 0 3 0 0
4AS0 9 17 0 0 16 16 3 14 10 0 0 0 0
2O63 12 15 0 0 13 16 12 9 12 0 3 0 0
3R00 10 14 0 0 10 14 3 6 15 0 7 0 0
2C3I 28 16 0 0 5 15 13 0 14 0 5 0 0
4LL5 0 16 0 0 15 16 14 10 9 0 4 0 0
4RC3 8 21 0 0 13 15 4 8 5 0 3 0 0
3VBV 23 22 0 0 12 16 13 10 14 0 2 0 0
3F2A 24 16 0 0 14 15 7 8 0 0 7 0 0
2XJ0 13 11 0 0 2 15 7 17 6 0 4 0 0
2BZK 0 18 0 0 17 17 13 0 4 0 0 0 0
3JXW 17 12 0 0 12 19 2 5 0 0 0 0 0
3R01 0 20 0 0 15 17 6 6 14 0 8 0 0
2OBJ 17 23 0 0 9 12 5 18 16 0 3 0 0
4ALU 22 12 0 0 13 15 3 3 16 0 5 0 0
4DTK 6 21 0 0 17 16 8 6 3 0 3 0 0
4GW8 17 13 0 0 7 16 0 0 7 0 7 8 0
4JX7 8 21 0 0 10 15 14 0 10 0 2 0 0
4XH6 0 23 0 0 14 17 11 2 15 0 0 0 0
5IPJ 12 17 0 0 15 16 3 4 15 0 0 0 0
3UIX 26 16 0 0 8 17 0 10 8 0 7 0 0
3MA3 0 15 0 0 12 15 6 0 5 0 5 0 0
4N70 0 17 0 0 9 17 13 4 16 0 4 0 0
2BZI 0 18 0 0 8 17 0 15 8 0 2 0 0
4BZN 24 16 0 0 13 17 2 4 13 0 2 0 0
3CXW 13 14 0 0 15 16 0 0 2 0 6 0 0
3JPV 16 13 0 0 7 17 8 0 12 0 3 0 0
3VBW 0 14 0 0 11 16 4 3 0 0 6 0 0
1XWS 0 15 0 0 7 17 8 16 9 0 2 0 0