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Updated November 2019

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Nomenclature

Short Name:
PIM2
Full Name:
Serine-threonine-protein kinase Pim-2
Alias:
  • EC 2.7.11.1
  • Pim-2h

Classification

Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
PIM
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 11040
Entrez-Protein Entry: NP_006866
GeneCards Entry: PIM2
KinBASE Entry: PIM2
OMIM Entry: 300295
Pfam Entry: Q9P1W9
PhosphoNET Entry: Q9P1W9
Phosphosite Plus Entry: 737
Protein Data Bank Entry: 2IWI
Source Entry: PIM2
UCSD-Nature Entry: A001823
UniProt Entry: Q9P1W9
Kinexus Products: PIM2
Serine/threonine-protein kinase Pim-2 pan-specific antibody AB-NK288-1
Serine/threonine-protein kinase Pim-2 pan-specific antibody AB-NK288-2
Serine/threonine-protein kinase Pim-2 T195 phosphosite-specific antibody AB-PK761
RPS6 (230-238) KinSub - 40S ribosomal protein S6 (K230-R238, human) peptide; p70S6K protein kinase substrate peptide - Powder PE-01ADQ95
Serine/threonine-protein kinase Pim-2 (P20-G35, human) peptide - Powder PE-01BER85
Serine/threonine-protein kinase Pim-2 (L282-G300, human) peptide - Powder PE-01BES85
Serine/threonine-protein kinase Pim-2 (E192-D198, human) pT195 phosphopeptide - Powder PE-04AOP95

General Links

ClustalW2
GPS-Cuckoo
Human Protein Atlas
Kinase.com
Kinase Research
Kinasource
Kinomer
Netphorest
NetworKIN
Phosida
PhosphoElm
Protein Blast
ScanSite
String

Structure

Mol. Mass (Da):
34,190
# Amino Acids:
311
# mRNA Isoforms:
1
mRNA Isoforms:
34,190 Da (311 AA; Q9P1W9)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
2IWI

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
32 286 Pkinase
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ Serine/threonine-protein kinase Pim-2 pan-specific antibody AB-NK288-1
○ Serine/threonine-protein kinase Pim-2 pan-specific antibody AB-NK288-2
○ Serine/threonine-protein kinase Pim-2 T195 phosphosite-specific antibody AB-PK761
○ RPS6 (230-238) KinSub - 40S ribosomal protein S6 (K230-R238, human) peptide; p70S6K protein kinase substrate peptide - Powder PE-01ADQ95
○ Serine/threonine-protein kinase Pim-2 (P20-G35, human) peptide - Powder PE-01BER85
○ Serine/threonine-protein kinase Pim-2 (L282-G300, human) peptide - Powder PE-01BES85
○ Serine/threonine-protein kinase Pim-2 (E192-D198, human) pT195 phosphopeptide - Powder PE-04AOP95
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:

S185+, S204-.
Threonine phosphorylated:

T3, T15, T195+, T200-.
Tyrosine phosphorylated:

Y32.
Ubiquitinated:
K40, K61, K89, K132, K165, K179.
 

Distribution

Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
  • adipose
    28

    603

    19

    1085

  • adrenal
    2

    51

    12

    31

  • bladder
    4

    77

    5

    41

  • brain
    38

    824

    55

    2026

  • breast
    28

    604

    14

    591

  • cervix
    67

    1438

    45

    3182

  • colon
    24

    524

    23

    673

  • heart
    100

    2156

    30

    5009

  • intestine
    15

    332

    10

    259

  • kidney
    5

    103

    64

    95

  • liver
    3

    70

    22

    59

  • lung
    23

    503

    133

    603

  • lymphnode
    13

    282

    17

    174

  • ovary
    2

    53

    12

    30

  • pancreas
    2

    52

    15

    47

  • pituitary
    3

    60

    9

    29

  • prostate
    5

    113

    191

    500

  • salivarygland
    4

    81

    15

    45

  • skeletalmuscle"
    1.4

    31

    54

    20

  • skin
    16

    346

    56

    376

  • spinalcord
    3

    66

    19

    42

  • spleen
    15

    323

    21

    291

  • stomach
    8

    180

    15

    102

  • testis
    3

    71

    15

    69

  • thymus
    8

    171

    19

    191

  • thyroid
    87

    1865

    35

    4023

  • tonsil
    9

    188

    20

    106

  • trachea
    6

    138

    15

    94

  • uterus
    3

    64

    15

    47

  • reticulocytes"
    7

    142

    14

    84

  • t-lymphocytes
    70

    1500

    18

    782

  • b-lymphocytes
    27

    592

    21

    654

  • neutrophils
    4

    79

    56

    131

  • macrophages
    35

    746

    31

    756

  • sperm
    3

    55

    22

    42

 

Evolution

Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
  • tableheader
    100

    100

    100
  • tableheader
    70.5

    70.5

    100
  • tableheader
    98.7

    99

    99
  • tableheader
    -

    -

    92
  • tableheader
    -

    -

    -
  • tableheader
    71.6

    73.6

    94
  • tableheader
    -

    -

    -
  • tableheader
    75.1

    78.1

    89
  • tableheader
    55.8

    67.8

    90
  • tableheader
    -

    -

    -
  • tableheader
    47.8

    57.7

    -
  • tableheader
    -

    -

    -
  • tableheader
    49.2

    63.2

    -
  • tableheader
    52.4

    67.8

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    37
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Binding Proteins

Examples of known interacting proteins
hiddentext
No. Name – UniProt ID
1 BAD - Q92934
2 ATXN1 - P54253
 

Regulation

Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
Down-regulated in response to enterovirus 71 (EV71) infection.
 

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.
Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name UniProt ID (Human) Phosphosite Location Phosphosite Sequence Effect of Phosphorylation
Bad Q92934 S118 GRELRRMSDEFVDSF -
Bad Q92934 S75 EIRSRHSSYPAGTED -
Bad Q92934 S99 PFRGRSRSAPPNLWA -
eIF4B P23588 S406 RPRERHPSWRSEETQ
Myc P01106 S329 AKRVKLDSVRVLRQI
 

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Kinections GIF
Matrix Type:
Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.
Domain #:
1
 

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's
Based on in vitro and/or in vivo phosphorylation data
Compound Name KD, Ki or IC50 (nM) PubChem ID ChEMBL ID PubMed ID
Staurosporine Kd = 1.9 nM 5279 18183025
A 443654 IC50 = 10 nM 10172943 379300
SB218078 IC50 < 25 nM 447446 289422 22037377
SureCN2212990 IC50 = 40 nM 24811794 493937 19256503
7-hydroxystaurosporine IC50 > 45 nM 72271 1236539
Ro-31-8220 IC50 < 60 nM 5083 6291
TTT-3002 IC50 < 60 nM
Gö7874 IC50 < 80 nM 5327863
AT9283 IC50 > 100 nM 24905142 19143567
GW5074 (Raf1 Kinase Inhibitor I) IC50 < 100 nM 5924208
Ruboxistaurin IC50 = 100 nM 153999 91829
Staurosporine aglycone IC50 = 100 nM 3035817 281948
AC1O6ZUA Kd = 207 nM 6539569 408019 19035792
A674563 Kd = 220 nM 11314340 379218 22037378
AG-E-60384 IC50 > 250 nM 6419741 413188 22037377
Lestaurtinib Kd = 250 nM 126565 22037378
STO609 IC50 > 250 nM 51371511 22037377
BX517 IC50 > 300 nM 11161844 228654
Gö6976 IC50 > 300 nM 3501 302449
SGI-1776 IC50 = 363 nM 19734450
1;9-Pyrazoloanthrone Kd = 460 nM 8515 7064 15711537
ALX-270-403-M001 IC50 = 500 nM 22037377
PKR Inhibitor; Negative Control IC50 = 500 nM 16760619 22037377
TBCA IC50 = 500 nM 1095828 22037377
GSK-3 Inhibitor IX IC50 < 600 nM 5287844 409450
PP242 IC50 < 600 nM 25243800
Alvocidib Kd = 650 nM 9910986 428690 15711537
GSK690693 Kd = 680 nM 16725726 494089 22037378
AS601245 IC50 < 800 nM 11422035 191384
IKK-2 Inhibitor VIII IC50 < 800 nM 66576999 368427
SureCN3470757 IC50 < 800 nM 11588244 375236
Enzastaurin Kd = 870 nM 176167 300138 22037378
Bisindolylmaleimide I IC50 > 1 µM 2396 7463 22037377
BMS-690514 Kd = 1 µM 11349170 21531814
K-252a; Nocardiopsis sp. IC50 > 1 µM 3813 281948 22037377
Kinome_714 IC50 > 1 µM 46886323 20346655
MK5108 IC50 > 1 µM 24748204 20053775
Silmitasertib IC50 > 1 µM 24748573 21174434
SNS314 IC50 > 1 µM 16047143 514582 18678489
Wortmannin IC50 > 1 µM 312145 428496 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
LKB1(AAK1 dual inhibitor) Kd < 1.25 µM 44588117 516312 19035792
JNK Inhibitor VIII Ki > 1.4 µM 11624601 210618 16759099
Kinome_3024 Ki > 1.4 µM 11539329 210963 16759099
Kinome_3027 Ki > 1.4 µM 11640926 378627 16759099
Kinome_3028 Ki > 1.4 µM 11590363 210928 16759099
CHEMBL248757 Ki > 1.424 µM 44444843 248757 17935989
CHEMBL398606 IC50 = 1.72 µM 11248502 398606 17887663
IPA-3 IC50 < 2 µM 521106 472940
KT5720 IC50 > 3 µM 3844 608532
ML-7 IC50 < 3 µM 4216 249089
N-Benzoylstaurosporine Kd = 3.1 µM 56603681 608533 22037378
SureCN4875304 IC50 > 3.5 µM 46871765 20472445
Cot-Tpl2 Inhibitor Compound 41 (Abbott) IC50 < 4 µM
Curcumin IC50 < 4 µM 5281767 116438
JNJ-28871063 IC50 > 4 µM 17747413 17975007
Quercetagetin IC50 < 4 µM 5281680 413552
GSK269962A IC50 > 4.5 µM 16095342 220241
H-1152; Glycyl IC50 > 4.5 µM 16760635
Kenpaullone IC50 > 4.5 µM 3820 296586
 

Disease Linkage

General Disease Association:

Cancer
Specific Cancer Types:
Colorectal adenocarcinomas; Mantle cell lymphomas (LCM)
Comments:
Pim2 appears to be a oncoprotein (OP), although it shows a level of bystander mutations typical of most proteins in human cancers. The active form of the protein kinase normally acts to promote tumour cell proliferation. Pim2 is linked to Mantle Cell Lymphomas (LCM), which are non-Hodgkin lymphomas in which is specifically a B-cell lymphoma is also associated the ATM (ataxia telangiectasia mutated) gene.
 
Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Barrett's esophagus epithelial metaplasia (%CFC= +104, p<0.032); Brain oligodendrogliomas (%CFC= +48, p<0.007); Cervical cancer (%CFC= -56, p<0.003); Classical Hodgkin lymphomas (%CFC= +57, p<0.001); Gastric cancer (%CFC= -59, p<0.024); Large B-cell lymphomas (%CFC= +195, p<0.0007); Lung adenocarcinomas (%CFC= +68, p<0.001); and Oral squamous cell carcinomas (OSCC) (%CFC= +50, p<0.105).
Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.
Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 24433 diverse cancer specimens. This rate is the same as the average rate of 0.075 % calculated for human protein kinases in general.
Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.4 % in 1052 large intestine cancers tested.
Frequency of Mutated Sites:

None > 1 in 20,654 cancer specimens
Comments:
Only 1 deletion and 1 insertion, and no complex mutations are noted on the COSMIC website. About 39% of the point mutations are silent and do not change the amino acid sequence of the protein kinase.
 
COSMIC Entry:
PIM2_ENST00000376509
OMIM Entry:
300295
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