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Updated November 2019

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Nomenclature

Short Name:
PFTAIRE2
Full Name:
ALS2CR7
Alias:
  • A2S7
  • EC 2.7.11.22
  • PFTAIRE protein kinase 2
  • PFTK2
  • Serine/threonine-protein kinase ALS2CR7
  • AL2S7
  • ALS2CR7
  • Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein
  • Amyotrophic lateral sclerosis 2 chromosomal region candidate gene protein 7
  • CDK15

Classification

Type:
Protein-serine/threonine kinase
Group:
CMGC
Family:
CDK
SubFamily:
TAIRE
 
 

Specific Links

Entrez-Gene Entry: 65061
Entrez-Protein Entry: NP_631897
KinBASE Entry: PFTAIRE2
Pfam Entry: Q96Q40
PhosphoNET Entry: Q96Q40
Phosphosite Plus Entry: 3760
ScanSite Entry: Q96Q40
UCSD-Nature Entry: A003635
UniProt Entry: Q96Q40
Kinexus Products: PFTAIRE2
Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein pan-specific antibody AB-NK004-2
Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein (P33-C50, human) peptide - Powder PE-01BEO70
Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein (C416-K433, human) peptide - Powder PE-01BEP80

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):
49,023
# Amino Acids:
435
# mRNA Isoforms:
5
mRNA Isoforms:
49,023 Da (435 AA; Q96Q40); 48,316 Da (429 AA; Q96Q40-5); 45,046 Da (400 AA; Q96Q40-3); 43,574 Da (384 AA; Q96Q40-4); 40,122 Da (358 AA; Q96Q40-2)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
103 387 Pkinase
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein pan-specific antibody AB-NK004-2
○ Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein (P33-C50, human) peptide - Powder PE-01BEO70
○ Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein (C416-K433, human) peptide - Powder PE-01BEP80
 

Post-translation Modifications

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

S77.
Threonine phosphorylated:

T170.
Tyrosine phosphorylated:

Y114, Y118.
Ubiquitinated:
K239.
 

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
    72

    1271

    18

    1340

  • adrenal
    0.3

    6

    6

    5

  • bladder
    -

    -

    -

    -

  • brain
    1.1

    19

    76

    25

  • breast
    29

    517

    27

    299

  • cervix
    0.5

    9

    27

    10

  • colon
    0.3

    6

    33

    6

  • heart
    0.2

    4

    5

    5

  • intestine
    0.1

    2

    3

    0

  • kidney
    3

    52

    29

    49

  • liver
    0.3

    6

    5

    7

  • lung
    53

    939

    23

    522

  • lymphnode
    -

    -

    -

    -

  • ovary
    0.2

    4

    3

    2

  • pancreas
    0.3

    6

    5

    5

  • pituitary
    0.5

    8

    15

    5

  • prostate
    0.8

    14

    92

    11

  • salivarygland
    0.1

    1

    3

    0

  • skeletalmuscle"
    3

    59

    21

    43

  • skin
    24

    433

    77

    198

  • spinalcord
    0.2

    3

    5

    3

  • spleen
    0.2

    3

    5

    2

  • stomach
    -

    -

    -

    -

  • testis
    1.2

    21

    3

    1

  • thymus
    0.2

    4

    5

    4

  • thyroid
    76

    1350

    53

    3308

  • tonsil
    0.1

    2

    3

    1

  • trachea
    0.1

    2

    3

    0

  • uterus
    0.1

    2

    3

    1

  • reticulocytes"
    10

    171

    14

    120

  • t-lymphocytes
    26

    459

    12

    38

  • b-lymphocytes
    100

    1768

    21

    3762

  • neutrophils
    0.1

    2

    36

    0

  • macrophages
    45

    796

    78

    700

  • sperm
    6

    112

    48

    124

 

Evolution

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

    100

    100
  • tableheader
    91

    91.3

    99
  • tableheader
    58.3

    59.6

    97
  • tableheader
    -

    -

    91
  • tableheader
    -

    -

    -
  • tableheader
    92

    94.8

    92.5
  • tableheader
    -

    -

    -
  • tableheader
    89.4

    92.9

    91
  • tableheader
    41.7

    56.6

    86
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    63.8

    73.9

    69
  • tableheader
    54.3

    68

    -
  • tableheader
    61.4

    72.9

    67
  • tableheader
    -

    -

    -
  • tableheader
    35.2

    46.4

    -
  • tableheader
    46.8

    59.7

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    33.1

    45.8

    -
  • tableheader
    36.5

    48.5

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Binding Proteins

Examples of known interacting proteins
hiddentext
No. Name – UniProt ID
1 CDK2 - P24941
2 CENPK - Q9BS16
 

Regulation

Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
 

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
BIRC5 (Survivin) O15392 T34 FLEGCACTPERMAEA +
 

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
R547 Kd = 7.2 nM 6918852 22037378
Foretinib Kd = 32 nM 42642645 1230609 22037378
AT7519 Kd = 62 nM 11338033 22037378
AST-487 Kd = 84 nM 11409972 574738 22037378
Staurosporine Kd = 260 nM 5279 22037378
Alvocidib Kd = 330 nM 9910986 428690 22037378
PHA-665752 Kd = 510 nM 10461815 450786 22037378
AC1NS7CD Kd = 740 nM 5329665 295136 22037378
SNS032 Kd = 740 nM 3025986 296468 22037378
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
Lestaurtinib Kd = 1.3 µM 126565 22037378
Bosutinib Kd = 1.6 µM 5328940 288441 22037378
A674563 Kd = 2.1 µM 11314340 379218 22037378
NVP-TAE684 Kd = 2.1 µM 16038120 509032 22037378
KW2449 Kd = 2.6 µM 11427553 1908397 22037378
Sorafenib Kd = 2.9 µM 216239 1336 19654408
BMS-690514 Kd < 3 µM 11349170 21531814
Enzastaurin Kd = 4.9 µM 176167 300138 22037378
 

Disease Linkage

General Disease Association:

Neurological disorders
Specific Diseases (Non-cancerous):

Amyotrophic lateral sclerosis (ALS); Primary lateral sclerosis (PLS)
Comments:
ALS is a rare neuronal disease affecting motor control. PFTAIRE2 may be associated with amyotrophic lateral sclerosis 2 (ALS2), which is an autosomal recessive form of juvenile ALS. Characteristics of ALS can include cramping, stiffness, muscle twitching, weakness, slurring words, chewing difficulties, and dysphagia (difficulty swallowing). Lateral Sclerosis (PLS) is a rare neuronal disease related to the Amyotrophic Lateral Sclerosis disorder.
 
Gene Expression in Cancers:

The COSMIC website notes an up-regulated expression score for PFTAIRE2 in diverse human cancers of 300, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than the average score of 60 for the human protein kinases.
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 25141 diverse cancer specimens. This rate is very similar (+ 6% higher) to 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: 0.34 % in 1270 large intestine cancers tested; 0.31 % in 1634 lung cancers tested; 0.29 % in 548 urinary tract cancers tested; 0.27 % in 603 endometrium cancers tested; 0.16 % in 864 skin cancers tested; 0.16 % in 589 stomach cancers tested; 0.12 % in 1316 breast cancers tested; 0.09 % in 1512 liver cancers tested; 0.09 % in 1276 kidney cancers tested; 0.04 % in 558 thyroid cancers tested; 0.03 % in 833 ovary cancers tested; 0.02 % in 1459 pancreas cancers tested; 0.01 % in 2082 central nervous system cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: V210M (3).
Comments:
Only 3 deletions, and no insertions or complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
CDK15
OMIM Entry:
616147
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