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Updated November 2019

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Nomenclature

Short Name:
ULK2
Full Name:
Serine-threonine-protein kinase ULK2
Alias:
  • EC 2.7.11.1
  • KIAA0623
  • Unc51.2
  • Unc-51-like kinase 2

Classification

Type:
Protein-serine/threonine kinase
Group:
Other
Family:
ULK
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 9706
Entrez-Protein Entry: NP_055498
GeneCards Entry: KIAA0623
KinBASE Entry: ULK2
OMIM Entry: 608650
Pfam Entry: Q8IYT8
PhosphoNET Entry: Q8IYT8
Phosphosite Plus Entry: 807
Source Entry: ULK2
UCSD-Nature Entry: A003024
UniProt Entry: Q8IYT8
Kinexus Products: ULK2
Unc 51 (C. elegans) like kinase 2 pan-specific antibody AB-NK354-1

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):
112694
# Amino Acids:
1036
# mRNA Isoforms:
1
mRNA Isoforms:
112,694 Da (1036 AA; Q8IYT8)
4D Structure:
Interacts (via C-terminus) with ATG13/KIAA0652.
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
9 271 Pkinase
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ Unc 51 (C. elegans) like kinase 2 pan-specific antibody AB-NK354-1
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K922.
Serine phosphorylated:

S104, S148, S150, S323, S574, S771, S1027.
Threonine phosphorylated:

T425, T576, T826, T844.
Tyrosine phosphorylated:

Y331, Y1018.
 

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
    37

    847

    51

    908

  • adrenal
    2

    38

    23

    24

  • bladder
    5

    122

    19

    116

  • brain
    16

    374

    171

    460

  • breast
    28

    641

    42

    499

  • cervix
    1.1

    25

    120

    17

  • colon
    7

    162

    57

    360

  • heart
    18

    411

    58

    503

  • intestine
    13

    292

    24

    221

  • kidney
    3

    73

    131

    95

  • liver
    2

    48

    46

    53

  • lung
    28

    636

    267

    649

  • lymphnode
    2

    54

    52

    56

  • ovary
    2

    41

    18

    21

  • pancreas
    3

    68

    39

    96

  • pituitary
    2

    42

    28

    19

  • prostate
    9

    208

    230

    1824

  • salivarygland
    4

    97

    31

    131

  • skeletalmuscle"
    4

    87

    133

    73

  • skin
    20

    456

    185

    466

  • spinalcord
    11

    261

    36

    291

  • spleen
    3

    61

    42

    60

  • stomach
    5

    111

    22

    99

  • testis
    13

    289

    32

    371

  • thymus
    3

    60

    35

    75

  • thyroid
    29

    669

    104

    1147

  • tonsil
    3

    64

    55

    162

  • trachea
    4

    92

    32

    109

  • uterus
    5

    105

    32

    115

  • reticulocytes"
    5

    122

    42

    75

  • t-lymphocytes
    21

    475

    30

    516

  • b-lymphocytes
    100

    2305

    56

    5396

  • neutrophils
    8

    183

    113

    502

  • macrophages
    34

    787

    104

    639

  • sperm
    23

    541

    61

    691

 

Evolution

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

    100

    100
  • tableheader
    99.3

    99.6

    99
  • tableheader
    94.6

    95.8

    98
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    95
  • tableheader
    -

    -

    -
  • tableheader
    93.6

    96.1

    94
  • tableheader
    22.1

    38.1

    94
  • tableheader
    -

    -

    -
  • tableheader
    86.7

    92.2

    -
  • tableheader
    20.9

    30.8

    87
  • tableheader
    20.9

    31.9

    80
  • tableheader
    75.6

    85.4

    76
  • tableheader
    -

    -

    -
  • tableheader
    35.3

    50.2

    32
  • tableheader
    38.5

    51.7

    -
  • tableheader
    33.1

    48.8

    31
  • 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 SYNGAP1 - Q96PV0
 

Regulation

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

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 = 790 pM 5279 22037378
NVP-TAE684 Kd = 1.8 nM 16038120 509032 22037378
TTT-3002 IC50 < 6 nM
Sunitinib Kd = 13 nM 5329102 535 19654408
R406 Kd = 19 nM 11984591 22037378
Cdk1/2 Inhibitor III IC50 > 50 nM 5330812 261720 22037377
K-252a; Nocardiopsis sp. IC50 > 50 nM 3813 281948 22037377
Dovitinib Kd = 54 nM 57336746 22037378
JNKIN8 IC50 < 60 nM 57340686
Lestaurtinib Kd = 60 nM 126565 22037378
SU14813 Kd = 65 nM 10138259 1721885 22037378
TG101348 Kd = 79 nM 16722836 1287853 22037378
Aurora A Inhibitor 23 (DF) Kd < 100 nM 21992004
JNKIN7 IC50 = 100 nM 57340685
SU6656 IC50 < 100 nM 5353978 605003
KW2449 Kd = 130 nM 11427553 1908397 22037378
SU11274 IC50 > 150 nM 9549297 261641 22037377
Ruxolitinib Kd = 190 nM 25126798 1789941 22037378
Aurora A Inhibitor 1 (DF) Kd < 200 nM 21992004
BCP9000906 IC50 > 250 nM 5494425 21156 22037377
SU11652 IC50 > 250 nM 24906267 13485 22037377
AST-487 Kd = 360 nM 11409972 574738 22037378
Nintedanib Kd = 380 nM 9809715 502835 22037378
Aurora A Inhibitor 29 (DF) Kd < 400 nM 21992004
Bosutinib Kd = 450 nM 5328940 288441 22037378
Alvocidib Kd = 470 nM 9910986 428690 22037378
JAK3 Inhibitor VI IC50 = 500 nM 16760524 22037377
PKR Inhibitor IC50 = 500 nM 6490494 235641 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
PHA-665752 Kd = 1.5 µM 10461815 450786 22037378
Crizotinib Kd = 1.6 µM 11626560 601719 22037378
GSK690693 Kd = 2.3 µM 16725726 494089 22037378
BMS-690514 Kd < 3 µM 11349170 21531814
PP242 Kd = 4.9 µM 25243800 22037378
 

Disease Linkage

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: Breast epithelial carcinomas (%CFC= -50, p<0.047); and Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +131, p<0.012).
Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. A K39R mutation in ULK2 can inhibit its phosphotransferase activity and decrease autophosphorylation.
Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 24433 diverse cancer specimens. This rate is only -24 % lower than 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: 0.2 % in 864 skin cancers tested; 0.19 % in 603 endometrium cancers tested; 0.18 % in 589 stomach cancers tested; 0.17 % in 1270 large intestine cancers tested; 0.15 % in 65 Meninges cancers tested; 0.12 % in 548 urinary tract cancers tested; 0.11 % in 273 cervix cancers tested; 0.08 % in 1512 liver cancers tested; 0.07 % in 710 oesophagus cancers tested; 0.06 % in 1634 lung cancers tested; 0.05 % in 1316 breast cancers tested; 0.04 % in 238 bone cancers tested; 0.03 % in 942 upper aerodigestive tract cancers tested; 0.03 % in 382 soft tissue cancers tested; 0.03 % in 2082 central nervous system cancers tested; 0.02 % in 1276 kidney cancers tested; 0.01 % in 881 prostate cancers tested; 0.01 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 1459 pancreas cancers tested;
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R821W (4); P702L (3).
Comments:
Only 7 deletions, 4 insertions and no complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
ULK2
OMIM Entry:
608650
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