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Updated November 2019

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Nomenclature

Short Name:
ULK3
Full Name:
Serine-threonine-protein kinase ULK3
Alias:
  • AL117482
  • DKFZP434C131
  • Hypothetical protein DKFZp434C131
  • Unc-51-like kinase 3

Classification

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

Specific Links

Entrez-Gene Entry: 25989
Entrez-Protein Entry: NP_056333
GeneCards Entry: FLJ90566
Pfam Entry: Q6PHR2
PhosphoNET Entry: Q6PHR2
Phosphosite Plus Entry: 2.8128e+006
Source Entry: ULK3
UCSD-Nature Entry: A003647
UniProt Entry: Q6PHR2
Kinexus Products: ULK3
Unc-51 (C. elegan) -like kinase 3 pan-specific antibody AB-NK355-1

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):
53,444
# Amino Acids:
472
# mRNA Isoforms:
4
mRNA Isoforms:
54,997 Da (483 AA; Q6PHR2-4); 53,444 Da (472 AA; Q6PHR2); 53,217 Da (470 AA; Q6PHR2-3); 24,402 Da (214 AA; Q6PHR2-2)
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
14 270 Pkinase
280 348 MIT
375 444 MIT
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ Unc-51 (C. elegan) -like kinase 3 pan-specific antibody AB-NK355-1
 

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
    74

    1349

    9

    896

  • adrenal
    4

    69

    1

    0

  • bladder
    -

    -

    -

    -

  • brain
    17

    318

    35

    405

  • breast
    51

    938

    10

    476

  • cervix
    5

    94

    9

    19

  • colon
    5

    88

    10

    34

  • heart
    100

    1832

    10

    3621

  • intestine
    -

    -

    -

    -

  • kidney
    16

    288

    32

    324

  • liver
    13

    231

    8

    166

  • lung
    54

    990

    25

    503

  • lymphnode
    -

    -

    -

    -

  • ovary
    -

    -

    -

    -

  • pancreas
    21

    391

    8

    308

  • pituitary
    5

    95

    5

    36

  • prostate
    15

    267

    205

    278

  • salivarygland
    -

    -

    -

    -

  • skeletalmuscle"
    8

    141

    25

    92

  • skin
    61

    1122

    28

    484

  • spinalcord
    28

    506

    8

    439

  • spleen
    39

    722

    8

    567

  • stomach
    -

    -

    -

    -

  • testis
    -

    -

    -

    -

  • thymus
    29

    534

    8

    415

  • thyroid
    85

    1566

    19

    1475

  • tonsil
    -

    -

    -

    -

  • trachea
    -

    -

    -

    -

  • uterus
    -

    -

    -

    -

  • reticulocytes"
    8

    155

    14

    100

  • t-lymphocytes
    -

    -

    -

    -

  • b-lymphocytes
    79

    1439

    11

    2336

  • neutrophils
    81

    1493

    43

    2273

  • macrophages
    45

    821

    26

    682

  • sperm
    49

    895

    13

    406

 

Evolution

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

    100

    100
  • tableheader
    99.1

    99.5

    99
  • tableheader
    73.7

    77.9

    -
  • tableheader
    -

    -

    97
  • tableheader
    -

    -

    -
  • tableheader
    75.3

    79

    95
  • tableheader
    -

    -

    -
  • tableheader
    94

    97.6

    94
  • tableheader
    93.6

    96.4

    95
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    78.1

    90

    79
  • tableheader
    72.8

    87.2

    74
  • tableheader
    71.1

    84.7

    71
  • tableheader
    -

    -

    -
  • tableheader
    40.1

    57.6

    46
  • tableheader
    44.1

    64.3

    -
  • tableheader
    23.8

    37.1

    -
  • tableheader
    48

    64.5

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    26.7

    41.6

    -
  • tableheader
    24.8

    36.3

    -
  • tableheader
    23.8

    35

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

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
ULK3 Q6PHR2 S300 KKDQEGDSAAALSLY
 

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 = 1.2 nM 5279 22037378
Lestaurtinib Kd = 4.9 nM 126565 22037378
R406 Kd = 7.1 nM 11984591 22037378
Hesperadin Kd < 10 nM 10142586 514409 19035792
NVP-TAE684 Kd = 11 nM 16038120 509032 22037378
K-252a; Nocardiopsis sp. IC50 < 25 nM 3813 281948 22037377
SU14813 Kd = 42 nM 10138259 1721885 22037378
Sunitinib Kd = 42 nM 5329102 535 19654408
AST-487 Kd = 57 nM 11409972 574738 22037378
Nintedanib Kd = 60 nM 9809715 502835 22037378
KW2449 Kd = 120 nM 11427553 1908397 22037378
SU11652 IC50 > 150 nM 24906267 13485 22037377
SU6656 IC50 > 150 nM 5353978 605003 22037377
Syk Inhibitor IC50 > 150 nM 6419747 104279 22037377
Dovitinib Kd = 170 nM 57336746 22037378
JAK3 Inhibitor VI IC50 > 250 nM 16760524 22037377
N-Benzoylstaurosporine IC50 > 250 nM 56603681 608533 22037377
SB218078 IC50 > 250 nM 447446 289422 22037377
TG101348 Kd = 290 nM 16722836 1287853 22037378
Tozasertib Kd = 310 nM 5494449 572878 22037378
Foretinib Kd = 450 nM 42642645 1230609 22037378
Bosutinib Kd = 460 nM 5328940 288441 22037378
SU11274 IC50 = 500 nM 9549297 261641 22037377
VEGFR2 Kinase Inhibitor II IC50 = 500 nM 5329155 88606 22037377
Erlotinib = 630 nM 176870 553
Axitinib Kd = 670 nM 6450551 1289926 22037378
AG112 IC50 > 1 µM 5328804 76589 22037377
PKR Inhibitor IC50 > 1 µM 6490494 235641 22037377
Purvalanol A IC50 > 1 µM 456214 23327 22037377
Semaxinib IC50 > 1 µM 5329098 276711 22037377
SU9516 IC50 > 1 µM 5289419 258805 22037377
Syk Inhibitor III IC50 > 1 µM 672296 596380 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
IKK-2 Inhibitor IV Kd < 1.25 µM 9903786 257167 19035792
SureCN5302803 Kd < 1.25 µM 24788740 19035792
Ruxolitinib Kd = 2.4 µM 25126798 1789941 22037378
AC1NS4N8 Kd < 2.5 µM 23649240 19035792
CHEMBL249097 Kd < 2.5 µM 25138012 249097 19035792
LKB1(AAK1 dual inhibitor) Kd < 2.5 µM 44588117 516312 19035792
BMS-690514 Kd < 4.5 µM 11349170 21531814
Dasatinib Kd = 4.6 µM 11153014 1421 22037378
Canertinib Kd = 4.7 µM 156414 31965 22037378
 

Disease Linkage

General Disease Association:

Cancer
Specific Cancer Types:
Chronic myeloid leukemias (CML)
Comments:
ULK3 attenuates positive regulation in cancer and multipotent progenitor cells. ULK3 was identified as a drug target for colon cancer.
 
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: Ovary adenocarcinomas (%CFC= +109, p<0.048); Prostate cancer (%CFC= +48, p<0.088); and Prostate cancer - metastatic (%CFC= +54, p<0.015).
Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. K44R and K139R mutations in ULK3 can lead to reduced phosphotransferase activity.
Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.05 % in 24433 diverse cancer specimens. This rate is only -31 % 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: 0.19 % in 1229 large intestine cancers tested; 0.18 % in 603 endometrium cancers tested; 0.17 % in 864 skin cancers tested; 0.14 % in 881 prostate cancers tested; 0.11 % in 555 stomach cancers tested; 0.08 % in 807 ovary cancers tested; 0.08 % in 1253 kidney cancers tested; 0.07 % in 1437 pancreas cancers tested; 0.07 % in 1289 breast cancers tested; 0.06 % in 382 soft tissue cancers tested; 0.05 % in 1608 lung cancers tested; 0.04 % in 558 thyroid cancers tested; 0.04 % in 548 urinary tract cancers tested; 0.03 % in 2030 central nervous system cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: M180T (3).
Comments:
Only 2 deletions, 3 insertions, and no complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
ULK3_ENST00000440863
OMIM Entry:
613472
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