Nomenclature
Short Name:
STLK5
    Full Name:
Serologically defined breast cancer antigen NY-BR-96
    Alias:
- LYK5
- Serologically defined breast cancer antigen NY-BR-96
- STE20-related adapter protein
- STRAD alpha
Classification
Type:
Protein-serine/threonine kinase
    Group:
STE
    Family:
STE20
    SubFamily:
STLK
    Structure
Mol. Mass (Da):
48,369
    # Amino Acids:
431
    # mRNA Isoforms:
6
    mRNA Isoforms:
48,369 Da (431 AA; Q7RTN6); 43,962 Da (394 AA; Q7RTN6-3); 41,701 Da (373 AA; Q7RTN6-5); 38,597 Da (348 AA; Q7RTN6-2); 34,625 Da (314 AA; Q7RTN6-6); 33,277 Da (299 AA; Q7RTN6-4)
    4D Structure:
NA
    1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment

Domain Distribution:
| Start | End | Domain | 
|---|---|---|
| 69 | 379 | Pkinase | 
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
       Serine phosphorylated:
S2, S46, S49, S52, S313.
Threonine phosphorylated:
T42, T329, T398, T419.
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:  
    98 98
 1126
 41
 1021
 
 15 15
 177
 15
 166
 
 21 21
 241
 2
 148
 
 40 40
 457
 131
 653
 
 63 63
 724
 42
 561
 
 9 9
 102
 92
 79
 
 4 4
 47
 47
 59
 
 92 92
 1065
 30
 1294
 
 31 31
 360
 17
 256
 
 12 12
 144
 87
 190
 
 18 18
 204
 21
 215
 
 88 88
 1013
 146
 688
 
 16 16
 179
 24
 88
 
 12 12
 140
 9
 129
 
 15 15
 171
 15
 199
 
 10 10
 120
 24
 121
 
 41 41
 478
 171
 1968
 
 10 10
 119
 9
 118
 
 11 11
 131
 89
 118
 
 50 50
 575
 160
 507
 
 33 33
 379
 13
 519
 
 26 26
 304
 17
 392
 
 19 19
 214
 4
 165
 
 43 43
 497
 9
 444
 
 32 32
 368
 13
 586
 
 78 78
 895
 80
 892
 
 14 14
 160
 27
 99
 
 13 13
 153
 9
 139
 
 15 15
 171
 9
 151
 
 25 25
 290
 42
 222
 
 71 71
 820
 36
 699
 
 100 100
 1153
 46
 1513
 
 4 4
 42
 58
 42
 
 78 78
 903
 104
 781
 
 99 99
 1137
 61
 1219
 
Evolution
Species Conservation
PhosphoNET % Identity:  
PhosphoNET % Similarity:  
  Homologene %
Identity:  
            PhosphoNET % Identity:  
PhosphoNET % Similarity:  
  Homologene %
Identity:  
    100 100
 100
 100
 34.1 34.1
 43.1
 95
 99.3 99.3
 99.7
 99
 - -
 -
 95
 - -
 -
 -
 88.1 88.1
 89.3
 97
 - -
 -
 -
 95.1 95.1
 97.6
 95
 84.9 84.9
 88.4
 93
 - -
 -
 -
 42.9 42.9
 54.6
 -
 73 73
 78.1
 86
 39.9 39.9
 54.7
 79
 35.2 35.2
 42.9
 72
 - -
 -
 -
 31.7 31.7
 48.2
 37.5
 - -
 -
 -
 - -
 -
 36
 42.4 42.4
 58.4
 -
 - -
 -
 -
 - -
 -
 -
 - -
 -
 -
 - -
 -
 -
 - -
 -
 -
 - -
 -
 -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
    Regulation
Activation:
NA
    Inhibition:
NA
    Synthesis:
NA
    Degradation:
NA
    
Protein Kinase Specificity
Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites
      
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
    Disease Linkage
General Disease Association:
Cancer, neurological disorders
Specific Diseases (Non-cancerous):
Polyhydramnios; Megalencephaly; Polyhydramnios, Megalencephaly, and Symptomatic Epilepsy
Comments:
A homozygous 7-kb deletion associated with STRADA is a cause of a syndrome characterized by polyhydramnios, megalencephaly and symptomatic epilepsy. 
 
   Specific Cancer Types:
 Breast cancer
Comments:
STLK5 is a serologically defined breast cancer antigen. The protein regulates cell polarity and invasion in LKB1-null cells, and plays critical role in cancer metastasis. STLK5 deficiency was found to associate with abnormal mTORC1 signalling during corticogenesis in humans and mice. The gene mutation associates with Peutz-Jeghers syndrome.  
 
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: Brain oligodendrogliomas (%CFC= -100, p<0.098); and Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -93, p<0.0001). The COSMIC website notes an up-regulated expression score for STLK5 in diverse human cancers of 671, which is 1.5-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 204 for this protein kinase in human cancers was 3.4-fold of 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: 0.06 % in 24939 diverse cancer specimens. This rate is only -22 % 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: 0.39 % in 589 stomach cancers tested; 0.34 % in 1093 large intestine cancers tested.
Frequency of Mutated Sites:
None > 3 in 20,222 cancer specimens
Comments:
Nine deletions (8 at R333fs*42), and no insertions or complex mutations are noted on the COSMIC website.
 

