STK11_HUMAN
Source:
PM23856902
PM22954596
Marked as 'Membrane associated protein'
Confidence:
medium (present in either hRBCD or BSc_CH or PM22954596)
Search PubMed for
(RBC AND this entry)
Gene names:
STK11
, LKB1, PJS
Protein names and data:
STK11_HUMAN
, Serine/threonine-protein kinase STK11; 2.7.11.1
, Liver kinase B1; LKB1; hLKB1; Renal carcinoma antigen NY-REN-19; Flags: Precursor
Lenght: 433 a.a.
Mass: 48636 Da
fasta formatted sequence
Function:
Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, leading to promote their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2: it thereby regulates inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neurons polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1 Also acts as a mediator p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways.
Catalytic activity:
ATP + a protein = ADP + a phosphoprotein.
Disease:
( OMIM:
175200
273300
602216
)
Peutz-Jeghers syndrome (PJS) [MIM:175200]: An autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. Note=The disease is caused by mutations affecting the gene represented in this entry. Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. Note=The gene represented in this entry may be involved in disease pathogenesis. Note=Defects in STK11 are associated with some sporadic cancers, especially lung cancers. Frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Defects promote lung cancerigenesis process, especially lung cancer progression and metastasis. Confers lung adenocarcinoma the ability to trans- differentiate into squamous cell carcinoma. Also able to promotes lung cancer metastasis, via both cancer-cell autonomous and non- cancer-cell autonomous mechanisms.
Cellular location:
Nucleus. Cytoplasm. Membrane (By similarity). Mitochondrion. Note=A small fraction localizes at membranes (By similarity). Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). Translocates to mitochondrion during apoptosis.
Tissue specificity:
Ubiquitously expressed. Strongest expression in testis and fetal liver.
Genetic variants
14 - 14
E -> K (in cervical cancer; somatic mutation). VAR_065627
16 - 16
E -> G (in PJS). VAR_065628
49 - 49
Y -> D (in melanoma; sporadic malignant; somatic mutation). VAR_033138
66 - 66
V -> M (in cervical carcinoma; somatic mutation). VAR_065629
67 - 67
L -> P (in PJS). VAR_006202
86 - 86
R -> G (in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39). VAR_065630
87 - 87
R -> K (in a metastatic melanoma sample; somatic mutation). VAR_041139
123 - 123
Q -> R (in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39). VAR_065631
135 - 135
G -> R (in melanoma; sporadic malignant; somatic mutation). VAR_033139
157 - 157
F -> S (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065632
160 - 160
L -> P (in cervical cancer; somatic mutation). VAR_065633
162 - 164
DGL -> NDM (in PJS). VAR_007920
163 - 163
G -> D (in TGCT; a tumor with seminoma and teratoma components; associated with severely impaired but detectable kinase activity; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_033140
170 - 170
Q -> P (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065634
171 - 171
G -> S (in colorectal cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065635
174 - 174
H -> R (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065636
176 - 176
D -> Y (in sporadic cancer; somatic mutation; Loss of kinase activity). VAR_065637
177 - 177
I -> N (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065638
181 - 181
N -> E (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39; requires 2 nucleotide substitutions). VAR_065639
194 - 194
D -> N (in PJS). VAR_007921
194 - 194
D -> V (in lung cancer; somatic mutation). VAR_065640
194 - 194
D -> Y (in melanoma; sporadic malignant; somatic mutation). VAR_033141
199 - 199
E -> K (in colorectal cancer; somatic mutation; impaired kinase activity). VAR_065641
199 - 199
E -> Q (in sporadic cancer; somatic mutation; does not affect kinase activity). VAR_065642
205 - 205
A -> T (in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39). VAR_065643
208 - 208
D -> N (in colorectal cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39). VAR_065644
215 - 215
G -> D (in colorectal cancer; somatic mutation). VAR_065645
216 - 216
S -> F (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065646
223 - 223
E -> V (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065647
230 - 230
T -> P (in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39). VAR_065648
231 - 231
F -> L (in cervical cancer; somatic mutation). VAR_065649
232 - 232
S -> P (in sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39). VAR_065650
239 - 239
W -> C (in PJS; late onset suggests reduced penetrance). VAR_033142
245 - 245
L -> R (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065651
247 - 247
Missing (in PJS). VAR_006203
250 - 250
T -> P (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065652
272 - 272
Y -> H (in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39). VAR_065653
277 - 277
D -> Y (in sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39). VAR_065654
281 - 281
P -> L (in ovarian carcinoma; somatic mutation). VAR_065655
285 - 285
L -> Q (in sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39). VAR_065656
297 - 297
R -> K (in PJS). VAR_007922
303 - 306
IRQH -> N (in PJS). VAR_033143
314 - 314
P -> H (in colorectal cancer; no effect heterotrimeric complex assembly with STRADA and CAB39). VAR_065657
315 - 315
P -> S (in PJS; pathogenicity uncertain; no effect heterotrimeric complex assembly with STRADA and CAB39). VAR_033144
324 - 324
P -> L (in gastric carcinoma; no effect heterotrimeric complex assembly with STRADA and CAB39). VAR_065658
354 - 354
F -> L (in colorectal cancer; somatic mutation). VAR_065659
367 - 367
T -> M (in colorectal cancer; somatic mutation). VAR_065660
Database cross-references
UniProt:
Q15831
Ensembl:
ENST00000326873
MIM:
175200
MIM:
273300
MIM:
602216
neXtProt:
NX_Q15831
Antibodypedia:
Q15831
(may not find the protein thus also not any antibody)
Local full text data:
click here
Users' comments
Login to add a comment.