Serine/threonine-protein kinase STK11 (STK11)
The protein contains 433 amino acids for an estimated molecular weight of 48636 Da.
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, thus promoting 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, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: 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, and 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 neuron 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 (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Activation of protein kinase activity
Anoikis
Autophagy
Axonogenesis
Canonical Wnt signaling pathway
Cell cycle arrest
Cell differentiation
Cellular response to DNA damage stimulus
Cellular response to UV-B
Dendrite extension
Energy reserve metabolic process
Establishment of cell polarity
Glucose homeostasis
Golgi localization
Insulin receptor signaling pathway
Intrinsic apoptotic signaling pathway by p53 class mediator
Negative regulation of canonical Wnt signaling pathway
Negative regulation of cell growth
Negative regulation of cell population proliferation
Negative regulation of cold-induced thermogenesis
Negative regulation of epithelial cell proliferation involved in prostate gland development
Negative regulation of lipid biosynthetic process
Negative regulation of TORC1 signaling
Nervous system development
Peptidyl-serine phosphorylation
Peptidyl-threonine phosphorylation
Positive regulation of autophagy
Positive regulation of axonogenesis
Positive regulation of gluconeogenesis
Positive regulation of peptidyl-tyrosine phosphorylation
Positive regulation of protein localization to nucleus
Positive regulation of protein serine/threonine kinase activity
Positive regulation of transforming growth factor beta receptor signaling pathway
Positive regulation of vesicle transport along microtubule
Positive thymic T cell selection
Protein autophosphorylation
Protein dephosphorylation
Protein heterooligomerization
Protein phosphorylation
Regulation of cell growth
Regulation of dendrite morphogenesis
Regulation of fatty acid biosynthetic process
Regulation of protein kinase B signaling
Regulation of signal transduction by p53 class mediator
Regulation of Wnt signaling pathway
Response to glucagon
Response to ionizing radiation
Response to lipid
Small molecule metabolic process
Spermatid development
Spermatogenesis
T cell receptor signaling pathway
TCR signalosome assembly
Tissue homeostasis
Vasculature development
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Membrane
Mitochondrion
Nucleoplasm
Nucleus
TCR signalosome
The reference OMIM entry for this protein is 175200
Peutz-jeghers syndrome; pjs
Polyposis, hamartomatous intestinal
Polyps-and-spots syndrome
A number sign (#) is used with this entry because Peutz-Jeghers syndrome (PJS) is caused by heterozygous mutation in the serine/threonine kinase STK11 gene (602216) on chromosome 19p13.
DESCRIPTION
Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by melanocytic macules of the lips, buccal mucosa, and digits; multiple gastrointestinal hamartomatous polyps; and an increased risk of various neoplasms.CLINICAL FEATURES
In the syndrome named for Peutz (1921) and Jeghers (Jeghers et al., 1949), polyps may occur in any part of the gastrointestinal tract but jejunal polyps are a consistent feature. Intussusception and bleeding are the usual symptoms. Melanin spots of the lips, buccal mucosa, and digits represent the second part of the syndrome. Malignant degeneration of the small intestinal polyps is rare. Metastases from a malignant polyp in Peutz-Jeghers syndrome was reported by Williams and Knudsen (1965). Dodds et al. (1972) found 15 cases of gastrointestinal carcinoma in Peutz-Jeghers syndrome: 5 in colon, 4 in duodenum, 4 in stomach, 1 in ileum, and 1 in both jejunum and stomach. In the family reported by Farmer et al. (1963), the father had only polyps, the son apparently only pigmentation, and the daughter both polyps and pigmentation. Kieselstein et al. (1969), who found polycystic kidney disease in the same family, also noted a dissociation of signs. Brigg et al. (1976) observed a case of presumed Peutz-Jeghers syndrome without spots or positive family history. Hamartomatous polyps were limited to the jejunum and caused bleeding. Griffith and Bisset (1980) reported 3 cases. In 2 of them, the family history was negative; in the third, the father and a paternal uncle had melanin spots of the lips but no history of intestinal disorder. Sommerhaug and Mason (1970) added the ureter to the sites of polyps described in the Peutz-Jeghers syndrome. Previously described extraintestinal sites include esophagus, bladder, renal pelvis, bronchus and nose. Burdick and Prior (1982) reported nonresectable adenocarcinoma of the jejunum arising in a Peutz-Jeghers polyp and accompanied by metastases in mesenteric lymph nodes. Two developed breast carcinoma of which 1 arose in a fibroadenoma. Three had benign ovarian tumors, 1 had a benign breast tumor and 1 had a benign colloid thyroid nodule. One of the cases (case 7) reported by Jeghers et al. (1949) died of pancreatic cancer. Bowlby (1986) reported pancreatic cancer in an adolescent boy with PJS. Affected females are prone to develop ovarian tumor, especially granulosa cell tumor (Christian et al., 1964). Wilson et al. (1986) described gynecomastia and multifocal and bilateral testicular tumors in a 6-year-old boy with PJS. The testicular tumors appear to be of Sertoli cell origin and most are calcifying. Two previously reported cases were found. Coen et al. (1991) reported the case of a 4-year-old boy with Peutz-Jeghers syndrome and bilateral sex-cord testicular tumors resulting in gynecomastia. Studies led to the conclusion that increase in aromatase activity (107910) in the gonadal tumors was responsible for estrogen excess and gynecomastia. Three other reported male patients with Peutz-Jeghers syndrome and gonadal tumors had presented with gynecomastia between birth and 6 years of age. They pointed out that multifocal sex-cord tumors were found in palpably normal testes. The occurrence of ovarian tumors far exceeds that of testicular tumors in this diso ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for STK11
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 175200 was added.