Casein kinase I isoform alpha (CSNK1A1)

The protein contains 337 amino acids for an estimated molecular weight of 38915 Da.

 

Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis (PubMed:11955436, PubMed:1409656, PubMed:18305108). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688). (updated: Nov. 22, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. 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.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 73

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VariantDescription
a breast pleomorphic lobular carcinoma sample; somatic mutation

The reference OMIM entry for this protein is 600505

Casein kinase i, alpha-1; csnk1a1
Ck1

CLONING

Tapia et al. (1994) isolated a cDNA encoding human casein kinase I from a fetal brain library using PCR primers based on the bovine sequence. The cDNA was sequenced and shown to have a predicted amino acid sequence identical to the bovine protein except that it contains 12 additional amino acids at the carboxyl end.

GENE FUNCTION

Jia et al. (2004) showed that protein kinase A (PKA; see 188830) and casein kinase I (CKI) regulate Smo (601500) cell surface accumulation and activity in response to hedgehog (Hh; see 600725). Blocking PKA or CKI activity in the Drosophila wing disc prevented Hh-induced Smo accumulation and attenuated pathway activity, whereas increasing PKA activity promoted Smo accumulation and pathway activation. Jia et al. (2004) showed that PKA and CKI phosphorylate Smo at several sites, and that phosphorylation-deficient forms of Smo fail to accumulate on the cell surface and are unable to transduce the Hh signal. Conversely, phosphorylation-mimicking Smo variants showed constitutive cell surface expression and signaling activity. Furthermore, Jia et al. (2004) found that the levels of Smo cell surface expression and activity correlated with its levels of phosphorylation. Jia et al. (2004) concluded that Hh induces progressive Smo phosphorylation by PKA and CKI, leading to elevation of Smo cell surface levels and signaling activity. Bidere et al. (2009) conducted parallel screens involving a mass spectrometry analysis of CARMA1 (607210) binding partners and an RNA interference screen for growth inhibition of the CBM-dependent 'activated B cell-like' (ABC) subtype of diffuse large B-cell lymphoma (DLBCL; see 605027). Bidere et al. (2009) reported that both screens identified CK1-alpha as a bifunctional regulator of NF-kappa-B (164011). CK1-alpha dynamically associates with the CBM complex on T cell receptor engagement to participate in cytokine production and lymphocyte proliferation. However, CK1-alpha kinase activity has a contrasting role by subsequently promoting the phosphorylation and inactivation of CARMA1. CK1-alpha has thus a dual 'gating' function which first promotes and then terminates receptor-induced NF-kappa-B. ABC DLBCL cells required CK1-alpha for constitutive NF-kappa-B activity, indicating that CK1-alpha functions as a conditionally essential malignancy gene. Elyada et al. (2011) showed that casein kinase I-alpha, a component of the beta-catenin (116806) destruction complex, is a critical regulator of the Wnt signaling (see 164820) pathway. Inducing the ablation of Csnk1a1 in the gut triggers massive Wnt activation, surprisingly without causing tumorigenesis. CKI-alpha-deficient epithelium shows many of the features of human colorectal tumors in addition to Wnt activation, in particular the induction of the DNA damage response and cellular senescence, both of which are thought to provide a barrier against malignant transformation. The epithelial DNA damage response in mice is accompanied by substantial activation of p53 (191170), suggesting that the p53 pathway may counteract the protumorigenic effects of Wnt hyperactivation. Notably, the transition from benign adenomas to invasive colorectal cancer in humans is typically linked to p53 inactivation, underscoring the importance of p53 as a safeguard against malignant progression; however, the mechanism of p53-mediated tumor suppression is unknown. Elyada et al. (2011) showed that the maintenance of intestinal homeostasis in ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600505 was added.