Mediates apoptosis and actin stress fiber dissolution. (updated: April 1, 2015)
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.
Total structural coverage: 32%
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The reference OMIM entry for this protein is 616563
Ste20-like protein kinase; slk
Long ste20-like protein kinase; losk
Kiaa0204
DESCRIPTION
SLK is a kinase with multiple functional domains that is predicted to regulate cytoskeletal organization and responses to apoptotic stimuli (Sabourin et al., 2000).
CLONING
By sequencing clones obtained from a size-fractionated KG-1 human myeloid leukemia cell line cDNA library, Nagase et al. (1996) cloned SLK, which they designated KIAA0204. The deduced 1,152-amino acid protein contains a serine/threonine protein kinase active-site motif and a protein kinase ATP-binding site motif. It shares significant similarity with human serine/threonine protein kinase KRS1 (STK3;
605030). Northern blot analysis detected KIAA0204 expression in all human tissues and cell lines tested, with highest expression in skeletal muscle and kidney. Sabourin et al. (2000) cloned mouse Slk, which shares over 90% nucleotide identity with human SLK. The deduced 1,202-amino acid mouse protein has a calculated molecular mass of 147 kD. It has an N-terminal Ste20-like domain, followed by a central microtubule- and nuclear-associated protein (MNAP) domain and a C-terminal AT1-46 (STK10;
603919) homology (ATH) domain. Slk also has a consensus caspase-3 (CASP3;
600636) cleavage site. Northern blot analysis detected Slk variants of about 6, 7, and 8 kb in all mouse tissues examined. Slk was expressed in distinct cytosolic domains in transfected CD2C12 myoblasts, with absence of Slk at focal adhesions. Slk had an apparent molecular mass of 220 kD by SDS-PAGE.
GENE FUNCTION
Sabourin et al. (2000) found that overexpression of mouse Slk induced dissolution of actin stress fibers and caused apoptosis in all transfected mammalian cells examined, including HeLa cells. Mutation and deletion analysis revealed that the N-terminal domain showed kinase activity and induced apoptosis in a kinase-dependent manner. The C-terminal ATH domain showed negative kinase regulatory activity and caused actin disassembly, cellular retraction, and apoptosis in a kinase-independent manner. Treatment of cells with several apoptosis-inducing agents resulted in caspase-3-dependent cleavage of Slk at the consensus caspase-3 cleavage site and at multiple nonconsensus sites. Caspase-3 released the N-terminal kinase domain as a 60-kD product in response to apoptotic stimuli. Different apoptotic triggers released novel and specific caspase-3-dependent Slk fragments. Dynactin (see DCTN1,
601143) is a multisubunit motor cofactor of dynein (see
600112) that is involved in cargo binding and processivity of dynein along microtubules. Using mouse and human constructs, Zhapparova et al. (2013) found that SLK phosphorylated a serine in the basic microtubule-binding domain of the minor p150(GLUED)1A isoform of DCTN1 and regulated dynactin centrosomal localization. This phosphorylation did not affect dynactin microtubule-organizing properties. Phosphorylation of p150(GLUED)1A was also involved in Golgi reorientation in polarized cells. The authors noted that the predominant isoform of DCTN1, p150(GLUED)1B, lacks 20 amino acids in the basic microtubule-binding region, including the serine phosphorylated by SLK.
MAPPING
By analysis of radiation hybrids and human-rodent hybrid panels, Nagase et al. (1996) mapped the SLK gene to chromosome 10. Hartz (2015) mapped the SLK gene to chromosome 10q24.33-q25.1 based on an alignment of the SLK sequence (GenBank GENBANK AB
002804) with the genomic sequence (GRCh38). ...
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May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616563 was added.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed