CKAP4
CKAP4 | |||
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Identifiers | |||
Gene ontology | |||
Molecular function | |||
Cellular component |
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Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 12: 106.24 – 106.3 Mb | Chr 10: 84.36 – 84.37 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Cytoskeleton-associated protein 4 is a protein that in humans is encoded by the CKAP4 gene.[5][6]
CKAP4 also historically known as CLIMP-63 (cytoskeleton-linking membrane protein 63), or just p63 (during the 1990s) is an abundant type II transmembrane protein residing predominantly in the endoplasmic reticulum (ER) of eukaryotic cells and encoded in higher vertebrates by the gene CKAP4.[7][8][9][10][11]
Discovery
CLIMP-63 was discovered in the early 1990s as the most S-palmitoylated protein during mitosis,[12][13] Nevertheless, the effect of this modification to date remains unclear. CLIMP-63 was extensively studied during the 1990s by the group of Hans-Peter Hauri (University of Basel, CH) which has characterized CLIMP-63's life in the ER. More recently, different groups have also reported CLIMP-63's presence at the plasma membrane acting as a ligand-activated receptor.[14][15][16] CLIMP-63 has also now been described as a marker in different cancers.[17]
Localization, molecular functions and regulation
CLIMP-63's cellular distribution has been assessed (and re-assessed) several times in the last two decades. The protein includes a cytosolic segment composed of positively charged amino acid (2–23) which might act as a preponderant motif for folding and ER localization.[18][19] Furthermore, CLIMP-63 was one of the first discovered ER-shaping proteins.[20] and is mostly known for participating in the generation and maintenance of the ER sheets [20][21] This is thought to occur after dimerization of CLIMP-63's luminal COILED-COIL domains in cis (two CLIMP-63 proteins of the same ER membrane layer) and/or trans (between two different ER membrane layers, across the ER lumen).[20] Multimerization might in addition limit CLIMP-63's diffusion out of ER-sheets.[22]
CLIMP-63 was also shown to bind microtubules through its cytoplasmic disordered tail which might help anchoring the ER-sheets to the cytoskeleton. This is regulated by phosphorylation of at least three serine residues of CLIMP-63's cytosolic tail (S3, S17 and S19) as phosphorylation interferes with CLIMP-63's microtubule binding capacity.[23]
In addition, CLIMP-63 can undergo another post-translational modification, S-palmitoylation, on cysteine 100 of its cytoplasmic domain. So far only the palmitoyl-acyltransferase ZDHHC2 has been identified as a potential regulator of CLIMP-63's palmitoylation but as ZDHHC2 resides mostly at the plasma membrane, supplementary investigations are needed.[24][25] The consequence of S-palmitoylation remain to be investigated but could play a role in the cell cycle as CLIMP-63's palmitoylation was reported to strongly increase during mitosis.[12]
Finally, CLIMP-63 has been shown by different groups to serve as a cell surface receptor for various extracellular ligands, in particular for
Diseases
More recently, CLIMP-63 has been related to different types of cancer prognosis. Upregulation of CLIMP-63 is observed in cholangio-cellular and hepatocellular carcinoma and it correlates with lymph node metastasis appearance.[17][26]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000136026 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046841 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8314870.
- ^ "Entrez Gene: CKAP4 cytoskeleton-associated protein 4".
- ^ "Gene: CKAP4 (ENSG00000136026) - Summary - Homo sapiens - Ensembl genome browser 89". may2017.archive.ensembl.org. Retrieved 2018-03-26.
- ^ "Gene: Ckap4 (ENSMUSG00000046841) - Summary - Mus musculus - Ensembl genome browser 89". may2017.archive.ensembl.org. Retrieved 2018-03-26.
- ^ pubmeddev. "PubMed Links for Gene (Select 10970) - PubMed - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-03-26.
- ^ pubmeddev. "PubMed Links for Gene (Select 216197) - PubMed - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-03-26.
- ^ "CKAP4 cytoskeleton associated protein 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-03-26.
- ^ PMID 1730740.
- PMID 8314869.
- ^ PMID 12913003.
- ^ S2CID 24903427.
- ^ PMID 19144824.
- ^ PMID 23665508.
- PMID 8027183.
- PMID 7673362.
- ^ PMID 11402071.
- PMID 21111237.
- S2CID 6766979.
- PMID 15703217.
- PMID 18296695.
- PMID 25849921.
- S2CID 37070876.
Further reading
- Sandoz PA, van der Goot FG (2015). "How many lives does CLIMP-63 have?". Biochemical Society Transactions. 43 (2): 222–228. PMID 25849921.
- Tuffy KM, Planey SB (2012). "Cytoskeleton-Associated Protein 4: Functions Beyond the Endoplasmic Reticulum in Physiology and Disease". ISRN Cell Biology. 2012: 1–11. .
- Bates SR (2009). "P63 (CKAP4) as an SP-A receptor: implications for surfactant turnover". Cellular Physiology and Biochemistry. 25 (1): 41–54. PMID 20054143.
External links
- Human CKAP4 genome location and CKAP4 gene details page in the UCSC Genome Browser.