Biology:AKAP4

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

A-kinase anchor protein 4 is a scaffold protein that in humans is encoded by the AKAP4 gene.[1][2][3] It involves in the intracellular signalling of protein kinase -A.[4] AKAP4 is called as cancer /testis antigen (CTA), it belongs to a class of tumour linked antigens categories by high expression in germ cells and cancer than normal tissues.[5] AKAP4 is not normally expressed in mRNA and protein level in MM cell line.[6]

Function

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is localized to the sperm flagellum and may be involved in the regulation of sperm motility. Alternative splicing of this gene results in two transcript variants encoding different isoforms.[3]

AKAP 4 protein belongs to the family of scaffold proteins and is involved in controlled mechanism of flagellar function.[7] In mice, AKAP4 is required for sperm development and male mice that lack AKAP4 are infertiel The fibrous sheath was not formed, flagellum become short and often some proteins associated with the fibrous sheath in this case they were very few or absent. Surprisingly, another component of flagellum was developed as normal. In the conclusion, they state that AKAP4 plays a pivotal role in the fibrous sheath and effect on the motility of sperm, in the absence of AKAP4 these activities affected due to a failure of signal transduction and glycolytic enzymes because they were not able to attach with the fibrous sheath.[7]

Clinical significance

AKAP4 is a potential biomarker for early diagnosis and immunotherapy of colon cancer.[8] AKAP4 may be implicated as a biomarker and immunotherapeutic target for cervical cancer.[9] AKAP4 is also a circulating biomarker for non-small cell lung cancer.[10] To detect the early stage breast cancer and diagnosis, AKAP4 is used as serum. Investigation was undertaken about AKAP4 with various clinical parameters which could be use as early detector biomarker to treat cancer by developing a tissue or serum.

AKAP4 is associated with diseases such as multiple myeloma, lung cancer, breast cancer and prostate cancer.[11]

AKAP4 is over expressed in multiple myeloma (MM)[12]

Interactions

AKAP4 has been shown to interact with:

References

  1. ↑ "An X-linked gene encodes a major human sperm fibrous sheath protein, hAKAP82. Genomic organization, protein kinase A-RII binding, and distribution of the precursor in the sperm tail". The Journal of Biological Chemistry 273 (48): 32135–41. November 1998. doi:10.1074/jbc.273.48.32135. PMID 9822690. 
  2. ↑ "Molecular cloning of human testis mRNA specifically expressed in haploid germ cells, having structural homology with the A-kinase anchoring proteins". Biochemical and Biophysical Research Communications 244 (2): 540–5. March 1998. doi:10.1006/bbrc.1998.8079. PMID 9514854. 
  3. ↑ 3.0 3.1 "Entrez Gene: AKAP4 A kinase (PRKA) anchor protein 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8852. 
  4. ↑ "Molecular genetic analysis of two human sperm fibrous sheath proteins, AKAP4 and AKAP3, in men with dysplasia of the fibrous sheath". Journal of Andrology 22 (2): 302–15. March 2001. PMID 11229805. 
  5. ↑ "Sperm fibrous sheath proteins: a potential new class of target antigens for use in human therapeutic cancer vaccines". Cancer Immunity 8: 8. April 2008. PMID 18433090. 
  6. ↑ "AKAP-4: a novel cancer testis antigen for multiple myeloma". British Journal of Haematology 140 (4): 465–8. February 2008. doi:10.1111/j.1365-2141.2007.06940.x. PMID 18217892. 
  7. ↑ 7.0 7.1 "Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility". Developmental Biology 248 (2): 331–42. August 2002. doi:10.1006/dbio.2002.0728. PMID 12167408. 
  8. ↑ "A novel cancer testis antigen target A-kinase anchor protein (AKAP4) for the early diagnosis and immunotherapy of colon cancer". Oncoimmunology 5 (2): e1078965. February 2016. doi:10.1080/2162402X.2015.1078965. PMID 27057472. 
  9. ↑ "Expression and humoral response of A-kinase anchor protein 4 in cervical cancer". International Journal of Gynecological Cancer 23 (4): 650–8. May 2013. doi:10.1097/IGC.0b013e31828a0698. PMID 23478221. 
  10. ↑ "AKAP4 is a circulating biomarker for non-small cell lung cancer". Oncotarget 6 (19): 17637–47. July 2015. doi:10.18632/oncotarget.3946. PMID 26160834. 
  11. ↑ "A novel cancer testis antigen, A-kinase anchor protein 4 (AKAP4) is a potential biomarker for breast cancer". PLOS ONE 8 (2): e57095. 2013-02-22. doi:10.1371/journal.pone.0057095. PMID 23451156. Bibcode: 2013PLoSO...857095S. 
  12. ↑ "Cloning of a novel human testis mRNA specifically expressed in testicular haploid germ cells, having unique palindromic sequences and encoding a leucine zipper dimerization motif". Biochemical and Biophysical Research Communications 243 (2): 561–5. February 1998. doi:10.1006/bbrc.1997.7943. PMID 9480848. 
  13. ↑ 13.0 13.1 "A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum". Biology of Reproduction 68 (6): 2241–8. June 2003. doi:10.1095/biolreprod.102.013466. PMID 12606363. 
  14. ↑ "Identification of tethering domains for protein kinase A type Ialpha regulatory subunits on sperm fibrous sheath protein FSC1". The Journal of Biological Chemistry 273 (51): 34384–90. December 1998. doi:10.1074/jbc.273.51.34384. PMID 9852104. 

Further reading

External links





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