AKAP4

A-kinase anchor protein 4 is a scaffold protein that in humans is encoded by the AKAP4 gene.[5][6][7] It involves in the intracellular signalling of protein kinase -A.[8] 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.[9] AKAP4 is not normally expressed in mRNA and protein level in MM cell line.[10]

AKAP4
Identifiers
AliasesAKAP4, AKAP 82, AKAP-4, AKAP82, CT99, FSC1, HI, PRKA4, hAKAP82, p82, A-kinase anchoring protein 4
External IDsOMIM: 300185 MGI: 102794 HomoloGene: 2887 GeneCards: AKAP4
Orthologs
SpeciesHumanMouse
Entrez

8852

11643

Ensembl

ENSG00000147081

ENSMUSG00000050089

UniProt

Q5JQC9

Q60662

RefSeq (mRNA)

NM_139289
NM_003886

NM_001042542
NM_009651

RefSeq (protein)

NP_003877
NP_647450

NP_001036007
NP_033781

Location (UCSC)Chr X: 50.19 – 50.2 MbChr X: 6.93 – 6.94 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[7]

AKAP 4 protein belongs to the family of scaffold proteins and is involved in controlled mechanism of flagellar function.[11] 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.[11]

Clinical significance

AKAP4 is a potential biomarker for early diagnosis and immunotherapy of colon cancer.[12] AKAP4 may be implicated as a biomarker and immunotherapeutic target for cervical cancer.[13] AKAP4 is also a circulating biomarker for non-small cell lung cancer.[14] 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.[15]

AKAP4 is over expressed in multiple myeloma (MM)[16]

Interactions

AKAP4 has been shown to interact with:

References
  1. GRCh38: Ensembl release 89: ENSG00000147081 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000050089 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Turner RM, Johnson LR, Haig-Ladewig L, Gerton GL, Moss SB (November 1998). "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. doi:10.1074/jbc.273.48.32135. PMID 9822690.
  6. Mohapatra B, Verma S, Shankar S, Suri A (March 1998). "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. doi:10.1006/bbrc.1998.8079. PMID 9514854.
  7. "Entrez Gene: AKAP4 A kinase (PRKA) anchor protein 4".
  8. Turner RM, Musse MP, Mandal A, Klotz K, Jayes FC, Herr JC, Gerton GL, Moss SB, Chemes HE (March 2001). "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. PMID 11229805.
  9. Chiriva-Internati M, Cobos E, Da Silva DM, Kast WM (April 2008). "Sperm fibrous sheath proteins: a potential new class of target antigens for use in human therapeutic cancer vaccines". Cancer Immunity. 8: 8. PMC 2935778. PMID 18433090.
  10. Chiriva-Internati M, Ferrari R, Yu Y, Hamrick C, Gagliano N, Grizzi F, Frezza E, Jenkins MR, Hardwick F, D'Cunha N, Kast WM, Cobos E (February 2008). "AKAP-4: a novel cancer testis antigen for multiple myeloma". British Journal of Haematology. 140 (4): 465–8. doi:10.1111/j.1365-2141.2007.06940.x. PMID 18217892. S2CID 31138294.
  11. Miki K, Willis WD, Brown PR, Goulding EH, Fulcher KD, Eddy EM (August 2002). "Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility". Developmental Biology. 248 (2): 331–42. doi:10.1006/dbio.2002.0728. PMID 12167408.
  12. Jagadish N, Parashar D, Gupta N, Agarwal S, Sharma A, Fatima R, Suri V, Kumar R, Gupta A, Lohiya NK, Suri A (February 2016). "A novel cancer testis antigen target A-kinase anchor protein (AKAP4) for the early diagnosis and immunotherapy of colon cancer". Oncoimmunology. 5 (2): e1078965. doi:10.1080/2162402X.2015.1078965. PMC 4801464. PMID 27057472.
  13. Agarwal S, Saini S, Parashar D, Verma A, Jagadish N, Batra A, Suri S, Bhatnagar A, Gupta A, Ansari AS, Lohiya NK, Suri A (May 2013). "Expression and humoral response of A-kinase anchor protein 4 in cervical cancer". International Journal of Gynecological Cancer. 23 (4): 650–8. doi:10.1097/IGC.0b013e31828a0698. PMID 23478221. S2CID 205679790.
  14. Gumireddy K, Li A, Chang DH, Liu Q, Kossenkov AV, Yan J, Korst RJ, Nam BT, Xu H, Zhang L, Ganepola GA, Showe LC, Huang Q (July 2015). "AKAP4 is a circulating biomarker for non-small cell lung cancer". Oncotarget. 6 (19): 17637–47. doi:10.18632/oncotarget.3946. PMC 4627334. PMID 26160834.
  15. Saini S, Jagadish N, Gupta A, Bhatnagar A, Suri A (2013-02-22). "A novel cancer testis antigen, A-kinase anchor protein 4 (AKAP4) is a potential biomarker for breast cancer". PLOS ONE. 8 (2): e57095. Bibcode:2013PLoSO...857095S. doi:10.1371/journal.pone.0057095. PMC 3579772. PMID 23451156.
  16. Shankar S, Mohapatra B, Suri A (February 1998). "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. doi:10.1006/bbrc.1997.7943. PMID 9480848.
  17. Brown PR, Miki K, Harper DB, Eddy EM (June 2003). "A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum". Biology of Reproduction. 68 (6): 2241–8. doi:10.1095/biolreprod.102.013466. PMID 12606363.
  18. Miki K, Eddy EM (December 1998). "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. doi:10.1074/jbc.273.51.34384. PMID 9852104.

Further reading


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