AKAP4

Last updated

AKAP4
Identifiers
Aliases AKAP4 , AKAP 82, AKAP-4, AKAP82, CT99, FSC1, HI, PRKA4, hAKAP82, p82, A-kinase anchoring protein 4
External IDs OMIM: 300185; MGI: 102794; HomoloGene: 2887; GeneCards: AKAP4; OMA:AKAP4 - orthologs
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 Mb Chr X: 6.93 – 6.94 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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 infertile. 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:

Related Research Articles

<span class="mw-page-title-main">X chromosome</span> Sex chromosome present in both sexes in the XY and X0 sex-determination systems

The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its unique properties by early researchers, which resulted in the naming of its counterpart Y chromosome, for the next letter in the alphabet, following its subsequent discovery.

<span class="mw-page-title-main">Axoneme</span> Protein structure forming the core of cilia and flagellae

In molecular biology, an axoneme, also called an axial filament, is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axoneme serves as the "skeleton" of these organelles, both giving support to the structure and, in some cases, the ability to bend. Though distinctions of function and length may be made between cilia and flagella, the internal structure of the axoneme is common to both.

<span class="mw-page-title-main">PRKACA</span> Protein-coding gene in the species Homo sapiens

The catalytic subunit α of protein kinase A is a key regulatory enzyme that in humans is encoded by the PRKACA gene. This enzyme is responsible for phosphorylating other proteins and substrates, changing their activity. Protein kinase A catalytic subunit is a member of the AGC kinase family, and contributes to the control of cellular processes that include glucose metabolism, cell division, and contextual memory. PKA Cα is part of a larger protein complex that is responsible for controlling when and where proteins are phosphorylated. Defective regulation of PKA holoenzyme activity has been linked to the progression of cardiovascular disease, certain endocrine disorders and cancers.

<span class="mw-page-title-main">PRKAR1A</span> Protein-coding gene in the species Homo sapiens

cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene.

<span class="mw-page-title-main">PRKAR2A</span> Protein-coding gene in the species Homo sapiens

cAMP-dependent protein kinase type II-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR2A gene.

<span class="mw-page-title-main">RhoC</span> Protein-coding gene in the species Homo sapiens

RhoC is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.

<span class="mw-page-title-main">AKAP5</span> Protein-coding gene in the species Homo sapiens

A-kinase anchor protein 5 is a protein that in humans is encoded by the AKAP5 gene.

<span class="mw-page-title-main">AKAP1</span> Protein-coding gene in the species Homo sapiens

A kinase anchor protein 1, mitochondrial is an enzyme that in humans is encoded by the AKAP1 gene.

<span class="mw-page-title-main">Sperm-associated antigen 9</span> Protein-coding gene in the species Homo sapiens

C-jun-amino-terminal kinase-interacting protein 4 is a scaffold protein that in humans is encoded by the SPAG9 gene.

<span class="mw-page-title-main">GAPDHS</span> Enzyme of the glycolysis metabolic pathway

Glyceraldehyde-3-phosphate dehydrogenase, spermatogenic or glyceraldehyde-3-phosphate dehydrogenase, testis-specific is an enzyme that in humans is encoded by the GAPDHS gene.

<span class="mw-page-title-main">SPA17</span> Protein-coding gene in the species Homo sapiens

Sperm surface protein Sp17 is a protein that in humans is encoded by the SPA17 gene.

<span class="mw-page-title-main">Sperm-associated antigen 6</span> Protein-coding gene in the species Homo sapiens

Sperm-associated antigen 6 is a protein that in humans is encoded by the SPAG6 gene.

<span class="mw-page-title-main">AKAP3</span> Protein-coding gene in humans

A-kinase anchor protein 3 is an enzyme that in humans is encoded by the AKAP3 gene.

<span class="mw-page-title-main">AKAP11</span> Human protein-coding gene

A-kinase anchor protein 11 is an enzyme that in humans is encoded by the AKAP11 gene.

<span class="mw-page-title-main">Sperm-associated antigen 1</span> Protein-coding gene in the species Homo sapiens

Sperm-associated antigen 1 is a protein that in humans is encoded by the SPAG1 gene.

<span class="mw-page-title-main">MYCBP</span> Protein-coding gene in the species Homo sapiens

C-Myc-binding protein is a protein that in humans is encoded by the MYCBP gene.

<span class="mw-page-title-main">CABYR</span> Protein-coding gene in humans

Calcium-binding tyrosine phosphorylation-regulated protein is a protein that in humans is encoded by the CABYR gene.

<span class="mw-page-title-main">Sperm protein associated with the nucleus, X-linked, family member A1</span> Protein-coding gene in the species Homo sapiens

Sperm protein associated with the nucleus on the X chromosome A is a protein that in humans is encoded by the SPANXA1 gene.

<span class="mw-page-title-main">AKAP2</span> Protein-coding gene in the species Homo sapiens

A-kinase anchor protein 2 is an enzyme that in humans is encoded by the AKAP2 gene. It is likely involved in establishing polarity in signaling systems or in integrating PKA-RII isoforms with downstream effectors to capture, amplify and focus diffuse, trans-cellular signals carried by cAMP. Malfunction of AKAP2 is associated with Kallmann Syndrome.

Anil Suri is a cancer researcher working in the field of Translational Cancer research at the National Institute of Immunology in New Delhi, India. He is a fellow of the Indian National Academy of Medical Sciences, editorial board member of Cancer Research, vice president of the Indian Society for the Study of Reproduction and Fertility (ISSRF), and was an Executive Member of Indian Association of Cancer Research.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000147081 – Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. doi:10.1002/j.1939-4640.2001.tb02184.x. 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. 1 2 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. 1 2 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.

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