ZXDC

ZXDC
Identifiers
Aliases	ZXDC , ZXDL, ZXD family zinc finger C
External IDs	OMIM: 615746 MGI: 1933108 HomoloGene: 82340 GeneCards: ZXDC
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3q21.3 Start 126,437,601 bp [1] End 126,475,891 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6 D1|6 Start 90,346,474 bp [2] End 90,380,472 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle right lobe of liver sural nerve ganglionic eminence right uterine tube body of pancreas gastric mucosa monocyte blood skin of abdomen Top expressed in ascending aorta aortic valve placenta secondary oocyte Paneth cell retinal pigment epithelium conjunctival fornix renal corpuscle supraoptic nucleus ankle More reference expression data BioGPS n/a
Gene ontology Molecular function DNA-binding transcription factor activity LRR domain binding C2H2 zinc finger domain binding protein binding metal ion binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus cellular component Biological process positive regulation of transcription, DNA-templated regulation of transcription, DNA-templated transcription, DNA-templated regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79364 80292 Ensembl ENSG00000070476 ENSMUSG00000034430 UniProt Q2QGD7 Q8C8V1 RefSeq (mRNA) NM_001040653 NM_025112 NM_030260 NM_173002 RefSeq (protein) NP_001035743 NP_079388 NP_084536 NP_766590 Location (UCSC) Chr 3: 126.44 – 126.48 Mb Chr 6: 90.35 – 90.38 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Zinc finger, X-linked, duplicated family member C (ZXDC) is a human CIITA-binding protein involved in the activation of major histocompatibility complex (MHC) class I and II. ^[5] For binding to occur, ZXDC must form an oligomeric complex with another copy of itself or with ZXDA, a related protein. ^[6] ZXDC is activated by sumoylation, a post-translational modification. ^[7] ZXDC plays a role in controlling immunological responses, cancer formation and progression, and cell proliferation, differentiation, and survival.

History

When Sakaue and colleagues searched for novel transcription factors involved in the development of Xenopus laevis, they discovered ZXDC (ZXD Family Zinc Finger C). This discovery was discovered in a research article that was published in 1998. They found a cDNA clone called "Xfin" that encodes a protein with two zinc finger C2H2 domains. ^[8]

Later research established the interspecies conservation of the Xfin protein, and the human equivalent was given the name ZXDC. It was discovered that the protein was broadly generated in human tissues and that a number of variables, including hypoxia, estrogen, and cytokines, controlled how the protein was expressed.

Structure

ZXDC is a protein composed of 455 amino acids in humans, with a molecular weight of approximately 49.9 kDa.

Near its C-terminus, the protein has two C2H2-type zinc finger domains that are likely to be involved in DNA binding and transcriptional control. A flexible linker region that separates the zinc fingers may provide more adaptability in binding to various DNA sequences.

Other domains found in ZXDC include a proline-rich region close to the N-terminus that may be important in protein-protein interactions and a central region that is projected to be intrinsically disordered. ZXDC also contains numerous other features in addition to the zinc fingers. Although the exact purpose of these domains is not yet known, they might assist in mediating interactions with other proteins or controlling the activity of the protein. ^[9]

ZXDC has mostly been investigated in the context of developmental biology and cell fate determination in animals. Studies in fruit flies, for instance, have demonstrated that protein is crucial for the development of particular cell types, such as the cell precursors of the sensory organs in the peripheral nervous system. ^[10]

Function

ZXDC is highly conserved between species, showing the significance of this gene for cellular function. ZXDC is a member of the zinc finger family of proteins that are crucial for the regulation of genes and cellular functions in a variety of organisms.

ZXDC (ZXD Family Zinc Finger C) is a protein-coding gene that controls biological processes such as cell division, proliferation, and apoptosis. This gene produces a protein with two C2H2-type zinc fingers that are a member of the ZXD family. ^[11]

Image of gsk3β.

ZXDC has been linked to the formation of numerous cancer forms and it regulates the advancement of the cell cycle. It is also known to interact with other proteins, including GSK3β, a serine/threonine protein kinase implicated in a number of signaling pathways, and p53, an important tumor suppressor. ^[12]

By regulating the expression of genes linked to the innate immune response, ZXDC has also been demonstrated to contribute to the regulation of immunological responses. As a result, it is believed that ZXDC could be a possible target for the creation of new remedies for autoimmune and cancerous conditions. ^[13]

ZXDC is involved in controlling the circadian clock in cells, which regulates the daily cycles of physiological processes.^{[ citation needed ]}

Isolation

ZXDC's solubility is not well described in the literature and may vary depending on a number of variables, including the protein's expression system, the buffering situation, and the presence of other proteins or chemicals. But studies have shown the effective separation of ZXDC using a variety of techniques, including gel filtration and affinity chromatography, suggesting that the protein is probably soluble in some circumstances. For instance, one study found superior amounts of soluble protein and pure recombinant ZXDC protein generated in Escherichia Coli using immobilized metal affinity chromatography (IMAC). ^[14]

Role in disease

Numerous cancers, including breast, lung, and colorectal cancer, have been linked to ZXDC, according to studies. It is also considered to be a possible therapeutic target for autoimmune and cancer conditions. ZXDC abnormality has been linked to cancer progression and an unfavorable prognosis.

In breast cancer, low ZXDC expression has been associated with tumor invasiveness, lymph node metastases, and poor prognosis. ZXDC suppresses the growth and migration of breast cancer cells, acting as a tumor suppressor.

The emergence of a more aggressive form of lung cancer has been correlated with decreased ZXDC expression. Studies have demonstrated that increasing ZXDC expression can prevent tumor development and invasion in lung cancer cells. ^[15]

In colorectal cancer, the loss of ZXDC expression has been connected to the advancement of the disease stage and lymph node metastasis. In addition, it has been proposed that ZXDC may function as a tumor suppressor by obstructing the Wnt/beta-catenin signaling pathway, which is frequently active in colorectal cancer.

Overall, these results indicate that ZXDC may be a key player in the initiation and development of cancer, and it may also hold interest as a diagnostic or therapeutic target for the treatment of cancer. To completely comprehend the processes underlying ZXDC's activity in cancer and to design specific treatments based on it, more study is necessary. ^[16]

References

1. GRCh38: Ensembl release 89: ENSG00000070476 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034430 - 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. Al-Kandari W, Jambunathan S, Navalgund V, Koneni R, Freer M, Parimi N, et al. (January 2007). "ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription". Molecular Immunology. 44 (4): 311–321. doi:10.1016/j.molimm.2006.02.029. PMC   1624858 . PMID   16600381.
6. Al-Kandari W, Koneni R, Navalgund V, Aleksandrova A, Jambunathan S, Fontes JD (June 2007). "The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription". Journal of Molecular Biology. 369 (5): 1175–1187. doi:10.1016/j.jmb.2007.04.033. PMC   1963517 . PMID   17493635.
7. Jambunathan S, Fontes JD (September 2007). "Sumoylation of the zinc finger protein ZXDC enhances the function of its transcriptional activation domain". Biological Chemistry. 388 (9): 965–972. doi:10.1515/BC.2007.106. PMID   17696781. S2CID   1007656.
8. Wargent ET, Martin-Gronert MS, Cripps RL, Heisler LK, Yeo GS, Ozanne SE, et al. (September 2020). "Developmental programming of appetite and growth in male rats increases hypothalamic serotonin (5-HT)5A receptor expression and sensitivity" (PDF). International Journal of Obesity. 44 (9): 1946–1957. doi:10.1038/s41366-020-0643-2. PMID   32719434. S2CID   220810612.
9. Al-Kandari W, Jambunathan S, Navalgund V, Koneni R, Freer M, Parimi N, et al. (January 2007). "ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription". Molecular Immunology. 44 (4): 311–321. doi:10.1016/j.molimm.2006.02.029. PMC   1624858 . PMID   16600381.
10. Seetharam A, Bai Y, Stuart GW (April 2010). "A survey of well conserved families of C2H2 zinc-finger genes in Daphnia". BMC Genomics. 11 (1): 276. doi: 10.1186/1471-2164-11-276 . PMC   2889900 . PMID   20433734.
11. Ozturk S, Kosebent EG, Talibova G, Bilmez Y, Tire B, Can A (February 2023). "Embryonic poly(A)-binding protein interacts with translation-related proteins and undergoes phosphorylation on the serine, threonine, and tyrosine residues in the mouse oocytes and early embryos". Journal of Assisted Reproduction and Genetics. 40 (4): 929–941. doi:10.1007/s10815-023-02746-7. PMC   10224904 . PMID   36823316. S2CID   257153864.
12. Bellanné-Chantelot C, Rabadan Moraes G, Schmaltz-Panneau B, Marty C, Vainchenker W, Plo I (July 2020). "Germline genetic factors in the pathogenesis of myeloproliferative neoplasms" (PDF). Blood Reviews. 42: 100710. doi: 10.1016/j.blre.2020.100710 . PMID   32532454. S2CID   219620040.
13. Ollila H, Wennerstrom A, Partinen M, Mignot E, Saarela J, Saavalainen P, Vaarala O, Tienari P, Perola M (January 2019). "Genetics of vaccination-related narcolepsy". European Neuropsychopharmacology. 29: S994. bioRxiv   10.1101/169623 . doi:10.1016/j.euroneuro.2017.08.379. S2CID   90650123.
14. Takenawa T, Kuramitsu Y, Wang Y, Okada F, Tokuda K, Kitagawa T, et al. (January 2013). "Proteomic analysis showed down-regulation of nucleophosmin in progressive tumor cells compared to regressive tumor cells". Anticancer Research. 33 (1): 153–160. PMID   23267140.
15. Hu J, Chen Z, Bao L, Zhou L, Hou Y, Liu L, et al. (July 2020). "Single-Cell Transcriptome Analysis Reveals Intratumoral Heterogeneity in ccRCC, which Results in Different Clinical Outcomes". Molecular Therapy. 28 (7): 1658–1672. doi:10.1016/j.ymthe.2020.04.023. PMC   7335756 . PMID   32396851.
16. O'Farrell HE, Bowman RV, Fong KM, Yang IA (May 2021). "Plasma Extracellular Vesicle miRNAs Can Identify Lung Cancer, Current Smoking Status, and Stable COPD". International Journal of Molecular Sciences. 22 (11): 5803. doi: 10.3390/ijms22115803 . PMC   8198071 . PMID   34071592.

External links

• ZXDC at NIH NCBI
• ZXDC at Uniprot
• ZXDC GeneCard