FANCE

Last updated
FANCE
Protein FANCE PDB 2ilr.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases FANCE , FACE, FAE, Fanconi anemia complementation group E, FA complementation group E
External IDs OMIM: 613976; MGI: 1920025; HomoloGene: 11066; GeneCards: FANCE; OMA:FANCE - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2178

72775

Ensembl

ENSG00000112039

ENSMUSG00000007570

UniProt

Q9HB96

n/a

RefSeq (mRNA)

NM_021922

NM_001163819
NM_001163820
NM_028348

RefSeq (protein)

NP_068741

n/a

Location (UCSC) Chr 6: 35.45 – 35.47 Mb Chr 17: 28.53 – 28.55 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Fanconi anemia, complementation group E protein is a protein that in humans is encoded by the FANCE gene. [5] [6] [7] The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, and FANCL. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA cross-linking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation groufcrp E. [7]

Contents

A nuclear complex containing FANCE protein (as well as FANCC, FANCF and FANCG) is essential for the activation of the FANCD2 protein to the mono-ubiquitinated isoform. [8] In normal, non-mutant cells, FANCD2 is mono-ubiquinated in response to DNA damage. FANCE together with FANCC acts as the substrate adapter for this reaction [9] Activated FANCD2 protein co-localizes with BRCA1 (breast cancer susceptibility protein) at ionizing radiation-induced foci and in synaptonemal complexes of meiotic chromosomes. Activated FANCD2 protein may function prior to the initiation of meiotic recombination, perhaps to prepare chromosomes for synapses, or to regulate subsequent recombination events. [8]

Gene Expression

FANCE is stated to have been expressed in 151 organs with the highest level in female gonads. [10]

Chromosomal Location

The location of the gene is in 6p21.31, where p is the short arm of chromosome 6 at position 21.31 [11]

The location at molecular level is in base pairs 35,452,339 to 35,467,106 on chromosome 6 (Homo sapiens Annotation Release 109, GRCh38.p12) [11]

Protein Characteristics

The main complex of FA contains a nuclear multi-subunit complex of notably 8 FA proteins. [12] This adds a single ubiquitin chain to the FANCD2 following DNA damage or duplicative pressure. [13]

For the collection of FANCC, FANCE is important in the nucleus and gathering of the core complex. Some characteristics of FANCE are that it can set itself up with ubiquitinated FANCD2, BRCA2 and constructed nuclear foci. Also, as it is the only member showing direct union with FANCD2 and gives the needed links between FA core complex and FANCD2. [14]

The structure of FANCE has an epitope on its surface that is found to be important for its binding with FANCD2. The existence of recurrent helical motif was not clear when analysis of amino acids was done.

Protein Structure

It consists of 13 α-helices, 1 310-helix and no β-strand. Long shaped, non-globular shape and 70 Å n size. Width of 30 Å and thickness 20 Å. The protein folds continuously in right-handed manner from N- to C- terminal. Identifying it is easy because of its helices at the end of C-end. [14]

Function

It restores DNA cross-links and is needed for nuclear accumulation of FANCC, delivering a critical bridge between FA complex and FANCD2. [15]

FANCE-deficient mice exhibit a reduced number of oocytes and disruption of prophase I of meiosis [16] indicating that FANCE has an essential role in meiosis.

Applications

Interactions

FANCE has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">Fanconi anemia</span> Medical condition

Fanconi anemia (FA) is a rare, autosomal recessive, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure.

<span class="mw-page-title-main">BRCA2</span> Gene known for its role in breast cancer

BRCA2 and BRCA2 are human genes and their protein products, respectively. The official symbol and the official name are maintained by the HUGO Gene Nomenclature Committee. One alternative symbol, FANCD1, recognizes its association with the FANC protein complex. Orthologs, styled Brca2 and Brca2, are common in other vertebrate species. BRCA2 is a human tumor suppressor gene, found in all humans; its protein, also called by the synonym breast cancer type 2 susceptibility protein, is responsible for repairing DNA.

<span class="mw-page-title-main">GSTP1</span> Protein-coding gene in the species Homo sapiens

Glutathione S-transferase P is an enzyme that in humans is encoded by the GSTP1 gene.

<span class="mw-page-title-main">Fanconi anemia, complementation group C</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group C protein is a protein that in humans is encoded by the FANCC gene. This protein delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA. Mutations in this gene result in Fanconi anemia, a human rare disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages.

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

Fanconi anaemia, complementation group A, also known as FAA, FACA and FANCA, is a protein which in humans is encoded by the FANCA gene. It belongs to the Fanconi anaemia complementation group (FANC) family of genes of which 12 complementation groups are currently recognized and is hypothesised to operate as a post-replication repair or a cell cycle checkpoint. FANCA proteins are involved in inter-strand DNA cross-link repair and in the maintenance of normal chromosome stability that regulates the differentiation of haematopoietic stem cells into mature blood cells.

<span class="mw-page-title-main">FANCD2</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN and FANCO.

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

Fanconi anemia group G protein is a protein that in humans is encoded by the FANCG gene.

<span class="mw-page-title-main">XRCC2</span> Protein-coding gene in the species Homo sapiens

DNA repair protein XRCC2 is a protein that in humans is encoded by the XRCC2 gene.

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

Fanconi anemia group F protein is a protein that in humans is encoded by the FANCF gene.

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

E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.

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

Fanconi anemia group B protein is a protein that in humans is encoded by the FANCB gene.

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

Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a protein which in humans is encoded by the FANCI gene. Mutations in the FANCI gene are known to cause Fanconi anemia.

<span class="mw-page-title-main">CCT3</span> Protein-coding gene in the species Homo sapiens

T-complex protein 1 subunit gamma is a protein that in humans is encoded by the CCT3 gene.

<span class="mw-page-title-main">ZNF24</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 24 is a protein that in humans is encoded by the ZNF24 gene.

<span class="mw-page-title-main">PALB2</span> Protein-coding gene in the species Homo sapiens

Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the PALB2 gene.

<span class="mw-page-title-main">ZBTB32</span> Protein-coding gene in the species Homo sapiens

Zinc finger and BTB domain-containing protein 32 is a protein that in humans is encoded by the 1960 bp ZBTB32 gene. The 52 kDa protein is a transcriptional repressor and the gene is expressed in T and B cells upon activation, but also significantly in testis cells. It is a member of the Poxviruses and Zinc-finger (POZ) and Krüppel (POK) family of proteins, and was identified in multiple screens involving either immune cell tumorigenesis or immune cell development.

<span class="mw-page-title-main">USP14</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-specific protease 14 is an enzyme that in humans is encoded by the USP14 gene.

<span class="mw-page-title-main">FANCM</span> Mammalian protein found in Homo sapiens

Fanconi anemia, complementation group M, also known as FANCM is a human gene. It is an emerging target in cancer therapy, in particular cancers with specific genetic deficiencies.

FANC proteins are a network of at least 15 proteins that are associated with a cell process known as the Fanconi anemia.

Alan D. D'Andrea is an American cancer researcher and the Fuller American Cancer Society Professor of Radiation Oncology at Harvard Medical School. D'Andrea's research at the Dana Farber Cancer Institute focuses on chromosome instability and cancer susceptibility. He is currently the director of the Center for DNA Damage and Repair and the director of the Susan F. Smith Center for Women's Cancer.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000112039 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000007570 – 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. ↑ Joenje H, Lo ten Foe JR, Oostra AB, van Berkel CG, Rooimans MA, Schroeder-Kurth T, Wegner RD, Gille JJ, Buchwald M, Arwert F (September 1995). "Classification of Fanconi anemia patients by complementation analysis: evidence for a fifth genetic subtype". Blood. 86 (6): 2156–60. doi: 10.1182/blood.V86.6.2156.bloodjournal8662156 . PMID   7662964.
  6. ↑ de Winter JP, Léveillé F, van Berkel CG, Rooimans MA, van Der Weel L, Steltenpool J, Demuth I, Morgan NV, Alon N, Bosnoyan-Collins L, Lightfoot J, Leegwater PA, Waisfisz Q, Komatsu K, Arwert F, Pronk JC, Mathew CG, Digweed M, Buchwald M, Joenje H (November 2000). "Isolation of a cDNA representing the Fanconi anemia complementation group E gene". American Journal of Human Genetics. 67 (5): 1306–8. doi:10.1016/S0002-9297(07)62959-0. PMC   1288571 . PMID   11001585.
  7. 1 2 "Entrez Gene: FANCE Fanconi anemia, complementation group E".
  8. 1 2 Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD (February 2001). "Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway". Molecular Cell. 7 (2): 249–62. doi: 10.1016/s1097-2765(01)00173-3 . PMID   11239454.
  9. ↑ van Twest S, Murphy VJ, Hodson C, Tan W, Swuec P, O'Rourke JJ, Heierhorst J, Crismani W, Deans AJ (January 2017). "Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway". Molecular Cell. 65 (2): 247–259. doi: 10.1016/j.molcel.2016.11.005 . hdl: 2434/618936 . PMID   27986371.
  10. ↑ "FANCE - Fanconi anemia group E protein - Homo sapiens (Human) - FANCE gene & protein". www.uniprot.org. Retrieved 2018-11-09.
  11. 1 2 "FANCE FA complementation group E [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-11-09.
  12. 1 2 3 4 Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG (February 2001). "Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway". Human Molecular Genetics. 10 (4): 423–9. doi: 10.1093/hmg/10.4.423 . PMID   11157805.
  13. ↑ Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD (February 2001). "Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway". Molecular Cell. 7 (2): 249–62. doi: 10.1016/S1097-2765(01)00173-3 . PMID   11239454.
  14. 1 2 Nookala RK, Hussain S, Pellegrini L (2007). "Insights into Fanconi Anaemia from the structure of human FANCE". Nucleic Acids Research. 35 (5): 1638–48. doi:10.1093/nar/gkm033. PMC   1865054 . PMID   17308347.
  15. 1 2 "Anti-FANCE antibody (ab126177) | Abcam". www.abcam.com. Retrieved 2018-11-09.
  16. ↑ Yin, H.; Suye, S.; Zhou, Z.; Cai, H.; Fu, C. (2022). "The reduction of oocytes and disruption of the meiotic prophase I in Fanconi anemia E-deficient mice". Reproduction. 164 (3): 71–82. doi:10.1530/REP-21-0421. PMID   35671285. S2CID   249432754.
  17. 1 2 Waisfisz Q, Saar K, Morgan NV, Altay C, Leegwater PA, de Winter JP, Komatsu K, Evans GR, Wegner RD, Reis A, Joenje H, Arwert F, Mathew CG, Pronk JC, Digweed M (May 1999). "The Fanconi anemia group E gene, FANCE, maps to chromosome 6p". American Journal of Human Genetics. 64 (5): 1400–5. doi:10.1086/302385. PMC   1377877 . PMID   10205272.
  18. ↑ de Winter JP, Léveillé F, van Berkel CG, Rooimans MA, van Der Weel L, Steltenpool J, Demuth I, Morgan NV, Alon N, Bosnoyan-Collins L, Lightfoot J, Leegwater PA, Waisfisz Q, Komatsu K, Arwert F, Pronk JC, Mathew CG, Digweed M, Buchwald M, Joenje H (November 2000). "Isolation of a cDNA representing the Fanconi anemia complementation group E gene". American Journal of Human Genetics. 67 (5): 1306–8. doi:10.1016/s0002-9297(07)62959-0. PMC   1288571 . PMID   11001585.
  19. 1 2 3 4 Taniguchi T, D'Andrea AD (October 2002). "The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC". Blood. 100 (7): 2457–62. doi: 10.1182/blood-2002-03-0860 . PMID   12239156.
  20. 1 2 3 4 5 Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ (July 2002). "FANCE: the link between Fanconi anaemia complex assembly and activity". The EMBO Journal. 21 (13): 3414–23. doi:10.1093/emboj/cdf355. PMC   125396 . PMID   12093742.
  21. ↑ Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W (October 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nature Genetics. 35 (2): 165–70. doi:10.1038/ng1241. PMID   12973351. S2CID   10149290.
  22. 1 2 Gordon SM, Buchwald M (July 2003). "Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems". Blood. 102 (1): 136–41. doi: 10.1182/blood-2002-11-3517 . PMID   12649160.
  23. ↑ Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG (June 2004). "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways". Human Molecular Genetics. 13 (12): 1241–8. doi: 10.1093/hmg/ddh135 . PMID   15115758.
  24. 1 2 Léveillé F, Blom E, Medhurst AL, Bier P, Laghmani M, Johnson M, Rooimans MA, Sobeck A, Waisfisz Q, Arwert F, Patel KJ, Hoatlin ME, Joenje H, de Winter JP (September 2004). "The Fanconi anemia gene product FANCF is a flexible adaptor protein". The Journal of Biological Chemistry. 279 (38): 39421–30. doi: 10.1074/jbc.M407034200 . PMID   15262960.

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