FANCB

Last updated
FANCB
Identifiers
Aliases FANCB , FA2, FAAP90, FAAP95, FAB, FACB, Fanconi anemia complementation group B, FA complementation group B
External IDs OMIM: 300515 MGI: 2448558 HomoloGene: 51880 GeneCards: FANCB
Orthologs
SpeciesHumanMouse
Entrez

2187

237211

Ensembl

ENSG00000181544

ENSMUSG00000047757

UniProt

Q8NB91

Q5XJY6

RefSeq (mRNA)

NM_001018113
NM_152633
NM_001324162

NM_001146081
NM_175027

RefSeq (protein)

NP_001018123
NP_001311091
NP_689846

NP_001139553
NP_778192

Location (UCSC) Chr X: 14.69 – 14.87 Mb Chr X: 163.76 – 163.78 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Fanconi anemia group B protein is a protein that in humans is encoded by the FANCB gene. [5] [6] [7]

Contents

Function

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 crosslinking 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 group B. Alternative splicing results in two transcript variants encoding the same protein. [7]


Gene

FANCB is the only gene known to cause X-linked Fanconi Anemia. In female carriers of FANCB mutations (one wild-type FANCB allele and one mutant FANCB allele) there is strong selection through X-inactivation for expression of only the wild-type allele. [8] In contrast, males have only one FANCB allele. Only male patients with Fanconi anemia have ever been linked to FANCB mutations, and they make up about 4% of cases. [9]

Mutation in the FANCB are highly associated with the development of the VACTERL-H constilation of birth defects. [10] In a cohort study of 19 children with FANCB variants, those with deletion of FANCB gene or truncation of FANCB protein demonstrate earlier-than-average onset of bone marrow failure and more severe congenital abnormalities compared with a large series of Fanconi Anemia individuals in published reports. This reflects the indispensable role of FANCB gene in cells. For FANCB missense variants, more variable severity is associated with the extent of residual activity. [11]

Protein

The FANCB gene product is FANCB protein. FANCB is a component of a "core complex" of nine Fanconi Anemia proteins: FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FAAP100 and FAAP20. The core complex localises to DNA damage sites during DNA replication where it catalyzes transfer of ubiquitin to FANCD2 and FANCI. [12] In particular, this reaction is necessary for the repair of DNA interstrand crosslinks, such as those formed by chemotherapy drugs cisplatin, mitomycin c and melphalan. [13]

Within the Fanconi anemia core complex, FANCB has an obligate interaction with FAAP100 and FANCL, to form a catalytic E3 RING ligase enzyme. FANCB creates a dimer interface within this subcomplex that is required for simultaneous ubiquitination of FANCD2 and FANCI. [14] Electron microscopy imaging of the FANCB-FANCL-FAAP100 complex revealed a symmetry that is centred on FANCB, and biochemical investigation confirmed that the entire complex is a dimer containing two of each subunit. [15] Further imaging reveals the overall architecture of the Fanconi Anemia core complex centres on FANCB protein. [15]

Meiosis

FANCB mutant mice are infertile and exhibit primordial germ cell defects during embryogenesis. The germ cells and testicular size are severely compromised in FANCB mutant mice. [16] FANCB protein is essential for spermatogenesis and likely has a role in the activation of the Fanconi anemia DNA repair pathway during meiosis. [16]

Related Research Articles

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

Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. 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), and 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.

<span class="mw-page-title-main">GSTP1</span>

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.

<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>

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">RAD51L3</span> Protein-coding gene in the species Homo sapiens

DNA repair protein RAD51 homolog 4 is a protein that in humans is encoded by the RAD51L3 gene.

<span class="mw-page-title-main">FANCF</span>

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

<span class="mw-page-title-main">FANCE</span>

Fanconi anemia, complementation group E protein is a protein that in humans is encoded by the FANCE gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, 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.

<span class="mw-page-title-main">TOP3A</span>

DNA topoisomerase 3-alpha is an enzyme that in humans is encoded by the TOP3A gene.

<span class="mw-page-title-main">FANCL</span>

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

<span class="mw-page-title-main">FANCI</span>

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">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>

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

<span class="mw-page-title-main">RMI1</span> Protein-coding gene in the species Homo sapiens

RecQ-mediated genome instability protein 1 is a protein that in humans is encoded by the RMI1 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 group of proteins associated with Fanconi anemia.

<span class="mw-page-title-main">Cancer syndrome</span> Genetic condition that predisposes a person to cancer

A cancer syndrome, or family cancer syndrome, is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancers and may also cause the early onset of these cancers. Cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.

<span class="mw-page-title-main">FAN1</span>

FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease and a member of the myotubularin-related class 1 cysteine-based protein tyrosine phosphatases. It is thought to play an important role in the Fanconi Anemia (FA) pathway.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000181544 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000047757 - 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, Oostra AB, Wijker M, di Summa FM, van Berkel CG, Rooimans MA, Ebell W, van Weel M, Pronk JC, Buchwald M, Arwert F (Nov 1997). "Evidence for at least eight Fanconi anemia genes". Am J Hum Genet. 61 (4): 940–4. doi:10.1086/514881. PMC   1715980 . PMID   9382107.
  6. ↑ Meetei AR, Levitus M, Xue Y, Medhurst AL, Zwaan M, Ling C, Rooimans MA, Bier P, Hoatlin M, Pals G, de Winter JP, Wang W, Joenje H (Oct 2004). "X-linked inheritance of Fanconi anemia complementation group B". Nat Genet. 36 (11): 1219–24. doi: 10.1038/ng1458 . PMID   15502827.
  7. 1 2 "Entrez Gene: FANCB Fanconi anemia, complementation group B".
  8. ↑ Meetei AR, Levitus M, Xue Y, Medhurst AL, Zwaan M, Ling C, Rooimans MA, Bier P, Hoatlin M, Pals G, de Winter JP, Wang W, Joenje H (November 2004). "X-linked inheritance of Fanconi anemia complementation group B". Nature Genetics. 36 (11): 1219–24. doi: 10.1038/ng1458 . PMID   15502827.
  9. ↑ Wang AT, Smogorzewska A (January 2015). "SnapShot: Fanconi anemia and associated proteins". Cell. 160 (1–2): 354–354.e1. doi: 10.1016/j.cell.2014.12.031 . PMID   25594185.
  10. ↑ Fiesco-Roa MO, Giri N, McReynolds LJ, Best AF, Alter BP (September 2019). "Genotype-phenotype associations in Fanconi anemia: A literature review". Blood Reviews. 37: 100589. doi:10.1016/j.blre.2019.100589. PMC   6730648 . PMID   31351673.
  11. ↑ Jung M, Ramanagoudr-Bhojappa R, van Twest S, Rosti RO, Murphy V, Tan W, et al. (April 2020). "Association of clinical severity with FANCB variant type in Fanconi anemia". Blood. 135 (18): 1588–1602. doi:10.1182/blood.2019003249. PMC   7193183 . PMID   32106311.
  12. ↑ Walden H, Deans AJ (2014). "The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder". Annual Review of Biophysics. 43: 257–78. doi:10.1146/annurev-biophys-051013-022737. PMID   24773018.
  13. ↑ Ceccaldi R, Sarangi P, D'Andrea AD (June 2016). "The Fanconi anaemia pathway: new players and new functions". Nature Reviews. Molecular Cell Biology. 17 (6): 337–49. doi:10.1038/nrm.2016.48. PMID   27145721. S2CID   1712640.
  14. ↑ 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 . PMID   27986371.
  15. 1 2 Swuec P, Renault L, Borg A, Shah F, Murphy VJ, van Twest S, Snijders AP, Deans AJ, Costa A (January 2017). "The FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2". Cell Reports. 18 (3): 611–623. doi:10.1016/j.celrep.2016.11.013. PMC   5266791 . PMID   27986592.
  16. 1 2 Kato Y, Alavattam KG, Sin HS, Meetei AR, Pang Q, Andreassen PR, Namekawa SH (2015). "FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis". Hum. Mol. Genet. 24 (18): 5234–49. doi:10.1093/hmg/ddv244. PMC   4550819 . PMID   26123487.
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