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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Fanconi anemia group B protein''' is a [[protein]] that in humans is encoded by the ''FANCB'' [[gene]].<ref name="pmid9382107">{{cite journal | vauthors = 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 | title = Evidence for at least eight Fanconi anemia genes | journal = Am J Hum Genet | volume = 61 | issue = 4 | pages = 940–4 |date=Nov 1997 | pmid = 9382107 | pmc = 1715980 | doi = 10.1086/514881 }}</ref><ref name="pmid15502827">{{cite journal | vauthors = 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 | title = X-linked inheritance of Fanconi anemia complementation group B | journal = Nat Genet | volume = 36 | issue = 11 | pages = 1219–24 |date=Oct 2004 | pmid = 15502827 | pmc = | doi = 10.1038/ng1458 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: FANCB Fanconi anemia, complementation group B| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2187| accessdate = }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Fanconi anemia, complementation group B
| HGNCid = 3583
| Symbol = FANCB
| AltSymbols =; FA2; FAAP90; FAAP95; FAB; FACB
| OMIM = 300515
| ECnumber = 
| Homologene = 51880
| MGIid = 2448558
| GeneAtlas_image1 = PBB_GE_FANCB_gnf1h06541_at_tn.png
| GeneAtlas_image2 = PBB_GE_FANCB_gnf1h06542_at_tn.png
| Function =  
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006281 |text = DNA repair}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2187
    | Hs_Ensembl = ENSG00000181544
    | Hs_RefseqProtein = NP_001018123
    | Hs_RefseqmRNA = NM_001018113
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 14771450
    | Hs_GenLoc_end = 14801112
    | Hs_Uniprot = Q8NB91
    | Mm_EntrezGene = 237211
    | Mm_Ensembl = ENSMUSG00000047757
    | Mm_RefseqmRNA = NM_175027
    | Mm_RefseqProtein = NP_778192
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = X
    | Mm_GenLoc_start = 160324807
    | Mm_GenLoc_end = 160341377
    | Mm_Uniprot = Q8K3C9
  }}
}}
'''Fanconi anemia, complementation group B''', also known as '''FANCB''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: FANCB Fanconi anemia, complementation group B| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2187| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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 [[Fanconi anemia, complementation group B|complementation group B]]. Alternative splicing results in two transcript variants encoding the same protein.<ref name="entrez" />
{{PBB_Summary
 
| section_title =
== Gene ==
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: FANCB Fanconi anemia, complementation group B| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2187| accessdate = }}</ref>
 
}}
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.<ref>{{cite journal | vauthors = 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 | title = X-linked inheritance of Fanconi anemia complementation group B | journal = Nature Genetics | volume = 36 | issue = 11 | pages = 1219–24 | date = November 2004 | pmid = 15502827 | doi = 10.1038/ng1458 }}</ref> 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.<ref>{{cite journal | vauthors = Wang AT, Smogorzewska A | title = SnapShot: Fanconi anemia and associated proteins | journal = Cell | volume = 160 | issue = 1–2 | pages = 354–354.e1 | date = January 2015 | pmid = 25594185 | doi = 10.1016/j.cell.2014.12.031 }}</ref>
 
== Protein ==
 
The FANCB gene product is FANCB protein. FANCB is a component of a "core complex" of nine Fanconi Anemia proteins: [[FANCA]], FANCB, [[Fanconi anemia, complementation group C|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]].<ref>{{cite journal | vauthors = Walden H, Deans AJ | title = The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder | journal = Annual Review of Biophysics | volume = 43 | pages = 257–78 | date = 2014 | pmid = 24773018 | doi = 10.1146/annurev-biophys-051013-022737 }}</ref> In particular, this reaction is necessary for the repair of DNA interstrand crosslinks, such as those formed by chemotherapy drugs [[cisplatin]], [[Mitomycin C|mitomycin c]] and [[melphalan]].<ref>{{cite journal | vauthors = Ceccaldi R, Sarangi P, D'Andrea AD | title = The Fanconi anaemia pathway: new players and new functions | journal = Nature Reviews. Molecular Cell Biology | volume = 17 | issue = 6 | pages = 337–49 | date = June 2016 | pmid = 27145721 | doi = 10.1038/nrm.2016.48 }}</ref>
 
Within the Fanconi anemia core complex, FANCB has an obligate interaction with FAAP100 and FANCL, to form a catalytic [[RING finger domain|E3 RING ligase]] enzyme. FANCB creates a dimer interface within this subcomplex that is required for simultaneous ubiquitination of FANCD2 and FANCI.<ref>{{cite journal | vauthors = van Twest S, Murphy VJ, Hodson C, Tan W, Swuec P, O'Rourke JJ, Heierhorst J, Crismani W, Deans AJ | title = Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway | journal = Molecular Cell | volume = 65 | issue = 2 | pages = 247–259 | date = January 2017 | pmid = 27986371 | doi = 10.1016/j.molcel.2016.11.005 }}</ref> 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<ref name=":0">{{cite journal | vauthors = Swuec P, Renault L, Borg A, Shah F, Murphy VJ, van Twest S, Snijders AP, Deans AJ, Costa A | title = The FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2 | journal = Cell Reports | volume = 18 | issue = 3 | pages = 611–623 | date = January 2017 | pmid = 27986592 | pmc = 5266791 | doi = 10.1016/j.celrep.2016.11.013 }}</ref>. Further imaging reveals the overall architecture of the Fanconi Anemia core complex centres on FANCB protein.<ref name=":0" />
 
==Meiosis==
 
FANCB mutant mice are [[Fertility#Infertility|infertile]] and exhibit primordial [[germ cell]] defects during [[embryogenesis]].  The germ cells and [[Testicle|testicular]] size are severely compromised in FANCB mutant mice.<ref name="Kato">{{cite journal |vauthors=Kato Y, Alavattam KG, Sin HS, Meetei AR, Pang Q, Andreassen PR, Namekawa SH |title=FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis |journal=Hum. Mol. Genet. |volume=24 |issue=18 |pages=5234–49 |year=2015 |pmid=26123487 |doi=10.1093/hmg/ddv244 |url=|pmc=4550819 }}</ref>  FANCB protein is essential for [[spermatogenesis]] and  likely has a role in the activation of the [[Fanconi anemia#Molecular basis|Fanconi anemia DNA repair]] pathway during [[meiosis]].<ref name="Kato" />


==References==
==References==
{{reflist|2}}
{{reflist}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Fei P, Yin J, Wang W |title=New advances in the DNA damage response network of Fanconi anemia and BRCA proteins. FAAP95 replaces BRCA2 as the true FANCB protein. |journal=Cell Cycle |volume=4 |issue= 1 |pages= 80-6 |year= 2006 |pmid= 15611632 |doi=  }}
*{{cite journal  | author=Muller YA, Ultsch MH, de Vos AM |title=The crystal structure of the extracellular domain of human tissue factor refined to 1.7 A resolution. |journal=J. Mol. Biol. |volume=256 |issue= 1 |pages= 144-59 |year= 1996 |pmid= 8609606 |doi= 10.1006/jmbi.1996.0073 }}
*{{cite journal  | author=Joenje H, Oostra AB, Wijker M, ''et al.'' |title=Evidence for at least eight Fanconi anemia genes. |journal=Am. J. Hum. Genet. |volume=61 |issue= 4 |pages= 940-4 |year= 1997 |pmid= 9382107 |doi=  }}
*{{cite journal  | author=Huang M, Syed R, Stura EA, ''et al.'' |title=The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex. |journal=J. Mol. Biol. |volume=275 |issue= 5 |pages= 873-94 |year= 1998 |pmid= 9480775 |doi=  }}
*{{cite journal  | author=Presta L, Sims P, Meng YG, ''et al.'' |title=Generation of a humanized, high affinity anti-tissue factor antibody for use as a novel antithrombotic therapeutic. |journal=Thromb. Haemost. |volume=85 |issue= 3 |pages= 379-89 |year= 2001 |pmid= 11307801 |doi=  }}
*{{cite journal  | author=Faelber K, Kirchhofer D, Presta L, ''et al.'' |title=The 1.85 A resolution crystal structures of tissue factor in complex with humanized Fab D3h44 and of free humanized Fab D3h44: revisiting the solvation of antigen combining sites. |journal=J. Mol. Biol. |volume=313 |issue= 1 |pages= 83-97 |year= 2001 |pmid= 11601848 |doi= 10.1006/jmbi.2001.5036 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Suzuki Y, Yamashita R, Shirota M, ''et al.'' |title=Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. |journal=Genome Res. |volume=14 |issue= 9 |pages= 1711-8 |year= 2004 |pmid= 15342556 |doi= 10.1101/gr.2435604 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Meetei AR, Levitus M, Xue Y, ''et al.'' |title=X-linked inheritance of Fanconi anemia complementation group B. |journal=Nat. Genet. |volume=36 |issue= 11 |pages= 1219-24 |year= 2004 |pmid= 15502827 |doi= 10.1038/ng1458 }}
*{{cite journal  | author=Meetei AR, Medhurst AL, Ling C, ''et al.'' |title=A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. |journal=Nat. Genet. |volume=37 |issue= 9 |pages= 958-63 |year= 2005 |pmid= 16116422 |doi= 10.1038/ng1626 }}
*{{cite journal  | author=Holden ST, Cox JJ, Kesterton I, ''et al.'' |title=Fanconi anaemia complementation group B presenting as X linked VACTERL with hydrocephalus syndrome. |journal=J. Med. Genet. |volume=43 |issue= 9 |pages= 750-4 |year= 2007 |pmid= 16679491 |doi= 10.1136/jmg.2006.041673 }}
*{{cite journal  | author=Nomura Y, Adachi N, Koyama H |title=Human Mus81 and FANCB independently contribute to repair of DNA damage during replication. |journal=Genes Cells |volume=12 |issue= 10 |pages= 1111-22 |year= 2007 |pmid= 17903171 |doi= 10.1111/j.1365-2443.2007.01124.x }}
}}
{{refend}}


{{protein-stub}}
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{{WikiDoc Sources}}

Latest revision as of 22:31, 5 September 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
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Fanconi anemia group B protein is a protein that in humans is encoded by the FANCB gene.[1][2][3]

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.[3]

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.[4] 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.[5]

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.[6] 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.[7]

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.[8] 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[9]. Further imaging reveals the overall architecture of the Fanconi Anemia core complex centres on FANCB protein.[9]

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.[10] FANCB protein is essential for spermatogenesis and likely has a role in the activation of the Fanconi anemia DNA repair pathway during meiosis.[10]

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 3.0 3.1 "Entrez Gene: FANCB Fanconi anemia, complementation group B".
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 9.0 9.1 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.
  10. ↑ 10.0 10.1 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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