FANCI

Last updated
FANCI
Identifiers
Aliases FANCI , KIAA1794, Fanconi anemia complementation group I, FA complementation group I
External IDs OMIM: 611360 MGI: 2384790 HomoloGene: 49530 GeneCards: FANCI
Orthologs
SpeciesHumanMouse
Entrez

55215

208836

Ensembl

ENSG00000140525

ENSMUSG00000039187

UniProt

Q9NVI1

Q8K368

RefSeq (mRNA)

NM_001113378
NM_018193
NM_001376910
NM_001376911

NM_145946

RefSeq (protein)

NP_001106849
NP_060663
NP_001363839
NP_001363840

NP_666058

Location (UCSC) Chr 15: 89.24 – 89.32 Mb Chr 7: 79.04 – 79.1 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a protein which in humans is encoded by the FANCI gene. [5] [6] [7] [8] [9] Mutations in the FANCI gene are known to cause Fanconi anemia. [10]

Contents

Function

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. 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 I. Alternative splicing results in two transcript variants encoding different isoforms. [5]

FANCI forms a heterodimer with FANCD2 protein. Both FANCD2 and FANCI are monoubiquitinated by the Fanconi anemia core complex subunit FANCL. FANCI monoubiquitination is essential for repairing DNA interstrand crosslinks, and clamps the protein on DNA together with its partner protein FANCD2. The monoubiquitinated FANCD2:FANCI complex coats DNA in a filament-like array, potentially as a way to protect DNA associated with stalled replication. [11]

In addition to proteins involved in DNA repair, FANCI interacts with proteins localized to the nucleolus, [12] [13] the nuclear body where ribosome biogenesis initiates. FANCI functions in the processing of the pre-ribosomal RNA (pre-rRNA) for the large ribosomal subunit, the transcription of pre-rRNA by RNAPI, maintaining levels of the mature 28S ribosomal RNA (rRNA), and the global cellular translation of proteins by ribosomes. [12] In the nucleolus, FANCI is predominantly in the deubiquitinated form and interacts with the large subunit of RNAPI and members of the PeBoW complex (PES1 and BOP1). [12] There may be another role for FA proteins outside the nucleolus in ribosome biogenesis or protein translation as FANCI and FANCD2 are the only FA proteins associated with polysomes. [14]

Meiosis

In mice, FANCI protein participates in meiotic recombination of germ cells, and deletion of the Fanci gene causes a strong meiotic phenotype and severe hypogonadism. [15] Fanci-/- male mice have completely impaired spermatogenesis, [15] [16] and female Fanci-/- mice produce no ovarian follicles. [15]

Related Research Articles

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

Fanconi anemia (FA) is a rare, AR, 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">Ribosomal RNA</span> RNA component of the ribosome, essential for protein synthesis in all living organisms

Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins. Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins by mass.

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

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">PES1</span> Protein-coding gene in the species Homo sapiens

Pescadillo homolog is a protein that in humans is encoded by the PES1 gene.

<span class="mw-page-title-main">KRR1</span> Protein-coding gene in humans

KRR1 small subunit processome component homolog is a protein that in humans is encoded by the KRR1 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">DDX56</span> Protein-coding gene in the species Homo sapiens

Probable ATP-dependent RNA helicase DDX56 is an enzyme that in humans is encoded by the DDX56 gene.

<span class="mw-page-title-main">60S ribosomal protein L18</span> Protein found in humans

60S ribosomal protein L18 is a protein that in humans is encoded by the RPL18 gene.

<span class="mw-page-title-main">SNX5</span> Protein-coding gene in the species Homo sapiens

Sorting nexin-5 is a protein that in humans is encoded by the SNX5 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">TEX10</span> Protein-coding gene in the species Homo sapiens

Testis-expressed sequence 10 protein is a protein that in humans is encoded by the TEX10 gene.

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

<span class="mw-page-title-main">FAN1</span> Protein-coding gene in the species Homo sapiens

FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease. It is thought to play an important role in the Fanconi Anemia (FA) pathway.

Ribosomopathies are diseases caused by abnormalities in the structure or function of ribosomal component proteins or rRNA genes, or other genes whose products are involved in ribosome biogenesis.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000140525 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000039187 - 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. 1 2 "Entrez Gene: FANCI".
  6. ↑ Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (April 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi: 10.1093/dnares/8.2.85 . PMID   11347906.
  7. ↑ Dorsman JC, Levitus M, Rockx D, Rooimans MA, Oostra AB, Haitjema A, et al. (2007). "Identification of the Fanconi anemia complementation group I gene, FANCI". Cellular Oncology. 29 (3): 211–218. doi: 10.1155/2007/151968 . PMC   4618213 . PMID   17452773.
  8. ↑ Sims AE, Spiteri E, Sims RJ, Arita AG, Lach FP, Landers T, et al. (June 2007). "FANCI is a second monoubiquitinated member of the Fanconi anemia pathway". Nature Structural & Molecular Biology. 14 (6): 564–567. doi:10.1038/nsmb1252. PMID   17460694. S2CID   40947913.
  9. ↑ Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER, Hurov KE, Luo J, et al. (April 2007). "Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair". Cell. 129 (2): 289–301. doi:10.1016/j.cell.2007.03.009. PMC   2175179 . PMID   17412408.
  10. ↑ Levitus M, Rooimans MA, Steltenpool J, Cool NF, Oostra AB, Mathew CG, et al. (April 2004). "Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes". Blood. 103 (7): 2498–2503. doi: 10.1182/blood-2003-08-2915 . PMID   14630800. S2CID   7033645.
  11. ↑ Tan W, van Twest S, Leis A, Bythell-Douglas R, Murphy VJ, Sharp M, et al. (March 2020). "Monoubiquitination by the human Fanconi anemia core complex clamps FANCI:FANCD2 on DNA in filamentous arrays". eLife. 9. doi: 10.7554/eLife.54128 . PMC   7156235 . PMID   32167469.
  12. 1 2 3 Sondalle SB, Longerich S, Ogawa LM, Sung P, Baserga SJ (February 2019). "Fanconi anemia protein FANCI functions in ribosome biogenesis". Proceedings of the National Academy of Sciences of the United States of America. 116 (7): 2561–2570. Bibcode:2019PNAS..116.2561S. doi: 10.1073/pnas.1811557116 . PMC   6377447 . PMID   30692263.
  13. ↑ Moriel-Carretero M, Ovejero S, Gérus-Durand M, Vryzas D, Constantinou A (December 2017). "Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors". The Journal of Cell Biology. 216 (12): 4007–4026. doi:10.1083/jcb.201702136. PMC   5716273 . PMID   29030393.
  14. ↑ Gueiderikh A, Maczkowiak-Chartois F, Rouvet G, Souquère-Besse S, Apcher S, Diaz JJ, Rosselli F (January 2021). "Fanconi anemia A protein participates in nucleolar homeostasis maintenance and ribosome biogenesis". Science Advances. 7 (1): eabb5414. Bibcode:2021SciA....7.5414G. doi:10.1126/sciadv.abb5414. PMC   7775781 . PMID   33523834.
  15. 1 2 3 Dubois EL, Guitton-Sert L, Béliveau M, Parmar K, Chagraoui J, Vignard J, et al. (August 2019). "A Fanci knockout mouse model reveals common and distinct functions for FANCI and FANCD2". Nucleic Acids Research. 47 (14): 7532–7547. doi:10.1093/nar/gkz514. PMC   6698648 . PMID   31219578.
  16. ↑ Xu L, Xu W, Li D, Yu X, Gao F, Qin Y, et al. (August 2021). "FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation". Cell Death & Disease. 12 (8): 780. doi:10.1038/s41419-021-04034-7. PMC   8353022 . PMID   34373449. (Erratum:  doi:10.1038/s41419-021-04096-7 . If the erratum has been checked and does not affect the cited material, please replace {{ Erratum |...}} with {{ Erratum |...|checked=yes}}.)

Further reading

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