SF3B1

Last updated

SF3B1
Protein SF3B1 PDB 2f9d.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SF3B1 , Hsh155, MDS, PRP10, PRPF10, SAP155, SF3b155, splicing factor 3b subunit 1
External IDs OMIM: 605590; MGI: 1932339; HomoloGene: 6696; GeneCards: SF3B1; OMA:SF3B1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001005526
NM_001308824
NM_012433

NM_031179

RefSeq (protein)

NP_001005526
NP_001295753
NP_036565

n/a

Location (UCSC) Chr 2: 197.39 – 197.44 Mb Chr 1: 54.99 – 55.03 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Splicing factor 3B subunit 1 is a protein that in humans is encoded by the SF3B1 gene. [5] [6]

Contents

Function

This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and U2 spliceosomal RNA, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms. [6]

Interactions

SF3B1 has been shown to interact with:

Clinical relevance

Mutations in this gene have been recurrently seen in cases of advanced chronic lymphocytic leukemia, [12] myelodysplastic syndromes [13] and breast cancer. [14] SF3B1 mutations are found in the vast majority of myelodysplastic syndrome with ring sideroblasts (MDS-RS) and MDS with ring sideroblasts and thrombocytosis (MDS-RS-T), so much so that mutated SF3B1 has become a diagnostic criterion for these per the 5th edition of the WHO Classification and the International Consensus Classification (ICC).

There is also an emerging body of evidence to suggest implications of SF3B1 mutations being involved in orbital melanoma[ citation needed ].

Inhibitors

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000115524 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025982 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. Wang C, Chua K, Seghezzi W, Lees E, Gozani O, Reed R (May 1998). "Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis". Genes & Development. 12 (10): 1409–1414. doi:10.1101/gad.12.10.1409. PMC   316838 . PMID   9585501.
  6. 1 2 "Entrez Gene: SF3B1 splicing factor 3b, subunit 1, 155kDa".
  7. Ajuh P, Kuster B, Panov K, Zomerdijk JC, Mann M, Lamond AI (December 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". The EMBO Journal. 19 (23): 6569–6581. doi:10.1093/emboj/19.23.6569. PMC   305846 . PMID   11101529.
  8. 1 2 3 4 Will CL, Urlaub H, Achsel T, Gentzel M, Wilm M, Lührmann R (September 2002). "Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein". The EMBO Journal. 21 (18): 4978–4988. doi:10.1093/emboj/cdf480. PMC   126279 . PMID   12234937.
  9. Boudrez A, Beullens M, Waelkens E, Stalmans W, Bollen M (August 2002). "Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1". The Journal of Biological Chemistry. 277 (35): 31834–31841. doi: 10.1074/jbc.M204427200 . PMID   12105215.
  10. 1 2 Das BK, Xia L, Palandjian L, Gozani O, Chyung Y, Reed R (October 1999). "Characterization of a protein complex containing spliceosomal proteins SAPs 49, 130, 145, and 155". Molecular and Cellular Biology. 19 (10): 6796–6802. doi:10.1128/mcb.19.10.6796. PMC   84676 . PMID   10490618.
  11. Will CL, Schneider C, MacMillan AM, Katopodis NF, Neubauer G, Wilm M, et al. (August 2001). "A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site". The EMBO Journal. 20 (16): 4536–4546. doi:10.1093/emboj/20.16.4536. PMC   125580 . PMID   11500380.
  12. Quesada V, Conde L, Villamor N, Ordóñez GR, Jares P, Bassaganyas L, et al. (December 2011). "Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia". Nature Genetics. 44 (1): 47–52. doi:10.1038/ng.1032. hdl: 10651/8189 . PMID   22158541. S2CID   205343043.
  13. Malcovati L, Papaemmanuil E, Bowen DT, Boultwood J, Della Porta MG, Pascutto C, et al. (December 2011). "Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms". Blood. 118 (24): 6239–6246. doi:10.1182/blood-2011-09-377275. PMC   3236114 . PMID   21998214.
  14. Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. (October 2012). "Comprehensive molecular portraits of human breast tumours". Nature. 490 (7418): 61–70. Bibcode:2012Natur.490...61T. doi:10.1038/nature11412. PMC   3465532 . PMID   23000897.

Further reading