SF3B1

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.

SF3B1 has been shown to interact with:

• CDC5L,{{cite journal | vauthors = Ajuh P, Kuster B, Panov K, Zomerdijk JC, Mann M, Lamond AI | title = Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry | journal = The EMBO Journal | volume = 19 | issue = 23 | pages = 6569–6581 | date = December 2000 | pmid = 11101529 | pmc = 305846 | doi = 10.1093/emboj/19.23.6569 }}
• DDX42,
• PPP1R8,{{cite journal | vauthors = Boudrez A, Beullens M, Waelkens E, Stalmans W, Bollen M | title = Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 35 | pages = 31834–31841 | date = August 2002 | pmid = 12105215 | doi = 10.1074/jbc.M204427200 | doi-access = free }}
• SF3B2,
• SF3B3,{{cite journal | vauthors = Will CL, Urlaub H, Achsel T, Gentzel M, Wilm M, Lührmann R | title = Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein | journal = The EMBO Journal | volume = 21 | issue = 18 | pages = 4978–4988 | date = September 2002 | pmid = 12234937 | pmc = 126279 | doi = 10.1093/emboj/cdf480 }}{{cite journal | vauthors = Das BK, Xia L, Palandjian L, Gozani O, Chyung Y, Reed R | title = Characterization of a protein complex containing spliceosomal proteins SAPs 49, 130, 145, and 155 | journal = Molecular and Cellular Biology | volume = 19 | issue = 10 | pages = 6796–6802 | date = October 1999 | pmid = 10490618 | pmc = 84676 | doi = 10.1128/mcb.19.10.6796 }}
• SF3B6,{{cite journal | vauthors = Will CL, Schneider C, MacMillan AM, Katopodis NF, Neubauer G, Wilm M, Lührmann R, Query CC | title = A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site | journal = The EMBO Journal | volume = 20 | issue = 16 | pages = 4536–4546 | date = August 2001 | pmid = 11500380 | pmc = 125580 | doi = 10.1093/emboj/20.16.4536 }}

Mutations in this gene have been recurrently seen in cases of advanced chronic lymphocytic leukemia,{{cite journal | vauthors = Quesada V, Conde L, Villamor N, Ordóñez GR, Jares P, Bassaganyas L, Ramsay AJ, Beà S, Pinyol M, Martínez-Trillos A, López-Guerra M, Colomer D, Navarro A, Baumann T, Aymerich M, Rozman M, Delgado J, Giné E, Hernández JM, González-Díaz M, Puente DA, Velasco G, Freije JM, Tubío JM, Royo R, Gelpí JL, Orozco M, Pisano DG, Zamora J, Vázquez M, Valencia A, Himmelbauer H, Bayés M, Heath S, Gut M, Gut I, Estivill X, López-Guillermo A, Puente XS, Campo E, López-Otín C | title = Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia | journal = Nature Genetics | volume = 44 | issue = 1 | pages = 47–52 | date = December 2011 | pmid = 22158541 | doi = 10.1038/ng.1032 | s2cid = 205343043 }} myelodysplastic syndromes{{cite journal | vauthors = Malcovati L, Papaemmanuil E, Bowen DT, Boultwood J, Della Porta MG, Pascutto C, Travaglino E, Groves MJ, Godfrey AL, Ambaglio I, Gallì A, Da Vià MC, Conte S, Tauro S, Keenan N, Hyslop A, Hinton J, Mudie LJ, Wainscoat JS, Futreal PA, Stratton MR, Campbell PJ, Hellström-Lindberg E, Cazzola M | title = Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms | journal = Blood | volume = 118 | issue = 24 | pages = 6239–6246 | date = December 2011 | pmid = 21998214 | pmc = 3236114 | doi = 10.1182/blood-2011-09-377275 }} and breast cancer.{{cite journal | vauthors = Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, Fulton LL, Dooling DJ, Ding L, Mardis ER, Wilson RK, Ally A, Balasundaram M, Butterfield YS, Carlsen R, Carter C, Chu A, Chuah E, Chun HJ, Coope RJ, Dhalla N, Guin R, Hirst C, Hirst M, Holt RA, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ | title = Comprehensive molecular portraits of human breast tumours | journal = Nature | volume = 490 | issue = 7418 | pages = 61–70 | date = October 2012 | pmid = 23000897 | pmc = 3465532 | doi = 10.1038/nature11412 | bibcode = 2012Natur.490...61T }} 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|date=March 2025}}.

• H3B-8800

{{reflist}}

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• {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–358 | date = April 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
• {{cite journal | vauthors = Gozani O, Potashkin J, Reed R | title = A potential role for U2AF-SAP 155 interactions in recruiting U2 snRNP to the branch site | journal = Molecular and Cellular Biology | volume = 18 | issue = 8 | pages = 4752–4760 | date = August 1998 | pmid = 9671485 | pmc = 109061 | doi = 10.1128/mcb.18.8.4752 | author-link2 = Judith Potashkin }}
• {{cite journal | vauthors = Das BK, Xia L, Palandjian L, Gozani O, Chyung Y, Reed R | title = Characterization of a protein complex containing spliceosomal proteins SAPs 49, 130, 145, and 155 | journal = Molecular and Cellular Biology | volume = 19 | issue = 10 | pages = 6796–6802 | date = October 1999 | pmid = 10490618 | pmc = 84676 | doi = 10.1128/mcb.19.10.6796 }}
• {{cite journal | vauthors = Pauling MH, McPheeters DS, Ares M | title = Functional Cus1p is found with Hsh155p in a multiprotein splicing factor associated with U2 snRNA | journal = Molecular and Cellular Biology | volume = 20 | issue = 6 | pages = 2176–2185 | date = March 2000 | pmid = 10688664 | pmc = 110834 | doi = 10.1128/MCB.20.6.2176-2185.2000 }}
• {{cite journal | vauthors = Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ | title = Shotgun sequencing of the human transcriptome with ORF expressed sequence tags | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3491–3496 | date = March 2000 | pmid = 10737800 | pmc = 16267 | doi = 10.1073/pnas.97.7.3491 | doi-access = free | bibcode = 2000PNAS...97.3491D }}
• {{cite journal | vauthors = Das R, Zhou Z, Reed R | title = Functional association of U2 snRNP with the ATP-independent spliceosomal complex E | journal = Molecular Cell | volume = 5 | issue = 5 | pages = 779–787 | date = May 2000 | pmid = 10882114 | doi = 10.1016/S1097-2765(00)80318-4 | doi-access = free }}
• {{cite journal | vauthors = Brand M, Moggs JG, Oulad-Abdelghani M, Lejeune F, Dilworth FJ, Stevenin J, Almouzni G, Tora L | title = UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation | journal = The EMBO Journal | volume = 20 | issue = 12 | pages = 3187–3196 | date = June 2001 | pmid = 11406595 | pmc = 150203 | doi = 10.1093/emboj/20.12.3187 }}
• {{cite journal | vauthors = Will CL, Schneider C, MacMillan AM, Katopodis NF, Neubauer G, Wilm M, Lührmann R, Query CC | title = A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site | journal = The EMBO Journal | volume = 20 | issue = 16 | pages = 4536–4546 | date = August 2001 | pmid = 11500380 | pmc = 125580 | doi = 10.1093/emboj/20.16.4536 }}
• {{cite journal | vauthors = Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ | title = Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis | journal = RNA | volume = 8 | issue = 4 | pages = 426–439 | date = April 2002 | pmid = 11991638 | pmc = 1370266 | doi = 10.1017/S1355838202021088 | doi-broken-date = 1 November 2024 }}
• {{cite journal | vauthors = Boudrez A, Beullens M, Waelkens E, Stalmans W, Bollen M | title = Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 35 | pages = 31834–31841 | date = August 2002 | pmid = 12105215 | doi = 10.1074/jbc.M204427200 | doi-access = free }}
• {{cite journal | vauthors = Will CL, Urlaub H, Achsel T, Gentzel M, Wilm M, Lührmann R | title = Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein | journal = The EMBO Journal | volume = 21 | issue = 18 | pages = 4978–4988 | date = September 2002 | pmid = 12234937 | pmc = 126279 | doi = 10.1093/emboj/cdf480 }}
• {{cite journal | vauthors = Golas MM, Sander B, Will CL, Lührmann R, Stark H | title = Molecular architecture of the multiprotein splicing factor SF3b | journal = Science | volume = 300 | issue = 5621 | pages = 980–984 | date = May 2003 | pmid = 12738865 | doi = 10.1126/science.1084155 | s2cid = 31046270 | bibcode = 2003Sci...300..980G }}
• {{cite journal | vauthors = Banerjee H, Rahn A, Gawande B, Guth S, Valcarcel J, Singh R | title = The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF 65) is essential in vivo but dispensable for activity in vitro | journal = RNA | volume = 10 | issue = 2 | pages = 240–253 | date = February 2004 | pmid = 14730023 | pmc = 1370536 | doi = 10.1261/rna.5153204 }}
• {{cite journal | vauthors = Will CL, Schneider C, Hossbach M, Urlaub H, Rauhut R, Elbashir S, Tuschl T, Lührmann R | title = The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2-dependent spliceosome | journal = RNA | volume = 10 | issue = 6 | pages = 929–941 | date = June 2004 | pmid = 15146077 | pmc = 1370585 | doi = 10.1261/rna.7320604 }}
• {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–12135 | date = August 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 | doi-access = free | bibcode = 2004PNAS..10112130B }}
• {{cite journal | vauthors = Lin KT, Lu RM, Tarn WY | title = The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo | journal = Molecular and Cellular Biology | volume = 24 | issue = 20 | pages = 9176–9185 | date = October 2004 | pmid = 15456888 | pmc = 517884 | doi = 10.1128/MCB.24.20.9176-9185.2004 }}

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