SF3B1

Splicing factor 3b, subunit 1, 155kDa
PDB rendering based on 2f9d.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2F9D​, 2F9J​, 2FHO​, 2PEH​, 3LQV​, 4OZ1​
Identifiers
Symbols	SF3B1 ; Hsh155; MDS; PRP10; PRPF10; SAP155; SF3b155
External IDs	OMIM: 605590 MGI: 1932339 HomoloGene: 6696 ChEMBL: 1229013 GeneCards: SF3B1 Gene
Gene ontology Molecular function • chromatin binding • protein binding • poly(A) RNA binding Cellular component • chromatin • nucleus • nucleoplasm • spliceosomal complex • U12-type spliceosomal complex • nuclear matrix • nuclear speck • small nuclear ribonucleoprotein complex • catalytic step 2 spliceosome Biological process • RNA splicing, via transesterification reactions • mRNA splicing, via spliceosome • blastocyst formation • RNA splicing • anterior/posterior pattern specification • gene expression Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	23451	81898
Ensembl	ENSG00000115524	ENSMUSG00000025982
UniProt	O75533	G5E866
RefSeq (mRNA)	NM_001005526	NM_031179
RefSeq (protein)	NP_001005526	NP_112456
Location (UCSC)	Chr 2: 197.39 – 197.44 Mb	Chr 1: 54.99 – 55.03 Mb
PubMed search

Splicing factor 3B subunit 1 is a protein that in humans is encoded by the SF3B1 gene.^[1][2]

This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, 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.^[2]

Interactions

SF3B1 has been shown to interact with:

• CDC5L,^[3]
• DDX42,^[4]
• PPP1R8,^[5]
• SF3B2,^[6][4]
• SF3B3,^[6][4]
• SF3B14,^[7][4]

Clinical relevance

Mutations in this gene have been recurrently seen in cases of advanced chronic lymphocytic leukemia,^[8] myelodysplastic syndromes^[9] and breast cancer.^[10]

References

1. Wang C, Chua K, Seghezzi W, Lees E, Gozani O, Reed R (Jul 1998). "Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis". Genes Dev 12 (10): 1409–1414. doi:10.1101/gad.12.10.1409. PMC 316838. PMID 9585501.
2. "Entrez Gene: SF3B1 splicing factor 3b, subunit 1, 155kDa".
3. 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". EMBO J. 19 (23): 6569–81. doi:10.1093/emboj/19.23.6569. PMC 305846. PMID 11101529.
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". EMBO J. 21 (18): 4978–88. doi:10.1093/emboj/cdf480. PMC 126279. PMID 12234937.
5. Boudrez A, Beullens M, Waelkens E, Stalmans W, Bollen M (August 2002). "Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1". J. Biol. Chem. 277 (35): 31834–41. doi:10.1074/jbc.M204427200. PMID 12105215.
6. 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". Mol. Cell. Biol. 19 (10): 6796–802. PMC 84676. PMID 10490618.
7. Will CL, Schneider C, MacMillan AM, Katopodis NF, Neubauer G, Wilm M, Lührmann R, Query CC (August 2001). "A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site". EMBO J. 20 (16): 4536–46. doi:10.1093/emboj/20.16.4536. PMC 125580. PMID 11500380.
8. 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 (2011). "Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia". Nat. Genet. 44 (1): 47–52. doi:10.1038/ng.1032. PMID 22158541.
9. 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 (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.
10. The Cancer Genome Atlas Network (2012). "Comprehensive molecular portraits of human breast tumours". Nature (Nature Publishing Group) 490 (7418): 61–70. doi:10.1038/nature11412. PMC 3465532. PMID 23000897. Retrieved 24 September 2012.

Further reading

• Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Gozani O, Potashkin J, Reed R (1998). "A potential role for U2AF-SAP 155 interactions in recruiting U2 snRNP to the branch site". Mol. Cell. Biol. 18 (8): 4752–60. PMC 109061. PMID 9671485.
• Das BK, Xia L, Palandjian L, et al. (2000). "Characterization of a protein complex containing spliceosomal proteins SAPs 49, 130, 145, and 155". Mol. Cell. Biol. 19 (10): 6796–802. PMC 84676. PMID 10490618.
• Pauling MH, McPheeters DS, Ares M (2000). "Functional Cus1p is found with Hsh155p in a multiprotein splicing factor associated with U2 snRNA". Mol. Cell. Biol. 20 (6): 2176–2185. doi:10.1128/MCB.20.6.2176-2185.2000. PMC 110834. PMID 10688664.
• Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–3496. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
• Das R, Zhou Z, Reed R (2000). "Functional association of U2 snRNP with the ATP-independent spliceosomal complex E". Mol. Cell 5 (5): 779–787. doi:10.1016/S1097-2765(00)80318-4. PMID 10882114.
• Brand M, Moggs JG, Oulad-Abdelghani M, et al. (2001). "UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation". EMBO J. 20 (12): 3187–3196. doi:10.1093/emboj/20.12.3187. PMC 150203. PMID 11406595.
• Will CL, Schneider C, MacMillan AM, et al. (2001). "A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site". EMBO J. 20 (16): 4536–4546. doi:10.1093/emboj/20.16.4536. PMC 125580. PMID 11500380.
• Jurica MS, Licklider LJ, Gygi SR, et al. (2002). "Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis". RNA 8 (4): 426–439. doi:10.1017/S1355838202021088. PMC 1370266. PMID 11991638.
• Boudrez A, Beullens M, Waelkens E, et al. (2002). "Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1". J. Biol. Chem. 277 (35): 31834–31841. doi:10.1074/jbc.M204427200. PMID 12105215.
• Will CL, Urlaub H, Achsel T, et al. (2002). "Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein". EMBO J. 21 (18): 4978–4988. doi:10.1093/emboj/cdf480. PMC 126279. PMID 12234937.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Golas MM, Sander B, Will CL, et al. (2003). "Molecular architecture of the multiprotein splicing factor SF3b". Science 300 (5621): 980–984. doi:10.1126/science.1084155. PMID 12738865.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
• Banerjee H, Rahn A, Gawande B, et al. (2004). "The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF 65) is essential in vivo but dispensable for activity in vitro". RNA 10 (2): 240–253. doi:10.1261/rna.5153204. PMC 1370536. PMID 14730023.
• Will CL, Schneider C, Hossbach M, et al. (2004). "The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2-dependent spliceosome". RNA 10 (6): 929–941. doi:10.1261/rna.7320604. PMC 1370585. PMID 15146077.
• Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–12135. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Lin KT, Lu RM, Tarn WY (2004). "The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo". Mol. Cell. Biol. 24 (20): 9176–9185. doi:10.1128/MCB.24.20.9176-9185.2004. PMC 517884. PMID 15456888.