SF3B1

SF3B1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2F9D, 2F9J, 2PEH, 3LQV, 4OZ1, 2FHO
Identifiers
Aliases	SF3B1 , Hsh155, MDS, PRP10, PRPF10, SAP155, SF3b155, splicing factor 3b subunit 1
External IDs	OMIM: 605590 MGI: 1932339 HomoloGene: 6696 GeneCards: SF3B1
Gene location (Human)
Chr.	Chromosome 2 (human)
End	197,435,079 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	55,027,481 bp
RNA expression pattern
	Top expressed in
	tibia; ; kidney; ; endometrium; ; lung; ; spleen; ; Body of pancreas;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	GO:0001948 protein binding ; mRNA binding ; RNA binding ;
Cellular component	U11/U12 snRNP ; catalytic step 2 spliceosome ; spliceosomal complex ; U12-type spliceosomal complex ; U2-type prespliceosome ; nucleus ; U2 snRNP ; nucleoplasm ; nuclear speck ; U2-type precatalytic spliceosome ;
Biological process	RNA splicing, via transesterification reactions ; positive regulation of gene expression, epigenetic ; mRNA splicing, via spliceosome ; spliceosomal complex assembly ; mRNA processing ; RNA splicing ;
	Sources:Amigo / QuickGO
Orthologs
	23451
	81898
	ENSG00000115524
	ENSMUSG00000025982
	O75533
	Q99NB9
	NM_001005526 ; NM_001308824 ; NM_012433
	NM_031179
	NP_001005526 ; NP_001295753 ; NP_036565
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated November 05, 2021

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

Function

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.^[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 60%-80% of patients with refractory anemia with ring sideroblasts (RARS; which is a myelodysplastic syndrome) or RARS with thrombocytosis (RARS-T; which is a myelodysplastic syndrome/myeloproliferative neoplasm). There is also an emerging body of evidence to suggest implications of SF3B1 mutations being involved in orbital melanoma.

Related Research Articles

snRNPs, or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs. The action of snRNPs is essential to the removal of introns from pre-mRNA, a critical aspect of post-transcriptional modification of RNA, occurring only in the nucleus of eukaryotic cells. Additionally, U7 snRNP is not involved in splicing at all, as U7 snRNP is responsible for processing the 3′ stem-loop of histone pre-mRNA.

U2 spliceosomal snRNAs are a species of small nuclear RNA (snRNA) molecules found in the major spliceosomal (Sm) machinery of virtually all eukaryotic organisms. In vivo, U2 snRNA along with its associated polypeptides assemble to produce the U2 small nuclear ribonucleoprotein (snRNP), an essential component of the major spliceosomal complex. The major spliceosomal-splicing pathway is occasionally referred to as U2 dependent, based on a class of Sm intron—found in mRNA primary transcripts—that are recognized exclusively by the U2 snRNP during early stages of spliceosomal assembly. In addition to U2 dependent intron recognition, U2 snRNA has been theorized to serve a catalytic role in the chemistry of pre-RNA splicing as well. Similar to ribosomal RNAs (rRNAs), Sm snRNAs must mediate both RNA:RNA and RNA:protein contacts and hence have evolved specialized, highly conserved, primary and secondary structural elements to facilitate these types of interactions.

U4 spliceosomal RNA Non-coding RNA component of the spliceosome

The U4 small nuclear Ribo-Nucleic Acid is a non-coding RNA component of the major or U2-dependent spliceosome – a eukaryotic molecular machine involved in the splicing of pre-messenger RNA (pre-mRNA). It forms a duplex with U6, and with each splicing round, it is displaced from the U6 snRNA in an ATP-dependent manner, allowing U6 to re-fold and create the active site for splicing catalysis. A recycling process involving protein Brr2 releases U4 from U6, while protein Prp24 re-anneals U4 and U6. The crystal structure of a 5′ stem-loop of U4 in complex with a binding protein has been solved.

snRNP70 also known as U1 small nuclear ribonucleoprotein 70 kDa is a protein that in humans is encoded by the SNRNP70 gene. snRNP70 is a small nuclear ribonucleoprotein that associates with U1 spliceosomal RNA, forming the U1snRNP a core component of the spliceosome. The U1-70K protein and other components of the spliceosome complex form detergent-insoluble aggregates in both sporadic and familial human cases of Alzheimer's disease. U1-70K co-localizes with Tau in neurofibrillary tangles in Alzheimer's disease.

Small nuclear ribonucleoprotein Sm D1 is a protein that in humans is encoded by the SNRPD1 gene.

Splicing factor, proline- and glutamine-rich is a protein that in humans is encoded by the SFPQ gene.

Splicing factor U2AF 35 kDa subunit is a protein that in humans is encoded by the U2AF1 gene.

Small nuclear ribonucleoprotein Sm D2 is a protein that in humans is encoded by the SNRPD2 gene. It belongs to the small nuclear ribonucleoprotein core protein family, and is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified.

Small nuclear ribonucleoprotein Sm D3 is a protein that in humans is encoded by the SNRPD3 gene.

Splicing factor 3 subunit 1 is a protein that in humans is encoded by the SF3A1 gene.

U4/U6 small nuclear ribonucleoprotein Prp3 is a protein that in humans is encoded by the PRPF3 gene.

Splicing factor 3A subunit 3 is a protein that in humans is encoded by the SF3A3 gene.

Small nuclear ribonucleoprotein F is a protein that in humans is encoded by the SNRPF gene.

Splicing factor 3A subunit 2 is a protein that in humans is encoded by the SF3A2 gene.

Splicing factor 3B subunit 2 is a protein that in humans is encoded by the SF3B2 gene.

Splicing factor 3B subunit 4 is a protein that in humans is encoded by the SF3B4 gene.

Splicing factor 3B subunit 3 is a protein that in humans is encoded by the SF3B3 gene.

U4/U6 small nuclear ribonucleoprotein Prp4 is a protein that in humans is encoded by the PRPF4 gene. The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. PRPF4 is 1 of several proteins that associate with U4 and U6 snRNPs.[supplied by OMIM]

Splicing factor 3B, 14 kDa subunit, also known as SF3B14, is a human gene.

Prp24 is a protein part of the pre-messenger RNA splicing process and aids the binding of U6 snRNA to U4 snRNA during the formation of spliceosomes. Found in eukaryotes from yeast to E. coli, fungi, and humans, Prp24 was initially discovered to be an important element of RNA splicing in 1989. Mutations in Prp24 were later discovered in 1991 to suppress mutations in U4 that resulted in cold-sensitive strains of yeast, indicating its involvement in the reformation of the U4/U6 duplex after the catalytic steps of splicing.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000115524 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025982 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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): 1409–14. doi:10.1101/gad.12.10.1409. PMC 316838 . PMID 9585501.
1 2 "Entrez Gene: SF3B1 splicing factor 3b, subunit 1, 155kDa".
↑ 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): 6569–81. doi:10.1093/emboj/19.23.6569. PMC 305846 . PMID 11101529.
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): 4978–88. doi:10.1093/emboj/cdf480. PMC 126279 . PMID 12234937.
↑ 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): 31834–41. doi: 10.1074/jbc.M204427200 . PMID 12105215.
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): 6796–802. doi:10.1128/mcb.19.10.6796. PMC 84676 . PMID 10490618.
↑ 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". The EMBO Journal. 20 (16): 4536–46. doi:10.1093/emboj/20.16.4536. PMC 125580 . PMID 11500380.
↑ 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 (January 2012). "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. PMID 22158541. S2CID 205343043.
↑ 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): 6239–46. doi:10.1182/blood-2011-09-377275. PMC 3236114 . PMID 21998214.
↑ Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; 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.

Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
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Gozani O, Potashkin J, Reed R (August 1998). "A potential role for U2AF-SAP 155 interactions in recruiting U2 snRNP to the branch site". Molecular and Cellular Biology. 18 (8): 4752–60. doi:10.1128/mcb.18.8.4752. PMC 109061 . PMID 9671485.
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): 6796–802. doi:10.1128/mcb.19.10.6796. PMC 84676 . PMID 10490618.
Pauling MH, McPheeters DS, Ares M (March 2000). "Functional Cus1p is found with Hsh155p in a multiprotein splicing factor associated with U2 snRNA". Molecular and Cellular Biology. 20 (6): 2176–85. doi:10.1128/MCB.20.6.2176-2185.2000. PMC 110834 . PMID 10688664.
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 (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–6. Bibcode:2000PNAS...97.3491D. doi: 10.1073/pnas.97.7.3491 . PMC 16267 . PMID 10737800.
Das R, Zhou Z, Reed R (May 2000). "Functional association of U2 snRNP with the ATP-independent spliceosomal complex E". Molecular Cell. 5 (5): 779–87. doi: 10.1016/S1097-2765(00)80318-4 . PMID 10882114.
Brand M, Moggs JG, Oulad-Abdelghani M, Lejeune F, Dilworth FJ, Stevenin J, Almouzni G, Tora L (June 2001). "UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation". The EMBO Journal. 20 (12): 3187–96. doi:10.1093/emboj/20.12.3187. PMC 150203 . PMID 11406595.
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". The EMBO Journal. 20 (16): 4536–46. doi:10.1093/emboj/20.16.4536. PMC 125580 . PMID 11500380.
Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ (April 2002). "Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis". RNA. 8 (4): 426–39. doi:10.1017/S1355838202021088. PMC 1370266 . PMID 11991638.
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): 31834–41. doi: 10.1074/jbc.M204427200 . PMID 12105215.
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): 4978–88. doi:10.1093/emboj/cdf480. PMC 126279 . PMID 12234937.
Golas MM, Sander B, Will CL, Lührmann R, Stark H (May 2003). "Molecular architecture of the multiprotein splicing factor SF3b". Science. 300 (5621): 980–4. Bibcode:2003Sci...300..980G. doi:10.1126/science.1084155. PMID 12738865. S2CID 31046270.
Banerjee H, Rahn A, Gawande B, Guth S, Valcarcel J, Singh R (February 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): 240–53. doi:10.1261/rna.5153204. PMC 1370536 . PMID 14730023.
Will CL, Schneider C, Hossbach M, Urlaub H, Rauhut R, Elbashir S, Tuschl T, Lührmann R (June 2004). "The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2-dependent spliceosome". RNA. 10 (6): 929–41. doi:10.1261/rna.7320604. PMC 1370585 . PMID 15146077.
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Lin KT, Lu RM, Tarn WY (October 2004). "The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo". Molecular and Cellular Biology. 24 (20): 9176–85. doi:10.1128/MCB.24.20.9176-9185.2004. PMC 517884 . PMID 15456888.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000115524 - Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid9585501-5] 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): 1409–14. doi:10.1101/gad.12.10.1409. PMC 316838 . PMID 9585501.

[entrez-6] 1 2 "Entrez Gene: SF3B1 splicing factor 3b, subunit 1, 155kDa".

[pmid11101529-7] 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): 6569–81. doi:10.1093/emboj/19.23.6569. PMC 305846 . PMID 11101529.

[pmid12234937-8] 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): 4978–88. doi:10.1093/emboj/cdf480. PMC 126279 . PMID 12234937.

[pmid12105215-9] 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): 31834–41. doi: 10.1074/jbc.M204427200 . PMID 12105215.

[pmid10490618-10] 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): 6796–802. doi:10.1128/mcb.19.10.6796. PMC 84676 . PMID 10490618.

[pmid11500380-11] 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". The EMBO Journal. 20 (16): 4536–46. doi:10.1093/emboj/20.16.4536. PMC 125580 . PMID 11500380.

[pmid22158541-12] 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 (January 2012). "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. PMID 22158541. S2CID 205343043.

[pmid21998214-13] 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): 6239–46. doi:10.1182/blood-2011-09-377275. PMC 3236114 . PMID 21998214.

[nature11412-14] Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; 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.

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