U2 small nuclear RNA auxiliary factor 1

This gene belongs to the splicing factor SR family of genes {{Citation needed|date=November 2020}}. U2AF1 is a subunit of the U2 Auxiliary Factor complex alongside a larger subunit, U2AF2. U2AF1 is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes a small (~35 kDa) subunit which plays a critical role in RNA splicing by recognizing and binding to AG nucleotides at the 3’ splice site to facilitate spliceosome assembly.{{cite journal |vauthors=Zamore PD, Green MR |title=Identification, purification, and biochemical characterization of U2 small nuclear ribonucleoprotein auxiliary factor |journal=PNAS |volume=86 |issue=23 |pages=9243–9247 |date=1989 |pmid=2531895 |doi=10.1073/pnas.86.23.9243 |doi-access=free |pmc=298470|bibcode=1989PNAS...86.9243Z }}{{cite journal |vauthors=Wu S, Romfo CM, Nilsen TW, Green MR |title=Functional recognition of the 3' splice site AG by the splicing factor U2AF35 |journal=Nature |volume=402 |issue=6763 |pages=832–5 |date=1999 |pmid=10617206 |doi=10.1038/45590 |bibcode=1999Natur.402..832W |s2cid=4405416 |doi-access=}} Alternatively spliced transcript variants encoding different isoforms have been identified {{Citation needed|date=November 2020}}. Somatic mutations in U2AF1 have been found in a range of human cancers, with a distinctive pattern of these mutations at the zinc fingers implicating a functional role under selection.{{cite journal |vauthors=Imielinski M, Berger AG, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair A, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansén S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Jänne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M |display-authors=44 |title=Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing |journal=Cell |volume=150 |issue=6 |pages=1107–1120 |date=2012 |doi=10.1016/j.cell.2012.08.029 |pmid=22980975 |pmc=3557932 |doi-access=free}} In lung cancers, these mutations affect alternative splicing of several transcripts, including oncogenic ROS1 fusions.{{cite journal |vauthors=Esfahani MS, Lee LJ, Jeon YJ, Flynn RA, Stehr H, Hui AB, Ishisoko N, Kildebeck E, Newman AM, Bratman SV, Porteus MH, Chang HY, Alizadeh AA, Diehn M |display-authors=6 |title=Functional significance of U2AF1 S34F mutations in lung adenocarcinomas |journal=Nature Communications |volume=10 |issue=1 |pages=5712 |date=December 2019 |pmid=31836708 |doi=10.1038/s41467-019-13392-y |doi-access=free |pmc=6911043 |bibcode=2019NatCo..10.5712E}}

U2af1 conditional deletion in mouse hematopoietic system leads to early lethality suggesting its important for hematopoietic stem cell maintenance and function {https://doi.org/10.1038/s41375-020-01116-x }.

U2 small nuclear RNA auxiliary factor 1 has been shown to interact with:

• ASF/SF2,{{cite journal |vauthors=Xiao SH, Manley JL |title=Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2 |journal=EMBO J. |volume=17 |issue=21 |pages=6359–67 |date=November 1998 |pmid=9799243 |pmc=1170960 |doi=10.1093/emboj/17.21.6359}}{{cite journal |vauthors=Zhang WJ, Wu JY |title=Functional properties of p54, a novel SR protein active in constitutive and alternative splicing |journal=Mol. Cell. Biol. |volume=16 |issue=10 |pages=5400–8 |date=October 1996 |pmid=8816452 |pmc=231539 |doi= 10.1128/MCB.16.10.5400}}
• NXF1,{{cite journal |vauthors=Zolotukhin AS, Tan W, Bear J, Smulevitch S, Felber BK |title=U2AF participates in the binding of TAP (NXF1) to mRNA |journal=J. Biol. Chem. |volume=277 |issue=6 |pages=3935–42 |date=February 2002 |pmid=11724776 |doi=10.1074/jbc.M107598200 |doi-access=free}}
• RP9,{{cite journal |vauthors=Maita H, Kitaura H, Keen TJ, Inglehearn CF, Ariga H, Iguchi-Ariga SM |title=PAP-1, the mutated gene underlying the RP9 form of dominant retinitis pigmentosa, is a splicing factor |journal=Exp. Cell Res. |volume=300 |issue=2 |pages=283–96 |date=November 2004 |pmid=15474994 |doi=10.1016/j.yexcr.2004.07.029}}
• SMNDC1,{{cite journal |vauthors=Little JT, Jurica MS |title=Splicing factor SPF30 bridges an interaction between the prespliceosome protein U2AF35 and tri-small nuclear ribonucleoprotein protein hPrp3 |journal=J. Biol. Chem. |volume=283 |issue=13 |pages=8145–52 |date=March 2008 |pmid=18211889 |doi=10.1074/jbc.M707984200 |doi-access=free}}
• U2AF2,{{cite journal |vauthors=Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue=7062 |pages=1173–8 |date=October 2005 |pmid=16189514 |doi=10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026}}{{cite journal |vauthors=Zhang M, Zamore PD, Carmo-Fonseca M, Lamond AI, Green MR |title=Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=18 |pages=8769–73 |date=September 1992 |pmid=1388271 |pmc=50002 |doi= 10.1073/pnas.89.18.8769 |bibcode=1992PNAS...89.8769Z|doi-access=free }} and
• ZRANB2.{{cite journal |vauthors=Adams DJ, van der Weyden L, Mayeda A, Stamm S, Morris BJ, Rasko JE |title=ZNF265--a novel spliceosomal protein able to induce alternative splicing |journal=J. Cell Biol. |volume=154 |issue=1 |pages=25–32 |date=July 2001 |pmid=11448987 |pmc=2196870 |doi= 10.1083/jcb.200010059}}

{{Reflist}}

{{Refbegin |2}}

• {{cite journal |vauthors=Zhang M, Zamore PD, Carmo-Fonseca M, Lamond AI, Green MR |title=Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=18 |pages=8769–8773 |year=1992 |pmid=1388271 |pmc=50002 |doi=10.1073/pnas.89.18.8769 |bibcode=1992PNAS...89.8769Z|doi-access=free }}
• {{cite journal |vauthors=Zamore PD, Green MR |title=Biochemical characterization of U2 snRNP auxiliary factor: an essential pre-mRNA splicing factor with a novel intranuclear distribution |journal=EMBO J. |volume=10 |issue=1 |pages=207–14 |year=1991 |pmid=1824937 |pmc=452631 |doi= 10.1002/j.1460-2075.1991.tb07937.x}}
• {{cite journal |vauthors=Wu JY, Maniatis T |title=Specific interactions between proteins implicated in splice site selection and regulated alternative splicing |journal=Cell |volume=75 |issue=6 |pages=1061–1070 |year=1994 |pmid=8261509 |doi=10.1016/0092-8674(93)90316-I |s2cid=22951690}}
• {{cite journal |vauthors=Zuo P, Maniatis T |title=The splicing factor U2AF35 mediates critical protein-protein interactions in constitutive and enhancer-dependent splicing |journal=Genes Dev. |volume=10 |issue=11 |pages=1356–1368 |year=1996 |pmid=8647433 |doi=10.1101/gad.10.11.1356 |doi-access=free}}
• {{cite journal |vauthors=Hong W, Bennett M, Xiao Y, Feld Kramer R, Wang C, Reed R |title=Association of U2 snRNP with the spliceosomal complex E |journal=Nucleic Acids Res. |volume=25 |issue=2 |pages=354–361 |year=1997 |pmid=9016565 |pmc=146436 |doi=10.1093/nar/25.2.354}}
• {{cite journal |vauthors=Tronchère H, Wang J, Fu XD |title=A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR proteins in splicing of pre-mRNA |journal=Nature |volume=388 |issue=6640 |pages=397–400 |year=1997 |pmid=9237760 |doi=10.1038/41137 |bibcode=1997Natur.388..397T |s2cid=4386808|doi-access=free }}
• {{cite journal |vauthors=Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD |title=SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells |journal=J. Cell Biol. |volume=140 |issue=4 |pages=737–750 |year=1998 |pmid=9472028 |pmc=2141757 |doi=10.1083/jcb.140.4.737}}
• {{cite journal |vauthors=Rudner DZ, Kanaar R, Breger KS, Rio DC |title=Interaction between subunits of heterodimeric splicing factor U2AF is essential in vivo |journal=Mol. Cell. Biol. |volume=18 |issue=4 |pages=1765–73 |year=1998 |pmid=9528748 |pmc=121406 |doi= 10.1128/MCB.18.4.1765}}
• {{cite journal |vauthors=Lallena MJ, Martínez C, Valcárcel J, Correas I |title=Functional association of nuclear protein 4.1 with pre-mRNA splicing factors |journal=J. Cell Sci. |volume=111 |issue=14 |pages=1963–71 |year=1998 |doi=10.1242/jcs.111.14.1963 |pmid=9645944 }}
• {{cite journal |vauthors=Gozani O, Potashkin J, Reed R |author-link2=Judith Potashkin|title=A potential role for U2AF-SAP 155 interactions in recruiting U2 snRNP to the branch site |journal=Mol. Cell. Biol. |volume=18 |issue=8 |pages=4752–60 |year=1998 |pmid=9671485 |pmc=109061 |doi= 10.1128/mcb.18.8.4752}}
• {{cite journal |vauthors=Neubauer G, King A, Rappsilber J, Calvio C, Watson M, Ajuh P, Sleeman J, Lamond A, Mann M |title=Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex |journal=Nat. Genet. |volume=20 |issue=1 |pages=46–50 |year=1998 |pmid=9731529 |doi=10.1038/1700 |s2cid=585778}}
• {{cite journal |vauthors=Xiao SH, Manley JL |title=Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2 |journal=EMBO J. |volume=17 |issue=21 |pages=6359–6367 |year=1999 |pmid=9799243 |pmc=1170960 |doi=10.1093/emboj/17.21.6359}}
• {{cite journal |vauthors=de Vries H, Rüegsegger U, Hübner W, Friedlein A, Langen H, Keller W |title=Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors |journal=EMBO J. |volume=19 |issue=21 |pages=5895–5904 |year=2000 |pmid=11060040 |pmc=305781 |doi=10.1093/emboj/19.21.5895}}
• {{cite journal |vauthors=Gama-Carvalho M, Carvalho MP, Kehlenbach A, Valcarcel J, Carmo-Fonseca M |title=Nucleocytoplasmic shuttling of heterodimeric splicing factor U2AF |journal=J. Biol. Chem. |volume=276 |issue=16 |pages=13104–13112 |year=2001 |pmid=11118443 |doi=10.1074/jbc.M008759200 |doi-access=free}}
• {{cite journal |vauthors=Adams DJ, van der Weyden L, Mayeda A, Stamm S, Morris BJ, Rasko JE |title=ZNF265--a novel spliceosomal protein able to induce alternative splicing |journal=J. Cell Biol. |volume=154 |issue=1 |pages=25–32 |year=2001 |pmid=11448987 |pmc=2196870 |doi=10.1083/jcb.200010059}}
• {{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=EMBO J. |volume=20 |issue=16 |pages=4536–4546 |year=2001 |pmid=11500380 |pmc=125580 |doi=10.1093/emboj/20.16.4536}}
• {{cite journal |vauthors=Nesic D, Krämer A |title=Domains in human splicing factors SF3a60 and SF3a66 required for binding to SF3a120, assembly of the 17S U2 snRNP, and prespliceosome formation |journal=Mol. Cell. Biol. |volume=21 |issue=19 |pages=6406–6417 |year=2001 |pmid=11533230 |pmc=99788 |doi=10.1128/MCB.21.19.6406-6417.2001}}
• {{cite journal |vauthors=Esfahani MS, Lee LJ, Jeon YJ, Flynn R, Stehr H, Hui A, Ishisoko N, Kildebeck E, Newman AM, Bratman SV, Porteus MH, Chang HY, Alizadeh AA, Diehn M |title=Functional significance of U2AF1 S34F mutations in lung adenocarcinomas |journal=Nature Communications |volume=10 |issue=1 |year=2019 |page=5712 |pmid=31836708 |pmc=6911043 |doi=10.1038/s41467-019-13392-y |bibcode=2019NatCo..10.5712E}}

{{Refend}}

• {{PDBe-KB2|Q01081|Splicing factor U2AF 35 kDa subunit}}

{{PDB Gallery|geneid=7307}}