U2 small nuclear RNA auxiliary factor 1

U2AF1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1JMT
Identifiers
Aliases	U2AF1 , FP793, RN, RNU2AF35, U2AFBP, U2 small nuclear RNA auxiliary factor 1
External IDs	OMIM: 191317; HomoloGene: 134334; GeneCards: U2AF1; OMA:U2AF1 - orthologs
Gene location (Human) Chr. Chromosome 21 (human) [1] Band 21q22.3 Start 43,092,956 bp [1] End 43,107,570 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in anterior pituitary left uterine tube bone marrow olfactory zone of nasal mucosa mucosa of transverse colon appendix stromal cell of endometrium right lung monocyte granulocyte n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function metal ion binding protein binding nucleic acid binding pre-mRNA 3'-splice site binding RNA binding RS domain binding Cellular component Cajal body nuclear speck catalytic step 2 spliceosome U2AF complex nucleoplasm spliceosomal complex nucleus Biological process termination of RNA polymerase II transcription positive regulation of protein targeting to mitochondrion mRNA processing mRNA export from nucleus regulation of autophagy of mitochondrion RNA splicing mRNA 3'-end processing RNA export from nucleus mRNA splicing, via spliceosome Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7307 n/a Ensembl ENSG00000160201 n/a UniProt Q01081 P0DN76 n/a RefSeq (mRNA) NM_001025203 NM_001025204 NM_006758 n/a RefSeq (protein) NP_001307575 NP_001307577 NP_001307579 NP_001307580 NP_001020374 NP_001020375 NP_006749 NP_001020374 NP_001020375 NP_006749 n/a Location (UCSC) Chr 21: 43.09 – 43.11 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Splicing factor U2AF 35 kDa subunit is a protein that in humans is encoded by the U2AF1 gene. ^{[3] [4] [5]}

Function

This gene belongs to the splicing factor SR family of genes ^{[ citation needed ]}. 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. ^[6] Alternatively spliced transcript variants encoding different isoforms have been identified ^{[ citation needed ]}. 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. ^[7] In lung cancers, these mutations affect alternative splicing of several transcripts, including oncogenic ROS1 fusions. ^[8] 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 }.

Interactions

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

• ASF/SF2, ^{[9] [10]}
• NXF1, ^[11]
• RP9, ^[12]
• SMNDC1, ^[13]
• U2AF2, ^{[14] [15]} and
• ZRANB2. ^[16]

References

1. GRCh38: Ensembl release 89: ENSG00000160201 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Lalioti MD, Gos A, Green MR, Rossier C, Morris MA, Antonarakis SE (January 1997). "The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3". Genomics. 33 (2): 298–300. doi:10.1006/geno.1996.0196. PMID   8660980.
4. Kalcheva I, Plass C, Sait S, Eddy R, Shows T, Watkins-Chow D, Camper S, Shibata H, Ueda T, Takagi N (Dec 1994). "Comparative mapping of the imprinted U2afbpL gene on mouse chromosome 11 and human chromosome 5". Cytogenet Cell Genet. 68 (1–2): 19–24. doi:10.1159/000133881. PMID   7956352.
5. "Entrez Gene: U2AF1 U2 small nuclear RNA auxiliary factor 1".
6. Zamore PD, Green MR (1989). "Identification, purification, and biochemical characterization of U2 small nuclear ribonucleoprotein auxiliary factor". PNAS. 86 (23): 9243–9247. Bibcode:1989PNAS...86.9243Z. doi: 10.1073/pnas.86.23.9243 . PMC   298470 . PMID   2531895.Wu S, Romfo CM, Nilsen TW, Green MR (1999). "Functional recognition of the 3' splice site AG by the splicing factor U2AF35". Nature. 402 (6763): 832–5. Bibcode:1999Natur.402..832W. doi:10.1038/45590. PMID   10617206. S2CID   4405416.
7. 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, et al. (2012). "Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing". Cell. 150 (6): 1107–1120. doi: 10.1016/j.cell.2012.08.029 . PMC   3557932 . PMID   22980975.
8. Esfahani MS, Lee LJ, Jeon YJ, Flynn RA, Stehr H, Hui AB, et al. (December 2019). "Functional significance of U2AF1 S34F mutations in lung adenocarcinomas". Nature Communications. 10 (1): 5712. Bibcode:2019NatCo..10.5712E. doi: 10.1038/s41467-019-13392-y . PMC   6911043 . PMID   31836708.
9. Xiao SH, Manley JL (November 1998). "Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2". EMBO J. 17 (21): 6359–67. doi:10.1093/emboj/17.21.6359. PMC   1170960 . PMID   9799243.
10. Zhang WJ, Wu JY (October 1996). "Functional properties of p54, a novel SR protein active in constitutive and alternative splicing". Mol. Cell. Biol. 16 (10): 5400–8. doi:10.1128/MCB.16.10.5400. PMC   231539 . PMID   8816452.
11. Zolotukhin AS, Tan W, Bear J, Smulevitch S, Felber BK (February 2002). "U2AF participates in the binding of TAP (NXF1) to mRNA". J. Biol. Chem. 277 (6): 3935–42. doi: 10.1074/jbc.M107598200 . PMID   11724776.
12. Maita H, Kitaura H, Keen TJ, Inglehearn CF, Ariga H, Iguchi-Ariga SM (November 2004). "PAP-1, the mutated gene underlying the RP9 form of dominant retinitis pigmentosa, is a splicing factor". Exp. Cell Res. 300 (2): 283–96. doi:10.1016/j.yexcr.2004.07.029. PMID   15474994.
13. Little JT, Jurica MS (March 2008). "Splicing factor SPF30 bridges an interaction between the prespliceosome protein U2AF35 and tri-small nuclear ribonucleoprotein protein hPrp3". J. Biol. Chem. 283 (13): 8145–52. doi: 10.1074/jbc.M707984200 . PMID   18211889.
14. 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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
15. Zhang M, Zamore PD, Carmo-Fonseca M, Lamond AI, Green MR (September 1992). "Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit". Proc. Natl. Acad. Sci. U.S.A. 89 (18): 8769–73. Bibcode:1992PNAS...89.8769Z. doi: 10.1073/pnas.89.18.8769 . PMC   50002 . PMID   1388271.
16. Adams DJ, van der Weyden L, Mayeda A, Stamm S, Morris BJ, Rasko JE (July 2001). "ZNF265--a novel spliceosomal protein able to induce alternative splicing". J. Cell Biol. 154 (1): 25–32. doi:10.1083/jcb.200010059. PMC   2196870 . PMID   11448987.

Further reading

• Zhang M, Zamore PD, Carmo-Fonseca M, Lamond AI, Green MR (1992). "Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit". Proc. Natl. Acad. Sci. U.S.A. 89 (18): 8769–8773. Bibcode:1992PNAS...89.8769Z. doi: 10.1073/pnas.89.18.8769 . PMC   50002 . PMID   1388271.
• Zamore PD, Green MR (1991). "Biochemical characterization of U2 snRNP auxiliary factor: an essential pre-mRNA splicing factor with a novel intranuclear distribution". EMBO J. 10 (1): 207–14. doi:10.1002/j.1460-2075.1991.tb07937.x. PMC   452631 . PMID   1824937.
• Wu JY, Maniatis T (1994). "Specific interactions between proteins implicated in splice site selection and regulated alternative splicing". Cell. 75 (6): 1061–1070. doi:10.1016/0092-8674(93)90316-I. PMID   8261509. S2CID   22951690.
• Zuo P, Maniatis T (1996). "The splicing factor U2AF35 mediates critical protein-protein interactions in constitutive and enhancer-dependent splicing". Genes Dev. 10 (11): 1356–1368. doi: 10.1101/gad.10.11.1356 . PMID   8647433.
• Hong W, Bennett M, Xiao Y, Feld Kramer R, Wang C, Reed R (1997). "Association of U2 snRNP with the spliceosomal complex E". Nucleic Acids Res. 25 (2): 354–361. doi:10.1093/nar/25.2.354. PMC   146436 . PMID   9016565.
• Tronchère H, Wang J, Fu XD (1997). "A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR proteins in splicing of pre-mRNA". Nature. 388 (6640): 397–400. Bibcode:1997Natur.388..397T. doi: 10.1038/41137 . PMID   9237760. S2CID   4386808.
• Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD (1998). "SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells". J. Cell Biol. 140 (4): 737–750. doi:10.1083/jcb.140.4.737. PMC   2141757 . PMID   9472028.
• Rudner DZ, Kanaar R, Breger KS, Rio DC (1998). "Interaction between subunits of heterodimeric splicing factor U2AF is essential in vivo". Mol. Cell. Biol. 18 (4): 1765–73. doi:10.1128/MCB.18.4.1765. PMC   121406 . PMID   9528748.
• Lallena MJ, Martínez C, Valcárcel J, Correas I (1998). "Functional association of nuclear protein 4.1 with pre-mRNA splicing factors". J. Cell Sci. 111 (14): 1963–71. doi:10.1242/jcs.111.14.1963. PMID   9645944.
• 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. doi:10.1128/mcb.18.8.4752. PMC   109061 . PMID   9671485.
• Neubauer G, King A, Rappsilber J, Calvio C, Watson M, Ajuh P, Sleeman J, Lamond A, Mann M (1998). "Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex". Nat. Genet. 20 (1): 46–50. doi:10.1038/1700. PMID   9731529. S2CID   585778.
• Xiao SH, Manley JL (1999). "Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2". EMBO J. 17 (21): 6359–6367. doi:10.1093/emboj/17.21.6359. PMC   1170960 . PMID   9799243.
• de Vries H, Rüegsegger U, Hübner W, Friedlein A, Langen H, Keller W (2000). "Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors". EMBO J. 19 (21): 5895–5904. doi:10.1093/emboj/19.21.5895. PMC   305781 . PMID   11060040.
• Gama-Carvalho M, Carvalho MP, Kehlenbach A, Valcarcel J, Carmo-Fonseca M (2001). "Nucleocytoplasmic shuttling of heterodimeric splicing factor U2AF". J. Biol. Chem. 276 (16): 13104–13112. doi: 10.1074/jbc.M008759200 . PMID   11118443.
• Adams DJ, van der Weyden L, Mayeda A, Stamm S, Morris BJ, Rasko JE (2001). "ZNF265--a novel spliceosomal protein able to induce alternative splicing". J. Cell Biol. 154 (1): 25–32. doi:10.1083/jcb.200010059. PMC   2196870 . PMID   11448987.
• Will CL, Schneider C, MacMillan AM, Katopodis NF, Neubauer G, Wilm M, Lührmann R, Query CC (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.
• Nesic D, Krämer A (2001). "Domains in human splicing factors SF3a60 and SF3a66 required for binding to SF3a120, assembly of the 17S U2 snRNP, and prespliceosome formation". Mol. Cell. Biol. 21 (19): 6406–6417. doi:10.1128/MCB.21.19.6406-6417.2001. PMC   99788 . PMID   11533230.
• 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 (2019). "Functional significance of U2AF1 S34F mutations in lung adenocarcinomas". Nature Communications. 10 (1): 5712. Bibcode:2019NatCo..10.5712E. doi:10.1038/s41467-019-13392-y. PMC   6911043 . PMID   31836708.

External links

• Overview of all the structural information available in the PDB for UniProt : Q01081 (Splicing factor U2AF 35 kDa subunit) at the PDBe-KB .