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)
End	43,107,570 bp
RNA expression pattern
	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
	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
	7307
	n/a
	ENSG00000160201
	n/a
	Q01081; P0DN76
	n/a
	NM_001025203; NM_001025204; NM_006758
	n/a
NP_001307575; NP_001307577; NP_001307579; NP_001307580; NP_001020374;
	NP_001020375; NP_006749; NP_001020374; NP_001020375; NP_006749
	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:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000160201 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ "Entrez Gene: U2AF1 U2 small nuclear RNA auxiliary factor 1".
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160201 – Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8660980-3] 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.

[pmid7956352-4] 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.

[entrez-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.

[pmid9799243-9] 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.

[pmid8816452-10] 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.

[pmid11724776-11] 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.

[pmid15474994-12] 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.

[pmid18211889-13] 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.

[pmid16189514-14] 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.

[pmid1388271-15] 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.

[pmid11448987-16] 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.

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Function

Interactions

References

Further reading

External links