U2AF2

U2AF2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1JMT, 1O0P, 1OPI, 1U2F, 2G4B, 2HZC, 2M0G, 2U2F, 2YH0, 2YH1, 3VAF, 3VAG, 3VAH, 3VAI, 3VAJ, 3VAK, 3VAL, 3VAM, 4FXW, 4TU7, 4TU8, 4TU9, 5EV1, 5EV3, 5EV4, 5EV2
Identifiers
Aliases	U2AF2, U2AF65, U2 small nuclear RNA auxiliary factor 2
External IDs	OMIM: 191318; MGI: 98886; HomoloGene: 110853; GeneCards: U2AF2; OMA:U2AF2 - orthologs
Gene location (Human)
Chr.	Chromosome 19 (human)
End	55,674,716 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	5,079,938 bp
RNA expression pattern
	Top expressed in
	right uterine tube; ; canal of the cervix; ; granulocyte; ; anterior pituitary; ; right ovary; ; body of uterus; ; right lobe of thyroid gland; ; left ovary; ; left lobe of thyroid gland; ; right hemisphere of cerebellum;
	Top expressed in
	ventricular zone; ; neural layer of retina; ; yolk sac; ; lip; ; epiblast; ; granulocyte; ; dentate gyrus of hippocampal formation granule cell; ; superior frontal gyrus; ; primary visual cortex; ; thymus;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	pre-mRNA 3'-splice site binding; poly-pyrimidine tract binding; protein binding; nucleic acid binding; enzyme binding; C2H2 zinc finger domain binding; RNA binding;
Cellular component	nuclear speck; U2AF complex; Prp19 complex; spliceosomal complex; commitment complex; U2-type prespliceosome; nucleus; nucleoplasm;
Biological process	mRNA splicing, via spliceosome; termination of RNA polymerase II transcription; positive regulation of protein targeting to mitochondrion; mRNA processing; mRNA export from nucleus; negative regulation of mRNA splicing, via spliceosome; regulation of autophagy of mitochondrion; positive regulation of RNA splicing; mRNA 3'-end processing; RNA splicing; RNA export from nucleus; negative regulation of protein ubiquitination;
	Sources:Amigo / QuickGO
Orthologs
	11338
	22185
	ENSG00000063244
	ENSMUSG00000030435
	P26368
	P26369
	NM_001012478; NM_007279
	NM_001205231; NM_133671
	NP_001012496; NP_009210
NP_001192160; NP_598432; NP_001390074; NP_001390075; NP_001390076;
	NP_001390077; NP_001390078; NP_001390079; NP_001390080; NP_001390083; NP_001390084; NP_001390085; NP_001390087; NP_001390088; NP_001390082
	Wikidata
View/Edit Human	View/Edit Mouse

Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene.^[5]

Function

U2 auxiliary factor (U2AF), composed of a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the U2AF large subunit, which contains a sequence-specific RNA-binding region with 3 RNA recognition motifs and an Arg/Ser-rich domain necessary for splicing. The large subunit binds to the polypyrimidine tract of introns early during spliceosome assembly. Multiple alternatively spliced transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date.^[6]

In humans and other tetrapods, it has been shown that without U2AF2, the splicing process is inhibited. However, in zebrafish and other teleosts the RNA splicing process can still occur on certain genes in the absence of U2AF2. This may be because 10% of genes have alternating TG and AC base pairs at the 3' splice site (3'ss) and 5' splice site (5'ss) respectively on each intron, which alters the secondary structure of the RNA and influences splicing.^[7]

Interactions

U2AF2 has been shown to interact with:

PUF60,^[8]^[9]
SF1,^[8]^[10]^[11]
SFRS11,^[12]
SFRS2IP,^[13]
SRPK2,^[8]^[14]
U2 small nuclear RNA auxiliary factor 1^[8]^[15] and
WT1.^[16]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000063244 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030435 – 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.
^ Zamore PD, Patton JG, Green MR (Mar 1992). "Cloning and domain structure of the mammalian splicing factor U2AF". Nature. 355 (6361): 609–14. doi:10.1038/355609a0. PMID 1538748. S2CID 4332390.
^ "Entrez Gene: U2AF2 U2 small nuclear RNA auxiliary factor 2".
^ Lin CL, Taggart AJ, Lim KH, Cygan KJ, Ferraris L, Creton R, Huang YT, Fairbrother WG (January 2016). "RNA structure replaces the need for U2AF2 in splicing". Genome Research. 26 (1): 12–23. doi:10.1101/gr.181008.114. PMC 4691745. PMID 26566657.
^ ^a ^b ^c ^d 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 (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
^ Berglund JA, Abovich N, Rosbash M (Mar 1998). "A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition". Genes Dev. 12 (6): 858–67. doi:10.1101/gad.12.6.858. PMC 316625. PMID 9512519.
^ Abovich N, Rosbash M (May 1997). "Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals". Cell. 89 (3): 403–12. doi:10.1016/s0092-8674(00)80221-4. PMID 9150140. S2CID 18466775.
^ Zhang WJ, Wu JY (Oct 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.
^ Zhang WJ, Wu JY (Feb 1998). "Sip1, a novel RS domain-containing protein essential for pre-mRNA splicing". Mol. Cell. Biol. 18 (2): 676–84. doi:10.1128/MCB.18.2.676. PMC 108778. PMID 9447963.
^ Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD (Feb 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): 737–50. doi:10.1083/jcb.140.4.737. PMC 2141757. PMID 9472028.
^ Zhang M, Zamore PD, Carmo-Fonseca M, Lamond AI, Green MR (Sep 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. doi:10.1073/pnas.89.18.8769. PMC 50002. PMID 1388271.
^ Davies RC, Calvio C, Bratt E, Larsson SH, Lamond AI, Hastie ND (Oct 1998). "WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes". Genes Dev. 12 (20): 3217–25. doi:10.1101/gad.12.20.3217. PMC 317218. PMID 9784496.

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): 8769–73. 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.
Zuo P, Maniatis T (1996). "The splicing factor U2AF35 mediates critical protein-protein interactions in constitutive and enhancer-dependent splicing". Genes Dev. 10 (11): 1356–68. doi:10.1101/gad.10.11.1356. PMID 8647433.
Zhang WJ, Wu JY (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.
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): 354–61. doi:10.1093/nar/25.2.354. PMC 146436. PMID 9016565.
Abovich N, Rosbash M (1997). "Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals". Cell. 89 (3): 403–12. doi:10.1016/S0092-8674(00)80221-4. PMID 9150140. S2CID 18466775.
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. doi:10.1038/41137. PMID 9237760. S2CID 4386808.
Fleckner J, Zhang M, Valcárcel J, Green MR (1997). "U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction". Genes Dev. 11 (14): 1864–72. doi:10.1101/gad.11.14.1864. PMID 9242493.
Zhang WJ, Wu JY (1998). "Sip1, a novel RS domain-containing protein essential for pre-mRNA splicing". Mol. Cell. Biol. 18 (2): 676–84. doi:10.1128/MCB.18.2.676. PMC 108778. PMID 9447963.
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): 737–50. doi:10.1083/jcb.140.4.737. PMC 2141757. PMID 9472028.
Berglund JA, Abovich N, Rosbash M (1998). "A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition". Genes Dev. 12 (6): 858–67. doi:10.1101/gad.12.6.858. PMC 316625. PMID 9512519.
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. 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.
Davies RC, Calvio C, Bratt E, Larsson SH, Lamond AI, Hastie ND (1998). "WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes". Genes Dev. 12 (20): 3217–25. doi:10.1101/gad.12.20.3217. PMC 317218. PMID 9784496.
Ito T, Muto Y, Green MR, Yokoyama S (1999). "Solution structures of the first and second RNA-binding domains of human U2 small nuclear ribonucleoprotein particle auxiliary factor (U2AF(65))". EMBO J. 18 (16): 4523–34. doi:10.1093/emboj/18.16.4523. PMC 1171527. PMID 10449418.
Wang X, Bruderer S, Rafi Z, Xue J, Milburn PJ, Krämer A, Robinson PJ (1999). "Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent protein kinase regulates spliceosome assembly". EMBO J. 18 (16): 4549–59. doi:10.1093/emboj/18.16.4549. PMC 1171529. PMID 10449420.
Ladomery MR, Slight J, Mc Ghee S, Hastie ND (1999). "Presence of WT1, the Wilm's tumor suppressor gene product, in nuclear poly(A)(+) ribonucleoprotein". J. Biol. Chem. 274 (51): 36520–6. doi:10.1074/jbc.274.51.36520. PMID 10593950.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000063244 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030435 – 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.

[pmid1538748-5] Zamore PD, Patton JG, Green MR (Mar 1992). "Cloning and domain structure of the mammalian splicing factor U2AF". Nature. 355 (6361): 609–14. doi:10.1038/355609a0. PMID 1538748. S2CID 4332390.

[entrez-6] "Entrez Gene: U2AF2 U2 small nuclear RNA auxiliary factor 2".

[BrownRNA-7] Lin CL, Taggart AJ, Lim KH, Cygan KJ, Ferraris L, Creton R, Huang YT, Fairbrother WG (January 2016). "RNA structure replaces the need for U2AF2 in splicing". Genome Research. 26 (1): 12–23. doi:10.1101/gr.181008.114. PMC 4691745. PMID 26566657.

[pmid16189514-8] 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 (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

[pmid17353931-9] Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

[pmid9512519-10] Berglund JA, Abovich N, Rosbash M (Mar 1998). "A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition". Genes Dev. 12 (6): 858–67. doi:10.1101/gad.12.6.858. PMC 316625. PMID 9512519.

[pmid9150140-11] Abovich N, Rosbash M (May 1997). "Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals". Cell. 89 (3): 403–12. doi:10.1016/s0092-8674(00)80221-4. PMID 9150140. S2CID 18466775.

[pmid8816452-12] Zhang WJ, Wu JY (Oct 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.

[pmid9447963-13] Zhang WJ, Wu JY (Feb 1998). "Sip1, a novel RS domain-containing protein essential for pre-mRNA splicing". Mol. Cell. Biol. 18 (2): 676–84. doi:10.1128/MCB.18.2.676. PMC 108778. PMID 9447963.

[pmid9472028-14] Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD (Feb 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): 737–50. doi:10.1083/jcb.140.4.737. PMC 2141757. PMID 9472028.

[pmid1388271-15] Zhang M, Zamore PD, Carmo-Fonseca M, Lamond AI, Green MR (Sep 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. doi:10.1073/pnas.89.18.8769. PMC 50002. PMID 1388271.

[pmid9784496-16] Davies RC, Calvio C, Bratt E, Larsson SH, Lamond AI, Hastie ND (Oct 1998). "WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes". Genes Dev. 12 (20): 3217–25. doi:10.1101/gad.12.20.3217. PMC 317218. PMID 9784496.

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Function

Interactions

References

Further reading