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FLASH GENE

Symbol

U2AF2

contributors: mct/npt/pgu - updated : 01-06-2015

HGNC name	U2 small nuclear RNA auxiliary factor 2
HGNC id	23156

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	19q13.42      Physical location : 56.165.415 - 56.186.081
Synonym name	splicing factor U2AF 65 kD subunit
	U2 snRNP auxiliary factor large subunit
	U2 (RNU2) small nuclear RNA auxiliary factor 2
	U2 small nuclear ribonucleoprotein auxiliary factor (65kD)
Synonym symbol(s)	U2AF65

DNA

TYPE	functioning gene
STRUCTURE	20.67 kb     12 Exon(s)

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed variant 1 12 splicing 3148 53 475 - 2009 18974054 variant 2 12 splicing 3136 53 471 - 2009 18974054 using an alternate in-frame splice site compared to variant 1 having the same N- and C-termini compared to variant 1

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive pharynx       highly   salivary gland       highly Endocrine adrenal gland       moderately Lymphoid/Immune lymph node       highly Reproductive male system prostate     moderately Respiratory respiratory tract larynx     moderately Visual eye       moderately

cell lineage
cell lines
fluid/secretion	moderately in lymph

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three RNA recognition motifs (RRM), tandem RNA recognition motifs recognizing polypyrimidine tract signals adjacent to 3 prime splice sites , tandem RRM domains that do not simply act as a binding scaffold but instead have an active role in quantitatively relating Py tract strength to splice site recognition and spliceosome assembly
	an arg/ser rich domain

mono polymer

heteromer , dimer , complex

HOMOLOGY

interspecies	ortholog to rattus U2af2 (100pc)
	homolog to drosophila U2af50 (74.9pc)
	ortholog to C. elegans uaf-1 (62.3pc)

Homologene

FAMILY

SR family of splicing factor

CATEGORY

RNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
text	distributed throughout the nucleoplasm, where transcription occurs, with additional concentration in nuclear speckles, where splicing factors accumulate when not engaged in splicing

basic FUNCTION	necessary for the splicing of pre-mRNA
	required for the export of mRNA out of the nucleus
	increasing the affinity of SF1 for BPS
	promoting 3'-end processing, which contributes to 3'-terminal exon definition
	SF1 and U2AF2 associate cooperatively with pre-mRNA and play a crucial role in 3 prime splice site recognition during early steps of spliceosome assembly
	essential pre-mRNA splicing factor for the initial stages of spliceosome assembly
	has a crucial role in the assembly of splicing complexes
	modulating the function of the PLE (poly(A)-limiting element)
	essential splicing factor in the recognition of the pre-mRNA 3' splice sites during the assembly of the splicing commitment complex
	SF1 and U2 auxiliary factor (U2AF2) cooperatively recognize the 3 prime splice site during the initial stages of pre-mRNA splicing
	involved in the nuclear export of mRNA
	both U2AF2 and PRPF19 are required for RNA polymerase II C-terminal domain-dependent splicing activation
	served as an adaptor to link expanded CAG RNA to NXF1 for RNA export
	plays a key role in regulating the nuclear export of expanded CAG RNA, and its temporal reduction in levels causes accumulation of expanded CAG RNA in the cell nucleus
	the essential splicing factors U2AF2 and SF1 cooperatively bind consensus sequences at the 3' end of introns
	plays a critical role in regulating the level of TERF1 through physical interaction and ubiquitin-mediated proteolysis
	intimate link between JMJD6 and U2AF2 in alternative splicing regulation, which has important implications in development and disease processes

CELLULAR PROCESS

nucleotide, RNA splicing

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	heterodimerizing with U2AF1 to form the essential splicing factor U2AF (U2 auxiliary factor)
	U2 snRNP auxiliary factor (U2AF) is an essential splicing factor composed of two subunits, a large, 65-kDa subunit (U2AF(65)) and a small subunit, U2AF(35)
	direct binding of SF1 to U2AF2 in both the nucleoplasm
	and nuclear speckles

INTERACTION

DNA

RNA	binding to the polypyrimidine tract of introns during spliceosome assembly
	directly interacts with expanded CAG RNA via its RRM3 domain

small molecule

protein	unphosphorylated SF1 via its N terminus
	SFRS2IP
	interacting with PUF60 (mutually enhance their affinity for binding polypyrimidine tract RNA in a cooperative fashion)
	compete with MBNL1 by binding to mutually exclusive RNA structures (binds the same region in a single-strand structure)
	RBM39 and ZC3H11A interacting wth U2AF2
	binding of U2AF2 to a polypyrimidine tract requires a flexible RNA backbone
	JMJD6 mediates splicing of FLT1 by interacting with U2AF2
	facilitates RNA export through its interaction with the export receptor NXF1
	interaction of ATXN1 with the splicing factors RBM17 and U2AF2
	ZRSR2 physically interacts with U2AF2, as well as SRSF1 and SRSF2, with a distinct function from its homologue, U2AF1
	essential pre-mRNA splicing factor, and a novel TERF1-interacting protein
	HNRNPM promotes exon 7 inclusion of SMN1 and SMN2 pre-mRNA through targeting an enhancer on exon 7 through recruiting U2AF2
	PRPF40B interacts directly with SF1 and associates with U2AF2
	U2AF2 interacts with SF1 and was shown to recruit the U2 snRNP to the spliceosome
	interacts with and hydroxylates multiple serine/arginine-rich (SR) proteins and SR related proteins, including U2AF2

cell & other

REGULATION

Other	proteolyzed during apoptosis (N-terminal fragment mainly accumulates in the nucleus within nuclear bodies and to a much lesser extent in the cytoplasm, whereas the C-terminal fragment is found in the cytoplasm, even in localization studies on apoptosis induction)
	post-translational hydroxylation catalyzed by JMJD6

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

knockdown of U2af50 (the Drosophila ortholog of U2AF2) expression intensified the accumulation of expanded CAG RNA in the nucleus and exacerbated RNA-mediated toxicity