U2AF4_HUMAN
ID U2AF4_HUMAN Reviewed; 220 AA.
AC Q8WU68; A6NKI8; Q56UU3;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Splicing factor U2AF 26 kDa subunit;
DE AltName: Full=U2 auxiliary factor 26;
DE AltName: Full=U2 small nuclear RNA auxiliary factor 1-like protein 4;
DE Short=U2AF1-like 4 {ECO:0000250|UniProtKB:Q8BGJ9};
DE AltName: Full=U2(RNU2) small nuclear RNA auxiliary factor 1-like protein 3;
DE Short=U2 small nuclear RNA auxiliary factor 1-like protein 3;
DE Short=U2AF1-like protein 3;
GN Name=U2AF1L4; Synonyms=U2AF1-RS3, U2AF1L3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=17312947; DOI=10.1080/10425170600807744;
RA Chen F., Ji C., Dou T., Zheng N., Qiu R., Peng J., Fang W., Feng C.,
RA Xie Y., Mao Y.;
RT "Cloning and characterization of a novel splice variant of human U2AF1L3
RT gene.";
RL DNA Seq. 17:282-286(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-13, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Zebisch A., Kolch W.;
RL Submitted (OCT-2008) to UniProtKB.
CC -!- FUNCTION: RNA-binding protein that function as a pre-mRNA splicing
CC factor. Plays a critical role in both constitutive and enhancer-
CC dependent splicing by mediating protein-protein interactions and
CC protein-RNA interactions required for accurate 3'-splice site
CC selection. Acts by enhancing the binding of U2AF2 to weak pyrimidine
CC tracts. Also participates in the regulation of alternative pre-mRNA
CC splicing. Activates exon 5 skipping of PTPRC during T-cell activation;
CC an event reversed by GFI1. Binds to RNA at the AG dinucleotide at the
CC 3'-splice site (By similarity). Shows a preference for AGC or AGA (By
CC similarity). {ECO:0000250|UniProtKB:Q8BGJ9}.
CC -!- SUBUNIT: Interacts with GFI1, U2AF2 and C1QBP.
CC {ECO:0000250|UniProtKB:Q8BGJ9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8BGJ9}. Nucleus
CC speckle {ECO:0000250|UniProtKB:Q8BGJ9}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8BGJ9}. Note=Interaction with C1QBP is required
CC for the nuclear translocation. Displays active nucleo-cytoplasmic
CC shuttling. {ECO:0000250|UniProtKB:Q8BGJ9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8WU68-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WU68-2; Sequence=VSP_029264, VSP_029265;
CC Name=3;
CC IsoId=Q8WU68-3; Sequence=VSP_029264;
CC -!- TISSUE SPECIFICITY: Isoform 2 is widely expressed. Isoform 3 is highly
CC expressed in heart, brain and lung, lower expressed in thymus and much
CC lower expressed in peripheral blood leukocytes.
CC {ECO:0000269|PubMed:17312947}.
CC -!- DOMAIN: The second zinc finger in necessary for interaction with GFI1
CC and for alternative pre-mRNA splicing events. {ECO:0000250}.
CC -!- DOMAIN: The region 162-220 is essential for the nuclear import of the
CC protein in spite of the absence of a nuclear localization signal (NLS).
CC This region is essential for the interaction with C1QBP, interaction
CC which is required for the nuclear translocation. This region may be
CC involved in the localization in nuclear dot-like structures and it also
CC confers the ability of nucleo-cytoplasmic shuttling.
CC {ECO:0000250|UniProtKB:Q8BGJ9}.
CC -!- SIMILARITY: Belongs to the splicing factor SR family. {ECO:0000305}.
CC -!- CAUTION: Orthologs of U2AF1L4 do not appear to exist in lower
CC eukaryotes, Drosophila, C. elegans, plants, or vertebrates such as
CC Xenopus or zebrafish. Existence of circadian and light-inducible
CC alternative splicing of U2AF1L4 similar to the mouse in human and rat
CC is not yet proven. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY569437; AAT72770.3; -; mRNA.
DR EMBL; AD000671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021186; AAH21186.1; -; mRNA.
DR CCDS; CCDS12473.1; -. [Q8WU68-2]
DR CCDS; CCDS42551.1; -. [Q8WU68-3]
DR RefSeq; NP_001035515.1; NM_001040425.2. [Q8WU68-3]
DR RefSeq; NP_659424.2; NM_144987.3. [Q8WU68-2]
DR AlphaFoldDB; Q8WU68; -.
DR SMR; Q8WU68; -.
DR BioGRID; 128270; 10.
DR IntAct; Q8WU68; 10.
DR iPTMnet; Q8WU68; -.
DR PhosphoSitePlus; Q8WU68; -.
DR BioMuta; U2AF1L4; -.
DR DMDM; 160358766; -.
DR EPD; Q8WU68; -.
DR jPOST; Q8WU68; -.
DR MassIVE; Q8WU68; -.
DR MaxQB; Q8WU68; -.
DR PeptideAtlas; Q8WU68; -.
DR PRIDE; Q8WU68; -.
DR ProteomicsDB; 74637; -. [Q8WU68-1]
DR ProteomicsDB; 74638; -. [Q8WU68-2]
DR ProteomicsDB; 74639; -. [Q8WU68-3]
DR Antibodypedia; 29506; 118 antibodies from 25 providers.
DR DNASU; 199746; -.
DR Ensembl; ENST00000292879.9; ENSP00000292879.4; ENSG00000161265.15. [Q8WU68-2]
DR Ensembl; ENST00000378975.8; ENSP00000368258.2; ENSG00000161265.15. [Q8WU68-3]
DR Ensembl; ENST00000412391.6; ENSP00000397645.2; ENSG00000161265.15. [Q8WU68-1]
DR GeneID; 199746; -.
DR KEGG; hsa:199746; -.
DR MANE-Select; ENST00000378975.8; ENSP00000368258.2; NM_001040425.3; NP_001035515.1. [Q8WU68-3]
DR UCSC; uc002obe.5; human. [Q8WU68-1]
DR CTD; 199746; -.
DR DisGeNET; 199746; -.
DR GeneCards; U2AF1L4; -.
DR HGNC; HGNC:23020; U2AF1L4.
DR HPA; ENSG00000161265; Low tissue specificity.
DR MIM; 601080; gene.
DR neXtProt; NX_Q8WU68; -.
DR OpenTargets; ENSG00000161265; -.
DR PharmGKB; PA164742763; -.
DR VEuPathDB; HostDB:ENSG00000161265; -.
DR GeneTree; ENSGT00950000183152; -.
DR HOGENOM; CLU_059852_1_0_1; -.
DR InParanoid; Q8WU68; -.
DR OMA; YQERPHG; -.
DR OrthoDB; 1340384at2759; -.
DR PhylomeDB; Q8WU68; -.
DR TreeFam; TF300143; -.
DR PathwayCommons; Q8WU68; -.
DR Reactome; R-HSA-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-HSA-72187; mRNA 3'-end processing.
DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR SignaLink; Q8WU68; -.
DR BioGRID-ORCS; 199746; 13 hits in 1080 CRISPR screens.
DR ChiTaRS; U2AF1L4; human.
DR GenomeRNAi; 199746; -.
DR Pharos; Q8WU68; Tbio.
DR PRO; PR:Q8WU68; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8WU68; protein.
DR Bgee; ENSG00000161265; Expressed in left lobe of thyroid gland and 96 other tissues.
DR ExpressionAtlas; Q8WU68; baseline and differential.
DR Genevisible; Q8WU68; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005681; C:spliceosomal complex; IBA:GO_Central.
DR GO; GO:0089701; C:U2AF complex; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030628; F:pre-mRNA 3'-splice site binding; IBA:GO_Central.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IBA:GO_Central.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR003954; RRM_dom_euk.
DR InterPro; IPR009145; U2AF_small.
DR InterPro; IPR000571; Znf_CCCH.
DR PANTHER; PTHR12620; PTHR12620; 1.
DR Pfam; PF00076; RRM_1; 1.
DR Pfam; PF00642; zf-CCCH; 2.
DR PRINTS; PR01848; U2AUXFACTOR.
DR SMART; SM00361; RRM_1; 1.
DR SMART; SM00356; ZnF_C3H1; 2.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS50103; ZF_C3H1; 2.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Metal-binding; mRNA processing; mRNA splicing; Nucleus; Reference proteome;
KW Repeat; RNA-binding; Spliceosome; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4"
FT CHAIN 2..220
FT /note="Splicing factor U2AF 26 kDa subunit"
FT /id="PRO_0000309740"
FT DOMAIN 65..147
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT ZN_FING 12..40
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 149..176
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 185..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..206
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.4"
FT VAR_SEQ 45..83
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17312947"
FT /id="VSP_029264"
FT VAR_SEQ 143..220
FT /note="ELSPVTDFRESCCRQYEMGECTRGGFCNFMHLRPISQNLQRQLYGRGPRRRS
FT PPRFHTGHHPRERNHRCSPDHWHGRF -> NVPEVASATSCICGPFPRTSRGSSMGGDP
FT GAGHPRGSILATIPERGTIGVPLITGMAASEALAPLPFTPNRDRCSWQDLSSKPPSLSC
FT PILPRLPGSIM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17312947"
FT /id="VSP_029265"
FT CONFLICT 109
FT /note="L -> V (in Ref. 3; AAH21186)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 220 AA; 25744 MW; 64BA09EEDE3FB093 CRC64;
MAEYLASIFG TEKDKVNCSF YFKIGVCRHG DRCSRLHNKP TFSQTIVLLN LYRNPQNTAQ
TADGSHCHVS DVEVQEHYDS FFEEVFTELQ EKYGEIEEMN VCDNLGDHLV GNVYVKFRRE
EDGERAVAEL SNRWFNGQAV HGELSPVTDF RESCCRQYEM GECTRGGFCN FMHLRPISQN
LQRQLYGRGP RRRSPPRFHT GHHPRERNHR CSPDHWHGRF
