ALRF2_MOUSE
ID ALRF2_MOUSE Reviewed; 218 AA.
AC Q9JJW6; Q8C869;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Aly/REF export factor 2;
DE AltName: Full=Alyref;
DE AltName: Full=RNA and export factor-binding protein 2;
GN Name=Alyref2; Synonyms=Ref2, Refbp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND INTERACTION
RP WITH NXF1.
RC TISSUE=Embryo;
RX PubMed=10786854; DOI=10.1017/s1355838200000078;
RA Stutz F., Bachi A., Doerks T., Braun I.C., Seraphin B., Wilm M., Bork P.,
RA Izaurralde E.;
RT "REF, an evolutionarily conserved family of hnRNP-like proteins, interacts
RT with TAP/Mex67p and participates in mRNA nuclear export.";
RL RNA 6:638-650(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION.
RX PubMed=11158589; DOI=10.1073/pnas.98.3.1030;
RA Rodrigues J.P., Rode M., Gatfield D., Blencowe B.J., Carmo-Fonseca M.,
RA Izaurralde E.;
RT "REF proteins mediate the export of spliced and unspliced mRNAs from the
RT nucleus.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1030-1035(2001).
RN [4]
RP FUNCTION, INTERACTION WITH NXF1, AND MUTAGENESIS OF ARG-24; ARG-29; ARG-30
RP AND ARG-32.
RX PubMed=18364396; DOI=10.1073/pnas.0709167105;
RA Hautbergue G.M., Hung M.L., Golovanov A.P., Lian L.Y., Wilson S.A.;
RT "Mutually exclusive interactions drive handover of mRNA from export
RT adaptors to TAP.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:5154-5159(2008).
RN [5]
RP METHYLATION AT ARG-24; ARG-32; ARG-37; ARG-40; ARG-166; ARG-171; ARG-173;
RP ARG-181; ARG-186 AND ARG-188.
RX PubMed=20129943; DOI=10.1093/nar/gkq033;
RA Hung M.L., Hautbergue G.M., Snijders A.P., Dickman M.J., Wilson S.A.;
RT "Arginine methylation of REF/ALY promotes efficient handover of mRNA to
RT TAP/NXF1.";
RL Nucleic Acids Res. 38:3351-3361(2010).
RN [6]
RP STRUCTURE BY NMR OF 1-155, INTERACTION WITH DDX39B AND NXF1/NXT1
RP HETERODIMER, DOMAIN, AND RNA BINDING.
RX PubMed=17000901; DOI=10.1261/rna.212106;
RA Golovanov A.P., Hautbergue G.M., Tintaru A.M., Lian L.Y., Wilson S.A.;
RT "The solution structure of REF2-I reveals interdomain interactions and
RT regions involved in binding mRNA export factors and RNA.";
RL RNA 12:1933-1948(2006).
RN [7]
RP STRUCTURE BY NMR OF 53-155 IN COMPLEXES WITH HHV-1 ICP27 PEPTIDE AND WITH
RP HVS ORF57 PEPTIDE, INTERACTION WITH HHV-1 ICP27 AND HVS ORF57, AND REGION.
RX PubMed=21253573; DOI=10.1371/journal.ppat.1001244;
RA Tunnicliffe R.B., Hautbergue G.M., Kalra P., Jackson B.R., Whitehouse A.,
RA Wilson S.A., Golovanov A.P.;
RT "Structural basis for the recognition of cellular mRNA export factor REF by
RT herpes viral proteins HSV-1 ICP27 and HVS ORF57.";
RL PLoS Pathog. 7:E1001244-E1001244(2011).
RN [8]
RP STRUCTURE BY NMR OF 53-155 IN COMPLEX WITH HHV-1 ICP27 PEPTIDE,
RP RNA-BINDING, REGION, AND INTERACTION WITH HHV-1 ICP27 PEPTIDE.
RX PubMed=24550725; DOI=10.1371/journal.ppat.1003907;
RA Tunnicliffe R.B., Hautbergue G.M., Wilson S.A., Kalra P., Golovanov A.P.;
RT "Competitive and cooperative interactions mediate RNA transfer from
RT herpesvirus saimiri ORF57 to the mammalian export adaptor ALYREF.";
RL PLoS Pathog. 10:E1003907-E1003907(2014).
CC -!- FUNCTION: Export adapter involved in spliced and unspliced mRNA nuclear
CC export. Binds mRNA which is transferred to the NXF1-NXT1 heterodimer
CC for export (TAP/NFX1 pathway); enhances NXF1-NXT1 RNA-binding activity.
CC {ECO:0000269|PubMed:10786854, ECO:0000269|PubMed:11158589,
CC ECO:0000269|PubMed:18364396}.
CC -!- SUBUNIT: Interacts (via N-terminus and RRM domain) with DDX39B and th
CC NXF1-NXT1 heterodimer. Interacts with HHV-1 ICP27 and HVS ORF57
CC proteins. {ECO:0000269|PubMed:10786854, ECO:0000269|PubMed:17000901,
CC ECO:0000269|PubMed:18364396, ECO:0000269|PubMed:21253573,
CC ECO:0000269|PubMed:24550725}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q86V81}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q86V81}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Refbp2-I;
CC IsoId=Q9JJW6-1; Sequence=Displayed;
CC Name=2; Synonyms=Refbp2-II;
CC IsoId=Q9JJW6-2; Sequence=VSP_008598;
CC -!- DOMAIN: The RRM domain and the N-terminal region (15-58) seem to be
CC involved in RNA binding. {ECO:0000269|PubMed:17000901}.
CC -!- PTM: Arginine methylation reduces RNA binding and enhances mRNA
CC transfer to the NXF1-NXT1 heterodimer for nuclear export.
CC {ECO:0000269|PubMed:20129943}.
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DR EMBL; AJ252141; CAB76384.1; -; mRNA.
DR EMBL; AK048243; BAC33282.1; -; mRNA.
DR CCDS; CCDS15497.1; -. [Q9JJW6-1]
DR RefSeq; NP_062357.3; NM_019484.4.
DR PDB; 2F3J; NMR; -; A=1-155.
DR PDB; 2KT5; NMR; -; A=53-155.
DR PDB; 2YKA; NMR; -; A=53-155.
DR PDBsum; 2F3J; -.
DR PDBsum; 2KT5; -.
DR PDBsum; 2YKA; -.
DR AlphaFoldDB; Q9JJW6; -.
DR BMRB; Q9JJW6; -.
DR SMR; Q9JJW6; -.
DR BioGRID; 207766; 4.
DR IntAct; Q9JJW6; 1.
DR STRING; 10090.ENSMUSP00000080242; -.
DR iPTMnet; Q9JJW6; -.
DR PhosphoSitePlus; Q9JJW6; -.
DR jPOST; Q9JJW6; -.
DR MaxQB; Q9JJW6; -.
DR PaxDb; Q9JJW6; -.
DR PeptideAtlas; Q9JJW6; -.
DR PRIDE; Q9JJW6; -.
DR ProteomicsDB; 296102; -. [Q9JJW6-1]
DR ProteomicsDB; 296103; -. [Q9JJW6-2]
DR TopDownProteomics; Q9JJW6-1; -. [Q9JJW6-1]
DR DNASU; 56009; -.
DR GeneID; 56009; -.
DR KEGG; mmu:56009; -.
DR CTD; 56009; -.
DR MGI; MGI:1913144; Alyref2.
DR eggNOG; KOG0533; Eukaryota.
DR InParanoid; Q9JJW6; -.
DR OrthoDB; 1369069at2759; -.
DR PhylomeDB; Q9JJW6; -.
DR BioGRID-ORCS; 56009; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Alyref2; mouse.
DR EvolutionaryTrace; Q9JJW6; -.
DR PRO; PR:Q9JJW6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9JJW6; protein.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; ISO:MGI.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0035145; C:exon-exon junction complex; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0000346; C:transcription export complex; ISO:MGI.
DR GO; GO:0062153; F:C5-methylcytidine-containing RNA binding; ISO:MGI.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:MGI.
DR GO; GO:0006406; P:mRNA export from nucleus; ISO:MGI.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0051028; P:mRNA transport; IDA:UniProtKB.
DR GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; ISO:MGI.
DR GO; GO:0000018; P:regulation of DNA recombination; ISO:MGI.
DR GO; GO:0031297; P:replication fork processing; ISO:MGI.
DR GO; GO:0006405; P:RNA export from nucleus; ISO:MGI.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0046784; P:viral mRNA export from host cell nucleus; ISO:MGI.
DR DisProt; DP03043; -.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR025715; FoP_C.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF13865; FoP_duplication; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM01218; FoP_duplication; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chaperone; Cytoplasm; Methylation;
KW mRNA processing; mRNA splicing; mRNA transport; Nucleus;
KW Reference proteome; RNA-binding; Spliceosome; Transport.
FT CHAIN 1..218
FT /note="Aly/REF export factor 2"
FT /id="PRO_0000081976"
FT DOMAIN 75..152
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 16..37
FT /note="Sufficient for RNA-binding, interaction with NXF1-
FT NXT1"
FT REGION 54..155
FT /note="Interaction with HHV-8 ORF57 protein and with ICP27
FT from HHV-1"
FT REGION 151..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 155..170
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 187..203
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 24
FT /note="Asymmetric dimethylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 24
FT /note="Omega-N-methylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 32
FT /note="Asymmetric dimethylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 32
FT /note="Omega-N-methylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 37
FT /note="Asymmetric dimethylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 37
FT /note="Omega-N-methylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 40
FT /note="Asymmetric dimethylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 40
FT /note="Omega-N-methylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 166
FT /note="Asymmetric dimethylarginine; by PRMT1; in vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 171
FT /note="Asymmetric dimethylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 171
FT /note="Omega-N-methylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 173
FT /note="Asymmetric dimethylarginine; by PRMT1; in vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 181
FT /note="Asymmetric dimethylarginine; by PRMT1; in vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 186
FT /note="Asymmetric dimethylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 186
FT /note="Omega-N-methylarginine; alternate; by PRMT1; in
FT vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT MOD_RES 188
FT /note="Asymmetric dimethylarginine; by PRMT1; in vitro"
FT /evidence="ECO:0000269|PubMed:20129943"
FT VAR_SEQ 198
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10786854"
FT /id="VSP_008598"
FT MUTAGEN 24
FT /note="R->E: Impairs interaction with NXF1."
FT /evidence="ECO:0000269|PubMed:18364396"
FT MUTAGEN 29
FT /note="R->E: Abolishes interaction with NXF1; when
FT associated with E-30."
FT /evidence="ECO:0000269|PubMed:18364396"
FT MUTAGEN 30
FT /note="R->E: Abolishes interaction with NXF1; when
FT associated with E-29."
FT /evidence="ECO:0000269|PubMed:18364396"
FT MUTAGEN 32
FT /note="R->E: Impairs interaction with NXF1."
FT /evidence="ECO:0000269|PubMed:18364396"
FT CONFLICT 151
FT /note="A -> T (in Ref. 2; BAC33282)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="S -> F (in Ref. 2; BAC33282)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="M -> R (in Ref. 2; BAC33282)"
FT /evidence="ECO:0000305"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:2F3J"
FT HELIX 9..17
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 28..32
FT /evidence="ECO:0007829|PDB:2F3J"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:2F3J"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:2F3J"
FT HELIX 88..97
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:2KT5"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:2F3J"
FT HELIX 125..134
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:2F3J"
FT STRAND 146..152
FT /evidence="ECO:0007829|PDB:2F3J"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:2F3J"
SQ SEQUENCE 218 AA; 23730 MW; 977901CECDCF18FC CRC64;
MADKMDMSLD DIIKLNRNQR RVNRGGGPRR NRPAIARGGR NRPAPYSRPK PLPDKWQHDL
FDSGCGGGEG VETGAKLLVS NLDFGVSDAD IQELFAEFGT LKKAAVDYDR SGRSLGTADV
HFERRADALK AMKQYKGVPL DGRPMDIQLV ASQIDPQRRP AQSGNRGGMT RSRGSGGFGG
RGSQGRGRGT GRNSKQQQLS AEELDAQLDA YNARMDTS
