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O08583

- THOC4_MOUSE

UniProt

O08583 - THOC4_MOUSE

Protein

THO complex subunit 4

Gene

Alyref

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Export adapter involved in nuclear export of spliced and unspliced mRNA. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway). Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm. TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC). In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B. Involved in transcription elongation and genome stability.
    Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation.

    GO - Molecular functioni

    1. nucleotide binding Source: InterPro
    2. RNA binding Source: MGI
    3. single-stranded DNA binding Source: MGI

    GO - Biological processi

    1. mRNA processing Source: UniProtKB-KW
    2. mRNA transport Source: UniProtKB-KW
    3. RNA splicing Source: UniProtKB-KW

    Keywords - Molecular functioni

    Chaperone

    Keywords - Biological processi

    mRNA processing, mRNA splicing, mRNA transport, Transport

    Keywords - Ligandi

    RNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_212343. Transport of the SLBP independent Mature mRNA.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    THO complex subunit 4
    Short name:
    Tho4
    Alternative name(s):
    Ally of AML-1 and LEF-1
    Aly/REF export factor
    REF1-I
    RNA and export factor-binding protein 1
    Transcriptional coactivator Aly/REF
    Gene namesi
    Name:Alyref
    Synonyms:Aly, Ref1, Refbp1, THOC4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:1341044. Alyref.

    Subcellular locationi

    Nucleus 1 Publication. Nucleus speckle By similarity. Cytoplasm 1 Publication
    Note: Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and DDX39B in the nucleus and nuclear speckles. Localizes to regions surrounding nuclear speckles known as perispeckles in which TREX complex assembly seems to occur By similarity. Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nuclear speck Source: UniProtKB-SubCell
    3. nucleus Source: MGI
    4. spliceosomal complex Source: UniProtKB-KW

    Keywords - Cellular componenti

    Cytoplasm, Nucleus, Spliceosome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 255254THO complex subunit 4PRO_0000081975Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei8 – 81PhosphoserineBy similarity
    Modified residuei50 – 501Omega-N-methylated arginineBy similarity
    Modified residuei85 – 851N6-acetyllysine1 Publication
    Modified residuei93 – 931PhosphoserineBy similarity
    Modified residuei140 – 1401Citrulline1 Publication
    Modified residuei203 – 2031Dimethylated arginine; alternateBy similarity
    Modified residuei203 – 2031Omega-N-methylated arginine; alternateBy similarity
    Modified residuei218 – 2181Omega-N-methylarginineBy similarity
    Modified residuei237 – 2371PhosphoserineBy similarity

    Post-translational modificationi

    Arg-50 and Arg-203 are dimethylated, probably to asymmetric dimethylarginine. Arginine methylation reduces RNA binding By similarity.By similarity
    Citrullinated by PADI4.1 Publication

    Keywords - PTMi

    Acetylation, Citrullination, Methylation, Phosphoprotein

    Proteomic databases

    MaxQBiO08583.
    PaxDbiO08583.
    PRIDEiO08583.

    PTM databases

    PhosphoSiteiO08583.

    Expressioni

    Tissue specificityi

    Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.1 Publication

    Gene expression databases

    BgeeiO08583.
    CleanExiMM_THOC4.
    GenevestigatoriO08583.

    Interactioni

    Subunit structurei

    Homomultimer. Is part of several complexes involved in mRNA processing and export. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; TREX seems to have a dynamic structure involving ATP-dependent remodeling; in the complex interacts (via C-terminus) directly with DDX39B and interacts directly with THOC1 and THOC2. Found in mRNA splicing-dependent exon junction complexes (EJC). Identified in the spliceosome C complex. Found in a mRNP complex with UPF3A and UPF3B. Interacts with RBM8A, NCBP1, THOC5, LEF1, RUNX1, EIF4A3, RNPS1, SRRM1, IWS1 and EXOSC1. Interacts with NXF1; the interaction is direct.1 Publication

    Protein-protein interaction databases

    BioGridi204102. 4 interactions.
    DIPiDIP-59977N.
    IntActiO08583. 2 interactions.
    MINTiMINT-1867899.

    Structurei

    Secondary structure

    1
    255
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi106 – 1116
    Helixi118 – 12811
    Beta strandi131 – 1377
    Beta strandi147 – 1537
    Helixi155 – 16511
    Beta strandi176 – 1805

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1NO8NMR-A77-182[»]
    ProteinModelPortaliO08583.
    SMRiO08583. Positions 1-187.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO08583.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini105 – 18278RRMPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni16 – 3722Sufficient for RNA-binding, interaction with NXF1-NXT1 heterodimerBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi21 – 229209Ala/Arg/Gly-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the THOC4 family.Curated
    Contains 1 RRM (RNA recognition motif) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG316507.
    GeneTreeiENSGT00410000025615.
    HOGENOMiHOG000239962.
    HOVERGENiHBG054806.
    InParanoidiQ0VBL5.
    KOiK12881.
    OMAiGNFNGNF.
    OrthoDBiEOG7RBZB9.
    PhylomeDBiO08583.
    TreeFamiTF313312.

    Family and domain databases

    Gene3Di3.30.70.330. 1 hit.
    InterProiIPR025715. FoP_duplication.
    IPR012677. Nucleotide-bd_a/b_plait.
    IPR000504. RRM_dom.
    [Graphical view]
    PfamiPF13865. FoP_duplication. 1 hit.
    PF00076. RRM_1. 1 hit.
    [Graphical view]
    SMARTiSM00360. RRM. 1 hit.
    [Graphical view]
    PROSITEiPS50102. RRM. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O08583-1) [UniParc]FASTAAdd to Basket

    Also known as: Refbp1-I

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MADKMDMSLD DIIKLNRSQR GGRGGGRGRG RAGSQGGRGG AVQAAARVNR    50
    GGGPMRNRPA IARGAAGGGR NRPAPYSRPK QLPDKWQHDL FDSGFGGGAG 100
    VETGGKLLVS NLDFGVSDAD IQELFAEFGT LKKAAVHYDR SGRSLGTADV 150
    HFERKADALK AMKQYNGVPL DGRPMNIQLV TSQIDTQRRP AQSINRGGMT 200
    RNRGSGGFGG GGTRRGTRGG SRGRGRGTGR NSKQQLSAEE LDAQLDAYNA 250
    RMDTS 255
    Length:255
    Mass (Da):26,940
    Last modified:January 23, 2007 - v3
    Checksum:iF597235EBDD47C17
    GO
    Isoform 2 (identifier: O08583-2) [UniParc]FASTAAdd to Basket

    Also known as: Refbp1-II

    The sequence of this isoform differs from the canonical sequence as follows:
         14-105: Missing.

    Show »
    Length:163
    Mass (Da):17,682
    Checksum:iD212F3ACD29C8B13
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei14 – 10592Missing in isoform 2. 1 PublicationVSP_008597Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U89876 mRNA. Translation: AAC53117.1.
    AJ252140 mRNA. Translation: CAB76383.1.
    AL663030 Genomic DNA. Translation: CAM27086.1.
    CH466558 Genomic DNA. Translation: EDL34770.1.
    BC120588 mRNA. Translation: AAI20589.1.
    BC137658 mRNA. Translation: AAI37659.1.
    AK035721 mRNA. Translation: BAC29168.1.
    CCDSiCCDS25744.1. [O08583-1]
    RefSeqiNP_035698.1. NM_011568.1. [O08583-1]
    UniGeneiMm.1886.

    Genome annotation databases

    EnsembliENSMUST00000026125; ENSMUSP00000026125; ENSMUSG00000025134. [O08583-1]
    GeneIDi21681.
    KEGGimmu:21681.
    UCSCiuc007mtl.1. mouse. [O08583-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U89876 mRNA. Translation: AAC53117.1 .
    AJ252140 mRNA. Translation: CAB76383.1 .
    AL663030 Genomic DNA. Translation: CAM27086.1 .
    CH466558 Genomic DNA. Translation: EDL34770.1 .
    BC120588 mRNA. Translation: AAI20589.1 .
    BC137658 mRNA. Translation: AAI37659.1 .
    AK035721 mRNA. Translation: BAC29168.1 .
    CCDSi CCDS25744.1. [O08583-1 ]
    RefSeqi NP_035698.1. NM_011568.1. [O08583-1 ]
    UniGenei Mm.1886.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1NO8 NMR - A 77-182 [» ]
    ProteinModelPortali O08583.
    SMRi O08583. Positions 1-187.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204102. 4 interactions.
    DIPi DIP-59977N.
    IntActi O08583. 2 interactions.
    MINTi MINT-1867899.

    PTM databases

    PhosphoSitei O08583.

    Proteomic databases

    MaxQBi O08583.
    PaxDbi O08583.
    PRIDEi O08583.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000026125 ; ENSMUSP00000026125 ; ENSMUSG00000025134 . [O08583-1 ]
    GeneIDi 21681.
    KEGGi mmu:21681.
    UCSCi uc007mtl.1. mouse. [O08583-1 ]

    Organism-specific databases

    CTDi 10189.
    MGIi MGI:1341044. Alyref.

    Phylogenomic databases

    eggNOGi NOG316507.
    GeneTreei ENSGT00410000025615.
    HOGENOMi HOG000239962.
    HOVERGENi HBG054806.
    InParanoidi Q0VBL5.
    KOi K12881.
    OMAi GNFNGNF.
    OrthoDBi EOG7RBZB9.
    PhylomeDBi O08583.
    TreeFami TF313312.

    Enzyme and pathway databases

    Reactomei REACT_212343. Transport of the SLBP independent Mature mRNA.

    Miscellaneous databases

    EvolutionaryTracei O08583.
    NextBioi 300988.
    PROi O08583.
    SOURCEi Search...

    Gene expression databases

    Bgeei O08583.
    CleanExi MM_THOC4.
    Genevestigatori O08583.

    Family and domain databases

    Gene3Di 3.30.70.330. 1 hit.
    InterProi IPR025715. FoP_duplication.
    IPR012677. Nucleotide-bd_a/b_plait.
    IPR000504. RRM_dom.
    [Graphical view ]
    Pfami PF13865. FoP_duplication. 1 hit.
    PF00076. RRM_1. 1 hit.
    [Graphical view ]
    SMARTi SM00360. RRM. 1 hit.
    [Graphical view ]
    PROSITEi PS50102. RRM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function."
      Bruhn L., Munnerlyn A., Grosschedl R.
      Genes Dev. 11:640-653(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Thymocyte.
    2. "REF, an evolutionarily conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export."
      Stutz F., Bachi A., Doerks T., Braun I.C., Seraphin B., Wilm M., Bork P., Izaurralde E.
      RNA 6:638-650(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH NXF1.
      Tissue: Embryo.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    6. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 190-255.
      Strain: C57BL/6J.
      Tissue: Urinary bladder.
    7. "REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus."
      Rodrigues J.P., Rode M., Gatfield D., Blencowe B.J., Carmo-Fonseca M., Izaurralde E.
      Proc. Natl. Acad. Sci. U.S.A. 98:1030-1035(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. Cited for: CITRULLINATION AT ARG-140.
    9. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-85, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.
    10. "Structure of the nuclear factor ALY: insights into post-transcriptional regulatory and mRNA nuclear export processes."
      Perez-Alvarado G.C., Martinez-Yamout M., Allen M.M., Grosschedl R., Dyson H.J., Wright P.E.
      Biochemistry 42:7348-7357(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 105-182.

    Entry informationi

    Entry nameiTHOC4_MOUSE
    AccessioniPrimary (citable) accession number: O08583
    Secondary accession number(s): Q0VBL5, Q8CBM4, Q9JJW7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 10, 2003
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 126 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3