O08583 (THOC4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Alyref
Synonyms:	Aly, Ref1, Refbp1, THOC4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	255 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the THO subcomplex of the TREX complex. The TREX complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It 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. The recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. DDX39B functions as a bridge between ALYREF/THOC4 and the THO complex By similarity. Ref.1 Ref.2 Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Plays a role in mRNA processing and export. Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation. May function as scaffold that mediates interactions between proteins and/or RNA. Integral part of the THO/TREX complex that is recruited to transcribed genes and travels with the RNA polymerase during elongation. Is part of the exon junction complex that remains associated with spliced mRNA and plays an important role in mRNA export and nonsense-mediated RNA decay By similarity. Ref.1 Ref.2
Subunit structure	Homomultimer. Component of the THO complex, which is composed of THOC1, THOC2, THOC5, THOC6 and THOC7. Together with THOC3, ALYREF/THOC4 and DDX39B, THO forms the transcription/export (TREX) complex. Interacts (via C-terminus) with the THO complex and with DDX39B. Interacts with THOC5 and NCBP1. Binds LEF1 and RUNX1. Is part of several complexes involved in mRNA processing and export. Associates with the spliceosome. Found in a mRNA splicing-dependent exon junction complex (EJC) with ACIN1, CASC3, DEK, EIF4A3, MAGOH, PNN, RBM8A, RNPS1, SAP18, SRRM1 and ALYREF/THOC4. Binds UL54 from Herpes simplex type 1 (strain KOS). Found in a mRNP complex with UPF3A and UPF3B. Interacts with BAT1, EIF4A3, RBM8A, RNPS1 and SRRM1. Identified in the spliceosome C complex By similarity. Binds NXF1 and RBM8A directly and is part of the exon junction complex (EJC) containing NCBP1, NCBP2, RNPS1, RBM8A, SRRM1, NXF1, UPF2, UPF3B, ALYREF/THOC4 and/or REFBP2 By similarity. Ref.2 Ref.7
Subcellular location	Nucleus. Nucleus speckle By similarity. Cytoplasm. Note: Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and DDX39B in the nucleus and nuclear speckles By similarity. Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. Ref.1
Tissue specificity	Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Ref.1
Post-translational modification	Arg-50 and Arg-203 are dimethylated, probably to asymmetric dimethylarginine By similarity.
Sequence similarities	Belongs to the THOC4 family. Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Biological process	Transport mRNA processing mRNA splicing mRNA transport
Cellular component	Cytoplasm Nucleus Spliceosome
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding
Molecular function	Chaperone
PTM	Acetylation Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Traceable author statement Ref.2. Source: MGI spliceosomal complex Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	RNA binding Inferred from direct assay Ref.2. Source: MGI nucleotide binding Inferred from electronic annotation. Source: InterPro single-stranded DNA binding Inferred from direct assay Ref.2. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O08583-1)

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.

Isoform 2 (identifier: O08583-2)

Also known as: Refbp1-II;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 255

254

THO complex subunit 4

PRO_0000081975

Regions

Domain

105 – 182

78

RRM

Compositional bias

21 – 229

209

Ala/Arg/Gly-rich

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

8

1

Phosphoserine By similarity

Modified residue

50

1

Omega-N-methylated arginine By similarity

Modified residue

93

1

Phosphoserine By similarity

Modified residue

203

1

Dimethylated arginine; alternate By similarity

Modified residue

203

1

Omega-N-methylated arginine; alternate By similarity

Modified residue

218

1

Omega-N-methylarginine

Modified residue

237

1

Phosphoserine Ref.8

Natural variations

Alternative sequence

14 – 105

92

Missing in isoform 2.

VSP_008597

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

255

Helix Strand Turn

Details...

Beta strand

106 – 111

6

Helix

118 – 128

11

Beta strand

131 – 137

7

Beta strand

147 – 153

7

Helix

155 – 165

11

Beta strand

176 – 180

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Refbp1-I) [UniParc]. Last modified January 23, 2007. Version 3. Checksum: F597235EBDD47C17	FASTA	255	26,940
	10 20 30 40 50 60 MADKMDMSLD DIIKLNRSQR GGRGGGRGRG RAGSQGGRGG AVQAAARVNR GGGPMRNRPA 70 80 90 100 110 120 IARGAAGGGR NRPAPYSRPK QLPDKWQHDL FDSGFGGGAG VETGGKLLVS NLDFGVSDAD 130 140 150 160 170 180 IQELFAEFGT LKKAAVHYDR SGRSLGTADV HFERKADALK AMKQYNGVPL DGRPMNIQLV 190 200 210 220 230 240 TSQIDTQRRP AQSINRGGMT RNRGSGGFGG GGTRRGTRGG SRGRGRGTGR NSKQQLSAEE 250 LDAQLDAYNA RMDTS
	Isoform 2 (Refbp1-II) [UniParc]. Checksum: D212F3ACD29C8B13	FASTA	163	17,682
	10 20 30 40 50 60 MADKMDMSLD DIIKLLVSNL DFGVSDADIQ ELFAEFGTLK KAAVHYDRSG RSLGTADVHF 70 80 90 100 110 120 ERKADALKAM KQYNGVPLDG RPMNIQLVTS QIDTQRRPAQ SINRGGMTRN RGSGGFGGGG 130 140 150 160 TRRGTRGGSR GRGRGTGRNS KQQLSAEELD AQLDAYNARM DTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] 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]	"The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling." Lejeune F., Ishigaki Y., Li X., Maquat L.E. EMBO J. 21:3536-3545(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH THE EXON JUNCTION COMPLEX.
[8]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237, MASS SPECTROMETRY. Tissue: Macrophage.
[9]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00114407.
IPI00122339.

RefSeq

NP_035698.1. NM_011568.1.

UniGene

Mm.1886.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NO8	NMR	-	A	77-182	[»]

ProteinModelPortal

O08583.

SMR

O08583. Positions 1-187.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59977N.

IntAct

O08583. 1 interaction.

PTM databases

PhosphoSite

O08583.

Proteomic databases

PaxDb

O08583.

PRIDE

O08583.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000026125; ENSMUSP00000026125; ENSMUSG00000025134.

GeneID

21681.

KEGG

mmu:21681.

UCSC

uc007mtl.1. mouse.

Organism-specific databases

CTD

10189.

MGI

MGI:1341044. Alyref.

Phylogenomic databases

eggNOG

NOG316507.

GeneTree

ENSGT00410000025615.

HOGENOM

HOG000239962.

HOVERGEN

HBG054806.

InParanoid

Q0VBL5.

KO

K12881.

OMA

IRNRPAI.

OrthoDB

EOG4MW87F.

Gene expression databases

Bgee

O08583.

CleanEx

MM_THOC4.

Genevestigator

O08583.

GermOnline

ENSMUSG00000025134. Mus musculus.

Family and domain databases

Gene3D

3.30.70.330. 1 hit.

InterPro

IPR025715. FoP_duplication.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]

Pfam

PF13865. FoP_duplication. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 1 hit.
[Graphical view]

PROSITE

PS50102. RRM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O08583.

NextBio

300988.

SOURCE

Search...

Entry information

Entry name

THOC4_MOUSE

Accession

Primary (citable) accession number: O08583
Secondary accession number(s): Q0VBL5, Q8CBM4, Q9JJW7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 112 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program