IF4A3_DANRE
ID IF4A3_DANRE Reviewed; 406 AA.
AC Q7ZVA6;
DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Eukaryotic initiation factor 4A-III;
DE Short=eIF-4A-III;
DE Short=eIF4A-III;
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:P38919};
DE AltName: Full=ATP-dependent RNA helicase DDX48;
DE AltName: Full=ATP-dependent RNA helicase eIF4A-3;
DE AltName: Full=DEAD box protein 48;
DE AltName: Full=Eukaryotic translation initiation factor 4A isoform 3;
GN Name=eif4a3; Synonyms=ddx48;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24360810; DOI=10.1016/j.ajhg.2013.11.020;
RA Favaro F.P., Alvizi L., Zechi-Ceide R.M., Bertola D., Felix T.M.,
RA de Souza J., Raskin S., Twigg S.R., Weiner A.M., Armas P., Margarit E.,
RA Calcaterra N.B., Andersen G.R., McGowan S.J., Wilkie A.O.,
RA Richieri-Costa A., de Almeida M.L., Passos-Bueno M.R.;
RT "A noncoding expansion in EIF4A3 causes Richieri-Costa-Pereira syndrome, a
RT craniofacial disorder associated with limb defects.";
RL Am. J. Hum. Genet. 94:120-128(2014).
CC -!- FUNCTION: ATP-dependent RNA helicase. Involved in pre-mRNA splicing as
CC component of the spliceosome. Core component of the splicing-dependent
CC multiprotein exon junction complex (EJC) deposited at splice junctions
CC on mRNAs. The EJC is a dynamic structure consisting of core proteins
CC and several peripheral nuclear and cytoplasmic associated factors that
CC join the complex only transiently either during EJC assembly or during
CC subsequent mRNA metabolism. The EJC marks the position of the exon-exon
CC junction in the mature mRNA for the gene expression machinery and the
CC core components remain bound to spliced mRNAs throughout all stages of
CC mRNA metabolism thereby influencing downstream processes including
CC nuclear mRNA export, subcellular mRNA localization, translation
CC efficiency and nonsense-mediated mRNA decay (NMD). Binds spliced mRNA
CC in sequence-independent manner, 20-24 nucleotides upstream of mRNA
CC exon-exon junctions (By similarity). Involved in craniofacial
CC development (PubMed:24360810). {ECO:0000250|UniProtKB:P38919,
CC ECO:0000269|PubMed:24360810}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000250|UniProtKB:P38919};
CC -!- SUBUNIT: Identified in the spliceosome C complex. Part of the mRNA
CC splicing-dependent exon junction complex (EJC) complex; the core
CC complex contains casc3, eif4a3, magoh and rbm8a.
CC {ECO:0000250|UniProtKB:P38919}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q3B8Q2}. Nucleus
CC speckle {ECO:0000250|UniProtKB:P38919}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q3B8Q2}. Note=Nucleocytoplasmic shuttling
CC protein. Travels to the cytoplasm as part of the exon junction complex
CC (EJC) bound to mRNA. {ECO:0000250|UniProtKB:Q3B8Q2}.
CC -!- DISRUPTION PHENOTYPE: Morpholino EIF4A3 knockdown results in multiple
CC defects in craniofacial structures. Fish morphants staged at 24 hpf
CC show eyes reduced in size, and dark and opaque zones in all brain
CC structures. In addition, the otic vesicle and the midbrain/hindbrain
CC border regions are barely detectable. Cartilage and bone staining
CC reveals underdevelopment of craniofacial cartilage, bone alterations,
CC and clefting of the lower jaw. The third through sixth pharyngeal
CC arches are underdeveloped in morphants. {ECO:0000269|PubMed:24360810}.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. eIF4A subfamily.
CC {ECO:0000305}.
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DR EMBL; BC045939; AAH45939.1; -; mRNA.
DR RefSeq; NP_957372.1; NM_201078.1.
DR AlphaFoldDB; Q7ZVA6; -.
DR SMR; Q7ZVA6; -.
DR IntAct; Q7ZVA6; 1.
DR MINT; Q7ZVA6; -.
DR STRING; 7955.ENSDARP00000027276; -.
DR PaxDb; Q7ZVA6; -.
DR GeneID; 394053; -.
DR KEGG; dre:394053; -.
DR CTD; 9775; -.
DR ZFIN; ZDB-GENE-040426-915; eif4a3.
DR eggNOG; KOG0328; Eukaryota.
DR InParanoid; Q7ZVA6; -.
DR OrthoDB; 726081at2759; -.
DR PhylomeDB; Q7ZVA6; -.
DR Reactome; R-DRE-1169408; ISG15 antiviral mechanism.
DR Reactome; R-DRE-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR Reactome; R-DRE-429947; Deadenylation of mRNA.
DR Reactome; R-DRE-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-DRE-72187; mRNA 3'-end processing.
DR Reactome; R-DRE-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-DRE-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR PRO; PR:Q7ZVA6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0071006; C:U2-type catalytic step 1 spliceosome; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0003724; F:RNA helicase activity; IBA:GO_Central.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IEA:UniProtKB-KW.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000629; RNA-helicase_DEAD-box_CS.
DR InterPro; IPR014014; RNA_helicase_DEAD_Q_motif.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00039; DEAD_ATP_HELICASE; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51195; Q_MOTIF; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Helicase; Hydrolase; mRNA processing;
KW mRNA splicing; mRNA transport; Nonsense-mediated mRNA decay;
KW Nucleotide-binding; Nucleus; Reference proteome; RNA-binding; Spliceosome;
KW Translation regulation; Transport.
FT CHAIN 1..406
FT /note="Eukaryotic initiation factor 4A-III"
FT /id="PRO_0000379480"
FT DOMAIN 64..234
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 245..406
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT MOTIF 33..61
FT /note="Q motif"
FT MOTIF 182..185
FT /note="DEAD box"
FT /evidence="ECO:0000305"
FT BINDING 55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P38919"
FT BINDING 60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P38919"
FT BINDING 77..84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 80..85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P38919"
FT BINDING 337
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P38919"
FT BINDING 362..366
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P38919"
SQ SEQUENCE 406 AA; 46468 MW; 765707C2F2E60695 CRC64;
MATAVVPVRK RILKEEDMTK IEFETSEEVD VTPTFDTMGL REDLLRGIYA YGFEKPSAIQ
QRAIKQIIKG RDVIAQSQSG TGKTATFCVS VLQCLDIQVR ETQALILAPT RELAGQIQKV
LLALGDYMNV QCHACIGGTN VGEDIRKLDY GQHVVAGTPG RVFDMIRRRS LRTRAIKMLV
LDEADEMLNK GFKEQIYDVY RYLPPATQVC LISATLPHEI LEMTNKFMTD PIRILVKRDE
LTLEGIKQFF VAVEREEWKF DTLCDLYDTL TITQAVIFCN TKRKVDWLTE KMREANFTVS
SMHGDMPQKE RESIMKEFRS GASRVLISTD VWARGLDVSQ VSLIINYDLP NNRELYIHRI
GRSGRYGRKG VAINFVKNDD IRILRDIEQY YSTQIDEMPM NVADLI
