P60842 (IF4A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic initiation factor 4A-I
Short name=eIF-4A-I
Short name=eIF4A-I
EC=3.6.4.13

Alternative name(s):
ATP-dependent RNA helicase eIF4A-1

Gene names

Name:	EIF4A1
Synonyms:	DDX2A, EIF4A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	406 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. Ref.15 Ref.16
Catalytic activity	ATP + H2O = ADP + phosphate.
Enzyme regulation	Helicase activity and function in translation are inhibited by interaction with PDCD4. Ref.15 Ref.16
Subunit structure	eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. Interacts with PAIP1, EIF4E and UPF2. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. May interact with NOM1. Interacts with PDCD4; this interferes with the interaction between EIF4A and EIF4G. Interacts with RBM4. Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.15 Ref.16
Sequence similarities	Belongs to the DEAD box helicase family. eIF4A subfamily. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.

Ontologies

Keywords
Biological process	Protein biosynthesis
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Helicase Hydrolase Initiation factor
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	nuclear-transcribed mRNA poly(A) tail shortening Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome eukaryotic translation initiation factor 4F complex Traceable author statement. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro RNA cap binding Traceable author statement. Source: UniProtKB mRNA binding Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction Ref.11Ref.6. Source: UniProtKB translation initiation factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF4G1	Q04637	7	EBI-73449,EBI-73711
EIF4G2	P78344	2	EBI-73449,EBI-296519
EIF4H	Q15056	2	EBI-73449,EBI-748492

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 406

406

Eukaryotic initiation factor 4A-I

PRO_0000054933

Regions

Domain

63 – 234

172

Helicase ATP-binding

Domain

245 – 406

162

Helicase C-terminal

Nucleotide binding

76 – 83

8

ATP By similarity

Motif

32 – 60

29

Q motif

Motif

182 – 185

4

DEAD box

Amino acid modifications

Modified residue

118

1

N6-acetyllysine Ref.13

Modified residue

158

1

Phosphothreonine Ref.12

Modified residue

174

1

N6-acetyllysine Ref.13

Modified residue

309

1

N6-acetyllysine Ref.13

Secondary structure

1

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406

Helix Strand Turn

Details...

Helix

34 – 36

3

Helix

41 – 50

10

Helix

57 – 68

12

Beta strand

72 – 75

4

Helix

82 – 93

12

Beta strand

103 – 106

4

Helix

110 – 124

15

Turn

125 – 128

4

Beta strand

131 – 134

4

Turn

143 – 145

3

Beta strand

146 – 149

4

Beta strand

153 – 157

5

Helix

159 – 167

9

Beta strand

178 – 183

6

Helix

184 – 189

6

Helix

193 – 202

10

Beta strand

208 – 214

7

Helix

218 – 227

10

Beta strand

232 – 235

4

Sequences

	Sequence		Length	Mass (Da)
	P60842 [UniParc]. Last modified April 13, 2004. Version 1. Checksum: 6EF89939F3045420	FASTA	406	46,154
	10 20 30 40 50 60 MSASQDSRSR DNGPDGMEPE GVIESNWNEI VDSFDDMNLS ESLLRGIYAY GFEKPSAIQQ 70 80 90 100 110 120 RAILPCIKGY DVIAQAQSGT GKTATFAISI LQQIELDLKA TQALVLAPTR ELAQQIQKVV 130 140 150 160 170 180 MALGDYMGAS CHACIGGTNV RAEVQKLQME APHIIVGTPG RVFDMLNRRY LSPKYIKMFV 190 200 210 220 230 240 LDEADEMLSR GFKDQIYDIF QKLNSNTQVV LLSATMPSDV LEVTKKFMRD PIRILVKKEE 250 260 270 280 290 300 LTLEGIRQFY INVEREEWKL DTLCDLYETL TITQAVIFIN TRRKVDWLTE KMHARDFTVS 310 320 330 340 350 360 AMHGDMDQKE RDVIMREFRS GSSRVLITTD LLARGIDVQQ VSLVINYDLP TNRENYIHRI 370 380 390 400 GRGGRFGRKG VAINMVTEED KRTLRDIETF YNTSIEEMPL NVADLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of human cDNA encoding eukaryotic initiation factor 4AI." Kim N.-S., Kato T., Abe N., Kato S. Nucleic Acids Res. 21:2012-2012(1993) [PubMed: 8493113] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow and Lung.
[6]	"Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation." Craig A.W.B., Haghighat A., Yu A.T.K., Sonenberg N. Nature 392:520-523(1998) [PubMed: 9548260] [Abstract] Cited for: INTERACTION WITH PAIP1.
[7]	"Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes." Mendell J.T., Medghalchi S.M., Lake R.G., Noensie E.N., Dietz H.C. Mol. Cell. Biol. 20:8944-8957(2000) [PubMed: 11073994] [Abstract] Cited for: INTERACTION WITH UPF2.
[8]	"Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact in a 1:1 ratio in vivo." Li W., Belsham G.J., Proud C.G. J. Biol. Chem. 276:29111-29115(2001) [PubMed: 11408474] [Abstract] Cited for: INTERACTION WITH EIF4E.
[9]	"Exportin 7 defines a novel general nuclear export pathway." Mingot J.-M., Bohnsack M.T., Jaekle U., Goerlich D. EMBO J. 23:3227-3236(2004) [PubMed: 15282546] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH XPO7; ARHGAP1; VPS26A; VPS29; VPS35 AND SFN.
[10]	"Identification of NOM1, a nucleolar, eIF4A binding protein encoded within the chromosome 7q36 breakpoint region targeted in cases of pediatric acute myeloid leukemia." Simmons H.M., Ruis B.L., Kapoor M., Hudacek A.W., Conklin K.F. Gene 347:137-145(2005) [PubMed: 15715967] [Abstract] Cited for: POSSIBLE INTERACTION WITH NOM1.
[11]	"Cell stress modulates the function of splicing regulatory protein RBM4 in translation control." Lin J.C., Hsu M., Tarn W.Y. Proc. Natl. Acad. Sci. U.S.A. 104:2235-2240(2007) [PubMed: 17284590] [Abstract] Cited for: INTERACTION WITH RBM4.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-158, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-118; LYS-174 AND LYS-309, MASS SPECTROMETRY.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Structural basis for translational inhibition by the tumour suppressor Pdcd4." Loh P.G., Yang H.S., Walsh M.A., Wang Q., Wang X., Cheng Z., Liu D., Song H. EMBO J. 28:274-285(2009) [PubMed: 19153607] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) IN COMPLEX WITH PDCD4, FUNCTION, SUBUNIT, ENZYME REGULATION.
[16]	"Crystal structure of the eIF4A-PDCD4 complex." Chang J.H., Cho Y.H., Sohn S.Y., Choi J.M., Kim A., Kim Y.C., Jang S.K., Cho Y. Proc. Natl. Acad. Sci. U.S.A. 106:3148-3153(2009) [PubMed: 19204291] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 20-406 IN COMPLEX WITH PDCD4, FUNCTION, ENZYME REGULATION, SUBUNIT.
[17]	"Comparative structural analysis of human DEAD-box RNA helicases." Schutz P., Karlberg T., van den Berg S., Collins R., Lehtio L., Hogbom M., Holmberg-Schiavone L., Tempel W., Park H.W., Hammarstrom M., Moche M., Thorsell A.G., Schuler H. PLoS ONE 5:0-0(2010) [PubMed: 20941364] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 20-236.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D13748 mRNA. Translation: BAA02897.1.
BT019880 mRNA. Translation: AAV38683.1.
BT019881 mRNA. Translation: AAV38684.1.
AK312630 mRNA. Translation: BAG35515.1.
CH471108 Genomic DNA. Translation: EAW90167.1.
CH471108 Genomic DNA. Translation: EAW90168.1.
BC009585 mRNA. Translation: AAH09585.1.
BC073752 mRNA. Translation: AAH73752.1.

IPI

IPI00025491.

PIR

S33681.

RefSeq

NP_001407.1. NM_001416.3.

UniGene

Hs.129673.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2G9N	X-ray	2.25	A/B	20-236	[»]
2ZU6	X-ray	2.80	A/C/D/F	20-406	[»]
3EIQ	X-ray	3.50	A/D	1-406	[»]

ProteinModelPortal

P60842.

SMR

P60842. Positions 22-400.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29755N.

IntAct

P60842. 30 interactions.

MINT

MINT-5001111.

STRING

P60842.

PTM databases

PhosphoSite

P60842.

Polymorphism databases

DMDM

46397463.

Proteomic databases

PRIDE

P60842.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000293831; ENSP00000293831; ENSG00000161960.

GeneID

1973.

KEGG

hsa:1973.

UCSC

uc002gho.1. human.

Organism-specific databases

CTD

1973.

GeneCards

GC17P007476.

H-InvDB

HIX0013502.
HIX0079958.

HGNC

HGNC:3282. EIF4A1.

HPA

CAB011689.

MIM

602641. gene.

neXtProt

NX_P60842.

PharmGKB

PA27710.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06292.

HOGENOM

HBG737336.

HOVERGEN

HBG107989.

OMA

NCHACIG.

OrthoDB

EOG4640C1.

PhylomeDB

P60842.

Enzyme and pathway databases

Pathway_Interaction_DB

mtor_4pathway. mTOR signaling pathway.

Reactome

REACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.
REACT_1762. 3' -UTR-mediated translational regulation.
REACT_71. Gene Expression.

Gene expression databases

Bgee

P60842.

CleanEx

HS_EIF4A1.

Genevestigator

P60842.

GermOnline

ENSG00000161960. Homo sapiens.

Family and domain databases

InterPro

IPR014001. DEAD-like_helicase.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR001650. Helicase_C.
IPR000629. RNA-helicase_DEAD-box_CS.
IPR014014. RNA_helicase_DEAD_Q_motif.
[Graphical view]

KO

K03257.

Pfam

PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
[Graphical view]

SMART

SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]

PROSITE

PS00039. DEAD_ATP_HELICASE. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51195. Q_MOTIF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

7987.

SOURCE

Search...

Entry information

Entry name

IF4A1_HUMAN

Accession

Primary (citable) accession number: P60842
Secondary accession number(s): B2R6L8 , D3DTP9, P04765, Q5U018, Q61516

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	April 13, 2004
Last modified:	January 25, 2012
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.