UniProt Accession

 IF4A1_HUMAN; P60842; B2R6L8; D3DTP9; J3QLC4; P04765; Q5U018; Q61516 

Genbank Protein ID

 D13748; BT019880; BT019881; AK312630; AC016876; CH471108; CH471108; CH471108; BC006210; BC009585; BC073752 

Genbank Nucleotide ID

 BAA02897.1; AAV38683.1; AAV38684.1; BAG35515.1; EAW90167.1; EAW90168.1; EAW90169.1; AAH09585.1; AAH73752.1 

Protein Name

 Eukaryotic initiation factor 4A-I 

Protein Synonyms/Alias

 eIF-4A-I; eIF4A-I; ATP-dependent RNA helicase eIF4A-1 

Gene Name

 EIF4A1 

Gene Synonyms/Alias

 DDX2A; EIF4A 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
54	IYAYGFEKPSAIQQR	ubiquitination	[1, 2, 3, 4, 5]
68	RAILPCIKGYDVIAQ	ubiquitination	[4, 6, 7]
118	ELAQQIQKVVMALGD	acetylation	[8]
118	ELAQQIQKVVMALGD	ubiquitination	[2, 7]
146	NVRAEVQKLQMEAPH	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
174	NRRYLSPKYIKMFVL	acetylation	[8]
174	NRRYLSPKYIKMFVL	ubiquitination	[2, 3, 4, 5, 6, 7]
177	YLSPKYIKMFVLDEA	ubiquitination	[1, 2, 4, 5, 6, 7]
193	EMLSRGFKDQIYDIF	acetylation	[9]
193	EMLSRGFKDQIYDIF	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
225	SDVLEVTKKFMRDPI	ubiquitination	[2, 4, 5, 6, 7]
226	DVLEVTKKFMRDPIR	ubiquitination	[7]
237	DPIRILVKKEELTLE	ubiquitination	[2, 6, 7]
238	PIRILVKKEELTLEG	ubiquitination	[2, 6, 7]
284	IFINTRRKVDWLTEK	ubiquitination	[2, 5, 6, 7]
291	KVDWLTEKMHARDFT	acetylation	[8]
291	KVDWLTEKMHARDFT	ubiquitination	[2, 5, 6, 7]
309	MHGDMDQKERDVIMR	acetylation	[8]
309	MHGDMDQKERDVIMR	ubiquitination	[2, 3, 4, 5, 6, 7]
369	RGGRFGRKGVAINMV	ubiquitination	[2, 3, 4, 5, 6, 7, 10, 11, 12, 13]
381	NMVTEEDKRTLRDIE	acetylation	[13, 14]
381	NMVTEEDKRTLRDIE	ubiquitination	[2, 3, 4, 5, 7, 11, 12, 13]

Reference

 [1] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [7] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [8] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [9] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [10] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [11] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [12] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [13] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [14] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 63 234 Helicase ATP-binding.
 DOMAIN 245 406 Helicase C-terminal.
 NP_BIND 76 83 ATP (By similarity).
 MOTIF 32 60 Q motif.
 MOTIF 182 185 DEAD box.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 4 4 Phosphoserine.
 MOD_RES 118 118 N6-acetyllysine.
 MOD_RES 174 174 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Helicase; Host-virus interaction; Hydrolase; Initiation factor; Nucleotide-binding; Phosphoprotein; Protein biosynthesis; Reference proteome; RNA-binding. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 406 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0016281; C:eukaryotic translation initiation factor 4F complex; TAS:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0008026; F:ATP-dependent helicase activity; IEA:InterPro.
 GO:0004386; F:helicase activity; TAS:UniProtKB.
 GO:0003729; F:mRNA binding; TAS:UniProtKB.
 GO:0000339; F:RNA cap binding; TAS:UniProtKB.
 GO:0008135; F:translation factor activity, nucleic acid binding; TAS:UniProtKB.
 GO:0003743; F:translation initiation factor activity; IEA:UniProtKB-KW.
 GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
 GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
 GO:0006413; P:translational initiation; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
 IPR014001; Helicase_ATP-bd.
 IPR001650; Helicase_C.
 IPR027417; P-loop_NTPase.
 IPR000629; RNA-helicase_DEAD-box_CS.
 IPR014014; RNA_helicase_DEAD_Q_motif. 

Pfam

 PF00270; DEAD
 PF00271; Helicase_C 

SMART

 SM00487; DEXDc
 SM00490; HELICc 

PROSITE

 PS00039; DEAD_ATP_HELICASE
 PS51192; HELICASE_ATP_BIND_1
 PS51194; HELICASE_CTER
 PS51195; Q_MOTIF 

PRINTS