Reviewed, UniProtKB/Swiss-Prot Q04637 (IF4G1_HUMAN)

Names and origin

Protein names

Recommended name:
    Eukaryotic translation initiation factor 4 gamma 1
      Short name=eIF-4-gamma 1
      Short name=eIF-4G 1
      Short name=eIF-4G1
Alternative name(s):
    p220

Gene names

Name:	EIF4G1
Synonyms:	EIF4F, EIF4G, EIF4GI

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	1600 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome.
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 eIF3, mutually exclusive with EIF4A1 or EIFA2, EIF4E and through its N-terminus with PAPBC1. Interacts through its C-terminus with the serine/threonine kinases MKNK1, and with MKNK2. Appears to act as a scaffold protein, holding these enzymes in place to phosphorylate EIF4E. Non-phosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. EIF4G1/EIF4G3 interacts with PABPC1 to bring about circularization of the mRNA. During rotaviral infection, rotavirus RNA-binding protein NSP3 interacts with EIF4G1 and takes the place of PABPC1. Rapamycin can attenuate insulin stimulation mediated by FKBPs. Interacts with EIF4E3. Interacts with MIF4GD.
Post-translational modification	Phosphorylated at multiple sites in vivo. Following infection by certain enteroviruses, rhinoviruses and aphthoviruses, EIF4G1 is cleaved by the viral protease 2A, or the leader protease in the case of aphthoviruses. This shuts down the capped cellular mRNA transcription.
Sequence similarities	Belongs to the eIF4G family. Contains 1 MI domain. Contains 1 MIF4G domain. Contains 1 W2 domain.
Sequence caution	The sequence BAA02185.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	Host-virus interaction Protein biosynthesis Translation regulation
Coding sequence diversity	Alternative initiation Alternative splicing Polymorphism
Ligand	RNA-binding
Molecular function	Initiation factor
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	RNA metabolic process Inferred from electronic annotation. Source: InterPro interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW regulation of translational initiation Ref.2 Ref.14 Non-traceable author statement. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome eukaryotic translation initiation factor 4F complex Ref.3 Traceable author statement. Source: ProtInc
Molecular function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.17 Ref.18 Ref.19 Ref.32 Inferred from physical interaction. Source: UniProtKB translation initiation factor activity Ref.2 Ref.14 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF4A1	P60842	3	EBI-73711,EBI-73449
EIF4A2	Q14240	2	EBI-73711,EBI-73473
EIF4E	P06730	1	EBI-73711,EBI-73440
Eif4e2	Q8BMB3	1	EBI-73711,EBI-398682	From a different organism.
GABARAPL2	P60520	1	EBI-73711,EBI-720116
HNRNPD	Q14103-1	1	EBI-73711,EBI-432527
HNRNPD	Q14103-2	1	EBI-73711,EBI-432533
HNRNPD	Q14103-3	1	EBI-73711,EBI-432539
HNRNPD	Q14103-4	1	EBI-73711,EBI-432545
MAGEA6	P43360	1	EBI-73711,EBI-1045155
MKNK1	Q9BUB5	1	EBI-73711,EBI-73837
PABPC1	P11940	1	EBI-73711,EBI-81531
PDCD4	Q53EL6	1	EBI-73711,EBI-935824
S7	P03536	1	EBI-73711,EBI-296448	From a different organism.

Alternative products

This entry describes 6 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Isoform 1 (identifier: Q04637-1)

Also known as: A;

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: Q04637-2)

The sequence of this isoform differs from the canonical sequence as follows:
     77-1225: Missing.

Notes: No experimental confirmation available.

Isoform B (identifier: Q04637-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: Missing.

Notes: Produced by alternative initiation at Met-41 of isoform 1.

Isoform C (identifier: Q04637-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-87: Missing.

Notes: Produced by alternative initiation at Met-88 of isoform 1.

Isoform D (identifier: Q04637-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-164: Missing.

Notes: Produced by alternative initiation at Met-165 of isoform 1.

Isoform E (identifier: Q04637-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-196: Missing.

Notes: Produced by alternative initiation at Met-197 of isoform 1.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1600

1600

Eukaryotic translation initiation factor 4 gamma 1

PRO_0000007786

Regions

Domain

565 – 792

228

MIF4G

Domain

1242 – 1364

123

MI

Domain

1434 – 1600

167

W2

Region

172 – 200

29

PABPC1-binding

Region

607 – 618

12

EIF4E-binding

Region

682 – 1086

405

eIF3/EIF4A-binding

Region

1451 – 1600

150

EIF4A-binding

Region

1586 – 1600

15

Necessary but not sufficient for MKNK1-binding

Compositional bias

454 – 467

14

Poly-Glu

Compositional bias

501 – 504

4

Poly-Ala

Sites

Site

674 – 675

2

Cleavage; by foot-and-mouth disease virus leader protease

Site

681 – 682

2

Cleavage; by enterovirus/rhinovirus protease 2A

Amino acid modifications

Modified residue

205

1

Phosphothreonine

Modified residue

207

1

Phosphothreonine

Modified residue

223

1

Phosphothreonine

Modified residue

594

1

Phosphotyrosine

Modified residue

647

1

Phosphothreonine

Modified residue

1093

1

Phosphoserine

Modified residue

1146

1

Phosphoserine

Modified residue

1148

1

Phosphoserine

Modified residue

1186

1

Phosphoserine

Modified residue

1188

1

Phosphoserine

Modified residue

1210

1

Phosphoserine

Modified residue

1232

1

Phosphoserine

Modified residue

1597

1

Phosphoserine

Natural variations

Alternative sequence

1 – 196

196

Missing in isoform E.

VSP_018723

Alternative sequence

1 – 164

164

Missing in isoform D.

VSP_018722

Alternative sequence

1 – 87

87

Missing in isoform C.

VSP_018721

Alternative sequence

1 – 40

40

Missing in isoform B.

VSP_018720

Alternative sequence

77 – 1225

1149

Missing in isoform 2.

VSP_013973

Natural variant

696

1

P → L in a colorectal cancer sample; somatic mutation.

VAR_036117

Experimental info

Mutagenesis

174 – 178

5

KRERK → AAAAA: Loss of PABPC1 binding; when associated with 184-AAAA-187

Mutagenesis

180

1

I → A: Loss of PABPC1 binding

Mutagenesis

182

1

I → A: Loss of PABPC1 binding

Mutagenesis

184 – 187

4

DPNQ → AAAA: Loss of PABPC1 binding; when associated with 174-AAAAA-178

Mutagenesis

192

1

I → A: Loss of PABPC1 binding

Mutagenesis

196

1

I → A: Loss of PABPC1 binding

Mutagenesis

612

1

Y → A or F: Abolishes binding to EIF4E

Mutagenesis

617 – 618

2

LL → AA: Abolishes binding to EIF4E

Mutagenesis

682

1

G → A, V, W, R or E: Reduced cleavage by protease 2A from human rhinovirus 2

Mutagenesis

769

1

L → A: Abolishes binding to EIF4A; when associated with A-772 and A-777

Mutagenesis

772

1

L → A: Abolishes binding to EIF4A; when associated with A-769 and A-777

Mutagenesis

777

1

F → A: Abolishes binding to EIF4A; when associated with A-769 and A-772

Mutagenesis

843 – 844

2

LL → AA: Abolishes binding to EIF4A; when associated with A-852 and K-853

Mutagenesis

852 – 853

2

FE → AK: Abolishes binding to EIF4A; when associated with A-843 and A-844

Mutagenesis

897

1

L → A: Abolishes binding to EIF4A; when associated with A-903 and A-906

Mutagenesis

903

1

I → A: Abolishes binding to EIF4A; when associated with A-897 and A-906

Mutagenesis

906

1

L → A: Abolishes binding to EIF4A; when associated with A-897 and A-903

Mutagenesis

975

1

R → A: Abolishes binding to EIF4A; when associated with A-978

Mutagenesis

978

1

F → A: Abolishes binding to EIF4A; when associated with A-975

Mutagenesis

986

1

L → A: Slightly reduced binding to EIF4A; when associated with A-991

Mutagenesis

991

1

W → A: Slightly reduced binding to EIF4A; when associated with A-986

Sequence conflict

30

1

P → R in AAC78443. Ref.8

Sequence conflict

138

1

L → F in AAC78443. Ref.3 Ref.7 Ref.8

Sequence conflict

149

1

R → Q in AAC78443. Ref.3 Ref.7 Ref.8

Sequence conflict

214

1

G → S in BAA02185. Ref.4

Sequence conflict

432

1

V → M in CAI46013. Ref.7

Sequence conflict

462

1

E → D in BAA02185. Ref.4

Sequence conflict

468

1

A → V in BAA02185. Ref.4

Sequence conflict

474

1

A → G in BAA02185. Ref.4

Sequence conflict

479

1

G → R in BAA02185. Ref.4

Sequence conflict

604

1

P → L in CAI46013. Ref.7

Sequence conflict

625 – 626

2

AS → CQ in BAA02185. Ref.4

Sequence conflict

697

1

Missing Ref.4 Ref.7

Sequence conflict

765

1

V → W in BAA02185. Ref.4

Sequence conflict

879

1

G → E in BAA02185. Ref.4

Sequence conflict

895

1

R → C in BAA02185. Ref.4

Sequence conflict

1105

1

K → Q in BAA02185. Ref.4

Sequence conflict

1122

1

N → I in BAA02185. Ref.4

Sequence conflict

1186

1

S → T in BAA02185. Ref.4

Sequence conflict

1385

1

C → Y in CAI46013. Ref.7

Sequence conflict

1472

1

Missing in BAA02185. Ref.4

Secondary structure

1

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1600

Helix Strand Turn

Details...

Beta strand

181 – 183

3

Helix

185 – 187

3