P23301 (IF5A1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic translation initiation factor 5A-1
Short name=eIF-5A-1

Alternative name(s):
Hypusine-containing protein HP2
eIF-4D

Gene names

Name:	HYP2
Synonyms:	TIF51A
Ordered Locus Names:	YEL034W
ORF Names:	SYGP-ORF21

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	157 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	mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity. Essential for polarized growth, a process necessary for G1/S transition. May mediate large range of effects of the polyamine spermidine in the cell. Ref.7 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.18 Ref.22 Ref.24
Subunit structure	Homodimer. Interacts with DYS1 and LIA1. Ref.14 Ref.17 Ref.23
Subcellular location	Cytoplasm. Note: Concentrates in the perinuclear region. Ref.13
Induction	Expressed in aerobic conditions. Ref.9
Post-translational modification	eIF-5A seems to be the only eukaryotic protein to have an hypusine residue which is a post-translational modification of a lysine by the addition of a butylamino group (from spermidine).
Miscellaneous	There are two genes for eIF-5A in yeast.
Sequence similarities	Belongs to the eIF-5A family.
Caution	Was originally thought (Ref.7) to be a translation initiation factor but further analysis (Ref.24 and Ref.22) clearly suggests that it is involved in translation elongation and not translation initiation. subclass.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm
Ligand	RNA-binding
Molecular function	Elongation factor
PTM	Acetylation Hypusine Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	peptidyl-lysine modification to hypusine Inferred from electronic annotation. Source: InterPro positive regulation of translational elongation Inferred from direct assay Ref.24. Source: SGD positive regulation of translational initiation Inferred from direct assay. Source: SGD positive regulation of translational termination Inferred from direct assay Ref.24. Source: SGD translational frameshifting Inferred from mutant phenotype Ref.24. Source: SGD
Cellular component	cytosolic ribosome Inferred from physical interaction Ref.17. Source: SGD mitochondrion Inferred from direct assay. Source: SGD
Molecular function	ribosome binding Inferred from physical interaction Ref.17. Source: SGD translation elongation factor activity Inferred from direct assay Ref.24. Source: SGD translation initiation factor activity Inferred from direct assay. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 157

156

Eukaryotic translation initiation factor 5A-1

PRO_0000142488

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.6

Modified residue

2

1

Phosphoserine Ref.6 Ref.10 Ref.19 Ref.21

Modified residue

15

1

Phosphoserine Ref.21

Modified residue

51

1

Hypusine

Modified residue

74

1

Phosphoserine Ref.19 Ref.21

Modified residue

149

1

Phosphoserine Ref.21

Experimental info

Mutagenesis

22

1

Q → H: Temperature-sensitive growth phenotype; when associated with F-93. Ref.20

Mutagenesis

24

1

S → P: Temperature-sensitive growth phenotype. Ref.20

Mutagenesis

39

1

C → Y: Temperature-sensitive growth phenotype. Lethal; when associated with L-83 and D-118 or with I-66 and D-118 or with D-118 and I-142 or with L-116 and D-118. Ref.13 Ref.20

Mutagenesis

50

1

G → A or P: Lethal. Ref.20

Mutagenesis

51

1

K → R: Impairs association to the ribosome and cell growth. Ref.16 Ref.17 Ref.20 Ref.23 Ref.24

Mutagenesis

52

1

H → A or D: Lethal. Ref.20

Mutagenesis

53

1

G → A or D: Lethal. Ref.20

Mutagenesis

54

1

H → D: Lethal. Ref.20

Mutagenesis

56

1

K → A: Temperature-sensitive growth phenotype. Ref.20

Mutagenesis

56

1

K → D: Lethal. Ref.20

Mutagenesis

57

1

V → D: Temperature-sensitive growth phenotype. Ref.20

Mutagenesis

63

1

D → V: Impairs programmed ribosomal frameshifting. Ref.24

Mutagenesis

66

1

T → I: Temperature-sensitive growth phenotype. Lethal; when associated with Y-39 and D-118. Ref.20

Mutagenesis

83

1

P → S or L: Temperature-sensitive growth phenotype. Lethal; when associated with Y-39 and D-118. Ref.13 Ref.20

Mutagenesis

93

1

L → F: Lethal. Ref.20

Mutagenesis

102

1

L → A: Temperature-sensitive growth phenotype. Ref.18

Mutagenesis

116

1

P → L: Temperature-sensitive growth phenotype; when associated with D-118. Lethal; when associated with Y-39 and D-118. Ref.20

Mutagenesis

118

1

G → D: Temperature-sensitive growth phenotype; when associated with L-116 or W-122 or F-140 or I-142. Lethal; when associated with Y-39 and I-66 or with Y-39 and L-83 or with Y-39 and L-116 or with Y-39 and F-140 or with Y-39 and I-142 or with N-120 and D-124. Ref.13 Ref.20

Mutagenesis

118

1

G → V: Temperature-sensitive growth phenotype; when associated with W-122. Ref.20

Mutagenesis

120

1

L → N: Lethal; when associated D-118 and D-124. Ref.20

Mutagenesis

122

1

D → W: Temperature-sensitive growth phenotype; when associated with V-118. Ref.20

Mutagenesis

124

1

L → D: Lethal; when associated D-118 and N-120. Ref.20

Mutagenesis

140

1

S → F: Temperature-sensitive growth phenotype; when associated with D-118. Lethal; when associated with Y-39 and D-118. Ref.20

Mutagenesis

142

1

M → I: Temperature-sensitive growth phenotype; when associated with D-118. Lethal; when associated with Y-39 and D-118. Ref.20

Mutagenesis

149

1

S → P in ts1159; temperature-sensitive growth phenotype and impairs programmed ribosomal frameshifting. Ref.12 Ref.20 Ref.24

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

157

Helix Strand Turn

Details...

Beta strand

19 – 22

4

Turn

23 – 25

3

Beta strand

32 – 34

3

Beta strand

37 – 47

11

Beta strand

56 – 64

9

Beta strand

70 – 82

13

Beta strand

87 – 91

5

Helix

123 – 126

4

Beta strand

135 – 140

6

Beta strand

145 – 150

6

Sequences

	Sequence		Length	Mass (Da)
	P23301 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 738F29CCC7820C47	FASTA	157	17,114
	10 20 30 40 50 60 MSDEEHTFET ADAGSSATYP MQCSALRKNG FVVIKSRPCK IVDMSTSKTG KHGHAKVHLV 70 80 90 100 110 120 AIDIFTGKKL EDLSPSTHNM EVPVVKRNEY QLLDIDDGFL SLMNMDGDTK DDVKAPEGEL 130 140 150 GDSLQTAFDE GKDLMVTIIS AMGEEAAISF KEAARTD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Translation initiation factor 5A and its hypusine modification are essential for cell viability in the yeast Saccharomyces cerevisiae." Schnier J., Schwelberger H.G., Smit-Mcbride Z., Kang H.A., Hershey J.W.B. Mol. Cell. Biol. 11:3105-3114(1991) [PubMed: 1903841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	Sandholzer U.R. Submitted (DEC-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: DBY874.
[3]	"Sequence determination of cDNA encoding yeast cycloheximide sensitivity factor (CH-SF) and its plausible role at a first peptide bond formation step in the initiation process of protein synthesis." Kitaoka Y., Miyazaki M. Nucleic Acids Symp. Ser. 22:69-70(1990) [PubMed: 2135872] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome V." Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E., Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S., Hyman R.W. , Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X., Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y., Botstein D., Davis R.W. Nature 387:78-81(1997) [PubMed: 9169868] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[5]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[6]	"Determination and mutational analysis of the phosphorylation site in the hypusine-containing protein Hyp2p." Klier H., Woehl T., Eckerskorn C., Magdolen V., Lottspeich F. FEBS Lett. 334:360-364(1993) [PubMed: 8243648] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, ACETYLATION AT SER-2, PHOSPHORYLATION AT SER-2.
[7]	"The mechanism of action of protein synthesis initiation factors from rabbit reticulocytes." Benne R., Hershey J.W.B. J. Biol. Chem. 253:3078-3087(1978) [PubMed: 641056] [Abstract] Cited for: FUNCTION.
[8]	"Hypusine formation in eukaryotic initiation factor 4D is not reversed when rates or specificity of protein synthesis is altered." Gordon E.D., Mora R., Meredith S.C., Lindquist S.L. J. Biol. Chem. 262:16590-16595(1987) [PubMed: 3119589] [Abstract] Cited for: HYPUSINE FORMATION.
[9]	"Translation initiation factor eIF-5A expressed from either of two yeast genes or from human cDNA. Functional identity under aerobic and anaerobic conditions." Schwelberger H.G., Kang H.A., Hershey J.W.B. J. Biol. Chem. 268:14018-14025(1993) [PubMed: 8314769] [Abstract] Cited for: INDUCTION.
[10]	"Translation initiation factor eIF-5A, the hypusine-containing protein, is phosphorylated on serine in Saccharomyces cerevisiae." Kang H.A., Schwelberger H.G., Hershey J.W.B. J. Biol. Chem. 268:14750-14756(1993) [PubMed: 8325852] [Abstract] Cited for: PHOSPHORYLATION AT SER-2.
[11]	"Effect of initiation factor eIF-5A depletion on protein synthesis and proliferation of Saccharomyces cerevisiae." Kang H.A., Hershey J.W.B. J. Biol. Chem. 269:3934-3940(1994) [PubMed: 8307948] [Abstract] Cited for: FUNCTION.
[12]	"A single amino acid substitution in yeast eIF-5A results in mRNA stabilization." Zuk D., Jacobson A. EMBO J. 17:2914-2925(1998) [PubMed: 9582285] [Abstract] Cited for: MUTAGENESIS OF SER-149, FUNCTION.
[13]	"Complex formation between deoxyhypusine synthase and its protein substrate, the eukaryotic translation initiation factor 5A (eIF5A) precursor." Lee Y.B., Joe Y.A., Wolff E.C., Dimitriadis E.K., Park M.H. Biochem. J. 340:273-281(1999) [PubMed: 10229683] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF CYS-39 AND PRO-83.
[14]	"Mapping eIF5A binding sites for Dys1 and Lia1: in vivo evidence for regulation of eIF5A hypusination." Thompson G.M., Cano V.S.P., Valentini S.R. FEBS Lett. 555:464-468(2003) [PubMed: 14675757] [Abstract] Cited for: INTERACTION WITH DYS1 AND LIA1.
[15]	"Pkc1 acts through Zds1 and Gic1 to suppress growth and cell polarity defects of a yeast eIF5A mutant." Zanelli C.F., Valentini S.R. Genetics 171:1571-1581(2005) [PubMed: 16157662] [Abstract] Cited for: FUNCTION.
[16]	"eIF5A binds to translational machinery components and affects translation in yeast." Zanelli C.F., Maragno A.L.C., Gregio A.P.B., Komili S., Pandolfi J.R., Mestriner C.A., Lustri W.R., Valentini S.R. Biochem. Biophys. Res. Commun. 348:1358-1366(2006) [PubMed: 16914118] [Abstract] Cited for: FUNCTION, ASSOCIATION WITH THE 80S RIBOSOME, MUTAGENESIS OF LYS-51.
[17]	"Tandem affinity purification revealed the hypusine-dependent binding of eukaryotic initiation factor 5A to the translating 80S ribosomal complex." Jao D.L., Chen K.Y. J. Cell. Biochem. 97:583-598(2006) [PubMed: 16215987] [Abstract] Cited for: INTERACTION WITH DYS1, ASSOCIATION WITH THE 80S RIBOSOME, MUTAGENESIS OF LYS-51.
[18]	"Rapid depletion of mutant eukaryotic initiation factor 5A at restrictive temperature reveals connections to actin cytoskeleton and cell cycle progression." Chatterjee I., Gross S.R., Kinzy T.G., Chen K.Y. Mol. Genet. Genomics 275:264-276(2006) [PubMed: 16408210] [Abstract] Cited for: MUTAGENESIS OF LEU-102, FUNCTION.
[19]	"Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae." Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., Elias J.E., Gygi S.P. J. Proteome Res. 6:1190-1197(2007) [PubMed: 17330950] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND SER-74, MASS SPECTROMETRY. Strain: ADR376.
[20]	"Structural modeling and mutational analysis of yeast eukaryotic translation initiation factor 5A reveal new critical residues and reinforce its involvement in protein synthesis." Dias C.A.O., Cano V.S.P., Rangel S.M., Apponi L.H., Frigieri M.C., Muniz J.R.C., Garcia W., Park M.H., Garratt R.C., Zanelli C.F., Valentini S.R. FEBS J. 275:1874-1888(2008) [PubMed: 18341589] [Abstract] Cited for: MUTAGENESIS OF GLN-22; SER-24; CYS-39; GLY-50; LYS-51; HIS-52; GLY-53; HIS-54; LYS-56; VAL-57; THR-66; PRO-83; LEU-93; PRO-116; GLY-118; LEU-120; ASP-122; LEU-124; SER-140; MET-142; SER-149 AND 116-PRO--ASP-157.
[21]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-15; SER-74 AND SER-149, MASS SPECTROMETRY.
[22]	"eIF5A has a function in the elongation step of translation in yeast." Gregio A.P.B., Cano V.P.S., Avaca J.S., Valentini S.R., Zanelli C.F. Biochem. Biophys. Res. Commun. 380:785-790(2009) [PubMed: 19338753] [Abstract] Cited for: FUNCTION.
[23]	"Dimerization of the yeast eukaryotic translation initiation factor 5A requires hypusine and is RNA dependent." Gentz P.M., Blatch G.L., Dorrington R.A. FEBS J. 276:695-706(2009) [PubMed: 19120453] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF LYS-51.
[24]	"Hypusine-containing protein eIF5A promotes translation elongation." Saini P., Eyler D.E., Green R., Dever T.E. Nature 459:118-121(2009) [PubMed: 19424157] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-51; ASP-63 AND SER-149.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M63541 Genomic DNA. Translation: AAA35155.1.
X56236 Genomic DNA. Translation: CAA39693.1.
D83166 mRNA. Translation: BAA11826.1.
U18779 Genomic DNA. Translation: AAB65008.1.
BK006939 Genomic DNA. Translation: DAA07619.1.

PIR

FIBYA1. A40259.

RefSeq

NP_010880.1. NM_001178849.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3ER0	X-ray	3.35	A/B	1-157	[»]

ProteinModelPortal

P23301.

SMR

P23301. Positions 12-157.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-4230N.

IntAct

P23301. 17 interactions.

MINT

MINT-545311.

STRING

P23301.

2D gel databases

SWISS-2DPAGE

P23301.

Proteomic databases

PeptideAtlas

P23301.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YEL034W; YEL034W; YEL034W.

GeneID

856677.

KEGG

sce:YEL034W.

NMPDR

fig|4932.3.peg.1932.

Organism-specific databases

SGD

S000000760. HYP2.

Phylogenomic databases

eggNOG

fuNOG08157.

GeneTree

EFGT00050000003235.

HOGENOM

HBG526951.

OrthoDB

EOG4B01ZQ.

Gene expression databases

ArrayExpress

P23301.

Genevestigator

P23301.

GermOnline

YEL034W. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR005824. KOW.
IPR012340. NA-bd_OB-fold.
IPR016027. NA-bd_OB-fold-like.
IPR019769. Trans_elong_IF5A_hypusine_site.
IPR001884. Transl_elong_IF5A.
IPR020189. Transl_elong_IF5A_C.
IPR014722. Transl_SH3-like_sub.
IPR008991. Translation_prot_SH3-like.
[Graphical view]

Gene3D

G3DSA:2.40.50.140. OB_NA_bd_sub. 1 hit.
G3DSA:2.30.30.30. Ribosomal_L2. 1 hit.

KO

K03263.

PANTHER

PTHR11673. EIF5A_hypusine. 1 hit.

Pfam

PF01287. eIF-5a. 1 hit.
PF00467. KOW. 1 hit.
[Graphical view]

PIRSF

PIRSF003025. eIF5A. 1 hit.

SUPFAM

SSF50249. Nucleic_acid_OB. 1 hit.
SSF50104. Transl_SH3_like. 1 hit.

TIGRFAMs

TIGR00037. EIF_5A. 1 hit.

PROSITE

PS00302. IF5A_HYPUSINE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

982702.

Entry information

Entry name

IF5A1_YEAST

Accession

Primary (citable) accession number: P23301
Secondary accession number(s): D3DLL5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	January 23, 2007
Last modified:	December 14, 2011
This is version 118 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program