Q15056 (IF4H_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic translation initiation factor 4H
Short name=eIF-4H

Alternative name(s):
Williams-Beuren syndrome chromosomal region 1 protein

Gene names

Name:	EIF4H
Synonyms:	KIAA0038, WBSCR1, WSCR1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	248 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	Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. Ref.9 Ref.10
Subunit structure	Interacts with HHV-1 Vhs. Ref.11
Subcellular location	Cytoplasm › perinuclear region By similarity.
Tissue specificity	The short isoform is the predominant isoform and is expressed alone in liver and skeletal muscle. Both isoforms are expressed in fibroblast, spleen, testis and bone marrow. Levels are high in lung and pancreas and low in heart, frontal cortex and kidney. Ref.1 Ref.2
Involvement in disease	EIF4H is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of EIF4H may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.
Sequence similarities	Contains 1 RRM (RNA recognition motif) domain.
Sequence caution	The sequence BAA05063.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Host-virus interaction Protein biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Disease	Williams-Beuren syndrome
Ligand	RNA-binding
Molecular function	Initiation factor
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	developmental growth Inferred from electronic annotation. Source: Compara regulation of translational initiation Traceable author statement Ref.8. Source: ProtInc sexual reproduction Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome eukaryotic translation initiation factor 4F complex Traceable author statement Ref.8. Source: ProtInc perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	nucleotide binding Inferred from electronic annotation. Source: InterPro translation initiation factor activity Traceable author statement Ref.8. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF4A1	P60842	2	EBI-748492,EBI-73449

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q15056-1)

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 Short (identifier: Q15056-2)

The sequence of this isoform differs from the canonical sequence as follows:
     137-156: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7
	Chain	2 – 248	247	Eukaryotic translation initiation factor 4H		PRO_0000081619
Regions
	Domain	42 – 118	77	RRM
	Region	137 – 157	21	HHV-1 Vhs binding site
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.7
	Modified residue	21	1	Phosphoserine Ref.14 Ref.16
	Modified residue	24	1	Phosphoserine Ref.14 Ref.16
	Modified residue	32	1	Phosphoserine Ref.13
Natural variations
	Alternative sequence	137 – 156	20	Missing in isoform Short.		VSP_005799

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified January 23, 2007. Version 5. Checksum: D3098B7270A9CF38	FASTA	248	27,385
	10 20 30 40 50 60 MADFDTYDDR AYSSFGGGRG SRGSAGGHGS RSQKELPTEP PYTAYVGNLP FNTVQGDIDA 70 80 90 100 110 120 IFKDLSIRSV RLVRDKDTDK FKGFCYVEFD EVDSLKEALT YDGALLGDRS LRVDIAEGRK 130 140 150 160 170 180 QDKGGFGFRK GGPDDRGMGS SRESRGGWDS RDDFNSGFRD DFLGGRGGSR PGDRRTGPPM 190 200 210 220 230 240 GSRFRDGPPL RGSNMDFREP TEEERAQRPR LQLKPRTVAT PLNQVANPNS AIFGGARPRE EVVQKEQE
	Isoform Short [UniParc]. Checksum: 3374AF6A7558B9F7	FASTA	228	25,200
	10 20 30 40 50 60 MADFDTYDDR AYSSFGGGRG SRGSAGGHGS RSQKELPTEP PYTAYVGNLP FNTVQGDIDA 70 80 90 100 110 120 IFKDLSIRSV RLVRDKDTDK FKGFCYVEFD EVDSLKEALT YDGALLGDRS LRVDIAEGRK 130 140 150 160 170 180 QDKGGFGFRK GGPDDRGFRD DFLGGRGGSR PGDRRTGPPM GSRFRDGPPL RGSNMDFREP 190 200 210 220 TEEERAQRPR LQLKPRTVAT PLNQVANPNS AIFGGARPRE EVVQKEQE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients." Osborne L.R., Martindale D.W., Scherer S.W., Shi X.-M., Huizenga J., Heng H.H.Q., Costa T., Pober B., Lew L., Brinkman J., Rommens J., Koop B.F., Tsui L.-C. Genomics 36:328-336(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM SHORT), TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23." Martindale D.W., Wilson M.D., Wang D., Burke R.D., Chen X., Duronio V., Koop B.F. Mamm. Genome 11:890-898(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[3]	"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1." Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S. DNA Res. 1:27-35(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). Tissue: Bone marrow.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
[5]	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].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). Tissue: Brain and Muscle.
[7]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-10, ACETYLATION AT ALA-2. Tissue: Platelet.
[8]	"Purification and characterization of a new eukaryotic protein translation factor. Eukaryotic initiation factor 4H." Richter-Cook N.J., Dever T.E., Hensold J.O., Merrick W.C. J. Biol. Chem. 273:7579-7587(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION.
[9]	"Further biochemical and kinetic characterization of human eukaryotic initiation factor 4H." Richter N.J., Rogers G.W. Jr., Hensold J.O., Merrick W.C. J. Biol. Chem. 274:35415-35424(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Modulation of the helicase activity of eIF4A by eIF4B, eIF4H, and eIF4F." Rogers G.W. Jr., Richter N.J., Lima W.F., Merrick W.C. J. Biol. Chem. 276:30914-30922(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"mRNA decay during herpes simplex virus (HSV) infections: protein-protein interactions involving the HSV virion host shutoff protein and translation factors eIF4H and eIF4A." Feng P., Everly D.N. Jr., Read G.S. J. Virol. 79:9651-9664(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HHV-1 VHS.
[12]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21 AND SER-24, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21 AND SER-24, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF045555 Genomic DNA. Translation: AAF75557.1. AF045555 Genomic DNA. Translation: AAC04859.2. D26068 mRNA. Translation: BAA05063.1. Different initiation. AK290676 mRNA. Translation: BAF83365.1. CH471200 Genomic DNA. Translation: EAW69616.1. CH471200 Genomic DNA. Translation: EAW69615.1. CH471200 Genomic DNA. Translation: EAW69617.1. CH471200 Genomic DNA. Translation: EAW69618.1. CH471200 Genomic DNA. Translation: EAW69619.1. BC010021 mRNA. Translation: AAH10021.1. BC021214 mRNA. Translation: AAH21214.1. BC066928 mRNA. Translation: AAH66928.1.
IPI	IPI00014263. IPI00375127.
RefSeq	NP_071496.1. NM_022170.1. NP_114381.1. NM_031992.1.
UniGene	Hs.520943.
3D structure databases
ProteinModelPortal	Q15056.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15056. 8 interactions.
STRING	9606.ENSP00000265753.
PTM databases
PhosphoSite	Q15056.
Polymorphism databases
DMDM	18276665.
Proteomic databases
PaxDb	Q15056.
PRIDE	Q15056.
Protocols and materials databases
DNASU	7458.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265753; ENSP00000265753; ENSG00000106682. ENST00000353999; ENSP00000265754; ENSG00000106682. ENST00000575843; ENSP00000460568; ENSG00000263344. ENST00000575925; ENSP00000458302; ENSG00000263344.
GeneID	7458.
KEGG	hsa:7458.
UCSC	uc003uad.1. human. uc003uae.1. human.
Organism-specific databases
CTD	7458.
GeneCards	GC07P073588.
HGNC	HGNC:12741. EIF4H.
HPA	HPA030542.
MIM	603431. gene.
neXtProt	NX_Q15056.
Orphanet	904. Williams syndrome.
PharmGKB	PA162384997.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0724.
HOGENOM	HOG000013063.
HOVERGEN	HBG018193.
InParanoid	Q15056.
OMA	PRTVSEP.
OrthoDB	EOG46DM3S.
PhylomeDB	Q15056.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins. REACT_1762. 3' -UTR-mediated translational regulation. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q15056.
Bgee	Q15056.
CleanEx	HS_EIF4H.
Genevestigator	Q15056.
Family and domain databases
Gene3D	3.30.70.330. 1 hit.
InterPro	IPR012677. Nucleotide-bd_a/b_plait. IPR000504. RRM_dom. [Graphical view]
Pfam	PF00076. RRM_1. 1 hit. [Graphical view]
SMART	SM00360. RRM. 1 hit. [Graphical view]
PROSITE	PS50102. RRM. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1293274.
ChiTaRS	EIF4H. human.
GenomeRNAi	7458.
NextBio	29206.
SOURCE	Search...

Entry information

Entry name

IF4H_HUMAN

Accession

Primary (citable) accession number: Q15056
Secondary accession number(s): A8K3R1, D3DXF6, D3DXF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 131 of the entry and version 5 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.