Q9HCK5 (AGO4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein argonaute-4
Short name=Argonaute4
Short name=hAgo4

Alternative name(s):
Eukaryotic translation initiation factor 2C 4
Short name=eIF-2C 4
Short name=eIF2C 4

Gene names

Name:	EIF2C4
Synonyms:	AGO4, KIAA1567

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	861 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for RNA-directed transcription and replication of the human hapatitis delta virus (HDV). Ref.3 Ref.6 Ref.7
Subunit structure	Interacts with EIF4B, IMP8, PRMT5, TNRC6A and TNRC6B. Ref.8
Subcellular location	Cytoplasm › P-body Ref.5 Ref.8.
Sequence similarities	Belongs to the argonaute family. Ago subfamily. Contains 1 PAZ domain. Contains 1 Piwi domain.
Sequence caution	The sequence BAB13393.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	RNA-mediated gene silencing Translation regulation
Cellular component	Cytoplasm
Ligand	RNA-binding
Molecular function	Ribonucleoprotein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mRNA catabolic process Inferred from direct assay Ref.6. Source: UniProtKB negative regulation of translation involved in gene silencing by miRNA Inferred from direct assay Ref.6. Source: UniProtKB
Cellular component	cytoplasmic mRNA processing body Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome
Molecular function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.8. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IPO8	O15397	3	EBI-2269696,EBI-358808

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 861	861	Protein argonaute-4		PRO_0000194063
Regions
	Domain	225 – 338	114	PAZ
	Domain	509 – 820	312	Piwi
Amino acid modifications
	Modified residue	798	1	Phosphoserine Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9HCK5 [UniParc]. Last modified November 14, 2003. Version 2. Checksum: F236FF05047534C1	FASTA	861	97,097
	10 20 30 40 50 60 MEALGPGPPA SLFQPPRRPG LGTVGKPIRL LANHFQVQIP KIDVYHYDVD IKPEKRPRRV 70 80 90 100 110 120 NREVVDTMVR HFKMQIFGDR QPGYDGKRNM YTAHPLPIGR DRVDMEVTLP GEGKDQTFKV 130 140 150 160 170 180 SVQWVSVVSL QLLLEALAGH LNEVPDDSVQ ALDVITRHLP SMRYTPVGRS FFSPPEGYYH 190 200 210 220 230 240 PLGGGREVWF GFHQSVRPAM WNMMLNIDVS ATAFYRAQPI IEFMCEVLDI QNINEQTKPL 250 260 270 280 290 300 TDSQRVKFTK EIRGLKVEVT HCGQMKRKYR VCNVTRRPAS HQTFPLQLEN GQAMECTVAQ 310 320 330 340 350 360 YFKQKYSLQL KYPHLPCLQV GQEQKHTYLP LEVCNIVAGQ RCIKKLTDNQ TSTMIKATAR 370 380 390 400 410 420 SAPDRQEEIS RLVKSNSMVG GPDPYLKEFG IVVHNEMTEL TGRVLPAPML QYGGRNKTVA 430 440 450 460 470 480 TPNQGVWDMR GKQFYAGIEI KVWAVACFAP QKQCREDLLK SFTDQLRKIS KDAGMPIQGQ 490 500 510 520 530 540 PCFCKYAQGA DSVEPMFKHL KMTYVGLQLI VVILPGKTPV YAEVKRVGDT LLGMATQCVQ 550 560 570 580 590 600 VKNVVKTSPQ TLSNLCLKIN AKLGGINNVL VPHQRPSVFQ QPVIFLGADV THPPAGDGKK 610 620 630 640 650 660 PSIAAVVGSM DGHPSRYCAT VRVQTSRQEI SQELLYSQEV IQDLTNMVRE LLIQFYKSTR 670 680 690 700 710 720 FKPTRIIYYR GGVSEGQMKQ VAWPELIAIR KACISLEEDY RPGITYIVVQ KRHHTRLFCA 730 740 750 760 770 780 DKTERVGKSG NVPAGTTVDS TITHPSEFDF YLCSHAGIQG TSRPSHYQVL WDDNCFTADE 790 800 810 820 830 840 LQLLTYQLCH TYVRCTRSVS IPAPAYYARL VAFRARYHLV DKDHDSAEGS HVSGQSNGRD 850 860 PQALAKAVQI HHDTQHTMYF A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O. DNA Res. 7:273-281(2000) [PubMed: 10997877] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs." Meister G., Landthaler M., Patkaniowska A., Dorsett Y., Teng G., Tuschl T. Mol. Cell 15:185-197(2004) [PubMed: 15260970] [Abstract] Cited for: ASSOCIATION WITH MIRNA.
[3]	"Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis." Pillai R.S., Artus C.G., Filipowicz W. RNA 10:1518-1525(2004) [PubMed: 15337849] [Abstract] Cited for: FUNCTION.
[4]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-798, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[5]	"Inhibition of translational initiation by Let-7 MicroRNA in human cells." Pillai R.S., Bhattacharyya S.N., Artus C.G., Zoller T., Cougot N., Basyuk E., Bertrand E., Filipowicz W. Science 309:1573-1576(2005) [PubMed: 16081698] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"Importance of translation and nonnucleolytic ago proteins for on-target RNA interference." Wu L., Fan J., Belasco J.G. Curr. Biol. 18:1327-1332(2008) [PubMed: 18771919] [Abstract] Cited for: FUNCTION.
[7]	"Capped small RNAs and MOV10 in human hepatitis delta virus replication." Haussecker D., Cao D., Huang Y., Parameswaran P., Fire A.Z., Kay M.A. Nat. Struct. Mol. Biol. 15:714-721(2008) [PubMed: 18552826] [Abstract] Cited for: FUNCTION.
[8]	"Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs." Weinmann L., Hoeck J., Ivacevic T., Ohrt T., Muetze J., Schwille P., Kremmer E., Benes V., Urlaub H., Meister G. Cell 136:496-507(2009) [PubMed: 19167051] [Abstract] Cited for: INTERACTION WITH EIF4B; IMP8; PRMT5; TNRC6A AND TNRC6B, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB046787 mRNA. Translation: BAB13393.1. Different initiation.
IPI	IPI00030602.
RefSeq	NP_060099.2. NM_017629.3.
UniGene	Hs.471492.
3D structure databases
ProteinModelPortal	Q9HCK5.
SMR	Q9HCK5. Positions 212-374, 432-564.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HCK5. 74 interactions.
STRING	Q9HCK5.
PTM databases
PhosphoSite	Q9HCK5.
Polymorphism databases
DMDM	38372393.
Proteomic databases
PRIDE	Q9HCK5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373210; ENSP00000362306; ENSG00000134698.
GeneID	192670.
KEGG	hsa:192670.
NMPDR	fig|9606.3.peg.839.
UCSC	uc001bzj.1. human.
Organism-specific databases
CTD	192670.
GeneCards	GC01P036273.
H-InvDB	HIX0199793.
HGNC	HGNC:18424. EIF2C4.
HPA	CAB012179.
MIM	607356. gene.
neXtProt	NX_Q9HCK5.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09089.
HOGENOM	HBG717005.
InParanoid	Q9HCK5.
OMA	GMPIVGN.
OrthoDB	EOG4229J0.
PhylomeDB	Q9HCK5.
Enzyme and pathway databases
Reactome	REACT_12472. Regulatory RNA pathways.
Gene expression databases
ArrayExpress	Q9HCK5.
Bgee	Q9HCK5.
CleanEx	HS_EIF2C4.
Genevestigator	Q9HCK5.
GermOnline	ENSG00000134698. Homo sapiens.
Family and domain databases
InterPro	IPR014811. DUF1785. IPR003100. PAZ. IPR003165. Piwi. IPR012337. RNaseH-like_dom. [Graphical view]
KO	K11593.
Pfam	PF08699. DUF1785. 1 hit. PF02170. PAZ. 1 hit. PF02171. Piwi. 1 hit. [Graphical view]
SMART	SM00949. PAZ. 1 hit. SM00950. Piwi. 1 hit. [Graphical view]
SUPFAM	SSF101690. PAZ. 1 hit. SSF53098. RNaseH_fold. 1 hit.
PROSITE	PS50821. PAZ. 1 hit. PS50822. PIWI. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	89373.
SOURCE	Search...

Entry information

Entry name

AGO4_HUMAN

Accession

Primary (citable) accession number: Q9HCK5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 14, 2003
Last sequence update:	November 14, 2003
Last modified:	January 25, 2012
This is version 76 of the entry and version 2 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.