O77503 (AGO2_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein argonaute-2
Short name=Argonaute2
EC=3.1.26.n2

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

Gene names

Name:	EIF2C2
Synonyms:	AGO2

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	840 AA.
Sequence status	Fragment.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include EIF2C2/AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by EIF2C2/AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions By similarity. HAMAP-Rule MF_03031
Catalytic activity	Endonucleolytic cleavage to 5'-phosphomonoester. HAMAP-Rule MF_03031
Subunit structure	Interacts with DICER1 through its Piwi domain and with TARBP2 during assembly of the RNA-induced silencing complex (RISC). Together, DICER1, EIF2C2/AGO2 and TARBP2 constitute the trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto EIF2C2/AGO2. EIF2C2/AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Note however that the term RISC has also been used to describe the trimeric RLC/miRLC. The formation of RISC complexes containing siRNAs rather than miRNAs appears to occur independently of DICER1. Interacts with EIF2C1/AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, EIF6, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in a RNA- and phosphorylation-independent manner By similarity. Interacts with LIMD1, WTIP and AJUBA. Interacts with TRIM71 By similarity. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H By similarity.
Subcellular location	Cytoplasm › P-body By similarity. Nucleus By similarity. Note: Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8 By similarity.
Domain	The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH) By similarity. HAMAP-Rule MF_03031
Post-translational modification	Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity By similarity. HAMAP-Rule MF_03031
Sequence similarities	Belongs to the argonaute family. Ago subfamily. Contains 1 PAZ domain. Contains 1 Piwi domain.
Sequence caution	The sequence AAC24323.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	RNA-mediated gene silencing Transcription Transcription regulation Translation regulation
Cellular component	Cytoplasm Nucleus
Ligand	Metal-binding RNA-binding
Molecular function	Endonuclease Hydrolase Nuclease Repressor Ribonucleoprotein
PTM	Hydroxylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	mRNA cleavage involved in gene silencing by miRNA Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of translation involved in gene silencing by miRNA Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of translational initiation Inferred from sequence or structural similarity. Source: UniProtKB pre-miRNA processing Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	RNA-induced silencing complex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasmic mRNA processing body Inferred from electronic annotation. Source: UniProtKB-SubCell mRNA cap binding complex Inferred from sequence or structural similarity. Source: UniProtKB micro-ribonucleoprotein complex Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell polysome Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	RNA 7-methylguanosine cap binding Inferred from sequence or structural similarity. Source: UniProtKB endoribonuclease activity, cleaving siRNA-paired mRNA Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW siRNA binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	‹1 – 840	›840	Protein argonaute-2 HAMAP-Rule MF_03031		PRO_0000194059
Regions
	Domain	216 – 329	114	PAZ
	Domain	498 – 799	302	Piwi
Sites
	Metal binding	578	1	Divalent metal cation By similarity
	Metal binding	650	1	Divalent metal cation By similarity
	Metal binding	788	1	Divalent metal cation By similarity
Amino acid modifications
	Modified residue	681	1	4-hydroxyproline By similarity
Experimental info
	Non-terminal residue	1	1

Sequences

	Sequence		Length	Mass (Da)
	O77503 [UniParc]. Last modified November 14, 2003. Version 2. Checksum: 1E703F9E31391F29	FASTA	840	95,306
	10 20 30 40 50 60 GYAFKPPPRP DFGTSGRTIK LQANFFEMDI PKIDIYHYEL DIKPEKCPRR VNREIVEHMV 70 80 90 100 110 120 QHFKAQIFGD RKPVFDGRKN LYTAMPLPIG REKVELEVTL PGEGKDRIFK VSIKWVSCVS 130 140 150 160 170 180 LQALHDALSG RLPSVPFETI QALDVVMRHL PSMRYTPVGR SFFTASEGCS NPLGGGREVW 190 200 210 220 230 240 FGFHQSVRPS LWKMMLNIDV SATAFYKAQP VIEFVCEVLD FKSIEEQQKP LTDSQRVKFT 250 260 270 280 290 300 KEIKGLKVEI THCGQMKRKY RVCNVTRRPA SHQTFPLQQE SGQTVECTVA QYFKDRHKLV 310 320 330 340 350 360 LRYPHLPCLQ VGQEQKHTYL PLEVCNIVAG QRCIKKLTDN QTSTMIRATA RSAPDRQEEI 370 380 390 400 410 420 SKLMRSASFN TDPYVREFGI MVKDEMTDVT GRVLQPPSIL YGGRNKAIAT PVQGVWDMRN 430 440 450 460 470 480 KQFHTGIEIK VWAIACFAPQ RQCTEVHLKS FTEQLRKISR DAGMPIQGQP CFCKYAQGAD 490 500 510 520 530 540 SVGPMFRHLK NTYAGLQLVV VILPGKTPVY AEVKRVGDTV LGMATQCVQM KNVQRTTPQT 550 560 570 580 590 600 LSNLCLKINV KLGGVNNILL PQGRPPVFQQ PVIFLGADVT HPPAGDGKKP SIAAVVGSMD 610 620 630 640 650 660 AHPNRYCATV RVQQHRQEII QDLAAMVREL LIQFYKSTRF KPTRIIFYRD GVSEGQFQQV 670 680 690 700 710 720 LHHELLAIRE ACIKLEKDYQ PGITFIVVQK RHHTRLFCTD KNERVGKSGN IPAGTTVDTK 730 740 750 760 770 780 ITHPTEFDFY LCSHAGIQGT SRPSHYHVLW DDNRFSSDEL QILTYQLCHT YVRCTRSVSI 790 800 810 820 830 840 PAPAYYAHLV AFRARYHLVD KEHDSAEGSH TSGQSNGRDH QALAKAVQVH QDTLRTMYFA

References

[1]	"Molecular cloning and characterization of a rabbit eIF2C protein." Zou C., Zhang Z., Wu S., Osterman J.C. Gene 211:187-194(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF005355 mRNA. Translation: AAC24323.1. Different initiation.
PIR	JC6569. PC6505.
RefSeq	NP_001076179.1. NM_001082710.1.
UniGene	Ocu.1816.
3D structure databases
ProteinModelPortal	O77503.
SMR	O77503. Positions 203-370.
ModBase	Search...
Protein-protein interaction databases
STRING	9986.ENSOCUP00000023891.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100009457.
Organism-specific databases
CTD	446823.
Phylogenomic databases
eggNOG	NOG279895.
HOGENOM	HOG000116043.
OrthoDB	EOG4229J0.
Family and domain databases
HAMAP	MF_03031. AGO2.
InterPro	IPR014811. DUF1785. IPR003100. PAZ. IPR003165. Piwi. IPR012337. RNaseH-like_dom. [Graphical view]
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...

Entry information

Entry name

AGO2_RABIT

Accession

Primary (citable) accession number: O77503

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 14, 2003
Last modified:	May 1, 2013
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