Q9UKV8 (AGO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein argonaute-2
Short name=Argonaute2
Short name=hAgo2
EC=3.1.26.n2

Alternative name(s):
Eukaryotic translation initiation factor 2C 2
Short name=eIF-2C 2
Short name=eIF2C 2
PAZ Piwi domain protein
Short name=PPD
Protein slicer

Gene names

Name:	EIF2C2
Synonyms:	AGO2

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	859 AA.
Sequence status	Complete.
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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32
Catalytic activity	Endonucleolytic cleavage to 5'-phosphomonoester. Ref.7
Enzyme regulation	Inhibited by EDTA. Ref.10
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. Interacts with LIMD1, WTIP and AJUBA. Interacts with TRIM71. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Ref.6 Ref.9 Ref.11 Ref.12 Ref.14 Ref.16 Ref.19 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37
Subcellular location	Cytoplasm › P-body. Nucleus. Note: Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8. Ref.12 Ref.17 Ref.19 Ref.21 Ref.23 Ref.30 Ref.32 Ref.34 Ref.37
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). 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. HAMAP-Rule MF_03031
Sequence similarities	Belongs to the argonaute family. Ago subfamily. Contains 1 PAZ domain. Contains 1 Piwi domain.
Biophysicochemical properties	Kinetic parameters: KM=1.1 nM for a synthetic 21-nucleotide single-stranded RNA Ref.7 Ref.18
Sequence caution	The sequence AAH07633.1 differs from that shown. Reason: Erroneous initiation. The sequence AAL76093.1 differs from that shown. Reason: cDNA contains a duplication of an internal sequence at the 5' end. The sequence BC125214 differs from that shown. Reason: Frameshift at position 450.

Ontologies

Keywords
Biological process	RNA-mediated gene silencing Transcription Transcription regulation Translation regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding RNA-binding
Molecular function	Endonuclease Hydrolase Nuclease Repressor Ribonucleoprotein
PTM	Hydroxylation Nitration
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Traceable author statement. Source: Reactome mRNA cleavage involved in gene silencing by miRNA Inferred from direct assay Ref.24. Source: UniProtKB negative regulation of translation involved in gene silencing by miRNA Inferred from direct assay PubMed 17671087Ref.33. Source: UniProtKB negative regulation of translational initiation Inferred from direct assay Ref.24Ref.33. Source: UniProtKB post-embryonic development Inferred from electronic annotation. Source: Compara pre-miRNA processing Inferred from direct assay PubMed 17671087. 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 direct assay Ref.16. Source: UniProtKB cytoplasmic mRNA processing body Inferred from direct assay Ref.37. Source: UniProtKB cytosol Traceable author statement. Source: Reactome mRNA cap binding complex Inferred from direct assay Ref.24. Source: UniProtKB micro-ribonucleoprotein complex Inferred from direct assay PubMed 17671087Ref.25. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell polysome Inferred from direct assay Ref.25. Source: UniProtKB
Molecular_function	RNA 7-methylguanosine cap binding Inferred from direct assay Ref.24. Source: UniProtKB endoribonuclease activity, cleaving siRNA-paired mRNA Inferred from direct assay Ref.24. Source: UniProtKB mRNA binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW siRNA binding Inferred from direct assay PubMed 17495927. Source: UniProtKB translation initiation factor activity Non-traceable author statement Ref.5. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DHX58	Q96C10	2	EBI-528269,EBI-744193
DICER1	Q9UPY3	7	EBI-528269,EBI-395506
IPO8	O15397	3	EBI-528269,EBI-358808
TBK1	Q9UHD2	2	EBI-528269,EBI-356402
TBKBP1	A7MCY6	2	EBI-528269,EBI-359969
TNRC6A	Q8NDV7	4	EBI-528269,EBI-2269715

Alternative products

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

Isoform 1 (identifier: Q9UKV8-1)

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 2 (identifier: Q9UKV8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     724-757: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 859

859

Protein argonaute-2 HAMAP-Rule MF_03031

PRO_0000194057

Regions

Domain

235 – 348

114

PAZ

Domain

517 – 818

302

Piwi

Sites

Metal binding

597

1

Divalent metal cation Probable

Metal binding

669

1

Divalent metal cation Probable

Metal binding

807

1

Divalent metal cation Probable

Amino acid modifications

Modified residue

2

1

Nitrated tyrosine By similarity

Modified residue

700

1

4-hydroxyproline Ref.30

Natural variations

Alternative sequence

724 – 757

34

Missing in isoform 2.

VSP_037001

Experimental info

Mutagenesis

140

1

L → W: No effect. Ref.10

Mutagenesis

470

1

F → V: No effect on miRNA-binding or target mRNA cleavage. Abrogates binding to the 7-methylguanosine cap of mRNA and prevents inhibition of translation. Ref.24

Mutagenesis

470

1

F → W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation. Ref.24

Mutagenesis

505

1

F → V: No effect on miRNA-binding or target mRNA cleavage. Abrogates binding to the 7-methylguanosine cap of mRNA and prevents inhibition of translation; when associated with V-470. Ref.24

Mutagenesis

505

1

F → W: No effect on binding to the 7-methylguanosine cap of mRNA or inhibition of translation. Ref.24

Mutagenesis

533

1

K → A: Impairs RNA cleavage. Ref.15

Mutagenesis

545

1

Q → A: Impairs RNA cleavage. Ref.15

Mutagenesis

570

1

K → A: Impairs RNA cleavage. Ref.15

Mutagenesis

597

1

D → A: Abrogates RNA cleavage but does not affect binding to siRNA or translational repression. Ref.10 Ref.18 Ref.29

Mutagenesis

633

1

Q → A: No effect. Ref.10

Mutagenesis

633

1

Q → R: Abrogates RNA cleavage. Binds siRNA. Ref.10

Mutagenesis

634

1

H → P or A: Abrogates RNA cleavage. Binds siRNA. Ref.10

Mutagenesis

669

1

D → A: Abrogates RNA cleavage but does not affect binding to siRNA. Ref.10 Ref.14 Ref.18

Mutagenesis

673

1

E → G: No effect on RNA cleavage. Ref.18

Mutagenesis

682

1

H → Y: No effect. Ref.10

Mutagenesis

683

1

E → G: No effect on RNA cleavage. Ref.18

Mutagenesis

700

1

P → A: Reduced protein stability. Ref.30

Mutagenesis

704

1

F → Y: No effect. Ref.10

Mutagenesis

744

1

T → Y: No effect. Ref.10

Mutagenesis

807

1

H → A or R: Abrogates RNA cleavage. Ref.18

Sequence conflict

564

1

C → W in AAF13034. Ref.5

Sequence conflict

589

1

Q → E in AAF13034. Ref.5

Sequence conflict

617

1

S → R in AAF13034. Ref.5

Sequence conflict

637

1

E → K in AAL76093. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

859

Helix Strand Turn

Details...

Beta strand

35 – 48

14

Beta strand

53 – 63

11

Helix

68 – 81

14

Helix

83 – 87

5

Beta strand

96 – 104

9

Beta strand

112 – 116

5

Beta strand

128 – 139

12

Helix

140 – 148

9

Beta strand

151 – 153

3

Helix

156 – 173

18

Beta strand

174 – 177

4

Beta strand

180 – 182

3

Beta strand

191 – 193

3

Beta strand

196 – 208

13

Beta strand

210 – 225

16

Helix

230 – 238

9

Helix

252 – 262

11

Beta strand

266 – 270

5

Beta strand

278 – 288

11

Turn

289 – 291

3

Beta strand

293 – 297

5

Beta strand

299 – 301

3

Beta strand

303 – 307

5

Helix

308 – 316

9

Beta strand

325 – 331

7

Turn

333 – 336

4

Beta strand

337 – 340

4

Helix

341 – 343

3

Beta strand

344 – 346

3

Helix

358 – 368

11

Helix

372 – 386

15

Helix

388 – 390

3

Helix

392 – 396

5

Beta strand

406 – 412

7

Beta strand

422 – 424

3

Beta strand

450 – 455

6

Turn

459 – 461

3

Helix

464 – 481

18

Beta strand

490 – 494

5

Helix

498 – 500

3

Helix

501 – 511

11

Beta strand

517 – 522

6

Helix

528 – 537

10

Turn

538 – 540

3

Beta strand

544 – 548

5

Helix

549 – 553

5

Helix

557 – 571

15

Helix

585 – 588

4

Beta strand

591 – 599

9

Beta strand

610 – 617

8

Beta strand

619 – 622

4

Beta strand

625 – 633

9

Helix

642 – 657

16

Beta strand

662 – 670

9

Helix

673 – 675

3

Helix

676 – 694

19

Beta strand

701 – 708

8

Beta strand

715 – 719

5

Helix

720 – 722

3

Turn

725 – 728

4

Beta strand

734 – 736

3

Beta strand

738 – 741

4

Beta strand

743 – 745

3

Beta strand

747 – 751

5

Beta strand

763 – 770

8

Helix

776 – 786

11

Beta strand

793 – 795

3

Helix

801 – 817

17

Helix

842 – 845

4

Helix

850 – 853

4

Turn

854 – 858

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 3. Checksum: 5C8552C43FC81345	FASTA	859	97,208
	10 20 30 40 50 60 MYSGAGPALA PPAPPPPIQG YAFKPPPRPD FGTSGRTIKL QANFFEMDIP KIDIYHYELD 70 80 90 100 110 120 IKPEKCPRRV NREIVEHMVQ HFKTQIFGDR KPVFDGRKNL YTAMPLPIGR DKVELEVTLP 130 140 150 160 170 180 GEGKDRIFKV SIKWVSCVSL QALHDALSGR LPSVPFETIQ ALDVVMRHLP SMRYTPVGRS 190 200 210 220 230 240 FFTASEGCSN PLGGGREVWF GFHQSVRPSL WKMMLNIDVS ATAFYKAQPV IEFVCEVLDF 250 260 270 280 290 300 KSIEEQQKPL TDSQRVKFTK EIKGLKVEIT HCGQMKRKYR VCNVTRRPAS HQTFPLQQES 310 320 330 340 350 360 GQTVECTVAQ YFKDRHKLVL RYPHLPCLQV GQEQKHTYLP LEVCNIVAGQ RCIKKLTDNQ 370 380 390 400 410 420 TSTMIRATAR SAPDRQEEIS KLMRSASFNT DPYVREFGIM VKDEMTDVTG RVLQPPSILY 430 440 450 460 470 480 GGRNKAIATP VQGVWDMRNK QFHTGIEIKV WAIACFAPQR QCTEVHLKSF TEQLRKISRD 490 500 510 520 530 540 AGMPIQGQPC FCKYAQGADS VEPMFRHLKN TYAGLQLVVV ILPGKTPVYA EVKRVGDTVL 550 560 570 580 590 600 GMATQCVQMK NVQRTTPQTL SNLCLKINVK LGGVNNILLP QGRPPVFQQP VIFLGADVTH 610 620 630 640 650 660 PPAGDGKKPS IAAVVGSMDA HPNRYCATVR VQQHRQEIIQ DLAAMVRELL IQFYKSTRFK 670 680 690 700 710 720 PTRIIFYRDG VSEGQFQQVL HHELLAIREA CIKLEKDYQP GITFIVVQKR HHTRLFCTDK 730 740 750 760 770 780 NERVGKSGNI PAGTTVDTKI THPTEFDFYL CSHAGIQGTS RPSHYHVLWD DNRFSSDELQ 790 800 810 820 830 840 ILTYQLCHTY VRCTRSVSIP APAYYAHLVA FRARYHLVDK EHDSAEGSHT SGQSNGRDHQ 850 ALAKAVQVHQ DTLRTMYFA
	Isoform 2 [UniParc]. Checksum: 464C15B9413608D4	FASTA	825	93,620
	10 20 30 40 50 60 MYSGAGPALA PPAPPPPIQG YAFKPPPRPD FGTSGRTIKL QANFFEMDIP KIDIYHYELD 70 80 90 100 110 120 IKPEKCPRRV NREIVEHMVQ HFKTQIFGDR KPVFDGRKNL YTAMPLPIGR DKVELEVTLP 130 140 150 160 170 180 GEGKDRIFKV SIKWVSCVSL QALHDALSGR LPSVPFETIQ ALDVVMRHLP SMRYTPVGRS 190 200 210 220 230 240 FFTASEGCSN PLGGGREVWF GFHQSVRPSL WKMMLNIDVS ATAFYKAQPV IEFVCEVLDF 250 260 270 280 290 300 KSIEEQQKPL TDSQRVKFTK EIKGLKVEIT HCGQMKRKYR VCNVTRRPAS HQTFPLQQES 310 320 330 340 350 360 GQTVECTVAQ YFKDRHKLVL RYPHLPCLQV GQEQKHTYLP LEVCNIVAGQ RCIKKLTDNQ 370 380 390 400 410 420 TSTMIRATAR SAPDRQEEIS KLMRSASFNT DPYVREFGIM VKDEMTDVTG RVLQPPSILY 430 440 450 460 470 480 GGRNKAIATP VQGVWDMRNK QFHTGIEIKV WAIACFAPQR QCTEVHLKSF TEQLRKISRD 490 500 510 520 530 540 AGMPIQGQPC FCKYAQGADS VEPMFRHLKN TYAGLQLVVV ILPGKTPVYA EVKRVGDTVL 550 560 570 580 590 600 GMATQCVQMK NVQRTTPQTL SNLCLKINVK LGGVNNILLP QGRPPVFQQP VIFLGADVTH 610 620 630 640 650 660 PPAGDGKKPS IAAVVGSMDA HPNRYCATVR VQQHRQEIIQ DLAAMVRELL IQFYKSTRFK 670 680 690 700 710 720 PTRIIFYRDG VSEGQFQQVL HHELLAIREA CIKLEKDYQP GITFIVVQKR HHTRLFCTDK 730 740 750 760 770 780 NERGTSRPSH YHVLWDDNRF SSDELQILTY QLCHTYVRCT RSVSIPAPAY YAHLVAFRAR 790 800 810 820 YHLVDKEHDS AEGSHTSGQS NGRDHQALAK AVQVHQDTLR TMYFA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 239-859 (ISOFORM 1). Tissue: Brain and Eye.
[3]	"miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs." Mourelatos Z., Dostie J., Paushkin S., Sharma A., Charroux B., Abel L., Rappsilber J., Mann M., Dreyfuss G. Genes Dev. 16:720-728(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 47-859 (ISOFORM 1).
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 275-859 (ISOFORM 1).
[5]	"Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence, genomic organization, localization to chromosomal bands 1p34-p35, and expression." Koesters R., Adams V., Betts D., Moos R., Schmid M., Siermann A., Hassam S., Weitz S., Lichter P., Heitz P.U., von Knebel Doeberitz M., Briner J. Genomics 61:210-218(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 483-859 (ISOFORM 1).
[6]	"Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer." Tahbaz N., Kolb F.A., Zhang H., Jaronczyk K., Filipowicz W., Hobman T.C. EMBO Rep. 5:189-194(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DICER1.
[7]	"RISC is a 5' phosphomonoester-producing RNA endonuclease." Martinez J., Tuschl T. Genes Dev. 18:975-980(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[8]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GEMIN4.
[10]	"Argonaute2 is the catalytic engine of mammalian RNAi." Liu J., Carmell M.A., Rivas F.V., Marsden C.G., Thomson J.M., Song J.-J., Hammond S.M., Joshua-Tor L., Hannon G.J. Science 305:1437-1441(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF LEU-140; ASP-597; GLN-633; HIS-634; ASP-669; HIS-682; PHE-704 AND THR-744.
[11]	"Human RISC couples microRNA biogenesis and posttranscriptional gene silencing." Gregory R.I., Chendrimada T.P., Cooch N., Shiekhattar R. Cell 123:631-640(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DICER1 AND TARBP2.
[12]	"Identification of novel argonaute-associated proteins." Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H., Luehrmann R., Tuschl T. Curr. Biol. 15:2149-2155(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DDX20; DICER1; GEMIN4; MOV10; PRMT5 AND TNRC6B, SUBCELLULAR LOCATION.
[13]	"TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing." Haase A.D., Jaskiewicz L., Zhang H., Laine S., Sack R., Gatignol A., Filipowicz W. EMBO Rep. 6:961-967(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"A human, ATP-independent, RISC assembly machine fueled by pre-miRNA." Maniataki E., Mourelatos Z. Genes Dev. 19:2979-2990(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DICER1 AND TARBP2, MUTAGENESIS OF ASP-669.
[15]	"Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein." Ma J.-B., Yuan Y.-R., Meister G., Pei Y., Tuschl T., Patel D.J. Nature 434:666-670(2005) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-533; GLN-545 AND LYS-570.
[16]	"TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing." Chendrimada T.P., Gregory R.I., Kumaraswamy E., Norman J., Cooch N., Nishikura K., Shiekhattar R. Nature 436:740-744(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DICER1 AND TARBP2.
[17]	"Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies." Sen G.L., Blau H.M. Nat. Cell Biol. 7:633-636(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[18]	"Purified Argonaute2 and an siRNA form recombinant human RISC." Rivas F.V., Tolia N.H., Song J.-J., Aragon J.P., Liu J., Hannon G.J., Joshua-Tor L. Nat. Struct. Mol. Biol. 12:340-349(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-597; ASP-669; GLU-673; GLU-683 AND HIS-807.
[19]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DCP1A AND XRN1, SUBCELLULAR LOCATION.
[20]	"Involvement of AGO1 and AGO2 in mammalian transcriptional silencing." Janowski B.A., Huffman K.E., Schwartz J.C., Ram R., Nordsell R., Shames D.S., Minna J.D., Corey D.R. Nat. Struct. Mol. Biol. 13:787-792(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[21]	"Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54." Chu C.-Y., Rana T.M. PLoS Biol. 4:E210-E210(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DDX6 AND EIF2C1, SUBCELLULAR LOCATION.
[22]	"Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies." Wichroski M.J., Robb G.B., Rana T.M. PLoS Pathog. 2:E41-E41(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APOBEC3G.
[23]	"AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2." Vasudevan S., Steitz J.A. Cell 128:1105-1118(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FXR1, SUBCELLULAR LOCATION.
[24]	"An mRNA m7G cap binding-like motif within human Ago2 represses translation." Kiriakidou M., Tan G.S., Lamprinaki S., De Planell-Saguer M., Nelson P.T., Mourelatos Z. Cell 129:1141-1151(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF PHE-470 AND PHE-505.
[25]	"Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells." Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M., Urlaub H., Meister G. EMBO Rep. 8:1052-1060(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ASSOCIATION WITH POLYSOMES AND MNRP, INTERACTION WITH DDB1; DDX5; DHX30; DHX36; DDX47; ELAVL1; HNRNPF; IGF2BP1; ILF3; MATR3; PABPC1; RBM4; SART3; UPF1 AND YBX1.
[26]	"RNA helicase A interacts with RISC in human cells and functions in RISC loading." Robb G.B., Rana T.M. Mol. Cell 26:523-537(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DHX9.
[27]	"MicroRNA silencing through RISC recruitment of eIF6." Chendrimada T.P., Finn K.J., Ji X., Baillat D., Gregory R.I., Liebhaber S.A., Pasquinelli A.E., Shiekhattar R. Nature 447:823-828(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH DICER1; EIF6; MOV10 AND TARBP2, ASSOCIATION WITH THE 60S RIBOSOME.
[28]	"Switching from repression to activation: microRNAs can up-regulate translation." Vasudevan S., Tong Y., Steitz J.A. Science 318:1931-1934(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[29]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-597.
[30]	"Prolyl 4-hydroxylation regulates Argonaute 2 stability." Qi H.H., Ongusaha P.P., Myllyharju J., Cheng D., Pakkanen O., Shi Y., Lee S.W., Peng J., Shi Y. Nature 455:421-424(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DICER1; P4HA1; P4HB; TNRC6A AND TNRC6B, SUBCELLULAR LOCATION, HYDROXYLATION AT PRO-700, MUTAGENESIS OF PRO-700.
[31]	"In vitro reconstitution of the human RISC-loading complex." MacRae I.J., Ma E., Zhou M., Robinson C.V., Doudna J.A. Proc. Natl. Acad. Sci. U.S.A. 105:512-517(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DICER1 AND TARBP2.
[32]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH IMP8, SUBCELLULAR LOCATION.
[33]	"RNA-binding motif protein 4 translocates to cytoplasmic granules and suppresses translation via argonaute2 during muscle cell differentiation." Lin J.C., Tarn W.Y. J. Biol. Chem. 284:34658-34665(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RBM4.
[34]	"LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing." James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M., Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J., Longmore G.D., Bushell M., Sharp T.V. Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH LIMD1; WTIP AND AJUBA.
[35]	"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].
[36]	"APOBEC3G inhibits microRNA-mediated repression of translation by interfering with the interaction between Argonaute-2 and MOV10." Liu C., Zhang X., Huang F., Yang B., Li J., Liu B., Luo H., Zhang P., Zhang H. J. Biol. Chem. 287:29373-29383(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MOV10.
[37]	"HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies." Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H. J. Virol. 86:11712-11724(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH APOBEC3A; APOBEC3C; APOBEC3F; APOBEC3G AND APOBEC3H.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AC067931 Genomic DNA. No translation available.
AC107375 Genomic DNA. No translation available.
BC007633 mRNA. Translation: AAH07633.1. Different initiation.
BC018727 mRNA. Translation: AAH18727.2.
BC125214 mRNA. No translation available.
AY077717 mRNA. Translation: AAL76093.1. Sequence problems.
BT007229 mRNA. Translation: AAP35893.1.
AF121255 mRNA. Translation: AAF13034.2.

IPI

IPI00745433.
IPI00929290.

RefSeq

NP_001158095.1. NM_001164623.1.
NP_036286.2. NM_012154.3.

UniGene

Hs.449415.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LUC	X-ray	1.69	A/B/C	439-575	[»]
3LUD	X-ray	2.10	A/B/C	439-575	[»]
3LUG	X-ray	1.85	A/B/C	439-575	[»]
3LUH	X-ray	2.00	A/B/C	439-575	[»]
3LUJ	X-ray	1.80	A/B/C	439-575	[»]
3LUK	X-ray	1.70	A/B/C	439-575	[»]
3QX8	X-ray	2.30	A/B/C	439-575	[»]
3QX9	X-ray	2.00	A/B/C	439-575	[»]
4EI1	X-ray	2.30	A	1-859	[»]
4EI3	X-ray	2.89	A	1-859	[»]
4F3T	X-ray	2.25	A	1-859	[»]

ProteinModelPortal

Q9UKV8.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29194N.

IntAct

Q9UKV8. 21 interactions.

MINT

MINT-1957975.

PTM databases

PhosphoSite

Q9UKV8.

Polymorphism databases

DMDM

229463006.

Proteomic databases

PaxDb

Q9UKV8.

PRIDE

Q9UKV8.

Protocols and materials databases

DNASU

27161.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000220592; ENSP00000220592; ENSG00000123908.
ENST00000519980; ENSP00000430176; ENSG00000123908.

GeneID

27161.

KEGG

hsa:27161.

UCSC

uc003yvn.3. human.
uc010meo.3. human.

Organism-specific databases

CTD

27161.

GeneCards

GC08M141541.

HGNC

HGNC:3263. EIF2C2.

HPA

CAB019309.

MIM

606229. gene.

neXtProt

NX_Q9UKV8.

PharmGKB

PA27694.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG279895.

HOGENOM

HOG000116043.

InParanoid

Q9UKV8.

KO

K11593.

OMA

AIKWMSC.

OrthoDB

EOG4229J0.

PhylomeDB

Q9UKV8.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q9UKV8.

Bgee

Q9UKV8.

CleanEx

HS_EIF2C2.

Genevestigator

Q9UKV8.

GermOnline

ENSG00000123908. Homo sapiens.

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...

Other

ChiTaRS

EIF2C2. human.

EvolutionaryTrace

Q9UKV8.

GenomeRNAi

27161.

NextBio

49946.

SOURCE

Search...

Entry information

Entry name

AGO2_HUMAN

Accession

Primary (citable) accession number: Q9UKV8
Secondary accession number(s): Q8TCZ5, Q8WV58, Q96ID1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 117 of the entry and version 3 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.