TNR6A_MOUSE
ID TNR6A_MOUSE Reviewed; 1896 AA.
AC Q3UHK8; F6ZMJ4;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2018, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Trinucleotide repeat-containing gene 6A protein;
GN Name=Tnrc6a; Synonyms=Kiaa1460;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=22187428; DOI=10.1074/jbc.m111.297937;
RA Jiang Z., Yu N., Kuang P., Chen M., Shao F., Martin G., Chui D.H.,
RA Cardoso W.V., Ai X., Lue J.;
RT "Trinucleotide repeat containing 6a (Tnrc6a)-mediated microRNA function is
RT required for development of yolk sac endoderm.";
RL J. Biol. Chem. 287:5979-5987(2012).
CC -!- FUNCTION: Plays a role in RNA-mediated gene silencing by both micro-
CC RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:22187428).
CC Required for miRNA-dependent repression of translation and for siRNA-
CC dependent endonucleolytic cleavage of complementary mRNAs by argonaute
CC family proteins (PubMed:22187428). As a scaffolding protein, associates
CC with argonaute proteins bound to partially complementary mRNAs, and can
CC simultaneously recruit CCR4-NOT and PAN deadenylase complexes (By
CC similarity). {ECO:0000250|UniProtKB:Q8NDV7,
CC ECO:0000269|PubMed:22187428}.
CC -!- SUBUNIT: Interacts with AGO2. Interacts with AGO1, AGO3 and AGO4.
CC Interacts with CNOT1; the interaction is direct and mediates the
CC association with the CCR4-NOT complex. Interacts with ZC3H12A.
CC Interacts with SND1. Interacts with GARRE1 (By similarity).
CC {ECO:0000250|UniProtKB:Q8NDV7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000250|UniProtKB:Q8NDV7}.
CC Note=Mammalian P-bodies are also known as GW bodies (GWBs).
CC {ECO:0000250|UniProtKB:Q8NDV7}.
CC -!- DEVELOPMENTAL STAGE: Detected in the yolk sac endoderm at embryonic
CC stage 9.5 dpc. {ECO:0000269|PubMed:22187428}.
CC -!- DISRUPTION PHENOTYPE: Development up until embryonic stage 9.5 dpc is
CC normal. After this point, mortality rates increase rapidly with less
CC than 5% survival at stage 12.5 dpc. The yolk sac endoderm is abnormally
CC thin with fewer mitotic cells. In addition there are fewer blood
CC islands in the yolk sac, associated with impaired hematopoiesis.
CC Expression of many miRNA-regulated genes in the yolk sac is abnormal,
CC and in particular there is marked derepression of genes involved in
CC regulation of apoptosis and the cell cycle. miRNA biogenesis is not
CC affected. {ECO:0000269|PubMed:22187428}.
CC -!- SIMILARITY: Belongs to the GW182 family. {ECO:0000305}.
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DR EMBL; AK147327; BAE27849.1; -; mRNA.
DR EMBL; AC138364; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC141887; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS57583.1; -.
DR RefSeq; NP_659174.3; NM_144925.3.
DR PDB; 5UMZ; X-ray; 1.90 A; D/E=1164-1172.
DR PDBsum; 5UMZ; -.
DR AlphaFoldDB; Q3UHK8; -.
DR SMR; Q3UHK8; -.
DR BioGRID; 231455; 6.
DR DIP; DIP-60538N; -.
DR IntAct; Q3UHK8; 3.
DR STRING; 10090.ENSMUSP00000091595; -.
DR iPTMnet; Q3UHK8; -.
DR PhosphoSitePlus; Q3UHK8; -.
DR EPD; Q3UHK8; -.
DR MaxQB; Q3UHK8; -.
DR PaxDb; Q3UHK8; -.
DR PRIDE; Q3UHK8; -.
DR ProteomicsDB; 258945; -.
DR Antibodypedia; 12719; 122 antibodies from 23 providers.
DR DNASU; 233833; -.
DR Ensembl; ENSMUST00000094053; ENSMUSP00000091595; ENSMUSG00000052707.
DR GeneID; 233833; -.
DR KEGG; mmu:233833; -.
DR CTD; 27327; -.
DR MGI; MGI:2385292; Tnrc6a.
DR VEuPathDB; HostDB:ENSMUSG00000052707; -.
DR eggNOG; ENOG502QPQQ; Eukaryota.
DR GeneTree; ENSGT00940000158180; -.
DR InParanoid; Q3UHK8; -.
DR OMA; VMNGTSI; -.
DR OrthoDB; 50428at2759; -.
DR PhylomeDB; Q3UHK8; -.
DR TreeFam; TF329702; -.
DR Reactome; R-MMU-426496; Post-transcriptional silencing by small RNAs.
DR Reactome; R-MMU-5578749; Transcriptional regulation by small RNAs.
DR BioGRID-ORCS; 233833; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Tnrc6a; mouse.
DR PRO; PR:Q3UHK8; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q3UHK8; protein.
DR Bgee; ENSMUSG00000052707; Expressed in ciliary body and 270 other tissues.
DR ExpressionAtlas; Q3UHK8; baseline and differential.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000932; C:P-body; ISS:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:MGI.
DR GO; GO:0016442; C:RISC complex; ISS:UniProtKB.
DR GO; GO:0060090; F:molecular adaptor activity; ISS:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0009267; P:cellular response to starvation; IDA:MGI.
DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB.
DR GO; GO:0032507; P:maintenance of protein location in cell; ISS:MGI.
DR GO; GO:0035195; P:miRNA-mediated gene silencing; ISO:MGI.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; ISS:UniProtKB.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISS:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; ISS:UniProtKB.
DR CDD; cd12711; RRM_TNRC6A; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR019486; Argonaute_hook_dom.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR032226; TNRC6_PABC-bd.
DR InterPro; IPR033501; TNRC6A.
DR InterPro; IPR034924; TNRC6A_RRM.
DR PANTHER; PTHR13020:SF28; PTHR13020:SF28; 2.
DR Pfam; PF10427; Ago_hook; 1.
DR Pfam; PF16608; TNRC6-PABC_bdg; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Phosphoprotein; Reference proteome; RNA-binding;
KW RNA-mediated gene silencing; Translation regulation.
FT CHAIN 1..1896
FT /note="Trinucleotide repeat-containing gene 6A protein"
FT /id="PRO_0000373980"
FT DOMAIN 1716..1788
FT /note="RRM"
FT REGION 1..917
FT /note="Interaction with argonaute family proteins"
FT /evidence="ECO:0000250"
FT REGION 1..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 159..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..488
FT /note="Sufficient for interaction with AGO1, AGO3 and AGO4"
FT /evidence="ECO:0000250"
FT REGION 255..331
FT /note="Sufficient for interaction with AGO2"
FT /evidence="ECO:0000250"
FT REGION 257..276
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 303..384
FT /note="Sufficient for interaction with AGO2"
FT /evidence="ECO:0000250"
FT REGION 325..424
FT /note="Sufficient for interaction with AGO2"
FT /evidence="ECO:0000250"
FT REGION 394..480
FT /note="Sufficient for interaction with AGO2"
FT /evidence="ECO:0000250"
FT REGION 396..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 487..736
FT /note="Sufficient for interaction with AGO2"
FT /evidence="ECO:0000250"
FT REGION 548..683
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 551..1279
FT /note="Sufficient for interaction with AGO1 and AGO4"
FT /evidence="ECO:0000250"
FT REGION 703..998
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1011..1126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1059..1129
FT /note="Sufficient for interaction with AGO2"
FT /evidence="ECO:0000250"
FT REGION 1143..1182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1234..1256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1273..1306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1360..1395
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1512..1570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1605..1896
FT /note="Sufficient for interaction with AGO2"
FT /evidence="ECO:0000250"
FT REGION 1659..1685
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..54
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..661
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 662..683
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..722
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 734..769
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 786..935
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 967..989
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1033..1047
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1078..1105
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1143..1157
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1273..1301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1661..1675
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 724
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT MOD_RES 863
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT MOD_RES 976
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT MOD_RES 1197
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT MOD_RES 1255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT MOD_RES 1406
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT MOD_RES 1520
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT MOD_RES 1804
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT MOD_RES 1825
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NDV7"
FT CONFLICT 587
FT /note="G -> E (in Ref. 1; BAE27849)"
SQ SEQUENCE 1896 AA; 203150 MW; 58858C69497903BF CRC64;
MRELEAKATK DVERNLSRDL VQEEEQLMEE KKKKKDDKKK KEAAQKKATE QKIKVPEQIK
PSVSQPQPAN SDNGTSTATS TNNNAKRATA SNQQPPPPQQ QQPQQEQQQQ QPQALPRYPR
EVPPRFRHQE HKQLLKRGQH FPVIAANLGS AVKVLNSQSE SSAVTNQQPQ NNGEVQNSKS
QSDINHNTSG SHYENCQRGP VSSTSDCSTS CKNAVNDLLE KEAWPSAPGS DPELAPECID
ADSASNSESE RNITVMASGN TGGEKDGLRN STGLGSQSKF VVGSSSNNVG HGSSTGPWGF
PHGALISTCQ VSVDAPESKP ESSNNRMNAW GTVSSSSNGG LNPSTLNSAS NHGAWPVLEN
NGLALKGPVG SGSSGINIQC STIGQMPNNQ NINSKVSGSS THGTWGSLQE TCEPEVSGTQ
KVSFSGQPQN ITTETTGPNN TTNFMTSSLP NSGSVQNNEL PTSNPGAWRV STMNHPQIQA
PSVMNGTSLS HLSNGESKTG GSYGTTWGAY GSNYSGDKCA GPNGQANGDT VNATLMQPGI
NGPMGTNFQV NTNKGGGVWE PGTVNSQSSP WGSGNGANSG GSRRGWGSPA QNTGTGLSSV
EWNKLPSNQH SNDSANGNGK KLTNGWKSTE EDDQGSATSQ TNEQNSVWAK AGGTVESDGS
AESTGRLEEK VTGESQSRDR RKIDQHTLLQ SIVNRTDLDP RVLSNSGWGQ TPIKQNTAWD
TETSPRGERK TDNGTEAWGS SATQTFNSGA CTDKTSPNSN DTSSVSGWGD PKPTLRWGDS
KGSNCQGGWE DDSAATGMIK SNQWGGCKED KSTWNDSQKS KQGWGDGQKS SQGWSISAGD
NWGESSRSNH WGEANKKSSS GGSDSDRSIS GWNELGKTSS FTWGNNINPN NSSGWDESSK
PNSSQGWGDP PKCNQSLGWG DSSKPVSSPD WNKQQDIVGS WGIPPATSKP PGTGWLGGPI
PAPAKEEEPT GWEEPSPESI RRKMEIDDGT SAWGDPSKYN YKNVNMWNKN IPEASGRSDQ
QAQMHRLLPA ASAVSSKETS SGSGWGEPWA EPSTPATTVD NGTSAWGKPI DSGPSWGEPI
TAASNASTWG SSSVGPQSLS KSGPKSMQDG WCGDDMPLPG SRPTGWEEEE DVEIGMWNSN
SSQELNSSLN WPPYTKKMSS KGLSGKKRRR ERGMMKGGNK QEDAWINPFV KQFSNISFSR
DSPEENVQSN KMDLSGGMLQ DKRMEIDKHS LNIGDYNRTV GKGPGSRPQI SKESSMERNP
YFDKNGNPNM FGVGNTAAQP RGMQQPPAQP LSSSQPNLRA QVPPPLLSPQ VPVSLLKYAP
NNGGLNPLFG PQQVAMLNQL SQLNQLSQIS QLQRLLAQQQ RAQSQRSAPS ANRQQQDQQG
RPLSVQQQMM QQSRQLDPSL LVKQQTPPSQ QPLHQPAMKS FLDNVMPHTT PELQKGPSPV
NAFSNFPIGL NSNLNVNMDM NSIKEPQSRL RKWTTVDSMS VNTSLDQNSS KHGAISSGFR
LEESPFVPYD FMNSSTSPAS PPGSIGDGWP RAKSPNGSSS VNWPPEFRPG EPWKGYPNID
PETDPYVTPG SVINSLSINT VREVDHLRDR NSGSSSSLNT TLPSTSAWSS IRASNYNVPL
SSTAQSTSAR NSDSKLTWSP GSVTNTSLAH ELWKVPLPPK NITAPSRPPP GLTGQKPPLS
TWDNSPLRVG GGWGNSDARY TPGSSWGESS SGRITNWLVL KNLTPQIDGS TLRTLCMQHG
PLITFHLNLP HGNALVRYSS KEEVVKAQKS LHMCVLGNTT ILAEFASEEE ISRFFAQSQS
LTPSPGWQSL GSSQSRLGSL DCSHSFSSRT DVNHWNGAGL SGANCGDLHG TSLWGTPHYS
TSLWGPPSSD PRGISSPSPI NAFLSVDHLG GGGESM
