TRAF6_DANRE
ID TRAF6_DANRE Reviewed; 542 AA.
AC Q6IWL4; Q1MTB3; Q7SXX1;
DT 09-FEB-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=TNF receptor-associated factor 6;
DE EC=2.3.2.27;
DE AltName: Full=E3 ubiquitin-protein ligase TRAF6;
DE AltName: Full=RING-type E3 ubiquitin transferase TRAF6 {ECO:0000305};
GN Name=traf6; ORFNames=si:dkey-56p7.3, zgc:63704;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Phelan P.E. III, Mellon M.T., Kim C.H.;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin ligase that, together with UBE2N and UBE2V1,
CC mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains
CC conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also
CC mediates ubiquitination of free/unanchored polyubiquitin chain that
CC leads to MAP3K7 activation. {ECO:0000250|UniProtKB:Q9Y4K3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q9Y4K3};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9Y4K3}.
CC -!- SUBUNIT: Homotrimer. Homooligomer. {ECO:0000250|UniProtKB:Q9Y4K3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y4K3}.
CC Cytoplasm, cell cortex {ECO:0000250|UniProtKB:Q9Y4K3}. Nucleus
CC {ECO:0000250|UniProtKB:Q9Y4K3}. Lipid droplet
CC {ECO:0000250|UniProtKB:P70196}.
CC -!- DOMAIN: The coiled coil domain mediates homo- and hetero-
CC oligomerization. {ECO:0000250}.
CC -!- DOMAIN: The MATH/TRAF domain binds to receptor cytoplasmic domains.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TNF receptor-associated factor family. A
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY616583; AAT37634.1; -; mRNA.
DR EMBL; AL929208; CAK11108.1; -; Genomic_DNA.
DR EMBL; BC055214; AAH55214.1; -; mRNA.
DR EMBL; BC171483; AAI71483.1; -; mRNA.
DR EMBL; BC171487; AAI71487.1; -; mRNA.
DR RefSeq; NP_001038217.1; NM_001044752.1.
DR PDB; 5VNZ; X-ray; 3.41 A; A/D=50-159.
DR PDB; 5VO0; X-ray; 3.90 A; A/D=50-213.
DR PDB; 6MYD; X-ray; 1.40 A; A/C=370-525.
DR PDBsum; 5VNZ; -.
DR PDBsum; 5VO0; -.
DR PDBsum; 6MYD; -.
DR AlphaFoldDB; Q6IWL4; -.
DR SMR; Q6IWL4; -.
DR STRING; 7955.ENSDARP00000036715; -.
DR PaxDb; Q6IWL4; -.
DR Ensembl; ENSDART00000038273; ENSDARP00000036715; ENSDARG00000028058.
DR Ensembl; ENSDART00000180847; ENSDARP00000151579; ENSDARG00000028058.
DR Ensembl; ENSDART00000191675; ENSDARP00000150477; ENSDARG00000028058.
DR GeneID; 554561; -.
DR KEGG; dre:554561; -.
DR CTD; 7189; -.
DR ZFIN; ZDB-GENE-030131-5735; traf6.
DR eggNOG; KOG0297; Eukaryota.
DR GeneTree; ENSGT00940000155426; -.
DR HOGENOM; CLU_021061_5_0_1; -.
DR InParanoid; Q6IWL4; -.
DR OMA; WMQKNNQ; -.
DR OrthoDB; 918518at2759; -.
DR PhylomeDB; Q6IWL4; -.
DR TreeFam; TF321154; -.
DR Reactome; R-DRE-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR Reactome; R-DRE-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-DRE-202424; Downstream TCR signaling.
DR Reactome; R-DRE-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-DRE-209543; p75NTR recruits signalling complexes.
DR Reactome; R-DRE-209560; NF-kB is activated and signals survival.
DR Reactome; R-DRE-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-DRE-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-DRE-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-DRE-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR Reactome; R-DRE-5689896; Ovarian tumor domain proteases.
DR Reactome; R-DRE-9020702; Interleukin-1 signaling.
DR Reactome; R-DRE-937039; IRAK1 recruits IKK complex.
DR Reactome; R-DRE-937042; IRAK2 mediated activation of TAK1 complex.
DR Reactome; R-DRE-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
DR Reactome; R-DRE-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
DR Reactome; R-DRE-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR Reactome; R-DRE-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR Reactome; R-DRE-975871; MyD88 cascade initiated on plasma membrane.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q6IWL4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 7.
DR Bgee; ENSDARG00000028058; Expressed in pharyngeal gill and 23 other tissues.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
DR GO; GO:0032813; F:tumor necrosis factor receptor superfamily binding; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045087; P:innate immune response; IMP:ZFIN.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; TAS:ZFIN.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IBA:GO_Central.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:ZFIN.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IDA:ZFIN.
DR GO; GO:0009615; P:response to virus; IDA:ZFIN.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IBA:GO_Central.
DR CDD; cd03776; MATH_TRAF6; 1.
DR Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.30.40.10; -; 3.
DR InterPro; IPR002083; MATH/TRAF_dom.
DR InterPro; IPR043211; TNF_rcpt-assoc_TRAF.
DR InterPro; IPR012227; TNF_rcpt-assoc_TRAF_met.
DR InterPro; IPR008974; TRAF-like.
DR InterPro; IPR027139; TRAF6.
DR InterPro; IPR037309; TRAF6_MATH.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR InterPro; IPR001293; Znf_TRAF.
DR PANTHER; PTHR10131; PTHR10131; 1.
DR PANTHER; PTHR10131:SF131; PTHR10131:SF131; 1.
DR Pfam; PF02176; zf-TRAF; 2.
DR PIRSF; PIRSF015614; TRAF; 1.
DR SMART; SM00061; MATH; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50144; MATH; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS50145; ZF_TRAF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Lipid droplet; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Transferase; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..542
FT /note="TNF receptor-associated factor 6"
FT /id="PRO_0000391612"
FT DOMAIN 374..520
FT /note="MATH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT ZN_FING 71..110
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 151..203
FT /note="TRAF-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207"
FT ZN_FING 204..260
FT /note="TRAF-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207"
FT REGION 32..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 311..373
FT /evidence="ECO:0000255"
FT COMPBIAS 36..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 489..496
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 13
FT /note="D -> G (in Ref. 1; AAT37634)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="P -> T (in Ref. 1; AAT37634 and 3; AAH55214)"
FT /evidence="ECO:0000305"
FT CONFLICT 84
FT /note="T -> A (in Ref. 3; AAH55214)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="I -> M (in Ref. 1; AAT37634)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="N -> S (in Ref. 1; AAT37634)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="L -> S (in Ref. 1; AAT37634 and 3; AAH55214)"
FT /evidence="ECO:0000305"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:5VNZ"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:5VNZ"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:5VNZ"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:5VNZ"
FT HELIX 92..100
FT /evidence="ECO:0007829|PDB:5VNZ"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:5VNZ"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:5VNZ"
FT HELIX 122..129
FT /evidence="ECO:0007829|PDB:5VNZ"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:5VNZ"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:5VNZ"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:5VNZ"
FT HELIX 149..155
FT /evidence="ECO:0007829|PDB:5VNZ"
FT HELIX 370..373
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 376..381
FT /evidence="ECO:0007829|PDB:6MYD"
FT HELIX 384..392
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 397..400
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 404..409
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 412..419
FT /evidence="ECO:0007829|PDB:6MYD"
FT TURN 425..429
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 430..438
FT /evidence="ECO:0007829|PDB:6MYD"
FT HELIX 443..445
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 452..458
FT /evidence="ECO:0007829|PDB:6MYD"
FT TURN 461..463
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 467..472
FT /evidence="ECO:0007829|PDB:6MYD"
FT HELIX 478..480
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 484..487
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 489..499
FT /evidence="ECO:0007829|PDB:6MYD"
FT HELIX 500..506
FT /evidence="ECO:0007829|PDB:6MYD"
FT STRAND 513..521
FT /evidence="ECO:0007829|PDB:6MYD"
SQ SEQUENCE 542 AA; 61806 MW; 23CA0DAFA380B133 CRC64;
MACNDVDKSS FDDVCCDSGH SSCAAAMEKE RESFLSPTEN PSTISVSSSM PPDQQGYDVE
FDPPLESKYE CPICLMGLRS AVQTPCGHRF CDSCIRKSIR DTGQKCPVDN EVLLEEQLFP
DNFAKREILS LTVKCSNFGC SEKMELRQLE KHLSQCRFAT APCPQCQESV PISHLDEHKS
QHCLQRIMTC PDCAGSFVYA VKQNHEQFCP FANTVCEYCE MELIRDQLAL HCDTDCLKAP
VACTFSTFGC REKMTRNELA QHMQEFTQMH MRYMAEFLRS QTLNNCTMPS AAAHLSSDDR
GASARSPDSC QCKQELLNLR ETVLELEGRL VRQDQQIREL CIHNDTQKNQ VTELRRKLVS
LEESTRELEA QQYQGIYVWR VENFSHHLRN QEAGQPIVLH SPPFYTGRPG YKLCLRLHLQ
TPSAPRCSNF ISLFVHTMQG EFDSQLSWPL QGTIRLAVLD QVEGQHHIEV METKPDLQAF
QRPTVMRNPK GFGYVTFLHL QALRQRGFVK EDVLLVRCEV TPRFDASLRR EGVQPRGPEP
SI
