TANK_MOUSE
ID TANK_MOUSE Reviewed; 448 AA.
AC P70347; Q61178;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=TRAF family member-associated NF-kappa-B activator;
DE AltName: Full=TRAF-interacting protein;
DE Short=I-TRAF;
GN Name=Tank; Synonyms=Itraf;
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 [MRNA], AND ALTERNATIVE SPLICING.
RX PubMed=8710854; DOI=10.1073/pnas.93.16.8241;
RA Rothe M., Xiong J., Shu H.-B., Williamson K., Goddard A., Goeddel D.V.;
RT "I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated
RT signal transduction.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:8241-8246(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/Kaplan; TISSUE=T-cell lymphoma;
RX PubMed=8608943; DOI=10.1101/gad.10.8.963;
RA Cheng G., Baltimore D.;
RT "TANK, a co-inducer with TRAF2 of TNF- and CD 40L-mediated NF-kappaB
RT activation.";
RL Genes Dev. 10:963-973(1996).
RN [3]
RP INTERACTION WITH IKBKG.
RX PubMed=12133833; DOI=10.1074/jbc.m205069200;
RA Chariot A., Leonardi A., Muller J., Bonif M., Brown K., Siebenlist U.;
RT "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator
RT NEMO connects IKK complexes with IKK epsilon and TBK1 kinases.";
RL J. Biol. Chem. 277:37029-37036(2002).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Adapter protein involved in I-kappa-B-kinase (IKK) regulation
CC which constitutively binds TBK1 and IKBKE playing a role in antiviral
CC innate immunity. Acts as a regulator of TRAF function by maintaining
CC them in a latent state. Blocks TRAF2 binding to LMP1 and inhibits LMP1-
CC mediated NF-kappa-B activation. Negatively regulates NF-kappaB
CC signaling and cell survival upon DNA damage. Plays a role as an adapter
CC to assemble ZC3H12A, USP10 in a deubiquitination complex which plays a
CC negative feedback response to attenuate NF-kappaB activation through
CC the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-
CC beta (IL1B) stimulation or upon DNA damage. Promotes UBP10-induced
CC deubiquitination of TRAF6 in response to DNA damage. May control
CC negatively TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1
CC and TNFR2. Essential for the efficient induction of IRF-dependent
CC transcription following infection with Sendai virus.
CC {ECO:0000250|UniProtKB:Q92844}.
CC -!- SUBUNIT: Homodimer (By similarity). Found in a deubiquitination complex
CC with TANK, USP10 and ZC3H12A; this complex inhibits genotoxic
CC stress- or interleukin-1-beta-mediated NF-kappaB activation by
CC promoting IKBKG or TRAF6 deubiquitination (By similarity). Interacts
CC with IKBKG; this interaction increases in response to DNA damage (By
CC similarity). Interacts with TRAF6; this interaction increases in
CC response to DNA damage and recruits USP10 to the ubiquitinated TRAF6
CC (By similarity). Interacts with USP10; this interaction increases in
CC response to DNA damage (By similarity). Interacts with TBK1 and IKBKE
CC (By similarity). Interacts also with TRAF1, TRAF2, and TRAF3 by binding
CC to their TRAF-C domains; the interaction with TRAF2 is disrupted by the
CC phosphorylation of TANK by IKBKE (By similarity). Interacts more
CC strongly with TRAF1 and TRAF2 than TRAF3 (By similarity). Part of a
CC ternary complex consisting of TANK, IKBKB and IKBKG (By similarity).
CC Interacts with IKBKG; the interaction is enhanced by IKBKE and TBK1
CC (PubMed:12133833). {ECO:0000250|UniProtKB:Q92844,
CC ECO:0000269|PubMed:12133833}.
CC -!- INTERACTION:
CC P70347; Q9WUN2: Tbk1; NbExp=7; IntAct=EBI-646116, EBI-764193;
CC P70347-1; P39428: Traf1; NbExp=12; IntAct=EBI-646125, EBI-520123;
CC P70347-1; P39429: Traf2; NbExp=7; IntAct=EBI-646125, EBI-520016;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Beta;
CC IsoId=P70347-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha;
CC IsoId=P70347-2; Sequence=VSP_004444;
CC Name=3; Synonyms=Gamma;
CC IsoId=P70347-3; Sequence=VSP_004445, VSP_004446;
CC Name=4;
CC IsoId=P70347-4; Sequence=VSP_004447, VSP_004448;
CC -!- TISSUE SPECIFICITY: Heart, brain, spleen, lung, liver, skeletal muscle,
CC kidney and testis.
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DR EMBL; U59864; AAC52781.1; -; mRNA.
DR EMBL; U51907; AAB02204.1; -; mRNA.
DR CCDS; CCDS16061.1; -. [P70347-1]
DR CCDS; CCDS50592.1; -. [P70347-2]
DR RefSeq; NP_001157544.1; NM_001164072.1.
DR RefSeq; NP_035659.1; NM_011529.2. [P70347-1]
DR RefSeq; XP_006499151.1; XM_006499088.3.
DR RefSeq; XP_017172402.1; XM_017316913.1.
DR AlphaFoldDB; P70347; -.
DR SMR; P70347; -.
DR BioGRID; 203965; 4.
DR DIP; DIP-33701N; -.
DR IntAct; P70347; 4.
DR MINT; P70347; -.
DR STRING; 10090.ENSMUSP00000108114; -.
DR iPTMnet; P70347; -.
DR PhosphoSitePlus; P70347; -.
DR EPD; P70347; -.
DR jPOST; P70347; -.
DR MaxQB; P70347; -.
DR PaxDb; P70347; -.
DR PRIDE; P70347; -.
DR ProteomicsDB; 263006; -. [P70347-1]
DR ProteomicsDB; 263007; -. [P70347-2]
DR ProteomicsDB; 263008; -. [P70347-3]
DR ProteomicsDB; 263009; -. [P70347-4]
DR Antibodypedia; 4155; 476 antibodies from 38 providers.
DR DNASU; 21353; -.
DR Ensembl; ENSMUST00000078074; ENSMUSP00000077219; ENSMUSG00000064289. [P70347-1]
DR Ensembl; ENSMUST00000112501; ENSMUSP00000108120; ENSMUSG00000064289. [P70347-2]
DR GeneID; 21353; -.
DR KEGG; mmu:21353; -.
DR UCSC; uc008juw.2; mouse. [P70347-1]
DR CTD; 10010; -.
DR MGI; MGI:107676; Tank.
DR VEuPathDB; HostDB:ENSMUSG00000064289; -.
DR eggNOG; ENOG502QRM3; Eukaryota.
DR GeneTree; ENSGT00390000008712; -.
DR HOGENOM; CLU_053153_0_0_1; -.
DR InParanoid; P70347; -.
DR OMA; EKPTVPC; -.
DR OrthoDB; 1288111at2759; -.
DR PhylomeDB; P70347; -.
DR Reactome; R-MMU-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR BioGRID-ORCS; 21353; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Tank; mouse.
DR PRO; PR:P70347; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P70347; protein.
DR Bgee; ENSMUSG00000064289; Expressed in granulocyte and 258 other tissues.
DR ExpressionAtlas; P70347; baseline and differential.
DR Genevisible; P70347; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:MGI.
DR GO; GO:0035800; F:deubiquitinase activator activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:1903003; P:positive regulation of protein deubiquitination; ISS:UniProtKB.
DR GO; GO:2000158; P:positive regulation of ubiquitin-specific protease activity; ISS:UniProtKB.
DR InterPro; IPR041641; CALCOCO1/2_Zn_UBZ1.
DR InterPro; IPR039669; TANK.
DR InterPro; IPR024581; TBD.
DR PANTHER; PTHR15249; PTHR15249; 1.
DR Pfam; PF12845; TBD; 1.
DR PROSITE; PS51905; ZF_UBZ1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; DNA damage; Metal-binding;
KW Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..448
FT /note="TRAF family member-associated NF-kappa-B activator"
FT /id="PRO_0000072428"
FT ZN_FING 416..443
FT /note="UBZ1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT REGION 35..65
FT /note="Necessary for interaction with ZC3H12A"
FT /evidence="ECO:0000250|UniProtKB:Q92844"
FT REGION 105..224
FT /note="Necessary for interaction with TRAF6"
FT /evidence="ECO:0000250|UniProtKB:Q92844"
FT REGION 166..205
FT /note="Interaction with TBK1 and IKBKE"
FT REGION 205..224
FT /note="TRAF family member interaction"
FT COILED 60..98
FT /evidence="ECO:0000255"
FT BINDING 419
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 422
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 439
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 443
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92844"
FT MOD_RES 246
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q92844"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92844"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92844"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92844"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92844"
FT VAR_SEQ 1..34
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8608943"
FT /id="VSP_004444"
FT VAR_SEQ 238..251
FT /note="GMSCVTAVTPRGLG -> ERRVCQLETTMCSM (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004445"
FT VAR_SEQ 252..448
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004446"
FT VAR_SEQ 391..395
FT /note="PFWKP -> VTVLH (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_004447"
FT VAR_SEQ 396..448
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_004448"
FT CONFLICT 68
FT /note="Missing (in Ref. 2; AAB02204)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 448 AA; 50939 MW; 313E704C881FB5F3 CRC64;
MSLKRHSLRR NACHLETRAG IPTILYSDAT GQRGMDKNIG EQLNRAYEAF RQACMDRDSA
VRELQQKQTE NYEQRIREQQ EQLSFQQNLI DRLKSQLLLV DSSRDNSYGY VPLLEDSDRR
KNNLTLDEPH DKVKLGTLRD KQSKVRRQEV SSGKESAKGL NIPLHHERDN IEKTFWDLKE
EFHRICLLAK AQKDHLSKLN IPDIATDTQC SVPIQCTDKT EKQEALFKPQ AKDDINRGMS
CVTAVTPRGL GRDEEDTSFE SLSKFNVKFP PMDNDSIFLH STPEAPSILA PATPETVCQD
RFNMEVRDNP GNFVKTEETL FEIQGIDPIT SAIQNLKTTD KTNPSNLRAT CLPAGDHNVF
YVNTFPLQDP PDAPFPSLDS PGKAVRGPQQ PFWKPFLNQD TDLVVPSDSD SELLKPLVCE
FCQELFPPSI TSRGDFLRHL NTHFNGET
