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Protein

TRAF family member-associated NF-kappa-B activator

Gene

TANK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Adapter protein involved in I-kappa-B-kinase (IKK) regulation which constitutively binds TBK1 and IKBKE playing a role in antiviral innate immunity. Acts as a regulator of TRAF function by maintaining them in a latent state. Blocks TRAF2 binding to LMP1 and inhibits LMP1-mediated NF-kappa-B activation. Negatively regulates NF-kappaB signaling and cell survival upon DNA damage (PubMed:25861989). Plays a role as an adapter to assemble ZC3H12A, USP10 in a deubiquitination complex which plays a negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Promotes UBP10-induced deubiquitination of TRAF6 in response to DNA damage (PubMed:25861989). May control negatively TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri394 – 420C2H2-typeAdd BLAST27

GO - Molecular functioni

  • deubiquitinase activator activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processDNA damage, Host-virus interaction
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7
R-HSA-933541 TRAF6 mediated IRF7 activation
R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
SignaLinkiQ92844

Names & Taxonomyi

Protein namesi
Recommended name:
TRAF family member-associated NF-kappa-B activator
Alternative name(s):
TRAF-interacting protein
Short name:
I-TRAF
Gene namesi
Name:TANK
Synonyms:ITRAF, TRAF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000136560.13
HGNCiHGNC:11562 TANK
MIMi603893 gene
neXtProtiNX_Q92844

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi182Q → A: Abolishes interaction with TRAF2 and TRAF3. 1 Publication1
Mutagenesisi184T → A: Abolishes interaction with TRAF2 and TRAF3. 1 Publication1
Mutagenesisi185D → A: Abolishes interaction with TRAF2; greatly diminishes interaction with TRAF3. 1 Publication1
Mutagenesisi188D → A: Diminishes interaction with TRAF2 and TRAF3. 1 Publication1
Mutagenesisi194F → A: Diminishes interaction with TRAF2 and TRAF3. 1 Publication1

Organism-specific databases

DisGeNETi10010
OpenTargetsiENSG00000136560
PharmGKBiPA36330

Polymorphism and mutation databases

BioMutaiTANK
DMDMi143811466

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000724271 – 425TRAF family member-associated NF-kappa-B activatorAdd BLAST425

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei126PhosphoserineCombined sources1
Modified residuei129PhosphoserineCombined sources1
Modified residuei178PhosphoserineCombined sources1
Modified residuei208PhosphoserineCombined sources1
Modified residuei213PhosphothreonineCombined sources1
Modified residuei225PhosphoserineCombined sources1
Modified residuei228PhosphoserineCombined sources1
Modified residuei341PhosphoserineCombined sources1
Modified residuei354PhosphoserineCombined sources1
Modified residuei357PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by IKBKE.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ92844
MaxQBiQ92844
PaxDbiQ92844
PeptideAtlasiQ92844
PRIDEiQ92844
ProteomicsDBi75537
75538 [Q92844-2]
75539 [Q92844-3]

PTM databases

iPTMnetiQ92844
PhosphoSitePlusiQ92844

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000136560 Expressed in 232 organ(s), highest expression level in bone marrow
CleanExiHS_TANK
HS_TRAF2
ExpressionAtlasiQ92844 baseline and differential
GenevisibleiQ92844 HS

Organism-specific databases

HPAiCAB010345
HPA037675
HPA037676

Interactioni

Subunit structurei

Homodimer. Found in a deubiquitination complex with TANK, USP10 and ZC3H12A; this complex inhibits genotoxic stress- or interleukin-1-beta-mediated NF-kappaB activation by promoting IKBKG or TRAF6 deubiquitination (PubMed:25861989). Interacts with IKBKG; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with TRAF6; this interaction increases in response to DNA damage and recruits USP10 to the ubiquitinated TRAF6 (PubMed:25861989). Interacts with USP10; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with ZC3H12A; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with TBK1 (PubMed:10581243, PubMed:21931631). Interacts with IKBKE (PubMed:17568778). Interacts also with TRAF1, TRAF2, and TRAF3 by binding to their TRAF-C domains; the interaction with TRAF2 is disrupted by the phosphorylation of TANK by IKBKE (PubMed:10759890, PubMed:12005438). Interacts more strongly with TRAF1 and TRAF2 than TRAF3 (PubMed:10759890, PubMed:12005438). Interacts with IKBKG; the interaction is enhanced by IKBKE and TBK1 (PubMed:12133833). Part of a ternary complex consisting of TANK, IKBKB and IKBKG (PubMed:12133833).7 Publications
(Microbial infection) Interacts with vaccinia virus protein C6 (PubMed:21931555).1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115328, 48 interactors
CORUMiQ92844
DIPiDIP-27516N
IntActiQ92844, 38 interactors
MINTiQ92844
STRINGi9606.ENSP00000259075

Structurei

Secondary structure

1425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ92844
SMRiQ92844
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92844

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 31Necessary for interaction with ZC3H12A1 PublicationAdd BLAST31
Regioni70 – 191Necessary for interaction with TRAF61 PublicationAdd BLAST122
Regioni133 – 172Interaction with TBK1 and IKBKEBy similarityAdd BLAST40
Regioni172 – 191TRAF family member interactionAdd BLAST20

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili22 – 62Sequence analysisAdd BLAST41

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri394 – 420C2H2-typeAdd BLAST27

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IGRF Eukaryota
ENOG410Y7D3 LUCA
GeneTreeiENSGT00390000008712
HOGENOMiHOG000231816
HOVERGENiHBG019299
InParanoidiQ92844
KOiK12650
OMAiNVKFPPT
OrthoDBiEOG091G0A8P
PhylomeDBiQ92844
TreeFamiTF336453

Family and domain databases

InterProiView protein in InterPro
IPR024581 TBD
PfamiView protein in Pfam
PF12845 TBD, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 12 potential isoforms that are computationally mapped.iShow all

Isoform Long (identifier: Q92844-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MDKNIGEQLN KAYEAFRQAC MDRDSAVKEL QQKTENYEQR IREQQEQLSL
60 70 80 90 100
QQTIIDKLKS QLLLVNSTQD NNYGCVPLLE DSETRKNNLT LDQPQDKVIS
110 120 130 140 150
GIAREKLPKV RRQEVSSPRK ETSARSLGSP LLHERGNIEK TFWDLKEEFH
160 170 180 190 200
KICMLAKAQK DHLSKLNIPD TATETQCSVP IQCTDKTDKQ EALFKPQAKD
210 220 230 240 250
DINRGAPSIT SVTPRGLCRD EEDTSFESLS KFNVKFPPMD NDSTFLHSTP
260 270 280 290 300
ERPGILSPAT SEAVCQEKFN MEFRDNPGNF VKTEETLFEI QGIDPIASAI
310 320 330 340 350
QNLKTTDKTK PSNLVNTCIR TTLDRAACLP PGDHNALYVN SFPLLDPSDA
360 370 380 390 400
PFPSLDSPGK AIRGPQQPIW KPFPNQDSDS VVLSGTDSEL HIPRVCEFCQ
410 420
AVFPPSITSR GDFLRHLNSH FNGET
Length:425
Mass (Da):47,816
Last modified:April 3, 2007 - v2
Checksum:i718D30CF03EB27FF
GO
Isoform Short (identifier: Q92844-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     111-117: RRQEVSS → DIASAES
     118-425: Missing.

Note: No experimental confirmation available.
Show »
Length:117
Mass (Da):13,426
Checksum:i22A8BEC63333011C
GO
Isoform 3 (identifier: Q92844-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     111-119: RRQEVSSPR → DIASAESSI
     120-425: Missing.

Note: No experimental confirmation available.
Show »
Length:119
Mass (Da):13,626
Checksum:i61E5B2A8BEC63333
GO

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EQA9E7EQA9_HUMAN
TRAF family member-associated NF-ka...
TANK
408Annotation score:
E7EVA2E7EVA2_HUMAN
TRAF family member-associated NF-ka...
TANK
238Annotation score:
E7EW82E7EW82_HUMAN
TRAF family member-associated NF-ka...
TANK
239Annotation score:
E7ENY2E7ENY2_HUMAN
TRAF family member-associated NF-ka...
TANK
190Annotation score:
E7EV32E7EV32_HUMAN
TRAF family member-associated NF-ka...
TANK
138Annotation score:
E7EWR8E7EWR8_HUMAN
TRAF family member-associated NF-ka...
TANK
105Annotation score:
E7EMT6E7EMT6_HUMAN
TRAF family member-associated NF-ka...
TANK
165Annotation score:
E7EM55E7EM55_HUMAN
TRAF family member-associated NF-ka...
TANK
125Annotation score:
E7ERM9E7ERM9_HUMAN
TRAF family member-associated NF-ka...
TANK
128Annotation score:
H7C3L4H7C3L4_HUMAN
TRAF family member-associated NF-ka...
TANK
275Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti83E → D in AAC50681 (PubMed:8710854).Curated1
Sequence conflicti88N → T in AAC50681 (PubMed:8710854).Curated1
Sequence conflicti92D → A in AAC50681 (PubMed:8710854).Curated1
Sequence conflicti142F → S in AAC50681 (PubMed:8710854).Curated1
Sequence conflicti195K → T in AAC50681 (PubMed:8710854).Curated1
Sequence conflicti226F → L in AAC50681 (PubMed:8710854).Curated1
Sequence conflicti303L → P in AAC50770 (PubMed:8855313).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051409292G → R. Corresponds to variant dbSNP:rs10183668Ensembl.1
Natural variantiVAR_051410358P → L. Corresponds to variant dbSNP:rs2229759Ensembl.1
Natural variantiVAR_051411394R → Q. Corresponds to variant dbSNP:rs3769969Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043702111 – 119RRQEVSSPR → DIASAESSI in isoform 3. 1 Publication9
Alternative sequenceiVSP_004442111 – 117RRQEVSS → DIASAES in isoform Short. 1 Publication7
Alternative sequenceiVSP_004443118 – 425Missing in isoform Short. 1 PublicationAdd BLAST308
Alternative sequenceiVSP_043703120 – 425Missing in isoform 3. 1 PublicationAdd BLAST306

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U59863 mRNA Translation: AAC50681.1
U63830 mRNA Translation: AAC50770.1
BT009855 mRNA Translation: AAP88857.1
AC009299 Genomic DNA No translation available.
AC009313 Genomic DNA No translation available.
CH471058 Genomic DNA Translation: EAX11374.1
CH471058 Genomic DNA Translation: EAX11375.1
CH471058 Genomic DNA Translation: EAX11377.1
BC003388 mRNA Translation: AAH03388.1
CCDSiCCDS2215.1 [Q92844-1]
CCDS46436.1 [Q92844-3]
RefSeqiNP_001186064.1, NM_001199135.1 [Q92844-1]
NP_004171.2, NM_004180.2 [Q92844-1]
NP_597841.1, NM_133484.1 [Q92844-3]
XP_016858585.1, XM_017003096.1 [Q92844-1]
XP_016858586.1, XM_017003097.1 [Q92844-1]
UniGeneiHs.132257

Genome annotation databases

EnsembliENST00000259075; ENSP00000259075; ENSG00000136560 [Q92844-1]
ENST00000392749; ENSP00000376505; ENSG00000136560 [Q92844-1]
ENST00000403609; ENSP00000385983; ENSG00000136560 [Q92844-3]
GeneIDi10010
KEGGihsa:10010
UCSCiuc002ubr.3 human [Q92844-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U59863 mRNA Translation: AAC50681.1
U63830 mRNA Translation: AAC50770.1
BT009855 mRNA Translation: AAP88857.1
AC009299 Genomic DNA No translation available.
AC009313 Genomic DNA No translation available.
CH471058 Genomic DNA Translation: EAX11374.1
CH471058 Genomic DNA Translation: EAX11375.1
CH471058 Genomic DNA Translation: EAX11377.1
BC003388 mRNA Translation: AAH03388.1
CCDSiCCDS2215.1 [Q92844-1]
CCDS46436.1 [Q92844-3]
RefSeqiNP_001186064.1, NM_001199135.1 [Q92844-1]
NP_004171.2, NM_004180.2 [Q92844-1]
NP_597841.1, NM_133484.1 [Q92844-3]
XP_016858585.1, XM_017003096.1 [Q92844-1]
XP_016858586.1, XM_017003097.1 [Q92844-1]
UniGeneiHs.132257

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KZZX-ray3.50B177-187[»]
1L0AX-ray2.90B178-195[»]
5H10X-ray3.21D/E/F178-185[»]
ProteinModelPortaliQ92844
SMRiQ92844
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115328, 48 interactors
CORUMiQ92844
DIPiDIP-27516N
IntActiQ92844, 38 interactors
MINTiQ92844
STRINGi9606.ENSP00000259075

PTM databases

iPTMnetiQ92844
PhosphoSitePlusiQ92844

Polymorphism and mutation databases

BioMutaiTANK
DMDMi143811466

Proteomic databases

EPDiQ92844
MaxQBiQ92844
PaxDbiQ92844
PeptideAtlasiQ92844
PRIDEiQ92844
ProteomicsDBi75537
75538 [Q92844-2]
75539 [Q92844-3]

Protocols and materials databases

DNASUi10010
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259075; ENSP00000259075; ENSG00000136560 [Q92844-1]
ENST00000392749; ENSP00000376505; ENSG00000136560 [Q92844-1]
ENST00000403609; ENSP00000385983; ENSG00000136560 [Q92844-3]
GeneIDi10010
KEGGihsa:10010
UCSCiuc002ubr.3 human [Q92844-1]

Organism-specific databases

CTDi10010
DisGeNETi10010
EuPathDBiHostDB:ENSG00000136560.13
GeneCardsiTANK
HGNCiHGNC:11562 TANK
HPAiCAB010345
HPA037675
HPA037676
MIMi603893 gene
neXtProtiNX_Q92844
OpenTargetsiENSG00000136560
PharmGKBiPA36330
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGRF Eukaryota
ENOG410Y7D3 LUCA
GeneTreeiENSGT00390000008712
HOGENOMiHOG000231816
HOVERGENiHBG019299
InParanoidiQ92844
KOiK12650
OMAiNVKFPPT
OrthoDBiEOG091G0A8P
PhylomeDBiQ92844
TreeFamiTF336453

Enzyme and pathway databases

ReactomeiR-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7
R-HSA-933541 TRAF6 mediated IRF7 activation
R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
SignaLinkiQ92844

Miscellaneous databases

ChiTaRSiTANK human
EvolutionaryTraceiQ92844
GeneWikiiTANK_(gene)
GenomeRNAii10010
PROiPR:Q92844
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136560 Expressed in 232 organ(s), highest expression level in bone marrow
CleanExiHS_TANK
HS_TRAF2
ExpressionAtlasiQ92844 baseline and differential
GenevisibleiQ92844 HS

Family and domain databases

InterProiView protein in InterPro
IPR024581 TBD
PfamiView protein in Pfam
PF12845 TBD, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTANK_HUMAN
AccessioniPrimary (citable) accession number: Q92844
Secondary accession number(s): D3DPB5, Q7Z4J6, Q92885
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: April 3, 2007
Last modified: September 12, 2018
This is version 181 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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