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Protein

TRAF family member-associated NF-kappa-B activator

Gene

TANK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to interleukin-1 Source: UniProtKB
  • cellular response to ionizing radiation Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • I-kappaB kinase/NF-kappaB signaling Source: GO_Central
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of protein deubiquitination Source: UniProtKB
  • positive regulation of ubiquitin-specific protease activity Source: UniProtKB
  • proteolysis Source: GOC
  • signal transduction Source: ProtInc
  • TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

DNA damage

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136560-MONOMER.
ReactomeiR-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

HGNCiHGNC:11562. TANK.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • protein complex Source: UniProtKB
Complete GO annotation...

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.

PTM databases

iPTMnetiQ92844.
PhosphoSitePlusiQ92844.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000136560.
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

Binary interactionsi

WithEntry#Exp.IntActNotes
APBA3O960182EBI-356349,EBI-6115839
CEP63Q96MT84EBI-356349,EBI-741977
HTTP428583EBI-356349,EBI-466029
IKBKEQ141644EBI-356349,EBI-307369
NSP034952EBI-356349,EBI-2548993From a different organism.
PLK1P533503EBI-356349,EBI-476768
SRSF11Q055193EBI-356349,EBI-1051785
SUMO1P631658EBI-356349,EBI-80140
SUMO2P619563EBI-356349,EBI-473220
TBK1Q9UHD27EBI-356349,EBI-356402
TP53BP2Q13625-33EBI-356349,EBI-10175039
TRAF2Q129334EBI-356349,EBI-355744
TRAF3Q131144EBI-356349,EBI-357631
VACWR022P173622EBI-356349,EBI-9519257From a different organism.

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115328. 46 interactors.
DIPiDIP-27516N.
IntActiQ92844. 38 interactors.
MINTiMINT-111947.
STRINGi9606.ENSP00000259075.

Structurei

Secondary structure

1425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi191 – 193Combined sources3

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[»]
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

Sequence similaritiesi

Contains 1 C2H2-type zinc finger.Curated

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

InterProiIPR024581. TBD.
[Graphical view]
PfamiPF12845. TBD. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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 rs10183668dbSNPEnsembl.1
Natural variantiVAR_051410358P → L.Corresponds to variant rs2229759dbSNPEnsembl.1
Natural variantiVAR_051411394R → Q.Corresponds to variant rs3769969dbSNPEnsembl.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

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[»]
ProteinModelPortaliQ92844.
SMRiQ92844.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115328. 46 interactors.
DIPiDIP-27516N.
IntActiQ92844. 38 interactors.
MINTiMINT-111947.
STRINGi9606.ENSP00000259075.

PTM databases

iPTMnetiQ92844.
PhosphoSitePlusiQ92844.

Polymorphism and mutation databases

BioMutaiTANK.
DMDMi143811466.

Proteomic databases

EPDiQ92844.
MaxQBiQ92844.
PaxDbiQ92844.
PeptideAtlasiQ92844.
PRIDEiQ92844.

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.
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

BioCyciZFISH:ENSG00000136560-MONOMER.
ReactomeiR-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.
PROiQ92844.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136560.
CleanExiHS_TANK.
HS_TRAF2.
ExpressionAtlasiQ92844. baseline and differential.
GenevisibleiQ92844. HS.

Family and domain databases

InterProiIPR024581. TBD.
[Graphical view]
PfamiPF12845. TBD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTANK_HUMAN
AccessioniPrimary (citable) accession number: Q92844
Secondary accession number(s): D3DPB5, Q7Z4J6, Q92885
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: April 3, 2007
Last modified: November 30, 2016
This is version 164 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.