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Protein

TNFAIP3-interacting protein 2

Gene

TNIP2

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

Functioni

Inhibits NF-kappa-B activation by blocking the interaction of RIPK1 with its downstream effector NEMO/IKBKG. Forms a ternary complex with NFKB1 and MAP3K8 but appears to function upstream of MAP3K8 in the TLR4 signaling pathway that regulates MAP3K8 activation. Involved in activation of the MEK/ERK signaling pathway during innate immune response; this function seems to be stimulus- and cell type specific. Required for stability of MAP3K8. Involved in regulation of apoptosis in endothelial cells; promotes TEK agonist-stimulated endothelial survival. May act as transcriptional coactivator when translocated to the nucleus. Enhances CHUK-mediated NF-kappa-B activation involving NF-kappa-B p50-p65 and p50-c-Rel complexes.6 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri397 – 429CCHC NOA-typePROSITE-ProRule annotationAdd BLAST33

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processApoptosis, Inflammatory response, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-5689896 Ovarian tumor domain proteases
SignaLinkiQ8NFZ5
SIGNORiQ8NFZ5

Names & Taxonomyi

Protein namesi
Recommended name:
TNFAIP3-interacting protein 2
Alternative name(s):
A20-binding inhibitor of NF-kappa-B activation 2
Short name:
ABIN-2
Fetal liver LKB1-interacting protein
Gene namesi
Name:TNIP2Imported
Synonyms:ABIN2, FLIP1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000168884.14
HGNCiHGNC:19118 TNIP2
MIMi610669 gene
neXtProtiNX_Q8NFZ5

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, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi62S → A: Reduces phosphorylation. 1 Publication1
Mutagenesisi146S → A: Reduces phosphorylation; reduces CHUK-mediated NF-kappa-B activation. 1 Publication1
Mutagenesisi309 – 310DF → NA: Abolishes ubiquitin binding. 1 Publication2
Mutagenesisi313 – 314ER → AA: Abolishes ubiquitin binding; loss of inhibitory activity on NF-kappa-B activation. 1 Publication2

Organism-specific databases

DisGeNETi79155
OpenTargetsiENSG00000168884
PharmGKBiPA134957006

Polymorphism and mutation databases

BioMutaiTNIP2
DMDMi74715616

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003225831 – 429TNFAIP3-interacting protein 2Add BLAST429

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7PhosphoserineCombined sources1

Post-translational modificationi

In vitro phosphorylated by CHUK.1 Publication
Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination probably leading to constitutive proteasomal degradation which can be impaired by IKK-A/CHUK or IKBKB probably involving deubiquitination.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8NFZ5
MaxQBiQ8NFZ5
PaxDbiQ8NFZ5
PeptideAtlasiQ8NFZ5
PRIDEiQ8NFZ5
ProteomicsDBi73398
73399 [Q8NFZ5-2]

PTM databases

iPTMnetiQ8NFZ5
PhosphoSitePlusiQ8NFZ5

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissues examined.1 Publication

Gene expression databases

BgeeiENSG00000168884 Expressed in 222 organ(s), highest expression level in left coronary artery
CleanExiHS_TNIP2
ExpressionAtlasiQ8NFZ5 baseline and differential
GenevisibleiQ8NFZ5 HS

Organism-specific databases

HPAiCAB020818
HPA049886
HPA063197

Interactioni

Subunit structurei

Interacts with STK11/LKB1, TNFAIP3, IKBKG, NFKB1, MAP3K8, TEK, RIPK1, CHUK, IKBKB and SMARCD1. Interacts with polyubiquitin.8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122573, 35 interactors
CORUMiQ8NFZ5
DIPiDIP-27617N
IntActiQ8NFZ5, 20 interactors
MINTiQ8NFZ5
STRINGi9606.ENSP00000321203

Structurei

Secondary structure

1429
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8NFZ5
SMRiQ8NFZ5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni289 – 347Ubiquitin-binding domain (UBD)Add BLAST59

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili29 – 117Sequence analysisAdd BLAST89
Coiled coili196 – 226Sequence analysisAdd BLAST31
Coiled coili255 – 340Sequence analysisAdd BLAST86

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri397 – 429CCHC NOA-typePROSITE-ProRule annotationAdd BLAST33

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IEB1 Eukaryota
ENOG410XRZP LUCA
GeneTreeiENSGT00390000009019
HOGENOMiHOG000049046
HOVERGENiHBG055553
InParanoidiQ8NFZ5
OMAiDCAEVKQ
OrthoDBiEOG091G0JC8
PhylomeDBiQ8NFZ5
TreeFamiTF332167

Family and domain databases

InterProiView protein in InterPro
IPR032419 CC2-LZ_dom
IPR022008 EABR
IPR034735 NEMO_ZF
PfamiView protein in Pfam
PF16516 CC2-LZ, 1 hit
PF12180 EABR, 1 hit
PROSITEiView protein in PROSITE
PS51801 ZF_CCHC_NOA, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 13 Publications (identifier: Q8NFZ5-1) [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
MSRDPGSGGW EEAPRAAAAL CTLYHEAGQR LRRLQDQLAA RDALIARLRA
60 70 80 90 100
RLAALEGDAA PSLVDALLEQ VARFREQLRR QEGGAAEAQM RQEIERLTER
110 120 130 140 150
LEEKEREMQQ LLSQPQHERE KEVVLLRRSM AEGERARAAS DVLCRSLANE
160 170 180 190 200
THQLRRTLTA TAHMCQHLAK CLDERQHAQR NVGERSPDQS EHTDGHTSVQ
210 220 230 240 250
SVIEKLQEEN RLLKQKVTHV EDLNAKWQRY NASRDEYVRG LHAQLRGLQI
260 270 280 290 300
PHEPELMRKE ISRLNRQLEE KINDCAEVKQ ELAASRTARD AALERVQMLE
310 320 330 340 350
QQILAYKDDF MSERADRERA QSRIQELEEK VASLLHQVSW RQDSREPDAG
360 370 380 390 400
RIHAGSKTAK YLAADALELM VPGGWRPGTG SQQPEPPAEG GHPGAAQRGQ
410 420
GDLQCPHCLQ CFSDEQGEEL LRHVAECCQ
Length:429
Mass (Da):48,700
Last modified:October 1, 2002 - v1
Checksum:i0F6B049C2B3483DC
GO
Isoform 21 Publication (identifier: Q8NFZ5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-107: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:322
Mass (Da):36,682
Checksum:i4B145A09A85133BE
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RGJ2D6RGJ2_HUMAN
TNFAIP3-interacting protein 2
TNIP2
346Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti153Q → H in CAC34835 (PubMed:11390377).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067969249Q → H Found in patients with gastrointestinal diffuse large cell lymphoma; impairs inhibitory activity on CARD11-induced NF-kappa-B activation. 1 PublicationCorresponds to variant dbSNP:rs116129895Ensembl.1
Natural variantiVAR_067970255E → K Found in patients with gastrointestinal diffuse large cell lymphoma; somatic mutation; impairs inhibitory activity on CARD11-induced NF-kappa-B activation and impairs interaction with TNFAIP3. 1 PublicationCorresponds to variant dbSNP:rs116412781Ensembl.1
Natural variantiVAR_039463396A → V2 PublicationsCorresponds to variant dbSNP:rs2269495Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0527011 – 107Missing in isoform 2. 1 PublicationAdd BLAST107

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ304866 mRNA Translation: CAC34835.1
AF372839 mRNA Translation: AAM21315.1
AK026176 mRNA Translation: BAB15382.1
AK096296 mRNA Translation: BAG53250.1
CH471131 Genomic DNA Translation: EAW82514.1
AL121750, AL110117 Genomic DNA Translation: CAM28233.1
CH471131 Genomic DNA Translation: EAW82516.1
BC002740 mRNA Translation: AAH02740.2
CCDSiCCDS3362.1 [Q8NFZ5-1]
CCDS54714.1 [Q8NFZ5-2]
RefSeqiNP_001154999.1, NM_001161527.1 [Q8NFZ5-2]
NP_001278945.1, NM_001292016.1
NP_077285.3, NM_024309.3 [Q8NFZ5-1]
UniGeneiHs.368551

Genome annotation databases

EnsembliENST00000315423; ENSP00000321203; ENSG00000168884 [Q8NFZ5-1]
ENST00000510267; ENSP00000427613; ENSG00000168884 [Q8NFZ5-2]
GeneIDi79155
KEGGihsa:79155
UCSCiuc003gff.3 human [Q8NFZ5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ304866 mRNA Translation: CAC34835.1
AF372839 mRNA Translation: AAM21315.1
AK026176 mRNA Translation: BAB15382.1
AK096296 mRNA Translation: BAG53250.1
CH471131 Genomic DNA Translation: EAW82514.1
AL121750, AL110117 Genomic DNA Translation: CAM28233.1
CH471131 Genomic DNA Translation: EAW82516.1
BC002740 mRNA Translation: AAH02740.2
CCDSiCCDS3362.1 [Q8NFZ5-1]
CCDS54714.1 [Q8NFZ5-2]
RefSeqiNP_001154999.1, NM_001161527.1 [Q8NFZ5-2]
NP_001278945.1, NM_001292016.1
NP_077285.3, NM_024309.3 [Q8NFZ5-1]
UniGeneiHs.368551

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5H07X-ray2.59C/D257-344[»]
ProteinModelPortaliQ8NFZ5
SMRiQ8NFZ5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122573, 35 interactors
CORUMiQ8NFZ5
DIPiDIP-27617N
IntActiQ8NFZ5, 20 interactors
MINTiQ8NFZ5
STRINGi9606.ENSP00000321203

PTM databases

iPTMnetiQ8NFZ5
PhosphoSitePlusiQ8NFZ5

Polymorphism and mutation databases

BioMutaiTNIP2
DMDMi74715616

Proteomic databases

EPDiQ8NFZ5
MaxQBiQ8NFZ5
PaxDbiQ8NFZ5
PeptideAtlasiQ8NFZ5
PRIDEiQ8NFZ5
ProteomicsDBi73398
73399 [Q8NFZ5-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000315423; ENSP00000321203; ENSG00000168884 [Q8NFZ5-1]
ENST00000510267; ENSP00000427613; ENSG00000168884 [Q8NFZ5-2]
GeneIDi79155
KEGGihsa:79155
UCSCiuc003gff.3 human [Q8NFZ5-1]

Organism-specific databases

CTDi79155
DisGeNETi79155
EuPathDBiHostDB:ENSG00000168884.14
GeneCardsiTNIP2
H-InvDBiHIX0164015
HGNCiHGNC:19118 TNIP2
HPAiCAB020818
HPA049886
HPA063197
MIMi610669 gene
neXtProtiNX_Q8NFZ5
OpenTargetsiENSG00000168884
PharmGKBiPA134957006
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEB1 Eukaryota
ENOG410XRZP LUCA
GeneTreeiENSGT00390000009019
HOGENOMiHOG000049046
HOVERGENiHBG055553
InParanoidiQ8NFZ5
OMAiDCAEVKQ
OrthoDBiEOG091G0JC8
PhylomeDBiQ8NFZ5
TreeFamiTF332167

Enzyme and pathway databases

ReactomeiR-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-5689896 Ovarian tumor domain proteases
SignaLinkiQ8NFZ5
SIGNORiQ8NFZ5

Miscellaneous databases

GeneWikiiTNIP2
GenomeRNAii79155
PROiPR:Q8NFZ5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168884 Expressed in 222 organ(s), highest expression level in left coronary artery
CleanExiHS_TNIP2
ExpressionAtlasiQ8NFZ5 baseline and differential
GenevisibleiQ8NFZ5 HS

Family and domain databases

InterProiView protein in InterPro
IPR032419 CC2-LZ_dom
IPR022008 EABR
IPR034735 NEMO_ZF
PfamiView protein in Pfam
PF16516 CC2-LZ, 1 hit
PF12180 EABR, 1 hit
PROSITEiView protein in PROSITE
PS51801 ZF_CCHC_NOA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTNIP2_HUMAN
AccessioniPrimary (citable) accession number: Q8NFZ5
Secondary accession number(s): B1AKS4
, B3KTY8, D3DVQ9, Q7L5L2, Q9BQR6, Q9H682
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: October 1, 2002
Last modified: November 7, 2018
This is version 126 of the entry and version 1 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

Documents

  1. Human chromosome 4
    Human chromosome 4: 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
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Main funding by: National Institutes of Health

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