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Protein

TNFAIP3-interacting protein 2

Gene

TNIP2

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

  • metal ion binding Source: UniProtKB-KW
  • polyubiquitin binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Inflammatory response, Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168884-MONOMER.
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

HGNCiHGNC:19118. TNIP2.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus Curated

GO - Cellular componenti

Complete GO annotation...

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.

PTM databases

iPTMnetiQ8NFZ5.
PhosphoSitePlusiQ8NFZ5.

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissues examined.1 Publication

Gene expression databases

BgeeiENSG00000168884.
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

WithEntry#Exp.IntActNotes
IKBKGQ9Y6K96EBI-359372,EBI-81279
MAP3K8P4127910EBI-359372,EBI-354900
NFKB1P198385EBI-359372,EBI-300010
NFKB1P19838-18EBI-359372,EBI-1452239
STK11Q158315EBI-359372,EBI-306838

GO - Molecular functioni

  • polyubiquitin binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122573. 33 interactors.
DIPiDIP-27617N.
IntActiQ8NFZ5. 20 interactors.
MINTiMINT-97349.
STRINGi9606.ENSP00000321203.

Structurei

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

Sequence similaritiesi

Contains 1 CCHC NOA-type zinc finger.PROSITE-ProRule annotation

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.
OMAiASDILCR.
OrthoDBiEOG091G0JC8.
PhylomeDBiQ8NFZ5.
TreeFamiTF332167.

Family and domain databases

InterProiIPR022008. EABR.
[Graphical view]
PfamiPF12180. EABR. 1 hit.
[Graphical view]
PROSITEiPS51801. ZF_CCHC_NOA. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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 rs116129895dbSNPEnsembl.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 rs116412781dbSNPEnsembl.1
Natural variantiVAR_039463396A → V.2 PublicationsCorresponds to variant rs2269495dbSNPEnsembl.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.
AL110117, AL121750 Genomic DNA. Translation: CAM28252.1.
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

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.
AL110117, AL121750 Genomic DNA. Translation: CAM28252.1.
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

ProteinModelPortaliQ8NFZ5.
SMRiQ8NFZ5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122573. 33 interactors.
DIPiDIP-27617N.
IntActiQ8NFZ5. 20 interactors.
MINTiMINT-97349.
STRINGi9606.ENSP00000321203.

PTM databases

iPTMnetiQ8NFZ5.
PhosphoSitePlusiQ8NFZ5.

Polymorphism and mutation databases

BioMutaiTNIP2.
DMDMi74715616.

Proteomic databases

EPDiQ8NFZ5.
MaxQBiQ8NFZ5.
PaxDbiQ8NFZ5.
PeptideAtlasiQ8NFZ5.
PRIDEiQ8NFZ5.

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.
GeneCardsiTNIP2.
H-InvDBHIX0164015.
HGNCiHGNC:19118. TNIP2.
HPAiCAB020818.
HPA049886.
HPA063197.
MIMi610669. gene.
neXtProtiNX_Q8NFZ5.
OpenTargetsiENSG00000168884.
PharmGKBiPA134957006.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEB1. Eukaryota.
ENOG410XRZP. LUCA.
GeneTreeiENSGT00390000009019.
HOGENOMiHOG000049046.
HOVERGENiHBG055553.
InParanoidiQ8NFZ5.
OMAiASDILCR.
OrthoDBiEOG091G0JC8.
PhylomeDBiQ8NFZ5.
TreeFamiTF332167.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168884-MONOMER.
ReactomeiR-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-HSA-5689896. Ovarian tumor domain proteases.
SignaLinkiQ8NFZ5.
SIGNORiQ8NFZ5.

Miscellaneous databases

GeneWikiiTNIP2.
GenomeRNAii79155.
PROiQ8NFZ5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168884.
CleanExiHS_TNIP2.
ExpressionAtlasiQ8NFZ5. baseline and differential.
GenevisibleiQ8NFZ5. HS.

Family and domain databases

InterProiIPR022008. EABR.
[Graphical view]
PfamiPF12180. EABR. 1 hit.
[Graphical view]
PROSITEiPS51801. ZF_CCHC_NOA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNIP2_HUMAN
AccessioniPrimary (citable) accession number: Q8NFZ5
Secondary accession number(s): B1AKS4
, B3KTY8, D3DVQ9, Q7L5L2, Q9BQR6, Q9H682
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: October 1, 2002
Last modified: November 2, 2016
This is version 110 of the entry and version 1 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

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. 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.