UniProtKB - Q8NFZ5 (TNIP2_HUMAN)
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Protein
TNFAIP3-interacting protein 2
Gene
TNIP2
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 397 – 429 | CCHC NOA-typePROSITE-ProRule annotationAdd BLAST | 33 |
GO - Molecular functioni
- K63-linked polyubiquitin modification-dependent protein binding Source: InterPro
- metal ion binding Source: UniProtKB-KW
- polyubiquitin modification-dependent protein binding Source: UniProtKB
- protein kinase binding Source: UniProtKB
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- CD40 signaling pathway Source: UniProtKB
- cellular response to lipopolysaccharide Source: UniProtKB
- I-kappaB kinase/NF-kappaB signaling Source: Ensembl
- inflammatory response Source: UniProtKB-KW
- interleukin-1-mediated signaling pathway Source: UniProtKB
- negative regulation of endothelial cell apoptotic process Source: UniProtKB
- positive regulation of B cell activation Source: UniProtKB
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of macrophage activation Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- protein deubiquitination Source: Reactome
- protein stabilization Source: UniProtKB
- stress-activated MAPK cascade Source: Reactome
- toll-like receptor 2 signaling pathway Source: UniProtKB
- toll-like receptor 3 signaling pathway Source: UniProtKB
- toll-like receptor 9 signaling pathway Source: UniProtKB
- transcription, DNA-templated Source: UniProtKB-KW
Keywordsi
Biological process | Apoptosis, Inflammatory response, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation. R-HSA-5689896. Ovarian tumor domain proteases. |
SignaLinki | Q8NFZ5. |
SIGNORi | Q8NFZ5. |
Names & Taxonomyi
Protein namesi | Recommended name: TNFAIP3-interacting protein 2Alternative name(s): A20-binding inhibitor of NF-kappa-B activation 2 Short name: ABIN-2 Fetal liver LKB1-interacting protein |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000168884.14. |
HGNCi | HGNC:19118. TNIP2. |
MIMi | 610669. gene. |
neXtProti | NX_Q8NFZ5. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 62 | S → A: Reduces phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 146 | S → A: Reduces phosphorylation; reduces CHUK-mediated NF-kappa-B activation. 1 Publication | 1 | |
Mutagenesisi | 309 – 310 | DF → NA: Abolishes ubiquitin binding. 1 Publication | 2 | |
Mutagenesisi | 313 – 314 | ER → AA: Abolishes ubiquitin binding; loss of inhibitory activity on NF-kappa-B activation. 1 Publication | 2 |
Organism-specific databases
DisGeNETi | 79155. |
OpenTargetsi | ENSG00000168884. |
PharmGKBi | PA134957006. |
Polymorphism and mutation databases
BioMutai | TNIP2. |
DMDMi | 74715616. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000322583 | 1 – 429 | TNFAIP3-interacting protein 2Add BLAST | 429 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 7 | PhosphoserineCombined sources | 1 |
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 conjugationProteomic databases
EPDi | Q8NFZ5. |
MaxQBi | Q8NFZ5. |
PaxDbi | Q8NFZ5. |
PeptideAtlasi | Q8NFZ5. |
PRIDEi | Q8NFZ5. |
PTM databases
iPTMneti | Q8NFZ5. |
PhosphoSitePlusi | Q8NFZ5. |
Expressioni
Tissue specificityi
Ubiquitously expressed in all tissues examined.1 Publication
Gene expression databases
Bgeei | ENSG00000168884. |
CleanExi | HS_TNIP2. |
ExpressionAtlasi | Q8NFZ5. baseline and differential. |
Genevisiblei | Q8NFZ5. HS. |
Organism-specific databases
HPAi | CAB020818. 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
- K63-linked polyubiquitin modification-dependent protein binding Source: InterPro
- polyubiquitin modification-dependent protein binding Source: UniProtKB
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 122573. 34 interactors. |
CORUMi | Q8NFZ5. |
DIPi | DIP-27617N. |
IntActi | Q8NFZ5. 20 interactors. |
MINTi | Q8NFZ5. |
STRINGi | 9606.ENSP00000321203. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 263 – 273 | Combined sources | 11 | |
Helixi | 276 – 336 | Combined sources | 61 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5H07 | X-ray | 2.59 | C/D | 257-344 | [»] | |
ProteinModelPortali | Q8NFZ5. | |||||
SMRi | Q8NFZ5. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 289 – 347 | Ubiquitin-binding domain (UBD)Add BLAST | 59 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 29 – 117 | Sequence analysisAdd BLAST | 89 | |
Coiled coili | 196 – 226 | Sequence analysisAdd BLAST | 31 | |
Coiled coili | 255 – 340 | Sequence analysisAdd BLAST | 86 |
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 397 – 429 | CCHC NOA-typePROSITE-ProRule annotationAdd BLAST | 33 |
Keywords - Domaini
Coiled coil, Zinc-fingerPhylogenomic databases
eggNOGi | ENOG410IEB1. Eukaryota. ENOG410XRZP. LUCA. |
GeneTreei | ENSGT00390000009019. |
HOGENOMi | HOG000049046. |
HOVERGENi | HBG055553. |
InParanoidi | Q8NFZ5. |
OMAi | FKSERAD. |
OrthoDBi | EOG091G0JC8. |
PhylomeDBi | Q8NFZ5. |
TreeFami | TF332167. |
Family and domain databases
InterProi | View protein in InterPro IPR032419. CC2-LZ_dom. IPR022008. EABR. IPR034735. NEMO_ZF. |
Pfami | View protein in Pfam PF16516. CC2-LZ. 1 hit. PF12180. EABR. 1 hit. |
PROSITEi | View protein in PROSITE PS51801. ZF_CCHC_NOA. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative 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.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 153 | Q → H in CAC34835 (PubMed:11390377).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_067969 | 249 | Q → 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_067970 | 255 | E → 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_039463 | 396 | A → V2 PublicationsCorresponds to variant dbSNP:rs2269495Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_052701 | 1 – 107 | Missing in isoform 2. 1 PublicationAdd BLAST | 107 |
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. |
CCDSi | CCDS3362.1. [Q8NFZ5-1] CCDS54714.1. [Q8NFZ5-2] |
RefSeqi | NP_001154999.1. NM_001161527.1. [Q8NFZ5-2] NP_001278945.1. NM_001292016.1. NP_077285.3. NM_024309.3. [Q8NFZ5-1] |
UniGenei | Hs.368551. |
Genome annotation databases
Ensembli | ENST00000315423; ENSP00000321203; ENSG00000168884. [Q8NFZ5-1] ENST00000510267; ENSP00000427613; ENSG00000168884. [Q8NFZ5-2] |
GeneIDi | 79155. |
KEGGi | hsa:79155. |
UCSCi | uc003gff.3. human. [Q8NFZ5-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | TNIP2_HUMAN | |
Accessioni | Q8NFZ5Primary (citable) accession number: Q8NFZ5 Secondary accession number(s): B1AKS4 Q9H682 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 26, 2008 |
Last sequence update: | October 1, 2002 | |
Last modified: | March 28, 2018 | |
This is version 121 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |