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UniProtKB - Q15025 (TNIP1_HUMAN)

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Protein

TNFAIP3-interacting protein 1

Gene

TNIP1

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

Functioni

Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases. Interacts with HIV-1 matrix protein and is packaged into virions and overexpression can inhibit viral replication. May regulate matrix nuclear localization, both nuclear import of PIC (Preintegration complex) and export of GAG polyprotein and viral genomic RNA during virion production. In case of infection, promotes association of IKBKG with Shigella flexneri E3 ubiquitin-protein ligase ipah9.8 p which in turn promotes polyubiquitination of IKBKG leading to its proteasome-dependent degradation and thus is perturbing NF-kappa-B activation during bacterial infection.5 Publications

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • mitogen-activated protein kinase binding Source: UniProtKB
  • polyubiquitin modification-dependent protein binding Source: GO_Central
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cellular response to lipopolysaccharide Source: GO_Central
  • defense response Source: ProtInc
  • glycoprotein biosynthetic process Source: UniProtKB
  • inflammatory response Source: UniProtKB-KW
  • leukocyte cell-cell adhesion Source: UniProtKB
  • modulation by symbiont of host I-kappaB kinase/NF-kappaB cascade Source: UniProtKB
  • MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
  • negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of viral genome replication Source: UniProtKB
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of protein deubiquitination Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • protein deubiquitination Source: Reactome
  • translation Source: ProtInc
View the complete GO annotation on QuickGO ...

Keywordsi

Biological processInflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-5689896 Ovarian tumor domain proteases

Names & Taxonomyi

Protein namesi
Recommended name:
TNFAIP3-interacting protein 1
Alternative name(s):
A20-binding inhibitor of NF-kappa-B activation 1
Short name:
ABIN-1
HIV-1 Nef-interacting protein
Nef-associated factor 1
Short name:
Naf1
Nip40-1
Virion-associated nuclear shuttling protein
Short name:
VAN
Short name:
hVAN
Gene namesi
Name:TNIP1
Synonyms:KIAA0113, NAF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000145901.14
HGNCiHGNC:16903 TNIP1
MIMi607714 gene
neXtProtiNX_Q15025

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
Mutagenesisi472D → N: Abolishes binding to polyubiquitin ('K-63'-linked and linear). 1 Publication1
Mutagenesisi552Y → F: Abolishes interaction with PI3K p85 regulatory subunit and abolishes interaction between SELPLG and PI3K p85 regulatory subunit. 1 Publication1

Organism-specific databases

DisGeNETi10318
OpenTargetsiENSG00000145901
Orphaneti536 Systemic lupus erythematosus
PharmGKBiPA128394573

Polymorphism and mutation databases

BioMutaiTNIP1
DMDMi20138952

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000966911 – 636TNFAIP3-interacting protein 1Add BLAST636

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei77PhosphoserineCombined sources1
Modified residuei284PhosphoserineCombined sources1
Modified residuei403PhosphoserineCombined sources1
Modified residuei438PhosphothreonineCombined sources1
Modified residuei442PhosphoserineCombined sources1
Modified residuei552Phosphotyrosine1 Publication1
Modified residuei571Asymmetric dimethylarginineBy similarity1
Modified residuei599Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei599Omega-N-methylarginine; alternateCombined sources1
Modified residuei627PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Tyr-552 by SRC-family kinases recruits phosphoinositide-3-kinase (PI3K) PIK3CD:p85 heterodimer which results in integrin activation and leukocyte adhesion to activated endothelium during inflammation.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ15025
MaxQBiQ15025
PaxDbiQ15025
PeptideAtlasiQ15025
PRIDEiQ15025
ProteomicsDBi60376
60377 [Q15025-2]

PTM databases

iPTMnetiQ15025
PhosphoSitePlusiQ15025

Expressioni

Tissue specificityi

Ubiquitous. Strongly expressed in peripheral blood lymphocytes, spleen and skeletal muscle, and is weakly expressed in the brain. In peripheral blood mononucleocytes, isoform 4 is mainly expressed and isoform 1 and isoform 7 are almost not expressed. Expression of isoform 1 and isoform 7 increases in leukemic cells.1 Publication

Gene expression databases

BgeeiENSG00000145901
CleanExiHS_NAF1
HS_TNIP1
ExpressionAtlasiQ15025 baseline and differential
GenevisibleiQ15025 HS

Organism-specific databases

HPAiHPA037893
HPA037894
HPA071950

Interactioni

Subunit structurei

Interacts with TNFAIP3 and IKBKG (polyubiquitinated); facilitates TNFAIP3-mediated de-ubiquitination of NEMO/IKBKG. Interacts with polyubiquitin. Interacts with MAPK1, SELPLG and PIK3CD. Interacts with IRAK1 (polyubiquitinated). Interacts with MYD88; the interaction is indicative for participation in an activated TLR-signaling complex. Interacts with HIV-1 matrix protein. Interacts with Shigella flexneri ipah9.8; the interaction promotes polyubiquitination of IKBKG.4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • mitogen-activated protein kinase binding Source: UniProtKB
  • polyubiquitin modification-dependent protein binding Source: GO_Central
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115602, 110 interactors
CORUMiQ15025
DIPiDIP-27577N
IntActiQ15025, 101 interactors
MINTiQ15025
STRINGi9606.ENSP00000317891

Structurei

3D structure databases

ProteinModelPortaliQ15025
SMRiQ15025
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni94 – 412Interaction with NefAdd BLAST319
Regioni351 – 367Interaction with Shigella flexneri ipah9.8Add BLAST17
Regioni431 – 588Required for inhibitory activity of TNF-induced NF-kappa-B activationBy similarityAdd BLAST158
Regioni452 – 510Ubiquitin-binding domain (UBD)Add BLAST59

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili20 – 73Sequence analysisAdd BLAST54
Coiled coili196 – 258Sequence analysisAdd BLAST63
Coiled coili294 – 535Sequence analysisAdd BLAST242

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi524 – 530Nuclear localization signalSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi539 – 636Pro-richAdd BLAST98

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IEGE Eukaryota
ENOG411180D LUCA
GeneTreeiENSGT00510000046908
HOGENOMiHOG000253048
HOVERGENiHBG019072
InParanoidiQ15025
OMAiMQGIKML
OrthoDBiEOG091G04AX
PhylomeDBiQ15025
TreeFamiTF351138

Family and domain databases

InterProiView protein in InterPro
IPR033372 TNIP1
PANTHERiPTHR31882:SF3 PTHR31882:SF3, 1 hit

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q15025-1) [UniParc]FASTAAdd to basket
Also known as: Alpha, FL

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
MEGRGPYRIY DPGGSVPSGE ASAAFERLVK ENSRLKEKMQ GIKMLGELLE 
        60         70         80         90        100
ESQMEATRLR QKAEELVKDN ELLPPPSPSL GSFDPLAELT GKDSNVTASP 
       110        120        130        140        150
TAPACPSDKP APVQKPPSSG TSSEFEVVTP EEQNSPESSS HANAMALGPL 
       160        170        180        190        200
PREDGNLMLH LQRLETTLSV CAEEPDHGQL FTHLGRMALE FNRLASKVHK 
       210        220        230        240        250
NEQRTSILQT LCEQLRKENE ALKAKLDKGL EQRDQAAERL REENLELKKL 
       260        270        280        290        300
LMSNGNKEGA SGRPGSPKME GTGKKAVAGQ QQASVTAGKV PEVVALGAAE 
       310        320        330        340        350
KKVKMLEQQR SELLEVNKQW DQHFRSMKQQ YEQKITELRQ KLADLQKQVT 
       360        370        380        390        400
DLEAEREQKQ RDFDRKLLLA KSKIEMEETD KEQLTAEAKE LRQKVKYLQD 
       410        420        430        440        450
QLSPLTRQRE YQEKEIQRLN KALEEALSIQ TPPSSPPTAF GSPEGAGALL 
       460        470        480        490        500
RKQELVTQNE LLKQQVKIFE EDFQRERSDR ERMNEEKEEL KKQVEKLQAQ 
       510        520        530        540        550
VTLSNAQLKA FKDEEKAREA LRQQKRKAKA SGERYHVEPH PEHLCGAYPY 
       560        570        580        590        600
AYPPMPAMVP HHGFEDWSQI RYPPPPMAME HPPPLPNSRL FHLPEYTWRL 
       610        620        630 
PCGGVRNPNQ SSQVMDPPTA RPTEPESPKN DREGPQ
Length:636
Mass (Da):71,864
Last modified:August 1, 1999 - v2
Checksum:iD81B96BEAD50D871
GO
Isoform 2 (identifier: Q15025-2) [UniParc]FASTAAdd to basket
Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     627-636: SPKNDREGPQ → PADLRLPRN

Show »
Length:635
Mass (Da):71,788
Checksum:iFE65D2CE6E7B185B
GO
Isoform 3 (identifier: Q15025-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: Missing.

Show »
Length:583
Mass (Da):66,012
Checksum:iA97F0EB85F9F39DE
GO
Isoform 4 (identifier: Q15025-4) [UniParc]FASTAAdd to basket
Also known as: Alpha2

The sequence of this isoform differs from the canonical sequence as follows:
     530-593: Missing.

Show »
Length:572
Mass (Da):64,500
Checksum:iD1E76C1FBBA59E63
GO
Isoform 5 (identifier: Q15025-5) [UniParc]FASTAAdd to basket
Also known as: Alpha4

The sequence of this isoform differs from the canonical sequence as follows:
     530-556: ASGERYHVEPHPEHLCGAYPYAYPPMP → SLQKMTVRGLSETRLCHLAPPSSCRAS
     557-636: Missing.

Note: Less effective in the NF-kappa-B inhibitory effect.
Show »
Length:556
Mass (Da):62,609
Checksum:i757B3E9B83C35F42
GO
Isoform 6 (identifier: Q15025-6) [UniParc]FASTAAdd to basket
Also known as: Beta2

The sequence of this isoform differs from the canonical sequence as follows:
     530-593: Missing.
     627-636: SPKNDREGPQ → PADLRLPRN

Show »
Length:571
Mass (Da):64,424
Checksum:i929F73D89B3D0A54
GO
Isoform 7 (identifier: Q15025-7) [UniParc]FASTAAdd to basket
Also known as: Alpha3, Beta3

The sequence of this isoform differs from the canonical sequence as follows:
     530-545: ASGERYHVEPHPEHLC → GTHRGCPRRLPERKVK
     546-636: Missing.

Show »
Length:545
Mass (Da):61,570
Checksum:i7F4AD5363F28608B
GO
Isoform 8 (identifier: Q15025-8) [UniParc]FASTAAdd to basket
Also known as: Beta4

The sequence of this isoform differs from the canonical sequence as follows:
     530-552: ASGERYHVEPHPEHLCGAYPYAY → SQLISDCQETRSHLHGVARASAG
     553-636: Missing.

Show »
Length:552
Mass (Da):62,103
Checksum:i699AD04365381366
GO

Sequence cautioni

The sequence AAB41438 differs from that shown. Reason: Frameshift at positions 152 and 154.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti148G → D in AAH12133 (PubMed:15489334).Curated1
Sequence conflicti178G → S in BAH13185 (PubMed:14702039).Curated1
Sequence conflicti299A → P in AAG42154 (PubMed:11090181).Curated1
Sequence conflicti299A → P in BAF34946 (PubMed:17016622).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051453103P → S. Corresponds to variant dbSNP:rs2303018Ensembl.1
Natural variantiVAR_051454146A → V. Corresponds to variant dbSNP:rs2233289Ensembl.1
Natural variantiVAR_051455151P → A. Corresponds to variant dbSNP:rs2233290Ensembl.1
Natural variantiVAR_051456233R → Q. Corresponds to variant dbSNP:rs2233292Ensembl.1
Natural variantiVAR_051457260A → V. Corresponds to variant dbSNP:rs2233295Ensembl.1
Natural variantiVAR_067965263R → W in patients with gastrointestinal diffuse large cell lymphoma. 1 PublicationCorresponds to variant dbSNP:rs117663772Ensembl.1
Natural variantiVAR_067966286T → M in patients with gastrointestinal diffuse large cell lymphoma; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs185683917Ensembl.1
Natural variantiVAR_067967374I → T in patients with gastrointestinal diffuse large cell lymphoma. 1 PublicationCorresponds to variant dbSNP:rs748495842Ensembl.1
Natural variantiVAR_067968476E → K in patients with gastrointestinal diffuse large cell lymphoma; somatic mutation; loss of inhibitory activity on CARD11- and TNF-induced NF-kappa-B activation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0452961 – 53Missing in isoform 3. 3 PublicationsAdd BLAST53
Alternative sequenceiVSP_055208530 – 593Missing in isoform 4 and isoform 6. 1 PublicationAdd BLAST64
Alternative sequenceiVSP_055209530 – 556ASGER…YPPMP → SLQKMTVRGLSETRLCHLAP PSSCRAS in isoform 5. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_055210530 – 552ASGER…YPYAY → SQLISDCQETRSHLHGVARA SAG in isoform 8. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_055211530 – 545ASGER…PEHLC → GTHRGCPRRLPERKVK in isoform 7. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_055212546 – 636Missing in isoform 7. 1 PublicationAdd BLAST91
Alternative sequenceiVSP_055213553 – 636Missing in isoform 8. 1 PublicationAdd BLAST84
Alternative sequenceiVSP_055214557 – 636Missing in isoform 5. 1 PublicationAdd BLAST80
Alternative sequenceiVSP_003913627 – 636SPKNDREGPQ → PADLRLPRN in isoform 2 and isoform 6. 3 Publications10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ011895 mRNA Translation: CAA09855.1
AJ011896 mRNA Translation: CAA09856.1
AY012155 mRNA Translation: AAG42154.1
AB177543 mRNA Translation: BAF34946.1
AB177544 mRNA Translation: BAF34947.1
AB252970 mRNA Translation: BAF48787.1
AB252971 mRNA Translation: BAF48788.1
AB252972 mRNA Translation: BAF48789.1
AB252973 mRNA Translation: BAF48790.1
AB252974 mRNA Translation: BAF48791.1
AB252975 mRNA Translation: BAF48792.1
AB252976 mRNA Translation: BAF48793.1
AB252977 mRNA Translation: BAF48794.1
AB252978 mRNA Translation: BAF48795.1
AB252979 mRNA Translation: BAF48796.1
AB252980 mRNA Translation: BAF48797.1
AB252981 mRNA Translation: BAF48798.1
D30755 mRNA Translation: BAA06416.2
AK299975 mRNA Translation: BAH13185.1
BX640647 mRNA Translation: CAE45793.1
AC008641 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW61688.1
CH471062 Genomic DNA Translation: EAW61689.1
CH471062 Genomic DNA Translation: EAW61690.1
CH471062 Genomic DNA Translation: EAW61691.1
BC012133 mRNA Translation: AAH12133.1
BC014008 mRNA Translation: AAH14008.1
U39403 mRNA Translation: AAC99999.1
U83844 mRNA Translation: AAB41438.1 Frameshift.
CCDSiCCDS34280.1 [Q15025-1]
CCDS58982.1 [Q15025-3]
CCDS58983.1 [Q15025-5]
CCDS58984.1 [Q15025-4]
CCDS58985.1 [Q15025-2]
RefSeqiNP_001239314.1, NM_001252385.1
NP_001239315.1, NM_001252386.1 [Q15025-3]
NP_001239319.1, NM_001252390.1 [Q15025-1]
NP_001239320.1, NM_001252391.1 [Q15025-1]
NP_001239321.1, NM_001252392.1 [Q15025-2]
NP_001239322.1, NM_001252393.1 [Q15025-2]
NP_001245383.1, NM_001258454.1 [Q15025-1]
NP_001245384.1, NM_001258455.1 [Q15025-4]
NP_001245385.1, NM_001258456.1 [Q15025-5]
NP_006049.3, NM_006058.4 [Q15025-1]
XP_006714814.1, XM_006714751.1 [Q15025-4]
XP_006714815.1, XM_006714752.2 [Q15025-6]
UniGeneiHs.355141
Hs.731557

Genome annotation databases

EnsembliENST00000315050; ENSP00000317891; ENSG00000145901 [Q15025-1]
ENST00000518977; ENSP00000430971; ENSG00000145901 [Q15025-2]
ENST00000520931; ENSP00000429891; ENSG00000145901 [Q15025-3]
ENST00000521591; ENSP00000430760; ENSG00000145901 [Q15025-1]
ENST00000522226; ENSP00000428187; ENSG00000145901 [Q15025-1]
ENST00000523200; ENSP00000431105; ENSG00000145901 [Q15025-4]
ENST00000523338; ENSP00000428243; ENSG00000145901 [Q15025-2]
ENST00000524280; ENSP00000429912; ENSG00000145901 [Q15025-5]
ENST00000610535; ENSP00000483944; ENSG00000145901 [Q15025-4]
ENST00000610874; ENSP00000484665; ENSG00000145901 [Q15025-5]
GeneIDi10318
KEGGihsa:10318
UCSCiuc003ltg.5 human [Q15025-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNIP1_HUMAN
AccessioniPrimary (citable) accession number: Q15025
Secondary accession number(s): A4F1W8
, A4F1W9, A4F1X2, A4F1X4, A4F1X5, A4F1X6, A4F1X7, A4F1X9, B7Z699, E7EPY1, E7ET96, O76008, Q05KP3, Q05KP4, Q6N077, Q96EL9, Q99833, Q9H1J3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: August 1, 1999
Last modified: June 20, 2018
This is version 171 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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

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