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Protein

Thioredoxin-interacting protein

Gene

TXNIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).4 Publications

GO - Molecular functioni

  • enzyme inhibitor activity Source: Ensembl
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-844456. The NLRP3 inflammasome.

Names & Taxonomyi

Protein namesi
Recommended name:
Thioredoxin-interacting protein
Alternative name(s):
Thioredoxin-binding protein 2
Vitamin D3 up-regulated protein 1
Gene namesi
Name:TXNIP
Synonyms:VDUP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:16952. TXNIP.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • mitochondrial intermembrane space Source: Ensembl
  • nucleus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi10628.
OpenTargetsiENSG00000265972.
PharmGKBiPA38194.

Polymorphism and mutation databases

BioMutaiTXNIP.
DMDMi74752618.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002504891 – 391Thioredoxin-interacting proteinAdd BLAST391

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi63Interchain
Cross-linki212Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei361PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated; undergoes polyubiquitination catalyzed by ITCH resulting in proteasomal degradation.1 Publication

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9H3M7.
MaxQBiQ9H3M7.
PaxDbiQ9H3M7.
PeptideAtlasiQ9H3M7.
PRIDEiQ9H3M7.

PTM databases

iPTMnetiQ9H3M7.
PhosphoSitePlusiQ9H3M7.
SwissPalmiQ9H3M7.

Expressioni

Inductioni

By 1,25-dihydroxyvitamin D-3 and TGFB1. Down-regulated in response to oxidative stress.3 Publications

Gene expression databases

BgeeiENSG00000117289.
CleanExiHS_TXNIP.
ExpressionAtlasiQ9H3M7. baseline and differential.
GenevisibleiQ9H3M7. HS.

Organism-specific databases

HPAiHPA031085.
HPA053694.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with TXN/thioredoxin through its redox-active site. Interacts with transcriptional repressors ZBTB16, ZBTB32 and HDAC1. Interacts (via C-terminus) with ITCH (via WW domains). Interacts with DDIT4.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ECDO959055EBI-1369170,EBI-2557598
VAV2P527352EBI-1369170,EBI-297549

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115872. 41 interactors.
IntActiQ9H3M7. 12 interactors.
MINTiMINT-1194670.
STRINGi9606.ENSP00000358323.

Structurei

Secondary structure

1391
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 16Combined sources9
Beta strandi20 – 22Combined sources3
Beta strandi26 – 34Combined sources9
Beta strandi39 – 41Combined sources3
Beta strandi43 – 58Combined sources16
Beta strandi61 – 76Combined sources16
Beta strandi79 – 81Combined sources3
Beta strandi83 – 85Combined sources3
Beta strandi89 – 91Combined sources3
Beta strandi93 – 95Combined sources3
Beta strandi97 – 104Combined sources8
Beta strandi111 – 114Combined sources4
Beta strandi116 – 130Combined sources15
Beta strandi137 – 142Combined sources6
Beta strandi144 – 146Combined sources3
Beta strandi148 – 150Combined sources3
Beta strandi160 – 167Combined sources8
Beta strandi177 – 185Combined sources9
Beta strandi187 – 190Combined sources4
Beta strandi194 – 203Combined sources10
Beta strandi205 – 207Combined sources3
Beta strandi209 – 223Combined sources15
Beta strandi226 – 238Combined sources13
Beta strandi246 – 256Combined sources11
Beta strandi269 – 281Combined sources13
Beta strandi288 – 298Combined sources11
Helixi334 – 337Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4GEIX-ray1.50A2-149[»]
4GEJX-ray2.90A/B/C/D/E/F/G/H/I/J2-149[»]
4GFXX-ray1.60A4-154[»]
4LL1X-ray2.00A/C3-317[»]
4LL4X-ray2.70A/C3-317[»]
4ROFX-ray2.03C/D327-338[»]
4ROJX-ray1.95D/E/F327-338[»]
5CQ2X-ray1.40B/C327-338[»]
5DF6X-ray1.78B/C371-382[»]
5DWSX-ray1.65B/D/F/H327-338[»]
5DZDX-ray1.57C/D327-338[»]
ProteinModelPortaliQ9H3M7.
SMRiQ9H3M7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the arrestin family.Curated

Phylogenomic databases

eggNOGiKOG3780. Eukaryota.
ENOG41102NY. LUCA.
GeneTreeiENSGT00550000074356.
HOGENOMiHOG000237328.
HOVERGENiHBG066469.
InParanoidiQ9H3M7.
OMAiLEDQPTG.
OrthoDBiEOG091G0B0Y.
PhylomeDBiQ9H3M7.
TreeFamiTF313650.

Family and domain databases

InterProiIPR011021. Arrestin-like_N.
IPR011022. Arrestin_C-like.
IPR014756. Ig_E-set.
[Graphical view]
PfamiPF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]
SMARTiSM01017. Arrestin_C. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9H3M7-1) [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
MVMFKKIKSF EVVFNDPEKV YGSGEKVAGR VIVEVCEVTR VKAVRILACG
60 70 80 90 100
VAKVLWMQGS QQCKQTSEYL RYEDTLLLED QPTGENEMVI MRPGNKYEYK
110 120 130 140 150
FGFELPQGPL GTSFKGKYGC VDYWVKAFLD RPSQPTQETK KNFEVVDLVD
160 170 180 190 200
VNTPDLMAPV SAKKEKKVSC MFIPDGRVSV SARIDRKGFC EGDEISIHAD
210 220 230 240 250
FENTCSRIVV PKAAIVARHT YLANGQTKVL TQKLSSVRGN HIISGTCASW
260 270 280 290 300
RGKSLRVQKI RPSILGCNIL RVEYSLLIYV SVPGSKKVIL DLPLVIGSRS
310 320 330 340 350
GLSSRTSSMA SRTSSEMSWV DLNIPDTPEA PPCYMDVIPE DHRLESPTTP
360 370 380 390
LLDDMDGSQD SPIFMYAPEF KFMPPPTYTE VDPCILNNNV Q
Length:391
Mass (Da):43,661
Last modified:March 1, 2001 - v1
Checksum:iB0FE2D35D0B0735A
GO
Isoform 2 (identifier: Q9H3M7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-83: MVMFKKIKSF...DTLLLEDQPT → MPPKHSLSHRCILSVTASLMATRFSFPS

Note: No experimental confirmation available.
Show »
Length:336
Mass (Da):37,319
Checksum:iB93B9E573BEE0996
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26K → R in AAB31977 (PubMed:8086474).Curated1
Sequence conflicti26K → R in AAT01927 (PubMed:17603038).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048334177R → Q.Corresponds to variant rs6674773dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0544011 – 83MVMFK…EDQPT → MPPKHSLSHRCILSVTASLM ATRFSFPS in isoform 2. 1 PublicationAdd BLAST83

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73591 mRNA. Translation: AAB31977.2.
AY594328 mRNA. Translation: AAT01927.2.
AB051901 Genomic DNA. Translation: BAB18859.1.
AK304670 mRNA. Translation: BAG65445.1.
AL138842, AL160282 Genomic DNA. Translation: CAI22351.1.
BC093702 mRNA. Translation: AAH93702.1.
BC093704 mRNA. Translation: AAH93704.1.
AF333001 Genomic DNA. Translation: AAK37514.1.
CCDSiCCDS72876.1. [Q9H3M7-1]
CCDS81368.1. [Q9H3M7-2]
RefSeqiNP_001300901.1. NM_001313972.1. [Q9H3M7-2]
NP_006463.3. NM_006472.5. [Q9H3M7-1]
UniGeneiHs.533977.
Hs.709057.

Genome annotation databases

EnsembliENST00000425134; ENSP00000396322; ENSG00000265972. [Q9H3M7-2]
ENST00000582401; ENSP00000462521; ENSG00000265972. [Q9H3M7-1]
GeneIDi10628.
KEGGihsa:10628.
UCSCiuc031utq.2. human. [Q9H3M7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73591 mRNA. Translation: AAB31977.2.
AY594328 mRNA. Translation: AAT01927.2.
AB051901 Genomic DNA. Translation: BAB18859.1.
AK304670 mRNA. Translation: BAG65445.1.
AL138842, AL160282 Genomic DNA. Translation: CAI22351.1.
BC093702 mRNA. Translation: AAH93702.1.
BC093704 mRNA. Translation: AAH93704.1.
AF333001 Genomic DNA. Translation: AAK37514.1.
CCDSiCCDS72876.1. [Q9H3M7-1]
CCDS81368.1. [Q9H3M7-2]
RefSeqiNP_001300901.1. NM_001313972.1. [Q9H3M7-2]
NP_006463.3. NM_006472.5. [Q9H3M7-1]
UniGeneiHs.533977.
Hs.709057.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4GEIX-ray1.50A2-149[»]
4GEJX-ray2.90A/B/C/D/E/F/G/H/I/J2-149[»]
4GFXX-ray1.60A4-154[»]
4LL1X-ray2.00A/C3-317[»]
4LL4X-ray2.70A/C3-317[»]
4ROFX-ray2.03C/D327-338[»]
4ROJX-ray1.95D/E/F327-338[»]
5CQ2X-ray1.40B/C327-338[»]
5DF6X-ray1.78B/C371-382[»]
5DWSX-ray1.65B/D/F/H327-338[»]
5DZDX-ray1.57C/D327-338[»]
ProteinModelPortaliQ9H3M7.
SMRiQ9H3M7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115872. 41 interactors.
IntActiQ9H3M7. 12 interactors.
MINTiMINT-1194670.
STRINGi9606.ENSP00000358323.

PTM databases

iPTMnetiQ9H3M7.
PhosphoSitePlusiQ9H3M7.
SwissPalmiQ9H3M7.

Polymorphism and mutation databases

BioMutaiTXNIP.
DMDMi74752618.

Proteomic databases

EPDiQ9H3M7.
MaxQBiQ9H3M7.
PaxDbiQ9H3M7.
PeptideAtlasiQ9H3M7.
PRIDEiQ9H3M7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000425134; ENSP00000396322; ENSG00000265972. [Q9H3M7-2]
ENST00000582401; ENSP00000462521; ENSG00000265972. [Q9H3M7-1]
GeneIDi10628.
KEGGihsa:10628.
UCSCiuc031utq.2. human. [Q9H3M7-1]

Organism-specific databases

CTDi10628.
DisGeNETi10628.
GeneCardsiTXNIP.
HGNCiHGNC:16952. TXNIP.
HPAiHPA031085.
HPA053694.
MIMi606599. gene.
neXtProtiNX_Q9H3M7.
OpenTargetsiENSG00000265972.
PharmGKBiPA38194.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3780. Eukaryota.
ENOG41102NY. LUCA.
GeneTreeiENSGT00550000074356.
HOGENOMiHOG000237328.
HOVERGENiHBG066469.
InParanoidiQ9H3M7.
OMAiLEDQPTG.
OrthoDBiEOG091G0B0Y.
PhylomeDBiQ9H3M7.
TreeFamiTF313650.

Enzyme and pathway databases

ReactomeiR-HSA-844456. The NLRP3 inflammasome.

Miscellaneous databases

ChiTaRSiTXNIP. human.
GeneWikiiTXNIP.
GenomeRNAii10628.
PROiQ9H3M7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117289.
CleanExiHS_TXNIP.
ExpressionAtlasiQ9H3M7. baseline and differential.
GenevisibleiQ9H3M7. HS.

Family and domain databases

InterProiIPR011021. Arrestin-like_N.
IPR011022. Arrestin_C-like.
IPR014756. Ig_E-set.
[Graphical view]
PfamiPF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]
SMARTiSM01017. Arrestin_C. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiTXNIP_HUMAN
AccessioniPrimary (citable) accession number: Q9H3M7
Secondary accession number(s): B4E3D3
, Q16226, Q6PML0, Q9BXG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: March 1, 2001
Last modified: November 2, 2016
This is version 124 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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.