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Protein

Thioredoxin-interacting protein

Gene

TXNIP

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

Keywordsi

Biological processCell cycle, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-844456 The NLRP3 inflammasome
SIGNORiQ9H3M7

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

EuPathDBiHostDB:ENSG00000265972.5
HGNCiHGNC:16952 TXNIP
MIMi606599 gene
neXtProtiNX_Q9H3M7

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

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
ProteomicsDBi80731

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

BgeeiENSG00000265972 Expressed in 244 organ(s), highest expression level in left lobe of thyroid gland
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115872, 73 interactors
IntActiQ9H3M7, 14 interactors
MINTiQ9H3M7
STRINGi9606.ENSP00000358323

Structurei

Secondary structure

1391
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9H3M7
SMRiQ9H3M7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the arrestin family.Curated

Phylogenomic databases

eggNOGiKOG3780 Eukaryota
ENOG41102NY LUCA
GeneTreeiENSGT00550000074356
HOGENOMiHOG000237328
HOVERGENiHBG066469
InParanoidiQ9H3M7
KOiK20910
OMAiISGMCDA
OrthoDBiEOG091G0B0Y
PhylomeDBiQ9H3M7
TreeFamiTF313650

Family and domain databases

Gene3Di2.60.40.640, 2 hits
InterProiView protein in InterPro
IPR011021 Arrestin-like_N
IPR014752 Arrestin_C
IPR011022 Arrestin_C-like
IPR014756 Ig_E-set
PfamiView protein in Pfam
PF02752 Arrestin_C, 1 hit
PF00339 Arrestin_N, 1 hit
SMARTiView protein in SMART
SM01017 Arrestin_C, 1 hit
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 dbSNP:rs6674773Ensembl.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

Similar proteinsi

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, 73 interactors
IntActiQ9H3M7, 14 interactors
MINTiQ9H3M7
STRINGi9606.ENSP00000358323

PTM databases

iPTMnetiQ9H3M7
PhosphoSitePlusiQ9H3M7
SwissPalmiQ9H3M7

Polymorphism and mutation databases

BioMutaiTXNIP
DMDMi74752618

Proteomic databases

EPDiQ9H3M7
MaxQBiQ9H3M7
PaxDbiQ9H3M7
PeptideAtlasiQ9H3M7
PRIDEiQ9H3M7
ProteomicsDBi80731

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
EuPathDBiHostDB:ENSG00000265972.5
GeneCardsiTXNIP
HGNCiHGNC:16952 TXNIP
HPAiHPA031085
HPA053694
MIMi606599 gene
neXtProtiNX_Q9H3M7
OpenTargetsiENSG00000265972
PharmGKBiPA38194
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3780 Eukaryota
ENOG41102NY LUCA
GeneTreeiENSGT00550000074356
HOGENOMiHOG000237328
HOVERGENiHBG066469
InParanoidiQ9H3M7
KOiK20910
OMAiISGMCDA
OrthoDBiEOG091G0B0Y
PhylomeDBiQ9H3M7
TreeFamiTF313650

Enzyme and pathway databases

ReactomeiR-HSA-844456 The NLRP3 inflammasome
SIGNORiQ9H3M7

Miscellaneous databases

ChiTaRSiTXNIP human
GeneWikiiTXNIP
GenomeRNAii10628
PROiPR:Q9H3M7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000265972 Expressed in 244 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_TXNIP
ExpressionAtlasiQ9H3M7 baseline and differential
GenevisibleiQ9H3M7 HS

Family and domain databases

Gene3Di2.60.40.640, 2 hits
InterProiView protein in InterPro
IPR011021 Arrestin-like_N
IPR014752 Arrestin_C
IPR011022 Arrestin_C-like
IPR014756 Ig_E-set
PfamiView protein in Pfam
PF02752 Arrestin_C, 1 hit
PF00339 Arrestin_N, 1 hit
SMARTiView protein in SMART
SM01017 Arrestin_C, 1 hit
SUPFAMiSSF81296 SSF81296, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTXNIP_HUMAN
AccessioniPrimary (citable) accession number: Q9H3M7
Secondary accession number(s): B4E3D3
, Q16226, Q6PML0, Q9BXG9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: March 1, 2001
Last modified: September 12, 2018
This is version 139 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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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