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Q9H3M7 (TXNIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thioredoxin-interacting protein
Alternative name(s):
Thioredoxin-binding protein 2
Vitamin D3 up-regulated protein 1
Gene names
Name:TXNIP
Synonyms:VDUP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length391 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.2 Ref.7 Ref.8 Ref.12

Subunit structure

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. Ref.2 Ref.7 Ref.10 Ref.12 Ref.13

Subcellular location

Cytoplasm By similarity.

Induction

By 1,25-dihydroxyvitamin D-3 and TGFB1. Down-regulated in response to oxidative stress. Ref.1 Ref.2 Ref.7

Post-translational modification

Ubiquitinated; undergoes polyubiquitination catalyzed by ITCH resulting in proteasomal degradation. Ref.10

Sequence similarities

Belongs to the arrestin family.

Ontologies

Keywords
   Biological processCell cycle
Transcription
Transcription regulation
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseTumor suppressor
   PTMDisulfide bond
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to tumor cell

Inferred from direct assay Ref.8. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

keratinocyte differentiation

Inferred from direct assay PubMed 14632196. Source: UniProtKB

negative regulation of cell division

Inferred from direct assay Ref.8. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

platelet-derived growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to progesterone

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 14632196. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

mitochondrial intermembrane space

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionenzyme inhibitor activity

Inferred from electronic annotation. Source: Ensembl

ubiquitin protein ligase binding

Inferred from physical interaction Ref.10. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 391391Thioredoxin-interacting protein
PRO_0000250489

Amino acid modifications

Modified residue3611Phosphoserine Ref.9
Disulfide bond63Interchain Ref.13
Cross-link212Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Natural variations

Natural variant1771R → Q.
Corresponds to variant rs6674773 [ dbSNP | Ensembl ].
VAR_048334

Experimental info

Sequence conflict261K → R in AAB31977. Ref.1
Sequence conflict261K → R in AAT01927. Ref.2

Secondary structure

......................... 391
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9H3M7 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: B0FE2D35D0B0735A

FASTA39143,661
        10         20         30         40         50         60 
MVMFKKIKSF EVVFNDPEKV YGSGEKVAGR VIVEVCEVTR VKAVRILACG VAKVLWMQGS 

        70         80         90        100        110        120 
QQCKQTSEYL RYEDTLLLED QPTGENEMVI MRPGNKYEYK FGFELPQGPL GTSFKGKYGC 

       130        140        150        160        170        180 
VDYWVKAFLD RPSQPTQETK KNFEVVDLVD VNTPDLMAPV SAKKEKKVSC MFIPDGRVSV 

       190        200        210        220        230        240 
SARIDRKGFC EGDEISIHAD FENTCSRIVV PKAAIVARHT YLANGQTKVL TQKLSSVRGN 

       250        260        270        280        290        300 
HIISGTCASW RGKSLRVQKI RPSILGCNIL RVEYSLLIYV SVPGSKKVIL DLPLVIGSRS 

       310        320        330        340        350        360 
GLSSRTSSMA SRTSSEMSWV DLNIPDTPEA PPCYMDVIPE DHRLESPTTP LLDDMDGSQD 

       370        380        390 
SPIFMYAPEF KFMPPPTYTE VDPCILNNNV Q 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of a novel cDNA from HL-60 cells treated with 1,25-dihydroxyvitamin D-3."
Chen K.-S., DeLuca H.F.
Biochim. Biophys. Acta 1219:26-32(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
[2]"Regulation of the bioavailability of thioredoxin in the lens by a specific thioredoxin-binding protein (TBP-2)."
Liyanage N.P.M., Fernando M.R., Lou M.F.
Exp. Eye Res. 85:270-279(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH TXN, INDUCTION.
Tissue: Lens.
[3]"Homo sapiens VDUP1 gene."
Toyama S.
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[6]"Cloning and characterization of human VDUP1 gene."
Park J.B.
Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-38.
[7]"VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression."
Han S.H., Jeon J.H., Ju H.R., Jung U., Kim K.Y., Yoo H.S., Lee Y.H., Song K.S., Hwang H.M., Na Y.S., Yang Y., Lee K.N., Choi I.
Oncogene 22:4035-4046(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION, INTERACTION WITH ZBTB16; ZBTB32 AND HDAC1.
[8]"hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip."
Shin K.H., Kim R.H., Kim R.H., Kang M.K., Park N.H.
Biochem. Biophys. Res. Commun. 372:880-885(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation."
Zhang P., Wang C., Gao K., Wang D., Mao J., An J., Xu C., Wu D., Yu H., Liu J.O., Yu L.
J. Biol. Chem. 285:8869-8879(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITCH, UBIQUITINATION BY ITCH.
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"TXNIP potentiates Redd1-induced mTOR suppression through stabilization of Redd1."
Jin H.O., Seo S.K., Kim Y.S., Woo S.H., Lee K.H., Yi J.Y., Lee S.J., Choe T.B., Lee J.H., An S., Hong S.I., Park I.C.
Oncogene 30:3792-3801(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DDIT4.
[13]"Structure of the N-terminal domain of human thioredoxin-interacting protein."
Polekhina G., Ascher D.B., Kok S.F., Beckham S., Wilce M., Waltham M.
Acta Crystallogr. D 69:333-344(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-149, SUBUNIT, INTERCHAIN DISULFIDE BOND.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S73591 mRNA. Translation: AAB31977.2.
AY594328 mRNA. Translation: AAT01927.2.
AB051901 Genomic DNA. Translation: BAB18859.1.
AL138842, AL160282 Genomic DNA. Translation: CAI22351.1.
BC093702 mRNA. Translation: AAH93702.1.
BC093704 mRNA. Translation: AAH93704.1.
AF333001 Genomic DNA. Translation: AAK37514.1.
RefSeqNP_006463.3. NM_006472.4.
UniGeneHs.533977.
Hs.709057.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalQ9H3M7.
SMRQ9H3M7. Positions 8-149.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115872. 13 interactions.
IntActQ9H3M7. 7 interactions.
MINTMINT-1194670.
STRING9606.ENSP00000358323.

PTM databases

PhosphoSiteQ9H3M7.

Polymorphism databases

DMDM74752618.

Proteomic databases

PaxDbQ9H3M7.
PRIDEQ9H3M7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369317; ENSP00000358323; ENSG00000117289.
GeneID10628.
KEGGhsa:10628.
UCSCuc001enn.4. human.

Organism-specific databases

CTD10628.
GeneCardsGC01P145438.
HGNCHGNC:16952. TXNIP.
HPACAB013291.
HPA031085.
MIM606599. gene.
neXtProtNX_Q9H3M7.
PharmGKBPA38194.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG325116.
HOGENOMHOG000237328.
HOVERGENHBG066469.
InParanoidQ9H3M7.
OMASILGCNI.
OrthoDBEOG7P02HT.
PhylomeDBQ9H3M7.
TreeFamTF313650.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9H3M7.
BgeeQ9H3M7.
CleanExHS_TXNIP.
GenevestigatorQ9H3M7.

Family and domain databases

InterProIPR011021. Arrestin-like_N.
IPR011022. Arrestin_C-like.
IPR014756. Ig_E-set.
[Graphical view]
PfamPF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]
SMARTSM01017. Arrestin_C. 1 hit.
[Graphical view]
SUPFAMSSF81296. SSF81296. 2 hits.
ProtoNetSearch...

Other

ChiTaRSTXNIP. human.
GeneWikiTXNIP.
GenomeRNAi10628.
NextBio40381.
PROQ9H3M7.
SOURCESearch...

Entry information

Entry nameTXNIP_HUMAN
AccessionPrimary (citable) accession number: Q9H3M7
Secondary accession number(s): Q16226, Q6PML0, Q9BXG9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM