Q9H3M7 (TXNIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thioredoxin-interacting protein

Alternative name(s):
Thioredoxin-binding protein 2
Vitamin D3 up-regulated protein 1

Gene names

Name:	TXNIP
Synonyms:	VDUP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	391 AA.
Sequence status	Complete.
Protein existence	Evidence 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.13
Subunit structure	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.11 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.11
Sequence similarities	Belongs to the arrestin family.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell 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: Compara 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: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara protein import into nucleus Inferred from electronic annotation. Source: Compara regulation of cell proliferation Inferred from electronic annotation. Source: Compara response to calcium ion Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara response to hydrogen peroxide Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to progesterone stimulus Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrial intermembrane space Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	enzyme inhibitor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 391	391	Thioredoxin-interacting protein		PRO_0000250489
Amino acid modifications
	Modified residue	361	1	Phosphoserine Ref.10
	Cross-link	212		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Natural variations
	Natural variant	177	1	R → Q. Corresponds to variant rs6674773 [ dbSNP | Ensembl ].		VAR_048334
Experimental info
	Sequence conflict	26	1	K → R in AAB31977. Ref.1
	Sequence conflict	26	1	K → R in AAT01927. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9H3M7 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: B0FE2D35D0B0735A	FASTA	391	43,661
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-212, MASS SPECTROMETRY.
[10]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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.
[12]	"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.
[13]	"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.
+	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.

IPI

IPI00007956.

RefSeq

NP_006463.3. NM_006472.3.
XP_003960218.1. XM_003960169.1.
XP_003960219.1. XM_003960170.1.

UniGene

Hs.533977.
Hs.726920.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4GEI	X-ray	1.50	A	2-149	[»]
4GEJ	X-ray	2.90	A/B/C/D/E/F/G/H/I/J	2-149	[»]

ProteinModelPortal

Q9H3M7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9H3M7. 5 interactions.

MINT

MINT-1194670.

STRING

9606.ENSP00000358323.

PTM databases

PhosphoSite

Q9H3M7.

Polymorphism databases

DMDM

74752618.

Proteomic databases

PaxDb

Q9H3M7.

PRIDE

Q9H3M7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369317; ENSP00000358323; ENSG00000117289.

GeneID

101060503.
10628.

KEGG

hsa:101060503.
hsa:10628.

UCSC

uc001enn.4. human.

Organism-specific databases

CTD

10628.

GeneCards

GC01P145438.

HGNC

HGNC:16952. TXNIP.

HPA

CAB013291.
HPA031085.

MIM

606599. gene.

neXtProt

NX_Q9H3M7.

PharmGKB

PA38194.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG325116.

HOGENOM

HOG000237328.

HOVERGEN

HBG066469.

InParanoid

Q9H3M7.

OMA

SILGCNI.

OrthoDB

EOG4XSKQ1.

PhylomeDB

Q9H3M7.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9H3M7.

Bgee

Q9H3M7.

CleanEx

HS_TXNIP.

Genevestigator

Q9H3M7.

GermOnline

ENSG00000117289. Homo sapiens.

Family and domain databases

InterPro

IPR011021. Arrestin-like_N.
IPR011022. Arrestin_C-like.
IPR014756. Ig_E-set.
[Graphical view]

Pfam

PF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]

SMART

SM01017. Arrestin_C. 1 hit.
[Graphical view]

SUPFAM

SSF81296. Ig_E-set. 2 hits.

ProtoNet

Search...

Other

ChiTaRS

TXNIP. human.

NextBio

40381.

SOURCE

Search...

Entry information

Entry name

TXNIP_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.