Q9NNW7 (TRXR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thioredoxin reductase 2, mitochondrial
EC=1.8.1.9

Alternative name(s):
Selenoprotein Z
Short name=SelZ
TR-beta
Thioredoxin reductase TR3

Gene names

Name:	TXNRD2
Synonyms:	KIAA1652, TRXR2

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	524 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.
Catalytic activity	Thioredoxin + NADP+ = thioredoxin disulfide + NADPH.
Cofactor	FAD By similarity.
Subunit structure	Homodimer. UniProtKB P38816
Subcellular location	Mitochondrion Ref.2 Ref.3.
Tissue specificity	Highly expressed in the prostate, ovary, liver, testis, uterus, colon and small intestine. Intermediate levels in brain, skeletal muscle, heart and spleen. Low levels in placenta, pancreas, thymus and peripheral blood leukocytes. According to Ref.5, high levels in kidney, whereas according to Ref.2, levels are low. Ref.2 Ref.3 Ref.5
Miscellaneous	The active site is a redox-active disulfide bond. The selenocysteine residue is essential for enzymatic activity By similarity. UniProtKB Q9Z0J5
Sequence similarities	Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
Sequence caution	The sequence AAD25167.1 differs from that shown. Reason: Erroneous initiation. The sequence AAG47635.1 differs from that shown. Reason: Erroneous termination at position 523. Translated as Sec.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism Selenocysteine
Domain	Redox-active center Transit peptide
Ligand	FAD Flavoprotein NADP
Molecular function	Oxidoreductase
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro heart development Inferred from electronic annotation. Source: Compara hemopoiesis Inferred from electronic annotation. Source: Compara response to oxygen radical Traceable author statement Ref.1. Source: UniProtKB
Cellular_component	mitochondrion Inferred from direct assay Ref.3. Source: UniProtKB
Molecular_function	NADP binding Inferred from electronic annotation. Source: InterPro flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro thioredoxin-disulfide reductase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NNW7-1)

Also known as: Alpha;

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.

Isoform 2 (identifier: Q9NNW7-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MAAMAVALRGLGGRFRWRTQAVAGGVRGAA → MEDQ

Isoform 3 (identifier: Q9NNW7-3)

Also known as: SelZf2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.

Isoform 4 (identifier: Q9NNW7-4)

Also known as: SelZf1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-247: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 36	36	Mitochondrion Potential
	Chain	37 – 524	488	Thioredoxin reductase 2, mitochondrial		PRO_0000030288
Regions
	Nucleotide binding	41 – 70	30	FAD By similarity
Sites
	Active site	497	1	Proton acceptor By similarity
Amino acid modifications
	Non-standard residue	523	1	Selenocysteine
	Disulfide bond	86 ↔ 91		Redox-active By similarity UniProtKB P00390
	Cross-link	522 ↔ 523		Cysteinyl-selenocysteine (Cys-Sec) By similarity
Natural variations
	Alternative sequence	1 – 247	247	Missing in isoform 4.		VSP_008306
	Alternative sequence	1 – 96	96	Missing in isoform 3.		VSP_008305
	Alternative sequence	1 – 30	30	MAAMA…VRGAA → MEDQ in isoform 2.		VSP_008304
	Natural variant	14	1	R → L. Corresponds to variant rs45593642 [ dbSNP | Ensembl ].		VAR_051777
	Natural variant	66	1	A → S. Ref.2 Ref.6 Ref.8 Corresponds to variant rs5748469 [ dbSNP | Ensembl ].		VAR_051778
	Natural variant	299	1	S → R. Corresponds to variant rs5992495 [ dbSNP | Ensembl ].		VAR_051779
	Natural variant	370	1	I → T. Ref.4 Ref.5 Ref.6 Corresponds to variant rs1139793 [ dbSNP | Ensembl ].		VAR_051780
Experimental info
	Sequence conflict	33	1	Missing in AAG47635. Ref.6
	Sequence conflict	285	1	R → K in AAG47635. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified February 26, 2008. Version 3. Checksum: B575A185A2183DAC	FASTA	524	56,507
	10 20 30 40 50 60 MAAMAVALRG LGGRFRWRTQ AVAGGVRGAA RGAAAGQRDY DLLVVGGGSG GLACAKEAAQ 70 80 90 100 110 120 LGRKVAVVDY VEPSPQGTRW GLGGTCVNVG CIPKKLMHQA ALLGGLIQDA PNYGWEVAQP 130 140 150 160 170 180 VPHDWRKMAE AVQNHVKSLN WGHRVQLQDR KVKYFNIKAS FVDEHTVCGV AKGGKEILLS 190 200 210 220 230 240 ADHIIIATGG RPRYPTHIEG ALEYGITSDD IFWLKESPGK TLVVGASYVA LECAGFLTGI 250 260 270 280 290 300 GLDTTIMMRS IPLRGFDQQM SSMVIEHMAS HGTRFLRGCA PSRVRRLPDG QLQVTWEDST 310 320 330 340 350 360 TGKEDTGTFD TVLWAIGRVP DTRSLNLEKA GVDTSPDTQK ILVDSREATS VPHIYAIGDV 370 380 390 400 410 420 VEGRPELTPI AIMAGRLLVQ RLFGGSSDLM DYDNVPTTVF TPLEYGCVGL SEEEAVARHG 430 440 450 460 470 480 QEHVEVYHAH YKPLEFTVAG RDASQCYVKM VCLREPPQLV LGLHFLGPNA GEVTQGFALG 490 500 510 520 IKCGASYAQV MRTVGIHPTC SEEVVKLRIS KRSGLDPTVT GCUG
	Isoform 2 (Beta) [UniParc]. Checksum: 7B255499E2F1881E	FASTA	498	53,970
	10 20 30 40 50 60 MEDQRGAAAG QRDYDLLVVG GGSGGLACAK EAAQLGRKVA VVDYVEPSPQ GTRWGLGGTC 70 80 90 100 110 120 VNVGCIPKKL MHQAALLGGL IQDAPNYGWE VAQPVPHDWR KMAEAVQNHV KSLNWGHRVQ 130 140 150 160 170 180 LQDRKVKYFN IKASFVDEHT VCGVAKGGKE ILLSADHIII ATGGRPRYPT HIEGALEYGI 190 200 210 220 230 240 TSDDIFWLKE SPGKTLVVGA SYVALECAGF LTGIGLDTTI MMRSIPLRGF DQQMSSMVIE 250 260 270 280 290 300 HMASHGTRFL RGCAPSRVRR LPDGQLQVTW EDSTTGKEDT GTFDTVLWAI GRVPDTRSLN 310 320 330 340 350 360 LEKAGVDTSP DTQKILVDSR EATSVPHIYA IGDVVEGRPE LTPIAIMAGR LLVQRLFGGS 370 380 390 400 410 420 SDLMDYDNVP TTVFTPLEYG CVGLSEEEAV ARHGQEHVEV YHAHYKPLEF TVAGRDASQC 430 440 450 460 470 480 YVKMVCLREP PQLVLGLHFL GPNAGEVTQG FALGIKCGAS YAQVMRTVGI HPTCSEEVVK 490 LRISKRSGLD PTVTGCUG
	Isoform 3 (SelZf2) [UniParc]. Checksum: CA7963D57A19ADAB	FASTA	428	46,841
	10 20 30 40 50 60 MHQAALLGGL IQDAPNYGWE VAQPVPHDWR KMAEAVQNHV KSLNWGHRVQ LQDRKVKYFN 70 80 90 100 110 120 IKASFVDEHT VCGVAKGGKE ILLSADHIII ATGGRPRYPT HIEGALEYGI TSDDIFWLKE 130 140 150 160 170 180 SPGKTLVVGA SYVALECAGF LTGIGLDTTI MMRSIPLRGF DQQMSSMVIE HMASHGTRFL 190 200 210 220 230 240 RGCAPSRVRR LPDGQLQVTW EDSTTGKEDT GTFDTVLWAI GRVPDTRSLN LEKAGVDTSP 250 260 270 280 290 300 DTQKILVDSR EATSVPHIYA IGDVVEGRPE LTPIAIMAGR LLVQRLFGGS SDLMDYDNVP 310 320 330 340 350 360 TTVFTPLEYG CVGLSEEEAV ARHGQEHVEV YHAHYKPLEF TVAGRDASQC YVKMVCLREP 370 380 390 400 410 420 PQLVLGLHFL GPNAGEVTQG FALGIKCGAS YAQVMRTVGI HPTCSEEVVK LRISKRSGLD PTVTGCUG
	Isoform 4 (SelZf1) [UniParc]. Checksum: 80F3E412BF2738F3	FASTA	277	30,291
	10 20 30 40 50 60 MRSIPLRGFD QQMSSMVIEH MASHGTRFLR GCAPSRVRRL PDGQLQVTWE DSTTGKEDTG 70 80 90 100 110 120 TFDTVLWAIG RVPDTRSLNL EKAGVDTSPD TQKILVDSRE ATSVPHIYAI GDVVEGRPEL 130 140 150 160 170 180 TPIAIMAGRL LVQRLFGGSS DLMDYDNVPT TVFTPLEYGC VGLSEEEAVA RHGQEHVEVY 190 200 210 220 230 240 HAHYKPLEFT VAGRDASQCY VKMVCLREPP QLVLGLHFLG PNAGEVTQGF ALGIKCGASY 250 260 270 AQVMRTVGIH PTCSEEVVKL RISKRSGLDP TVTGCUG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases." Sun Q.-A., Wu Y., Zappacosta F., Jeang K.-T., Lee B.J., Hatfield D.L., Gladyshev V.N. J. Biol. Chem. 274:24522-24530(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Cloning, sequencing and functional expression of a novel human thioredoxin reductase." Gasdaska P.Y., Berggren M.M., Berry M.J., Powis G. FEBS Lett. 442:105-111(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT SER-66. Tissue: Fetal heart and Placenta.
[3]	"Human mitochondrial thioredoxin reductase: cDNA cloning, expression and genomic organization." Miranda-Vizuete A., Damdimopoulos A.E., Pedrajas J.R., Gustafsson J.-A., Spyrou G. Eur. J. Biochem. 261:405-412(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Adrenal gland and Testis.
[4]	Toji S., Yano M., Tamai K. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), VARIANT THR-370.
[5]	"Novel selenoproteins identified in silico and in vivo by using a conserved RNA structural motif." Lescure A., Gautheret D., Carbon P., Krol A. J. Biol. Chem. 274:38147-38154(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, VARIANT THR-370. Tissue: Cervix carcinoma.
[6]	Kim J.-R., Lee Y.H., Lee S.-R., Kim B.H., Rhee S.G., Kim J.H. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), VARIANTS SER-66 AND THR-370.
[7]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] OF 40-524, VARIANT SER-66. Tissue: Skin.
[9]	"Heterogeneity within animal thioredoxin reductases: evidence for alternative first exon splicing." Sun Q.-A., Zappacosta F., Factor V.M., Wirth P.J., Hatfield D.L., Gladyshev V.N. J. Biol. Chem. 276:3106-3114(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF171054 mRNA. Translation: AAD51324.1.
AF106697 mRNA. Translation: AAD19597.1.
AF044212 mRNA. Translation: AAD25167.1. Different initiation.
AB019694 mRNA. Translation: BAA77601.2.
AB019695 mRNA. Translation: BAA77602.2.
AF166126 mRNA. Translation: AAF21431.1.
AF166127 mRNA. Translation: AAF21432.1.
AF201385 mRNA. Translation: AAG47635.1. Sequence problems.
AC000078 Genomic DNA. No translation available.
AC000080 Genomic DNA. No translation available.
AC000090 Genomic DNA. No translation available.
BC007489 mRNA. Translation: AAH07489.3.

IPI

IPI00220566.
IPI00883598.
IPI01018202.
IPI01021422.

RefSeq

NP_006431.2. NM_006440.3.

UniGene

Hs.443430.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W1E	model	-	A/B	36-524	[»]

ProteinModelPortal

Q9NNW7.

ModBase

Search...

PTM databases

PhosphoSite

Q9NNW7.

Polymorphism databases

DMDM

182705230.

Proteomic databases

PaxDb

Q9NNW7.

PRIDE

Q9NNW7.

Protocols and materials databases

DNASU

10587.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000400521; ENSP00000383365; ENSG00000184470.

GeneID

10587.

KEGG

hsa:10587.

UCSC

uc002zqq.1. human.
uc021wlj.1. human.

Organism-specific databases

CTD

10587.

GeneCards

GC22M019863.

H-InvDB

HIX0016244.

HGNC

HGNC:18155. TXNRD2.

HPA

CAB002007.
HPA003323.

MIM

606448. gene.

neXtProt

NX_Q9NNW7.

Orphanet

154. Familial isolated dilated cardiomyopathy.

PharmGKB

PA38302.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1249.

HOVERGEN

HBG004959.

InParanoid

Q9NNW7.

KO

K00384.

OMA

VMRTVGI.

PhylomeDB

Q9NNW7.

Gene expression databases

ArrayExpress

Q9NNW7.

Bgee

Q9NNW7.

Genevestigator

Q9NNW7.

GermOnline

ENSG00000184470. Homo sapiens.

Family and domain databases

Gene3D

3.30.390.30. 1 hit.

InterPro

IPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR012999. Pyr_OxRdtase_I_AS.
IPR001327. Pyr_OxRdtase_NAD-bd_dom.
IPR006338. Thioredoxin/glutathione_Rdtase.
[Graphical view]

PANTHER

PTHR22912:SF23. PTHR22912:SF23. 1 hit.

Pfam

PF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]

PRINTS

PR00368. FADPNR.

SUPFAM

SSF55424. FAD/NAD-linked_reductase_dimer. 1 hit.

TIGRFAMs

TIGR01438. TGR. 1 hit.

PROSITE

PS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9NNW7.

ChEMBL

CHEMBL2403.

ChiTaRS

TXNRD2. human.

GenomeRNAi

10587.

NextBio

40203.

SOURCE

Search...

Entry information

Entry name

TRXR2_HUMAN

Accession

Primary (citable) accession number: Q9NNW7
Secondary accession number(s): O95840 , Q96IJ2, Q9H2Z5, Q9NZV3, Q9NZV4, Q9P2Y0, Q9P2Y1, Q9UQU8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	February 26, 2008
Last modified:	May 1, 2013
This is version 128 of the entry and version 3 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.