Q16881 (TRXR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thioredoxin reductase 1, cytoplasmic
Short name=TR
EC=1.8.1.9

Alternative name(s):
Gene associated with retinoic and interferon-induced mortality 12 protein
Short name=GRIM-12
Short name=Gene associated with retinoic and IFN-induced mortality 12 protein
KM-102-derived reductase-like factor
Thioredoxin reductase TR1

Gene names

Name:	TXNRD1
Synonyms:	GRIM12, KDRF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	649 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid. Ref.3 Ref.12 Ref.14 Ref.18
Catalytic activity	Thioredoxin + NADP+ = thioredoxin disulfide + NADPH.
Cofactor	Binds 1 FAD per subunit.
Subunit structure	Homodimer. Isoform 4 interacts with ESR1 and ESR2. Interacts with HERC5. Ref.12 Ref.14 Ref.16
Subcellular location	Cytoplasm By similarity Ref.14. Isoform 4: Cytoplasm. Nucleus Ref.14. Isoform 5: Cytoplasm Ref.14.
Tissue specificity	Isoform 1 is expressed predominantly in Leydig cells (at protein level). Also expressed in ovary, spleen, heart, liver, kidney and pancreas and in a number of cancer cell lines. Isoform 4 is widely expressed with highest levels in kidney, testis, uterus, ovary, prostate, placenta and fetal liver. Ref.2 Ref.14 Ref.18
Induction	Isoform 5 is induced by a combination of interferon-beta and retinoic acid (at protein level). Isoform 1 is induced by estradiol or testosterone in HeLa cells. Ref.3 Ref.18
Domain	The N-terminal glutaredoxin domain found in isoform 1 does not contain the C-P-Y-C redox-active motif normally found in glutaredoxins and has been found to be inactive in classical glutaredoxin assays. Ref.13
Post-translational modification	The N-terminus of isoform 5 is blocked. ISGylated Probable. Ref.16
Miscellaneous	The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity.
Sequence similarities	Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. Contains 1 glutaredoxin domain.
Sequence caution	The sequence AAB35418.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec. The sequence AAC69621.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec. The sequence AAF15900.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec. The sequence AAV38446.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec. The sequence AAZ67916.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec. The sequence BAA13674.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec. The sequence CAA04503.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec. The sequence CAA62629.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec. The sequence CAG38744.1 differs from that shown. Reason: Erroneous termination at position 648. Translated as Sec.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism Selenocysteine
Domain	Redox-active center
Ligand	FAD Flavoprotein NADP
Molecular function	Oxidoreductase
PTM	Acetylation Disulfide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro cellular lipid metabolic process Traceable author statement. Source: Reactome electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW nucleobase-containing small molecule interconversion Traceable author statement. Source: Reactome signal transduction Non-traceable author statement. Source: ProtInc transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome nucleolus Inferred from direct assay. Source: HPA
Molecular function	NADP binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro thioredoxin-disulfide reductase activity Inferred from experiment. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q16881-1)

Also known as: V; TXNRD1_v3;

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.

Note: Minor isoform.

Isoform 2 (identifier: Q16881-2)

Also known as: II; TXNRD1_v4;

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: Missing.
     107-138: LEGTLSELAAETDLPVVFVKQRKIGGHGPTLK → MLSRLVLNSWAQAIIRPRPPKVLGLQVTTFSE

Isoform 3 (identifier: Q16881-3)

Also known as: III; TXNRD1_v5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.
     52-100: TADSRALLQA...VPYFVLELDQ → MQQVMLTCKG...LTRSALLLCH

Isoform 4 (identifier: Q16881-4)

Also known as: IV; TXNRD1_v2; TrxR1b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: Missing.
     99-101: DQT → MSC

Isoform 5 (identifier: Q16881-5)

Also known as: I; TXNRD1_v1; TrxR1a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-150: Missing.

Note: Major isoform. The N-terminus of the sequence is processed into a mature form that lacks residues Met-151 and Asn-152 at the N-terminus.

Isoform 6 (identifier: Q16881-6)

Also known as: VI;

The sequence of this isoform differs from the canonical sequence as follows:
     1-139: MGCAEGKAVA...IGGHGPTLKA → MPVDDYWLCL...QERNVQFGLA

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 649

649

Thioredoxin reductase 1, cytoplasmic

PRO_0000030286

Regions

Domain

56 – 156

101

Glutaredoxin

Nucleotide binding

192 – 209

18

FAD By similarity

Sites

Active site

622

1

Proton acceptor By similarity

Amino acid modifications

Non-standard residue

648

1

Selenocysteine Ref.11

Modified residue

161

1

Phosphotyrosine Ref.15

Modified residue

163

1

Phosphotyrosine Ref.15

Modified residue

239

1

N6-acetyllysine Ref.19

Modified residue

281

1

Phosphotyrosine Ref.15 Ref.17

Modified residue

405

1

N6-acetyllysine Ref.19

Modified residue

572

1

Phosphotyrosine Ref.15

Disulfide bond

209 ↔ 214

Redox-active By similarity

Cross-link

647 ↔ 648

Cysteinyl-selenocysteine (Cys-Sec) By similarity

Natural variations

Alternative sequence

1 – 150

150

Missing in isoform 5.

VSP_031558

Alternative sequence

1 – 139

139

MGCAE…PTLKA → MPVDDYWLCLPASCARPFVQ TVRVVQSCPHCCWFPGVLPS VPEPLRMPAMLPTGSHSAVL PPSHCSTAPPSTSQEPSSSA DPKLCLSPPTSDSRQERNVQ FGLA in isoform 6.

VSP_031559

Alternative sequence

1 – 106

106

Missing in isoform 2.

VSP_031560

Alternative sequence

1 – 98

98

Missing in isoform 4.

VSP_031561

Alternative sequence

1 – 51

51

Missing in isoform 3.

VSP_031562

Alternative sequence

52 – 100

49

TADSR…LELDQ → MQQVMLTCKGVNRGHAVPAG PGRKPRPRRSSRLLAGEKHL TRSALLLCH in isoform 3.

VSP_031563

Alternative sequence

99 – 101

3

DQT → MSC in isoform 4.

VSP_031564

Alternative sequence

107 – 138

32

LEGTL…GPTLK → MLSRLVLNSWAQAIIRPRPP KVLGLQVTTFSE in isoform 2.

VSP_031565

Natural variant

365

1

D → G. Ref.1 Ref.4
Corresponds to variant rs1127954 [ dbSNP | Ensembl ].

VAR_051776

Experimental info

Sequence conflict

153

1

G → S in AAQ62473. Ref.4

Sequence conflict

181

1

A → P in AAF15900. Ref.6

Sequence conflict

194

1

V → G in AAF15900. Ref.6

Sequence conflict

200

1

G → E in AAQ62469. Ref.4

Sequence conflict

202

1

R → K in AAQ62463. Ref.4

Sequence conflict

215

1

I → N in AAQ62463. Ref.4

Sequence conflict

306

1

R → S in AAB35418. Ref.1

Sequence conflict

306

1

R → S in CAA62629. Ref.1

Sequence conflict

306

1

R → S in AAL15432. Ref.4

Sequence conflict

365

1

D → N in AAC69621. Ref.3

Sequence conflict

449

1

K → R in CAG38744. Ref.7

Sequence conflict

641

1

S → R in AAC69621. Ref.3

Secondary structure

1

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649

Helix Strand Turn

Details...

Beta strand

12 – 18

7

Helix

22 – 32

11

Turn

33 – 35

3

Beta strand

38 – 41

4

Helix

57 – 62

6

Helix

64 – 83

20

Turn

84 – 87

4

Helix

98 – 122

25

Beta strand

126 – 128

3

Beta strand

130 – 136

7

Beta strand

139 – 144

6

Beta strand

149 – 159

11

Beta strand

163 – 165

3

Helix

173 – 176

4

Helix

180 – 183

4

Beta strand

192 – 196

5

Helix

200 – 211

12

Beta strand

216 – 222

7

Helix

230 – 242

13

Beta strand

246 – 260

15

Beta strand

266 – 277

12

Beta strand

279 – 289

11

Beta strand

293 – 296

4

Beta strand

298 – 300

3

Turn

302 – 306

5

Turn

311 – 313

3

Beta strand

329 – 331

3

Helix

343 – 358

16

Beta strand

372 – 374

3

Beta strand

376 – 378

3

Beta strand

380 – 384

5

Helix

387 – 394

8

Helix

396 – 398

3

Beta strand

399 – 406

8

Helix

409 – 411

3

Turn

412 – 415

4

Beta strand

421 – 428

8

Helix

429 – 431

3

Beta strand

434 – 442

9

Helix

445 – 457

13

Helix

462 – 467

6

Helix

475 – 480

6

Turn

486 – 488

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (V) (TXNRD1_v3) [UniParc]. Last modified February 26, 2008. Version 3. Checksum: 5A51C3F77EB03EFE	FASTA	649	70,906
	10 20 30 40 50 60 MGCAEGKAVA AAAPTELQTK GKNGDGRRRS AKDHHPGKTL PENPAGFTST ATADSRALLQ 70 80 90 100 110 120 AYIDGHSVVI FSRSTCTRCT EVKKLFKSLC VPYFVLELDQ TEDGRALEGT LSELAAETDL 130 140 150 160 170 180 PVVFVKQRKI GGHGPTLKAY QEGRLQKLLK MNGPEDLPKS YDYDLIIIGG GSGGLAAAKE 190 200 210 220 230 240 AAQYGKKVMV LDFVTPTPLG TRWGLGGTCV NVGCIPKKLM HQAALLGQAL QDSRNYGWKV 250 260 270 280 290 300 EETVKHDWDR MIEAVQNHIG SLNWGYRVAL REKKVVYENA YGQFIGPHRI KATNNKGKEK 310 320 330 340 350 360 IYSAERFLIA TGERPRYLGI PGDKEYCISS DDLFSLPYCP GKTLVVGASY VALECAGFLA 370 380 390 400 410 420 GIGLDVTVMV RSILLRGFDQ DMANKIGEHM EEHGIKFIRQ FVPIKVEQIE AGTPGRLRVV 430 440 450 460 470 480 AQSTNSEEII EGEYNTVMLA IGRDACTRKI GLETVGVKIN EKTGKIPVTD EEQTNVPYIY 490 500 510 520 530 540 AIGDILEDKV ELTPVAIQAG RLLAQRLYAG STVKCDYENV PTTVFTPLEY GACGLSEEKA 550 560 570 580 590 600 VEKFGEENIE VYHSYFWPLE WTIPSRDNNK CYAKIICNTK DNERVVGFHV LGPNAGEVTQ 610 620 630 640 GFAAALKCGL TKKQLDSTIG IHPVCAEVFT TLSVTKRSGA SILQAGCUG
	Isoform 2 (II) (TXNRD1_v4) [UniParc]. Checksum: 990DB8D334659B4D	FASTA	543	59,787
	10 20 30 40 50 60 MLSRLVLNSW AQAIIRPRPP KVLGLQVTTF SEAYQEGRLQ KLLKMNGPED LPKSYDYDLI 70 80 90 100 110 120 IIGGGSGGLA AAKEAAQYGK KVMVLDFVTP TPLGTRWGLG GTCVNVGCIP KKLMHQAALL 130 140 150 160 170 180 GQALQDSRNY GWKVEETVKH DWDRMIEAVQ NHIGSLNWGY RVALREKKVV YENAYGQFIG 190 200 210 220 230 240 PHRIKATNNK GKEKIYSAER FLIATGERPR YLGIPGDKEY CISSDDLFSL PYCPGKTLVV 250 260 270 280 290 300 GASYVALECA GFLAGIGLDV TVMVRSILLR GFDQDMANKI GEHMEEHGIK FIRQFVPIKV 310 320 330 340 350 360 EQIEAGTPGR LRVVAQSTNS EEIIEGEYNT VMLAIGRDAC TRKIGLETVG VKINEKTGKI 370 380 390 400 410 420 PVTDEEQTNV PYIYAIGDIL EDKVELTPVA IQAGRLLAQR LYAGSTVKCD YENVPTTVFT 430 440 450 460 470 480 PLEYGACGLS EEKAVEKFGE ENIEVYHSYF WPLEWTIPSR DNNKCYAKII CNTKDNERVV 490 500 510 520 530 540 GFHVLGPNAG EVTQGFAAAL KCGLTKKQLD STIGIHPVCA EVFTTLSVTK RSGASILQAG CUG
	Isoform 3 (III) (TXNRD1_v5) [UniParc]. Checksum: 81F496F5BB85A49E	FASTA	598	65,567
	10 20 30 40 50 60 MQQVMLTCKG VNRGHAVPAG PGRKPRPRRS SRLLAGEKHL TRSALLLCHT EDGRALEGTL 70 80 90 100 110 120 SELAAETDLP VVFVKQRKIG GHGPTLKAYQ EGRLQKLLKM NGPEDLPKSY DYDLIIIGGG 130 140 150 160 170 180 SGGLAAAKEA AQYGKKVMVL DFVTPTPLGT RWGLGGTCVN VGCIPKKLMH QAALLGQALQ 190 200 210 220 230 240 DSRNYGWKVE ETVKHDWDRM IEAVQNHIGS LNWGYRVALR EKKVVYENAY GQFIGPHRIK 250 260 270 280 290 300 ATNNKGKEKI YSAERFLIAT GERPRYLGIP GDKEYCISSD DLFSLPYCPG KTLVVGASYV 310 320 330 340 350 360 ALECAGFLAG IGLDVTVMVR SILLRGFDQD MANKIGEHME EHGIKFIRQF VPIKVEQIEA 370 380 390 400 410 420 GTPGRLRVVA QSTNSEEIIE GEYNTVMLAI GRDACTRKIG LETVGVKINE KTGKIPVTDE 430 440 450 460 470 480 EQTNVPYIYA IGDILEDKVE LTPVAIQAGR LLAQRLYAGS TVKCDYENVP TTVFTPLEYG 490 500 510 520 530 540 ACGLSEEKAV EKFGEENIEV YHSYFWPLEW TIPSRDNNKC YAKIICNTKD NERVVGFHVL 550 560 570 580 590 GPNAGEVTQG FAAALKCGLT KKQLDSTIGI HPVCAEVFTT LSVTKRSGAS ILQAGCUG
	Isoform 4 (IV) (TXNRD1_v2) (TrxR1b) [UniParc]. Checksum: F54B034AADF51E5B	FASTA	551	60,419
	10 20 30 40 50 60 MSCEDGRALE GTLSELAAET DLPVVFVKQR KIGGHGPTLK AYQEGRLQKL LKMNGPEDLP 70 80 90 100 110 120 KSYDYDLIII GGGSGGLAAA KEAAQYGKKV MVLDFVTPTP LGTRWGLGGT CVNVGCIPKK 130 140 150 160 170 180 LMHQAALLGQ ALQDSRNYGW KVEETVKHDW DRMIEAVQNH IGSLNWGYRV ALREKKVVYE 190 200 210 220 230 240 NAYGQFIGPH RIKATNNKGK EKIYSAERFL IATGERPRYL GIPGDKEYCI SSDDLFSLPY 250 260 270 280 290 300 CPGKTLVVGA SYVALECAGF LAGIGLDVTV MVRSILLRGF DQDMANKIGE HMEEHGIKFI 310 320 330 340 350 360 RQFVPIKVEQ IEAGTPGRLR VVAQSTNSEE IIEGEYNTVM LAIGRDACTR KIGLETVGVK 370 380 390 400 410 420 INEKTGKIPV TDEEQTNVPY IYAIGDILED KVELTPVAIQ AGRLLAQRLY AGSTVKCDYE 430 440 450 460 470 480 NVPTTVFTPL EYGACGLSEE KAVEKFGEEN IEVYHSYFWP LEWTIPSRDN NKCYAKIICN 490 500 510 520 530 540 TKDNERVVGF HVLGPNAGEV TQGFAAALKC GLTKKQLDST IGIHPVCAEV FTTLSVTKRS 550 GASILQAGCU G
	Isoform 5 (I) (TXNRD1_v1) (TrxR1a) [UniParc]. Checksum: C24BAEB4A573EABE	FASTA	499	54,754
	10 20 30 40 50 60 MNGPEDLPKS YDYDLIIIGG GSGGLAAAKE AAQYGKKVMV LDFVTPTPLG TRWGLGGTCV 70 80 90 100 110 120 NVGCIPKKLM HQAALLGQAL QDSRNYGWKV EETVKHDWDR MIEAVQNHIG SLNWGYRVAL 130 140 150 160 170 180 REKKVVYENA YGQFIGPHRI KATNNKGKEK IYSAERFLIA TGERPRYLGI PGDKEYCISS 190 200 210 220 230 240 DDLFSLPYCP GKTLVVGASY VALECAGFLA GIGLDVTVMV RSILLRGFDQ DMANKIGEHM 250 260 270 280 290 300 EEHGIKFIRQ FVPIKVEQIE AGTPGRLRVV AQSTNSEEII EGEYNTVMLA IGRDACTRKI 310 320 330 340 350 360 GLETVGVKIN EKTGKIPVTD EEQTNVPYIY AIGDILEDKV ELTPVAIQAG RLLAQRLYAG 370 380 390 400 410 420 STVKCDYENV PTTVFTPLEY GACGLSEEKA VEKFGEENIE VYHSYFWPLE WTIPSRDNNK 430 440 450 460 470 480 CYAKIICNTK DNERVVGFHV LGPNAGEVTQ GFAAALKCGL TKKQLDSTIG IHPVCAEVFT 490 TLSVTKRSGA SILQAGCUG
	Isoform 6 (VI) [UniParc]. Checksum: 9C635E1C6EA94934	FASTA	614	67,266
	10 20 30 40 50 60 MPVDDYWLCL PASCARPFVQ TVRVVQSCPH CCWFPGVLPS VPEPLRMPAM LPTGSHSAVL 70 80 90 100 110 120 PPSHCSTAPP STSQEPSSSA DPKLCLSPPT SDSRQERNVQ FGLAYQEGRL QKLLKMNGPE 130 140 150 160 170 180 DLPKSYDYDL IIIGGGSGGL AAAKEAAQYG KKVMVLDFVT PTPLGTRWGL GGTCVNVGCI 190 200 210 220 230 240 PKKLMHQAAL LGQALQDSRN YGWKVEETVK HDWDRMIEAV QNHIGSLNWG YRVALREKKV 250 260 270 280 290 300 VYENAYGQFI GPHRIKATNN KGKEKIYSAE RFLIATGERP RYLGIPGDKE YCISSDDLFS 310 320 330 340 350 360 LPYCPGKTLV VGASYVALEC AGFLAGIGLD VTVMVRSILL RGFDQDMANK IGEHMEEHGI 370 380 390 400 410 420 KFIRQFVPIK VEQIEAGTPG RLRVVAQSTN SEEIIEGEYN TVMLAIGRDA CTRKIGLETV 430 440 450 460 470 480 GVKINEKTGK IPVTDEEQTN VPYIYAIGDI LEDKVELTPV AIQAGRLLAQ RLYAGSTVKC 490 500 510 520 530 540 DYENVPTTVF TPLEYGACGL SEEKAVEKFG EENIEVYHSY FWPLEWTIPS RDNNKCYAKI 550 560 570 580 590 600 ICNTKDNERV VGFHVLGPNA GEVTQGFAAA LKCGLTKKQL DSTIGIHPVC AEVFTTLSVT 610 KRSGASILQA GCUG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of a human thioredoxin reductase." Gasdaska P.Y., Gasdaska J.R., Cochran S., Powis G. FEBS Lett. 373:5-9(1995) [PubMed: 7589432] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), PROTEIN SEQUENCE OF 153-161; 307-315 AND 585-607, VARIANT GLY-365. Tissue: Placenta.
[2]	"Cloning and characterization of a novel oxidoreductase KDRF from a human bone marrow-derived stromal cell line KM-102." Koishi R., Kawashima I., Yoshimura C., Sugawara M., Serizawa N. J. Biol. Chem. 272:2570-2577(1997) [PubMed: 8999974] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), PROTEIN SEQUENCE OF 122-127 AND 147-151, TISSUE SPECIFICITY. Tissue: Bone marrow stroma.
[3]	"Thioredoxin reductase mediates cell death effects of the combination of beta interferon and retinoic acid." Hofman E.R., Boyanapalli M., Lindner D.J., Weihua X., Hassel B.A., Jagus R., Gutierrez P.L., Kalvakolanu D.V. Mol. Cell. Biol. 18:6493-6504(1998) [PubMed: 9774665] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, INDUCTION. Tissue: Mammary carcinoma.
[4]	"Evidence for intriguingly complex transcription of human thioredoxin reductase 1." Rundloef A.-K., Janard M., Miranda-Vizuete A., Arner E.S. Free Radic. Biol. Med. 36:641-656(2004) [PubMed: 14980707] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5), VARIANT GLY-365. Tissue: Mammary gland, Ovary, Testis and Thymus.
[5]	"Identification by ddPCR of thioredoxin reductase as a vitamin D regulated gene in human osteoblasts." Schuetze N., Bachthaler M., Lechner A., Koehrle J., Jakob F. Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[6]	"Cloning and sequencing of thioredoxin reductase gene from human brain." Xu L., Dai R., Xu J.Y. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). Tissue: Brain.
[7]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
[8]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
[9]	NIEHS SNPs program Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). Tissue: Lung.
[11]	"Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene." Gladyshev V.N., Jeang K.-T., Stadtman T.C. Proc. Natl. Acad. Sci. U.S.A. 93:6146-6151(1996) [PubMed: 8650234] [Abstract] Cited for: PROTEIN SEQUENCE OF 307-316; 449-456; 466-476 AND 638-649, MASS SPECTROMETRY, BLOCKAGE OF N-TERMINUS, SELENOCYSTEINE AT SEC-648.
[12]	"A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity." Tamura T., Stadtman T.C. Proc. Natl. Acad. Sci. U.S.A. 93:1006-1011(1996) [PubMed: 8577704] [Abstract] Cited for: FUNCTION, HOMODIMERIZATION, CHARACTERIZATION, PRESENCE OF SELENOCYSTEINE.
[13]	"Alternative splicing involving the thioredoxin reductase module in mammals: a glutaredoxin-containing thioredoxin reductase 1." Su D., Gladyshev V.N. Biochemistry 43:12177-12188(2004) [PubMed: 15379556] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3; 4; 5 AND 6), DOMAIN.
[14]	"An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling." Damdimopoulos A.E., Miranda-Vizuete A., Treuter E., Gustafsson J.-A., Spyrou G. J. Biol. Chem. 279:38721-38729(2004) [PubMed: 15199063] [Abstract] Cited for: FUNCTION, INTERACTION WITH ESR1 AND ESR2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY (ISOFORM 4).
[15]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-161; TYR-163; TYR-281 AND TYR-572, MASS SPECTROMETRY.
[16]	"HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets." Wong J.J., Pung Y.F., Sze N.S., Chin K.C. Proc. Natl. Acad. Sci. U.S.A. 103:10735-10740(2006) [PubMed: 16815975] [Abstract] Cited for: INTERACTION WITH HERC5, ISGYLATION.
[17]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-281, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[18]	"Induction of cell membrane protrusions by the N-terminal glutaredoxin domain of a rare splice variant of human thioredoxin reductase 1." Dammeyer P., Damdimopoulos A.E., Nordman T., Jimenez A., Miranda-Vizuete A., Arner E.S.J. J. Biol. Chem. 283:2814-2821(2008) [PubMed: 18042542] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION (ISOFORM 1).
[19]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-239 AND LYS-405, MASS SPECTROMETRY.
[20]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis." Fritz-Wolf K., Urig S., Becker K. J. Mol. Biol. 370:116-127(2007) [PubMed: 17512005] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) (ISOFORM 5).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X91247 mRNA. Translation: CAA62629.1. Sequence problems.
S79851 mRNA. Translation: AAB35418.1. Sequence problems.
D88687 mRNA. Translation: BAA13674.1. Sequence problems.
AF077367 mRNA. Translation: AAC69621.1. Sequence problems.
AY057105 mRNA. Translation: AAL15432.1.
AY344081 mRNA. Translation: AAQ62461.1.
AY344083 mRNA. Translation: AAQ62462.1.
AY344084 mRNA. Translation: AAQ62463.1.
AY344086 mRNA. Translation: AAQ62464.1.
AY344087 mRNA. Translation: AAQ62465.1.
AY344089 mRNA. Translation: AAQ62466.1.
AY344092 mRNA. Translation: AAQ62467.1.
AY344093 mRNA. Translation: AAQ62468.1.
AY344095 mRNA. Translation: AAQ62469.1.
AY344096 mRNA. Translation: AAQ62470.1.
AY344670 mRNA. Translation: AAQ62471.1.
AY344673 mRNA. Translation: AAQ62472.1.
AY344679 mRNA. Translation: AAQ62473.1.
AJ001050 mRNA. Translation: CAA04503.1. Sequence problems.
AF208018 mRNA. Translation: AAF15900.1. Sequence problems.
CR536506 mRNA. Translation: CAG38744.1. Sequence problems.
BT019640 mRNA. Translation: AAV38446.1. Sequence problems.
DQ157758 Genomic DNA. Translation: AAZ67916.1. Sequence problems.
BC018122 mRNA. Translation: AAH18122.2.

IPI

IPI00554786.
IPI00783641.
IPI00847482.
IPI00871867.
IPI00885213.
IPI00983068.

PIR

S66677.

RefSeq

NP_001087240.1. NM_001093771.1.
NP_003321.3. NM_003330.2.
NP_877393.1. NM_182729.1.
NP_877419.1. NM_182742.1.
NP_877420.1. NM_182743.1.

UniGene

Hs.728817.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W1C	model	-	A/B	161-649	[»]
2CFY	X-ray	2.70	A/B/C/D/E/F	151-649	[»]
2J3N	X-ray	2.80	A/B/C/D/E/F	151-649	[»]
2ZZ0	X-ray	2.80	A/B/C/D	150-649	[»]
2ZZB	X-ray	3.20	A/B/C/D	150-649	[»]
2ZZC	X-ray	2.60	A/B/C/D	150-649	[»]
3QFA	X-ray	2.20	A/B	151-646	[»]
3QFB	X-ray	2.60	A/B	151-646	[»]

ProteinModelPortal

Q16881.

SMR

Q16881. Positions 55-649.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16881. 3 interactions.

MINT

MINT-1525880.

STRING

Q16881.

PTM databases

PhosphoSite

Q16881.

Polymorphism databases

DMDM

172046253.

2D gel databases

REPRODUCTION-2DPAGE

IPI00554786.

Proteomic databases

PRIDE

Q16881.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000429002; ENSP00000412045; ENSG00000198431.

GeneID

7296.

KEGG

hsa:7296.

Organism-specific databases

CTD

7296.

GeneCards

GC12P104609.

H-InvDB

HIX0010939.

HGNC

HGNC:12437. TXNRD1.

HPA

CAB004607.
CAB015834.
HPA001395.

MIM

601112. gene.

neXtProt

NX_Q16881.

PharmGKB

PA37093.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12063.

GeneTree

ENSGT00390000007578.

HOVERGEN

HBG004959.

InParanoid

Q16881.

OrthoDB

EOG4H463K.

PhylomeDB

Q16881.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q16881.

Bgee

Q16881.

Genevestigator

Q16881.

GermOnline

ENSG00000211449. Homo sapiens.

Family and domain databases

InterPro

IPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR002109. Glutaredoxin.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR012999. Pyr_OxRdtase_I_AS.
IPR001327. Pyr_OxRdtase_NAD-bd_dom.
IPR012336. Thioredoxin-like_fold.
IPR006338. Thioredoxin/glutathione_Rdtase.
[Graphical view]

Gene3D

G3DSA:3.30.390.30. Pyr_redox_dim. 1 hit.
G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.

KO

K00384.

PANTHER

PTHR22912:SF23. Reduct_Se. 1 hit.

Pfam

PF00462. Glutaredoxin. 1 hit.
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.
SSF52833. Thiordxn-like_fd. 1 hit.

TIGRFAMs

TIGR01438. TGR. 1 hit.

PROSITE

PS00195. GLUTAREDOXIN_1. False negative.
PS51354. GLUTAREDOXIN_2. 1 hit.
PS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

28527.

SOURCE

Search...

Entry information

Entry name

TRXR1_HUMAN

Accession

Primary (citable) accession number: Q16881
Secondary accession number(s): Q6FI31 , Q6VB40, Q6VB41, Q6VB42, Q6VBP2, Q6VBP3, Q6VBP4, Q6VBP5, Q6VBP9, Q6VBQ0, Q6YNQ1, Q76P53, Q7LA96, Q8WVC8, Q99475, Q9UES8, Q9UH79

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 26, 2008
Last modified:	January 25, 2012
This is version 143 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.