CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012755
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Thioredoxin reductase 1, cytoplasmic 
Protein Synonyms/Alias
 TR; Gene associated with retinoic and interferon-induced mortality 12 protein; GRIM-12; Gene associated with retinoic and IFN-induced mortality 12 protein; KM-102-derived reductase-like factor; Thioredoxin reductase TR1 
Gene Name
 TXNRD1 
Gene Synonyms/Alias
 GRIM12; KDRF 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
179SGGLAAAKEAAQYGKubiquitination[1, 2]
187EAAQYGKKVMVLDFVubiquitination[2, 3]
217VNVGCIPKKLMHQAAubiquitination[2, 3]
218NVGCIPKKLMHQAALubiquitination[2, 4, 5]
239DSRNYGWKVEETVKHacetylation[6]
239DSRNYGWKVEETVKHubiquitination[1, 2]
245WKVEETVKHDWDRMIubiquitination[1, 2]
274RVALREKKVVYENAYubiquitination[2, 5]
300TNNKGKEKIYSAERFubiquitination[2]
324YLGIPGDKEYCISSDubiquitination[2]
385FDQDMANKIGEHMEEubiquitination[1, 2]
396HMEEHGIKFIRQFVPubiquitination[1, 2]
405IRQFVPIKVEQIEAGacetylation[6]
405IRQFVPIKVEQIEAGubiquitination[1, 2, 3, 4, 5, 7]
449GRDACTRKIGLETVGubiquitination[1, 2, 3, 5]
458GLETVGVKINEKTGKubiquitination[1, 2]
465KINEKTGKIPVTDEEubiquitination[1, 2]
514LYAGSTVKCDYENVPubiquitination[2]
539ACGLSEEKAVEKFGEubiquitination[2]
574DNNKCYAKIICNTKDubiquitination[2]
580AKIICNTKDNERVVGubiquitination[1, 2]
607QGFAAALKCGLTKKQubiquitination[2, 3]
613LKCGLTKKQLDSTIGubiquitination[2]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [7] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 56 156 Glutaredoxin.
 NP_BIND 192 209 FAD (By similarity).
 ACT_SITE 622 622 Proton acceptor (By similarity).
 MOD_RES 281 281 Phosphotyrosine.
 DISULFID 209 214 Redox-active (By similarity).
 CROSSLNK 647 648 Cysteinyl-selenocysteine (Cys-Sec) (By  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Disulfide bond; Electron transport; FAD; Flavoprotein; NADP; Nucleus; Oxidoreductase; Phosphoprotein; Polymorphism; Redox-active center; Reference proteome; Selenocysteine; Transport; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 649 AA 
Protein Sequence
MGCAEGKAVA AAAPTELQTK GKNGDGRRRS AKDHHPGKTL PENPAGFTST ATADSRALLQ 60
AYIDGHSVVI FSRSTCTRCT EVKKLFKSLC VPYFVLELDQ TEDGRALEGT LSELAAETDL 120
PVVFVKQRKI GGHGPTLKAY QEGRLQKLLK MNGPEDLPKS YDYDLIIIGG GSGGLAAAKE 180
AAQYGKKVMV LDFVTPTPLG TRWGLGGTCV NVGCIPKKLM HQAALLGQAL QDSRNYGWKV 240
EETVKHDWDR MIEAVQNHIG SLNWGYRVAL REKKVVYENA YGQFIGPHRI KATNNKGKEK 300
IYSAERFLIA TGERPRYLGI PGDKEYCISS DDLFSLPYCP GKTLVVGASY VALECAGFLA 360
GIGLDVTVMV RSILLRGFDQ DMANKIGEHM EEHGIKFIRQ FVPIKVEQIE AGTPGRLRVV 420
AQSTNSEEII EGEYNTVMLA IGRDACTRKI GLETVGVKIN EKTGKIPVTD EEQTNVPYIY 480
AIGDILEDKV ELTPVAIQAG RLLAQRLYAG STVKCDYENV PTTVFTPLEY GACGLSEEKA 540
VEKFGEENIE VYHSYFWPLE WTIPSRDNNK CYAKIICNTK DNERVVGFHV LGPNAGEVTQ 600
GFAAALKCGL TKKQLDSTIG IHPVCAEVFT TLSVTKRSGA SILQAGCUG 649 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0009055; F:electron carrier activity; IEA:InterPro.
 GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
 GO:0045340; F:mercury ion binding; IEA:Compara.
 GO:0016174; F:NAD(P)H oxidase activity; IEA:Compara.
 GO:0050661; F:NADP binding; IEA:InterPro.
 GO:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
 GO:0033797; F:selenate reductase activity; IEA:Compara.
 GO:0004791; F:thioredoxin-disulfide reductase activity; EXP:Reactome.
 GO:0042537; P:benzene-containing compound metabolic process; IEA:Compara.
 GO:0008283; P:cell proliferation; IEA:Compara.
 GO:0045454; P:cell redox homeostasis; IEA:InterPro.
 GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
 GO:0071280; P:cellular response to copper ion; IEA:Compara.
 GO:0071455; P:cellular response to hyperoxia; IEA:Compara.
 GO:0022900; P:electron transport chain; IEA:UniProtKB-KW.
 GO:0006749; P:glutathione metabolic process; IEA:Compara.
 GO:0070276; P:halogen metabolic process; IEA:Compara.
 GO:0042744; P:hydrogen peroxide catabolic process; IEA:Compara.
 GO:0001707; P:mesoderm formation; IEA:Compara.
 GO:0042191; P:methylmercury metabolic process; IEA:Compara.
 GO:0070995; P:NADPH oxidation; IEA:Compara.
 GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
 GO:0001890; P:placenta development; IEA:Compara.
 GO:0010942; P:positive regulation of cell death; IEA:Compara.
 GO:0051262; P:protein tetramerization; IEA:Compara.
 GO:0048678; P:response to axon injury; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0010269; P:response to selenium ion; IEA:Compara.
 GO:0016259; P:selenocysteine metabolic process; IEA:Compara.
 GO:0007165; P:signal transduction; NAS:ProtInc. 
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. 
Pfam
 PF00462; Glutaredoxin
 PF00070; Pyr_redox
 PF07992; Pyr_redox_2
 PF02852; Pyr_redox_dim 
SMART
  
PROSITE
 PS00195; GLUTAREDOXIN_1
 PS51354; GLUTAREDOXIN_2
 PS00076; PYRIDINE_REDOX_1 
PRINTS
 PR00368; FADPNR.