ID GLRX3_HUMAN Reviewed; 335 AA. AC O76003; B3KMP7; B3KMQ5; D3DRG2; Q5JV01; Q96CE0; Q9P1B0; Q9P1B1; DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 26-SEP-2003, sequence version 2. DT 27-MAR-2024, entry version 218. DE RecName: Full=Glutaredoxin-3; DE AltName: Full=PKC-interacting cousin of thioredoxin {ECO:0000303|PubMed:10636891}; DE Short=PICOT {ECO:0000303|PubMed:10636891}; DE AltName: Full=PKC-theta-interacting protein; DE Short=PKCq-interacting protein; DE AltName: Full=Thioredoxin-like protein 2; GN Name=GLRX3; Synonyms=PICOT {ECO:0000303|PubMed:10636891}, TXNL2; GN ORFNames=HUSSY-22; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH PRKCQ, RP AND VARIANTS HIS-21 AND SER-123. RC TISSUE=Liver, Spleen, and T-cell lymphoma; RX PubMed=10636891; DOI=10.1074/jbc.275.3.1902; RA Witte S., Villalba M., Bi K., Liu Y., Isakov N., Altman A.; RT "Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by RT PICOT, a novel protein kinase C-interacting protein with a thioredoxin RT homology domain."; RL J. Biol. Chem. 275:1902-1909(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Melanocyte; RX PubMed=11124703; RX DOI=10.1002/1097-0061(200101)18:1<69::aid-yea647>3.0.co;2-h; RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., RA Zimbello R., Lanfranchi G., Valle G.; RT "Characterization of 16 novel human genes showing high similarity to yeast RT sequences."; RL Yeast 18:69-80(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-21 AND SER-123. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-21 AND SER-123. RC TISSUE=Bone marrow, and Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 59-79; 115-130; 218-231; 246-253; 309-319 AND 323-332. RC TISSUE=Fetal brain cortex; RA Lubec G., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [8] RP SUBUNIT, MUTAGENESIS OF CYS-159 AND CYS-261, AND METAL. RX PubMed=20226171; DOI=10.1016/j.bbrc.2010.03.016; RA Haunhorst P., Berndt C., Eitner S., Godoy J.R., Lillig C.H.; RT "Characterization of the human monothiol glutaredoxin 3 (PICOT) as iron- RT sulfur protein."; RL Biochem. Biophys. Res. Commun. 394:372-376(2010). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP INTERACTION WITH BOLA2. RX PubMed=22309771; DOI=10.1021/bi2019089; RA Li H., Mapolelo D.T., Randeniya S., Johnson M.K., Outten C.E.; RT "Human glutaredoxin 3 forms [2Fe-2S]-bridged complexes with human BolA2."; RL Biochemistry 51:1687-1696(2012). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117 AND SER-120, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP FUNCTION. RX PubMed=23615448; DOI=10.1091/mbc.e12-09-0648; RA Haunhorst P., Hanschmann E.M., Brautigam L., Stehling O., Hoffmann B., RA Muhlenhoff U., Lill R., Berndt C., Lillig C.H.; RT "Crucial function of vertebrate glutaredoxin 3 (PICOT) in iron homeostasis RT and hemoglobin maturation."; RL Mol. Biol. Cell 24:1895-1903(2013). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP FUNCTION, AND INTERACTION WITH BOLA2. RX PubMed=26613676; DOI=10.1021/jacs.5b10592; RA Banci L., Camponeschi F., Ciofi-Baffoni S., Muzzioli R.; RT "Elucidating the molecular function of human BOLA2 in GRX3-dependent RT anamorsin maturation pathway."; RL J. Am. Chem. Soc. 137:16133-16143(2015). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH BOLA2, AND RP MUTAGENESIS OF CYS-159; 159-TRP-PRO-160; CYS-261 AND 299-TRP-PRO-300. RX PubMed=27519415; DOI=10.1074/jbc.m116.744946; RA Frey A.G., Palenchar D.J., Wildemann J.D., Philpott C.C.; RT "A glutaredoxin-BolA complex serves as an iron-sulfur cluster chaperone for RT the cytosolic cluster assembly machinery."; RL J. Biol. Chem. 291:22344-22356(2016). RN [19] RP STRUCTURE BY NMR OF 1-119. RG RIKEN structural genomics initiative (RSGI); RT "The solution structure of the thioredoxin domain of human thioredoxin-like RT protein 2."; RL Submitted (APR-2007) to the PDB data bank. CC -!- FUNCTION: Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) CC cluster assembly factor that facilitates [2Fe-2S] cluster insertion CC into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). CC Acts as a critical negative regulator of cardiac hypertrophy and a CC positive inotropic regulator (By similarity). Required for hemoglobin CC maturation (PubMed:23615448). Does not possess any thyoredoxin activity CC since it lacks the conserved motif that is essential for catalytic CC activity. {ECO:0000250|UniProtKB:Q9CQM9, ECO:0000269|PubMed:23615448, CC ECO:0000269|PubMed:26613676, ECO:0000269|PubMed:27519415}. CC -!- SUBUNIT: Homodimer; the homodimer is independent of 2Fe-2S clusters CC (PubMed:27519415). Heterotrimer; forms a heterotrimeric complex CC composed by two BOLA2 molecules and one GLRX3 molecule; linked by [2Fe- CC 2S] clusters (PubMed:22309771, PubMed:26613676, PubMed:27519415). CC Interacts (via N-terminus) with PRKCQ/PKC-theta (PubMed:10636891). CC Interacts (via C-terminus) with CSRP3 (By similarity). Interacts with CC CSRP2 (By similarity). {ECO:0000250|UniProtKB:Q9CQM9, CC ECO:0000269|PubMed:10636891, ECO:0000269|PubMed:22309771, CC ECO:0000269|PubMed:26613676, ECO:0000269|PubMed:27519415}. CC -!- INTERACTION: CC O76003; P82987: ADAMTSL3; NbExp=3; IntAct=EBI-374781, EBI-10221726; CC O76003; Q96Q83: ALKBH3; NbExp=3; IntAct=EBI-374781, EBI-6658697; CC O76003; Q9Y3E2: BOLA1; NbExp=14; IntAct=EBI-374781, EBI-1049556; CC O76003; A0A087WZT3: BOLA2-SMG1P6; NbExp=3; IntAct=EBI-374781, EBI-12006120; CC O76003; Q9H3K6: BOLA2B; NbExp=3; IntAct=EBI-374781, EBI-1642537; CC O76003; Q53S33: BOLA3; NbExp=5; IntAct=EBI-374781, EBI-12086950; CC O76003; Q16790: CA9; NbExp=9; IntAct=EBI-374781, EBI-12259996; CC O76003; Q13191: CBLB; NbExp=3; IntAct=EBI-374781, EBI-744027; CC O76003; Q86Y33-5: CDC20B; NbExp=3; IntAct=EBI-374781, EBI-11983537; CC O76003; Q5T4B2: CERCAM; NbExp=3; IntAct=EBI-374781, EBI-12261896; CC O76003; Q9UFW8: CGGBP1; NbExp=3; IntAct=EBI-374781, EBI-723153; CC O76003; Q6FI81: CIAPIN1; NbExp=22; IntAct=EBI-374781, EBI-750511; CC O76003; Q6FI81-1: CIAPIN1; NbExp=2; IntAct=EBI-374781, EBI-16172762; CC O76003; P27658: COL8A1; NbExp=3; IntAct=EBI-374781, EBI-747133; CC O76003; Q9NWS6: FAM118A; NbExp=3; IntAct=EBI-374781, EBI-8638992; CC O76003; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-374781, EBI-10172181; CC O76003; O76003: GLRX3; NbExp=3; IntAct=EBI-374781, EBI-374781; CC O76003; Q9P2W3: GNG13; NbExp=3; IntAct=EBI-374781, EBI-11427343; CC O76003; P28799: GRN; NbExp=9; IntAct=EBI-374781, EBI-747754; CC O76003; Q9BQS7-3: HEPH; NbExp=3; IntAct=EBI-374781, EBI-22734368; CC O76003; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-374781, EBI-3918847; CC O76003; Q13422: IKZF1; NbExp=3; IntAct=EBI-374781, EBI-745305; CC O76003; P22301: IL10; NbExp=3; IntAct=EBI-374781, EBI-1031632; CC O76003; P78412: IRX6; NbExp=5; IntAct=EBI-374781, EBI-12100506; CC O76003; Q8NEP7: KLHDC9; NbExp=5; IntAct=EBI-374781, EBI-12214879; CC O76003; Q5T749: KPRP; NbExp=3; IntAct=EBI-374781, EBI-10981970; CC O76003; Q15323: KRT31; NbExp=3; IntAct=EBI-374781, EBI-948001; CC O76003; O76015: KRT38; NbExp=3; IntAct=EBI-374781, EBI-1047263; CC O76003; P60412: KRTAP10-11; NbExp=4; IntAct=EBI-374781, EBI-10217483; CC O76003; P60370: KRTAP10-5; NbExp=6; IntAct=EBI-374781, EBI-10172150; CC O76003; P60410: KRTAP10-8; NbExp=8; IntAct=EBI-374781, EBI-10171774; CC O76003; P60411: KRTAP10-9; NbExp=8; IntAct=EBI-374781, EBI-10172052; CC O76003; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-374781, EBI-11953334; CC O76003; Q9BYQ6: KRTAP4-11; NbExp=8; IntAct=EBI-374781, EBI-10302392; CC O76003; Q9BQ66: KRTAP4-12; NbExp=7; IntAct=EBI-374781, EBI-739863; CC O76003; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-374781, EBI-10172511; CC O76003; Q9BYR3: KRTAP4-4; NbExp=3; IntAct=EBI-374781, EBI-11958132; CC O76003; Q9BYR2: KRTAP4-5; NbExp=5; IntAct=EBI-374781, EBI-11993254; CC O76003; Q9BYR0: KRTAP4-7; NbExp=3; IntAct=EBI-374781, EBI-10302547; CC O76003; Q6L8G4: KRTAP5-11; NbExp=3; IntAct=EBI-374781, EBI-11993296; CC O76003; Q6L8H2: KRTAP5-3; NbExp=7; IntAct=EBI-374781, EBI-11974251; CC O76003; Q6L8H1: KRTAP5-4; NbExp=3; IntAct=EBI-374781, EBI-11963072; CC O76003; Q6L8G9: KRTAP5-6; NbExp=7; IntAct=EBI-374781, EBI-10250562; CC O76003; P26371: KRTAP5-9; NbExp=8; IntAct=EBI-374781, EBI-3958099; CC O76003; Q9BYQ4: KRTAP9-2; NbExp=8; IntAct=EBI-374781, EBI-1044640; CC O76003; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-374781, EBI-1043191; CC O76003; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-374781, EBI-11958364; CC O76003; Q5TA82: LCE2D; NbExp=6; IntAct=EBI-374781, EBI-10246750; CC O76003; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-374781, EBI-739832; CC O76003; O60336: MAPKBP1; NbExp=6; IntAct=EBI-374781, EBI-947402; CC O76003; P53582: METAP1; NbExp=3; IntAct=EBI-374781, EBI-1051435; CC O76003; Q6UVY6: MOXD1; NbExp=7; IntAct=EBI-374781, EBI-7134667; CC O76003; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-374781, EBI-945833; CC O76003; P34130: NTF4; NbExp=3; IntAct=EBI-374781, EBI-3907456; CC O76003; Q96PB7: OLFM3; NbExp=3; IntAct=EBI-374781, EBI-10292253; CC O76003; Q92824: PCSK5; NbExp=3; IntAct=EBI-374781, EBI-751290; CC O76003; Q99471: PFDN5; NbExp=3; IntAct=EBI-374781, EBI-357275; CC O76003; O15162: PLSCR1; NbExp=4; IntAct=EBI-374781, EBI-740019; CC O76003; Q04759: PRKCQ; NbExp=5; IntAct=EBI-374781, EBI-374762; CC O76003; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-374781, EBI-1504830; CC O76003; Q6P9E2: RECK; NbExp=3; IntAct=EBI-374781, EBI-10253121; CC O76003; O76081: RGS20; NbExp=4; IntAct=EBI-374781, EBI-1052678; CC O76003; O76081-6: RGS20; NbExp=3; IntAct=EBI-374781, EBI-10178530; CC O76003; Q92922: SMARCC1; NbExp=3; IntAct=EBI-374781, EBI-355653; CC O76003; Q9BT81: SOX7; NbExp=3; IntAct=EBI-374781, EBI-7239117; CC O76003; O95793: STAU1; NbExp=3; IntAct=EBI-374781, EBI-358174; CC O76003; Q9BX79-6: STRA6; NbExp=3; IntAct=EBI-374781, EBI-12140683; CC O76003; P15884: TCF4; NbExp=3; IntAct=EBI-374781, EBI-533224; CC O76003; O95988: TCL1B; NbExp=5; IntAct=EBI-374781, EBI-727338; CC O76003; Q86YD3: TMEM25; NbExp=4; IntAct=EBI-374781, EBI-10260688; CC O76003; Q13077: TRAF1; NbExp=5; IntAct=EBI-374781, EBI-359224; CC O76003; Q9NQ86: TRIM36; NbExp=6; IntAct=EBI-374781, EBI-2341518; CC O76003; Q8IWZ5: TRIM42; NbExp=6; IntAct=EBI-374781, EBI-5235829; CC O76003; Q16851: UGP2; NbExp=3; IntAct=EBI-374781, EBI-743729; CC O76003; Q8NCP5: ZBTB44; NbExp=3; IntAct=EBI-374781, EBI-5658292; CC O76003; Q15973: ZNF124; NbExp=3; IntAct=EBI-374781, EBI-2555767; CC O76003; Q9UQR1: ZNF148; NbExp=3; IntAct=EBI-374781, EBI-2688184; CC O76003; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-374781, EBI-11741890; CC O76003; Q9BUY5: ZNF426; NbExp=3; IntAct=EBI-374781, EBI-743265; CC O76003; Q9ULM2: ZNF490; NbExp=3; IntAct=EBI-374781, EBI-1105370; CC O76003; Q6NX49: ZNF544; NbExp=3; IntAct=EBI-374781, EBI-2841978; CC O76003; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-374781, EBI-10251462; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:27519415}. CC Cytoplasm, cell cortex {ECO:0000269|PubMed:10636891}. Cytoplasm, CC myofibril, sarcomere, Z line {ECO:0000250|UniProtKB:Q9CQM9}. Note=Under CC the plasma membrane (By similarity). After PMA stimulation, GLRX3 and CC PRKCQ/PKC-theta translocate to a more extended submembrane area (By CC similarity). In the Z line, found associated with CSRP3 (By CC similarity). {ECO:0000250|UniProtKB:Q9CQM9}. CC -!- TISSUE SPECIFICITY: Expressed in heart, spleen, testis and, to a lower CC extent, in thymus and peripheral blood leukocytes. Weakly expressed in CC lung, placenta, colon and small intestine. CC -!- DOMAIN: The thioredoxin domain lacks the two redox-active cysteines. CC This strongly suggests that it lacks thioredoxin activity. CC {ECO:0000305}. CC -!- MISCELLANEOUS: Silencing of Grx3 in HeLa cells decreases the activities CC of several cytosolic Fe/S proteins, such as ACO1, a major component of CC post-transcriptional iron regulation. As a consequence, Grx3-depleted CC cells show decreased levels of ferritin and increased levels of CC transferrin receptor, features characteristic of cellular iron CC starvation (PubMed:23615448). {ECO:0000305|PubMed:23615448}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF118649; AAF28841.1; -; mRNA. DR EMBL; AF118652; AAF28844.1; -; mRNA. DR EMBL; AJ010841; CAA09375.1; -; mRNA. DR EMBL; AK022131; BAG51067.1; -; mRNA. DR EMBL; AK021926; BAG51059.1; -; mRNA. DR EMBL; AL139123; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49152.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49154.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49155.1; -; Genomic_DNA. DR EMBL; BC005289; AAH05289.1; -; mRNA. DR EMBL; BC014372; AAH14372.2; -; mRNA. DR CCDS; CCDS7661.1; -. DR RefSeq; NP_001186797.1; NM_001199868.1. DR RefSeq; NP_006532.2; NM_006541.4. DR PDB; 2DIY; NMR; -; A=1-117. DR PDB; 2WZ9; X-ray; 1.55 A; A=1-125. DR PDB; 2YAN; X-ray; 1.90 A; A/B=232-334. DR PDB; 3ZYW; X-ray; 1.84 A; A/B=130-232. DR PDBsum; 2DIY; -. DR PDBsum; 2WZ9; -. DR PDBsum; 2YAN; -. DR PDBsum; 3ZYW; -. DR AlphaFoldDB; O76003; -. DR BMRB; O76003; -. DR SMR; O76003; -. DR BioGRID; 115793; 219. DR ComplexPortal; CPX-6861; BOLA2-GLRX3 iron-sulfur cluster assembly complex. DR CORUM; O76003; -. DR DIP; DIP-31306N; -. DR IntAct; O76003; 132. DR MINT; O76003; -. DR STRING; 9606.ENSP00000357633; -. DR GlyGen; O76003; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O76003; -. DR MetOSite; O76003; -. DR PhosphoSitePlus; O76003; -. DR SwissPalm; O76003; -. DR BioMuta; GLRX3; -. DR REPRODUCTION-2DPAGE; IPI00008552; -. DR CPTAC; CPTAC-206; -. DR CPTAC; CPTAC-207; -. DR EPD; O76003; -. DR jPOST; O76003; -. DR MassIVE; O76003; -. DR MaxQB; O76003; -. DR PaxDb; 9606-ENSP00000357633; -. DR PeptideAtlas; O76003; -. DR ProteomicsDB; 50341; -. DR Pumba; O76003; -. DR Antibodypedia; 32521; 414 antibodies from 31 providers. DR DNASU; 10539; -. DR Ensembl; ENST00000331244.10; ENSP00000330836.5; ENSG00000108010.12. DR Ensembl; ENST00000368644.5; ENSP00000357633.1; ENSG00000108010.12. DR Ensembl; ENST00000481034.1; ENSP00000435445.1; ENSG00000108010.12. DR GeneID; 10539; -. DR KEGG; hsa:10539; -. DR MANE-Select; ENST00000331244.10; ENSP00000330836.5; NM_006541.5; NP_006532.2. DR UCSC; uc001lkm.3; human. DR AGR; HGNC:15987; -. DR CTD; 10539; -. DR DisGeNET; 10539; -. DR GeneCards; GLRX3; -. DR HGNC; HGNC:15987; GLRX3. DR HPA; ENSG00000108010; Low tissue specificity. DR MIM; 612754; gene. DR neXtProt; NX_O76003; -. DR OpenTargets; ENSG00000108010; -. DR PharmGKB; PA162389829; -. DR VEuPathDB; HostDB:ENSG00000108010; -. DR eggNOG; KOG0911; Eukaryota. DR GeneTree; ENSGT00550000075030; -. DR HOGENOM; CLU_026126_12_2_1; -. DR InParanoid; O76003; -. DR OMA; CEPCTAV; -. DR OrthoDB; 1038at2759; -. DR PhylomeDB; O76003; -. DR TreeFam; TF314151; -. DR PathwayCommons; O76003; -. DR Reactome; R-HSA-917937; Iron uptake and transport. DR SignaLink; O76003; -. DR BioGRID-ORCS; 10539; 235 hits in 1164 CRISPR screens. DR ChiTaRS; GLRX3; human. DR EvolutionaryTrace; O76003; -. DR GeneWiki; GLRX3; -. DR GenomeRNAi; 10539; -. DR Pharos; O76003; Tbio. DR PRO; PR:O76003; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; O76003; Protein. DR Bgee; ENSG00000108010; Expressed in buccal mucosa cell and 202 other cell types or tissues. DR ExpressionAtlas; O76003; baseline and differential. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; NAS:ComplexPortal. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; IPI:ComplexPortal. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005080; F:protein kinase C binding; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; IDA:UniProtKB. DR GO; GO:0045454; P:cell redox homeostasis; IDA:ComplexPortal. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IDA:ComplexPortal. DR GO; GO:0016226; P:iron-sulfur cluster assembly; IDA:ComplexPortal. DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISS:UniProtKB. DR GO; GO:0097428; P:protein maturation by iron-sulfur cluster transfer; IDA:UniProtKB. DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:UniProtKB. DR CDD; cd03028; GRX_PICOT_like; 2. DR CDD; cd02984; TRX_PICOT; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 3. DR InterPro; IPR002109; Glutaredoxin. DR InterPro; IPR033658; GRX_PICOT-like. DR InterPro; IPR004480; Monothiol_GRX-rel. DR InterPro; IPR036249; Thioredoxin-like_sf. DR InterPro; IPR013766; Thioredoxin_domain. DR NCBIfam; TIGR00365; Grx4 family monothiol glutaredoxin; 1. DR PANTHER; PTHR10293; GLUTAREDOXIN FAMILY MEMBER; 1. DR PANTHER; PTHR10293:SF73; GLUTAREDOXIN-3; 1. DR Pfam; PF00462; Glutaredoxin; 2. DR Pfam; PF00085; Thioredoxin; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 3. DR PROSITE; PS51354; GLUTAREDOXIN_2; 2. DR PROSITE; PS51352; THIOREDOXIN_2; 1. DR Genevisible; O76003; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Iron; KW Iron-sulfur; Metal-binding; Phosphoprotein; Reference proteome; Repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712" FT CHAIN 2..335 FT /note="Glutaredoxin-3" FT /id="PRO_0000120019" FT DOMAIN 2..117 FT /note="Thioredoxin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT DOMAIN 144..236 FT /note="Glutaredoxin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686" FT DOMAIN 237..335 FT /note="Glutaredoxin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686" FT BINDING 159 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000305|PubMed:20226171, FT ECO:0000305|PubMed:27519415" FT BINDING 261 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000305|PubMed:20226171, FT ECO:0000305|PubMed:27519415" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712" FT MOD_RES 117 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 120 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 21 FT /note="Q -> H (in dbSNP:rs13991)" FT /evidence="ECO:0000269|PubMed:10636891, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334" FT /id="VAR_016875" FT VARIANT 123 FT /note="P -> S (in dbSNP:rs2274217)" FT /evidence="ECO:0000269|PubMed:10636891, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334" FT /id="VAR_016876" FT MUTAGEN 159 FT /note="C->S: Loss of 2Fe-2S-binding; when associated with FT S-261. Loss of 2Fe-2S-binding and interaction with BOLA2; FT when associated with 197-D-A-198." FT /evidence="ECO:0000269|PubMed:20226171, FT ECO:0000269|PubMed:27519415" FT MUTAGEN 197..198 FT /note="WP->DA: Loss of 2Fe-2S-binding and interaction with FT BOLA2; when associated with S-159." FT /evidence="ECO:0000269|PubMed:27519415" FT MUTAGEN 261 FT /note="C->S: Loss of 2Fe-2S-binding; when associated with FT S-159. Loss of 2Fe-2S-binding and interaction with BOLA2; FT when associated with 299-D-A-300." FT /evidence="ECO:0000269|PubMed:20226171, FT ECO:0000269|PubMed:27519415" FT MUTAGEN 299..300 FT /note="WP->DA: Loss of 2Fe-2S-binding and interaction with FT BOLA2; when associated with S-261." FT /evidence="ECO:0000269|PubMed:27519415" FT CONFLICT 2 FT /note="A -> E (in Ref. 2; CAA09375)" FT /evidence="ECO:0000305" FT CONFLICT 67 FT /note="K -> R (in Ref. 3; BAG51067)" FT /evidence="ECO:0000305" FT CONFLICT 210 FT /note="I -> T (in Ref. 3; BAG51059)" FT /evidence="ECO:0000305" FT STRAND 13..16 FT /evidence="ECO:0007829|PDB:2WZ9" FT HELIX 19..28 FT /evidence="ECO:0007829|PDB:2WZ9" FT TURN 29..31 FT /evidence="ECO:0007829|PDB:2WZ9" FT STRAND 34..39 FT /evidence="ECO:0007829|PDB:2WZ9" FT HELIX 44..59 FT /evidence="ECO:0007829|PDB:2WZ9" FT STRAND 63..69 FT /evidence="ECO:0007829|PDB:2WZ9" FT TURN 70..72 FT /evidence="ECO:0007829|PDB:2WZ9" FT HELIX 74..79 FT /evidence="ECO:0007829|PDB:2WZ9" FT STRAND 84..92 FT /evidence="ECO:0007829|PDB:2WZ9" FT STRAND 95..103 FT /evidence="ECO:0007829|PDB:2WZ9" FT HELIX 105..115 FT /evidence="ECO:0007829|PDB:2WZ9" FT HELIX 133..141 FT /evidence="ECO:0007829|PDB:3ZYW" FT STRAND 143..152 FT /evidence="ECO:0007829|PDB:3ZYW" FT STRAND 154..159 FT /evidence="ECO:0007829|PDB:3ZYW" FT HELIX 160..171 FT /evidence="ECO:0007829|PDB:3ZYW" FT STRAND 177..180 FT /evidence="ECO:0007829|PDB:3ZYW" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:3ZYW" FT HELIX 185..195 FT /evidence="ECO:0007829|PDB:3ZYW" FT STRAND 202..205 FT /evidence="ECO:0007829|PDB:3ZYW" FT STRAND 208..211 FT /evidence="ECO:0007829|PDB:3ZYW" FT HELIX 213..221 FT /evidence="ECO:0007829|PDB:3ZYW" FT HELIX 225..228 FT /evidence="ECO:0007829|PDB:3ZYW" FT HELIX 233..243 FT /evidence="ECO:0007829|PDB:2YAN" FT STRAND 245..254 FT /evidence="ECO:0007829|PDB:2YAN" FT STRAND 256..259 FT /evidence="ECO:0007829|PDB:2YAN" FT HELIX 263..273 FT /evidence="ECO:0007829|PDB:2YAN" FT STRAND 279..282 FT /evidence="ECO:0007829|PDB:2YAN" FT HELIX 283..285 FT /evidence="ECO:0007829|PDB:2YAN" FT HELIX 287..297 FT /evidence="ECO:0007829|PDB:2YAN" FT STRAND 304..307 FT /evidence="ECO:0007829|PDB:2YAN" FT STRAND 310..313 FT /evidence="ECO:0007829|PDB:2YAN" FT HELIX 315..323 FT /evidence="ECO:0007829|PDB:2YAN" FT HELIX 327..331 FT /evidence="ECO:0007829|PDB:2YAN" SQ SEQUENCE 335 AA; 37432 MW; 46D644413D9EDFDA CRC64; MAAGAAEAAV AAVEEVGSAG QFEELLRLKA KSLLVVHFWA PWAPQCAQMN EVMAELAKEL PQVSFVKLEA EGVPEVSEKY EISSVPTFLF FKNSQKIDRL DGAHAPELTK KVQRHASSGS FLPSANEHLK EDLNLRLKKL THAAPCMLFM KGTPQEPRCG FSKQMVEILH KHNIQFSSFD IFSDEEVRQG LKAYSSWPTY PQLYVSGELI GGLDIIKELE ASEELDTICP KAPKLEERLK VLTNKASVML FMKGNKQEAK CGFSKQILEI LNSTGVEYET FDILEDEEVR QGLKAYSNWP TYPQLYVKGE LVGGLDIVKE LKENGELLPI LRGEN //