GLRX3_HUMAN
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 03-AUG-2022, entry version 209.
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: BOLA2B; 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}.
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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; 192.
DR ComplexPortal; CPX-6861; BOLA2-GLRX3 iron-sulfur cluster assembly complex.
DR CORUM; O76003; -.
DR DIP; DIP-31306N; -.
DR IntAct; O76003; 126.
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; O76003; -.
DR PeptideAtlas; O76003; -.
DR PRIDE; O76003; -.
DR ProteomicsDB; 50341; -.
DR Antibodypedia; 32521; 380 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 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; MNEVVLE; -.
DR OrthoDB; 1449534at2759; -.
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; 231 hits in 1084 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 200 other tissues.
DR ExpressionAtlas; O76003; baseline and differential.
DR Genevisible; O76003; HS.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IC: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:0097573; F:glutathione oxidoreductase activity; IEA:InterPro.
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:cellular iron ion homeostasis; IBA:GO_Central.
DR GO; GO:0055072; P: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 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 PANTHER; PTHR10293; PTHR10293; 1.
DR Pfam; PF00462; Glutaredoxin; 2.
DR Pfam; PF00085; Thioredoxin; 1.
DR SUPFAM; SSF52833; SSF52833; 3.
DR TIGRFAMs; TIGR00365; TIGR00365; 1.
DR PROSITE; PS51354; GLUTAREDOXIN_2; 2.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
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
