GLRX3_MOUSE
ID GLRX3_MOUSE Reviewed; 337 AA.
AC Q9CQM9; Q5I0V8; Q9JLZ2;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Glutaredoxin-3;
DE AltName: Full=PKC-interacting cousin of thioredoxin;
DE Short=PICOT;
DE AltName: Full=PKC-theta-interacting protein;
DE Short=PKCq-interacting protein;
DE AltName: Full=Thioredoxin-like protein 2;
GN Name=Glrx3; Synonyms=Picot, Txnl2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Kidney, and Mammary tumor;
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 [4]
RP PROTEIN SEQUENCE OF 82-94.
RC TISSUE=Brain;
RA Lubec G., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [5]
RP FUNCTION, AND OVEREXPRESSION.
RX PubMed=16809552; DOI=10.1161/01.res.0000234780.06115.2c;
RA Jeong D., Cha H., Kim E., Kang M., Yang D.K., Kim J.M., Yoon P.O., Oh J.G.,
RA Bernecker O.Y., Sakata S., Le T.T., Cui L., Lee Y.H., Kim do H., Woo S.H.,
RA Liao R., Hajjar R.J., Park W.J.;
RT "PICOT inhibits cardiac hypertrophy and enhances ventricular function and
RT cardiomyocyte contractility.";
RL Circ. Res. 99:307-314(2006).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, OVEREXPRESSION, AND INTERACTION WITH CSRP2
RP AND CSRP3.
RX PubMed=18258855; DOI=10.1161/circresaha.107.165985;
RA Jeong D., Kim J.M., Cha H., Oh J.G., Park J., Yun S.H., Ju E.S., Jeon E.S.,
RA Hajjar R.J., Park W.J.;
RT "PICOT attenuates cardiac hypertrophy by disrupting calcineurin-NFAT
RT signaling.";
RL Circ. Res. 102:711-719(2008).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18929570; DOI=10.1016/j.yjmcc.2008.09.124;
RA Cha H., Kim J.M., Oh J.G., Jeong M.H., Park C.S., Park J., Jeong H.J.,
RA Park B.K., Lee Y.-H., Jeong D., Yang D.K., Bernecker O.Y., Kim do H.,
RA Hajjar R.J., Park W.J.;
RT "PICOT is a critical regulator of cardiac hypertrophy and cardiomyocyte
RT contractility.";
RL J. Mol. Cell. Cardiol. 45:796-803(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP STRUCTURE BY NMR OF 241-336.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the picot homology 2 domain of the mouse pkc-
RT interacting cousin of thioredoxin protein.";
RL Submitted (NOV-2004) 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 (By similarity). Acts as a critical
CC negative regulator of cardiac hypertrophy and a positive inotropic
CC regulator (PubMed:16809552, PubMed:18258855, PubMed:18929570). Required
CC for hemoglobin maturation. Does not possess any thyoredoxin activity
CC since it lacks the conserved motif that is essential for catalytic
CC activity (By similarity). {ECO:0000250|UniProtKB:O76003,
CC ECO:0000269|PubMed:16809552, ECO:0000269|PubMed:18258855,
CC ECO:0000269|PubMed:18929570}.
CC -!- SUBUNIT: Homodimer; the homodimer is independent of 2Fe-2S clusters.
CC Heterotrimer; forms a heterotrimeric complex composed by two BOLA2
CC molecules and one GLRX3 molecule; linked by [2Fe-2S] clusters.
CC Interacts (via N-terminus) with PRKCQ/PKC-theta (By similarity).
CC Interacts (via C-terminus) with CSRP3 (PubMed:18258855). Interacts with
CC CSRP2 (PubMed:18258855). {ECO:0000250|UniProtKB:O76003,
CC ECO:0000269|PubMed:18258855}.
CC -!- INTERACTION:
CC Q9CQM9; Q8WTY4: Ciapin1; NbExp=4; IntAct=EBI-4319195, EBI-2943068;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O76003}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:18258855}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000269|PubMed:18258855}. Note=Under the plasma membrane
CC (PubMed:18258855). After PMA stimulation, GLRX3 and PRKCQ/PKC-theta
CC translocate to a more extended submembrane area (PubMed:18258855). In
CC the Z line, found associated with CSRP3 (PubMed:18258855).
CC {ECO:0000269|PubMed:18258855}.
CC -!- DOMAIN: The thioredoxin domain lacks the two redox-active cysteines.
CC This strongly suggests that it lacks thioredoxin activity.
CC {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Homozygous null mutants die in utero some time
CC between 12.5 and 14.5 dpc. 12.5 dpc embryos have a smaller body size
CC and hemorrhage in the head. Heterozygous mutants are fertile and show
CC no abnormalities in growth and development, cardiomyocytes exhibit
CC significantly reduced contractility. {ECO:0000269|PubMed:18929570}.
CC -!- MISCELLANEOUS: Transgenic mice with cardiac-specific Glrx3
CC overexpression show that it is a potent inhibitor of cardiac
CC hypertrophy induced by pressure overload (transverse aortic
CC constriction). In addition, overexpression dramatically increases the
CC ventricular function and cardiomyocyte contractility.
CC {ECO:0000269|PubMed:16809552, ECO:0000269|PubMed:18258855,
CC ECO:0000269|PubMed:18929570}.
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; AF118650; AAF28842.1; -; mRNA.
DR EMBL; AK010354; BAB26874.1; -; mRNA.
DR EMBL; AK017371; BAB30712.1; -; mRNA.
DR EMBL; AK147158; BAE27724.1; -; mRNA.
DR EMBL; AK152446; BAE31225.1; -; mRNA.
DR EMBL; AK152634; BAE31376.1; -; mRNA.
DR EMBL; AK155190; BAE33105.1; -; mRNA.
DR EMBL; AK167672; BAE39721.1; -; mRNA.
DR EMBL; BC033506; AAH33506.1; -; mRNA.
DR EMBL; BC087885; AAH87885.1; -; mRNA.
DR CCDS; CCDS21948.1; -.
DR RefSeq; NP_075629.2; NM_023140.5.
DR PDB; 1WIK; NMR; -; A=241-336.
DR PDBsum; 1WIK; -.
DR AlphaFoldDB; Q9CQM9; -.
DR SMR; Q9CQM9; -.
DR BioGRID; 206004; 8.
DR IntAct; Q9CQM9; 4.
DR MINT; Q9CQM9; -.
DR STRING; 10090.ENSMUSP00000066621; -.
DR iPTMnet; Q9CQM9; -.
DR PhosphoSitePlus; Q9CQM9; -.
DR SwissPalm; Q9CQM9; -.
DR REPRODUCTION-2DPAGE; IPI00315550; -.
DR REPRODUCTION-2DPAGE; Q9CQM9; -.
DR EPD; Q9CQM9; -.
DR jPOST; Q9CQM9; -.
DR MaxQB; Q9CQM9; -.
DR PaxDb; Q9CQM9; -.
DR PeptideAtlas; Q9CQM9; -.
DR PRIDE; Q9CQM9; -.
DR ProteomicsDB; 267635; -.
DR Antibodypedia; 32521; 380 antibodies from 31 providers.
DR DNASU; 30926; -.
DR Ensembl; ENSMUST00000064404; ENSMUSP00000066621; ENSMUSG00000031068.
DR GeneID; 30926; -.
DR KEGG; mmu:30926; -.
DR UCSC; uc009kew.1; mouse.
DR CTD; 10539; -.
DR MGI; MGI:1353653; Glrx3.
DR VEuPathDB; HostDB:ENSMUSG00000031068; -.
DR eggNOG; KOG0911; Eukaryota.
DR GeneTree; ENSGT00550000075030; -.
DR HOGENOM; CLU_026126_12_2_1; -.
DR InParanoid; Q9CQM9; -.
DR OMA; MNEVVLE; -.
DR OrthoDB; 1449534at2759; -.
DR PhylomeDB; Q9CQM9; -.
DR TreeFam; TF314151; -.
DR BioGRID-ORCS; 30926; 15 hits in 74 CRISPR screens.
DR ChiTaRS; Glrx3; mouse.
DR EvolutionaryTrace; Q9CQM9; -.
DR PRO; PR:Q9CQM9; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9CQM9; protein.
DR Bgee; ENSMUSG00000031068; Expressed in embryonic brain and 138 other tissues.
DR ExpressionAtlas; Q9CQM9; baseline and differential.
DR Genevisible; Q9CQM9; MM.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0097573; F:glutathione oxidoreductase activity; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; ISS:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; ISO:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IBA:GO_Central.
DR GO; GO:0055072; P:iron ion homeostasis; ISO:MGI.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; ISO:MGI.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IMP:UniProtKB.
DR GO; GO:0097428; P:protein maturation by iron-sulfur cluster transfer; ISS:UniProtKB.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IMP: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:0000250|UniProtKB:O76003"
FT CHAIN 2..337
FT /note="Glutaredoxin-3"
FT /id="PRO_0000120020"
FT DOMAIN 2..119
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DOMAIN 144..238
FT /note="Glutaredoxin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT DOMAIN 239..337
FT /note="Glutaredoxin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT BINDING 161
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:O76003"
FT BINDING 263
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:O76003"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O76003"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O76003"
FT CONFLICT 76
FT /note="P -> T (in Ref. 1; AAF28842)"
FT /evidence="ECO:0000305"
FT HELIX 241..245
FT /evidence="ECO:0007829|PDB:1WIK"
FT STRAND 248..256
FT /evidence="ECO:0007829|PDB:1WIK"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:1WIK"
FT HELIX 266..275
FT /evidence="ECO:0007829|PDB:1WIK"
FT STRAND 280..287
FT /evidence="ECO:0007829|PDB:1WIK"
FT HELIX 289..299
FT /evidence="ECO:0007829|PDB:1WIK"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:1WIK"
FT STRAND 310..315
FT /evidence="ECO:0007829|PDB:1WIK"
FT HELIX 317..326
FT /evidence="ECO:0007829|PDB:1WIK"
FT HELIX 330..334
FT /evidence="ECO:0007829|PDB:1WIK"
SQ SEQUENCE 337 AA; 37778 MW; 74A1C65621B28FA0 CRC64;
MAAGAAEAGE AAVAVVEVGS AQQFEELLRL KTKSLLVVHF WAPWAPQCVQ MNDVMAELAK
EHPHVSFVKL EAEAVPEVSE KYEISSVPTF LFFKNSQKVD RLDGAHAPEL TKKVQRHVSS
GAFPPSTNEH LKEDLSLRLK KLTHAAPCML FMKGTPQEPR CGFSKQMVEI LHKHNIQFSS
FDIFSDEEVR QGLKTYSNWP TYPQLYVSGE LIGGLDIIKE LEASEELDTI CPKAPKLEER
LKVLTNKASV MLFMKGNKQE AKCGFSKQIL EILNSTGVEY ETFDILEDEE VRQGLKTFSN
WPTYPQLYVR GDLVGGLDIV KELKDNGELL PILKGEN
