GLRX3_RAT
ID GLRX3_RAT Reviewed; 337 AA.
AC Q9JLZ1; Q5RK11;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 152.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=Sprague-Dawley;
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] (ISOFORM 1).
RC TISSUE=Ovary;
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 [3]
RP PROTEIN SEQUENCE OF 23-29; 82-94; 102-112; 133-138; 174-190; 311-321 AND
RP 325-334, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RA Lubec G., Chen W.-Q.;
RL Submitted (FEB-2007) to UniProtKB.
RN [5]
RP FUNCTION, AND INDUCTION.
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 OVEREXPRESSION.
RX PubMed=18479680; DOI=10.1016/j.cellimm.2008.04.005;
RA Kato N., Motohashi S., Okada T., Ozawa T., Mashima K.;
RT "PICOT, protein kinase C theta-interacting protein, is a novel regulator of
RT FcepsilonRI-mediated mast cell activation.";
RL Cell. Immunol. 251:62-67(2008).
RN [7]
RP FUNCTION, AND INTERACTION WITH CSRP3.
RC STRAIN=Sprague-Dawley;
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).
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). Required for hemoglobin
CC maturation (By similarity). 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:0000250|UniProtKB:Q9CQM9, ECO:0000269|PubMed:16809552,
CC ECO:0000269|PubMed:18258855}.
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 (By similarity). {ECO:0000250|UniProtKB:O76003,
CC ECO:0000250|UniProtKB:Q9CQM9, ECO:0000269|PubMed:18258855}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O76003}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:O76003}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000250|UniProtKB:Q9CQM9}. Note=Under the plasma membrane (By
CC similarity). After PMA stimulation, GLRX3 and PRKCQ/PKC-theta
CC translocate to a more extended submembrane area (By similarity). In the
CC Z line, found associated with CSRP3 (By similarity).
CC {ECO:0000250|UniProtKB:Q9CQM9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JLZ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JLZ1-2; Sequence=VSP_012927;
CC -!- INDUCTION: In neonatal cardiomyocytes after exposure to the
CC hypertrophic agonists EDN1 (ET-1) or phenylephrine (PE). In transverse
CC aortic constriction (TAC) induced cardiac hypertrophy in adult hearts.
CC {ECO:0000269|PubMed:16809552}.
CC -!- DOMAIN: The thioredoxin domain lacks the two redox-active cysteines.
CC This strongly suggests that it lacks thioredoxin activity.
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DR EMBL; AF118651; AAF28843.1; -; mRNA.
DR EMBL; BC086381; AAH86381.1; -; mRNA.
DR RefSeq; NP_116003.2; NM_032614.2. [Q9JLZ1-1]
DR AlphaFoldDB; Q9JLZ1; -.
DR SMR; Q9JLZ1; -.
DR IntAct; Q9JLZ1; 2.
DR STRING; 10116.ENSRNOP00000022406; -.
DR iPTMnet; Q9JLZ1; -.
DR PhosphoSitePlus; Q9JLZ1; -.
DR jPOST; Q9JLZ1; -.
DR PaxDb; Q9JLZ1; -.
DR PRIDE; Q9JLZ1; -.
DR Ensembl; ENSRNOT00000022406; ENSRNOP00000022406; ENSRNOG00000016227. [Q9JLZ1-1]
DR GeneID; 58815; -.
DR KEGG; rno:58815; -.
DR UCSC; RGD:69414; rat. [Q9JLZ1-1]
DR CTD; 10539; -.
DR RGD; 69414; Glrx3.
DR eggNOG; KOG0911; Eukaryota.
DR GeneTree; ENSGT00550000075030; -.
DR InParanoid; Q9JLZ1; -.
DR OMA; MNEVVLE; -.
DR OrthoDB; 1449534at2759; -.
DR PhylomeDB; Q9JLZ1; -.
DR TreeFam; TF314151; -.
DR PRO; PR:Q9JLZ1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016227; Expressed in testis and 20 other tissues.
DR ExpressionAtlas; Q9JLZ1; baseline and differential.
DR Genevisible; Q9JLZ1; RN.
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; IDA:RGD.
DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0030018; C:Z disc; ISO:RGD.
DR GO; GO:0097573; F:glutathione oxidoreductase activity; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; ISS:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; ISO:RGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IBA:GO_Central.
DR GO; GO:0055072; P:iron ion homeostasis; ISO:RGD.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; ISO:RGD.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISO:RGD.
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; ISO:RGD.
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 Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Iron; Iron-sulfur; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4"
FT CHAIN 2..337
FT /note="Glutaredoxin-3"
FT /id="PRO_0000120021"
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:0000269|Ref.4"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O76003"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O76003"
FT VAR_SEQ 94..151
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10636891"
FT /id="VSP_012927"
SQ SEQUENCE 337 AA; 37849 MW; DA1E3DA9C0DBC22C CRC64;
MAAGAAEAAE AAVAVVEVGS ARQFEELLRL KTKSLLVVHF WAPWAPQCVQ MNDVMAELAK
EHPHVSFVKL EAEAVPEVSE KYEISSVPTF LFFKNSQKVD RLDGAHAPEL TKKVQRHVSS
GSFPPSTNEH VKEDLNLRLK KLTHAAPCML FMKGTPQEPR CGFSKQMVEI LHKHNIQFSS
FDIFSDEEVR QGLKTYSNWP TYPQLYVSGE LIGGLDIIKE LEASEELDTI CPKAPKLEER
LKVLTNKASV MLFMKGNKQE AKCGFSKQIL EILNSTGVEY ETFDILEDEE VRQGLKTFSN
WPTYPQLYVR GDLVGGLDIV KELKDNGELL PILKGEN
