Full text data of GLRX3
GLRX3
(PICOT, TXNL2)
[Confidence: low (only semi-automatic identification from reviews)]
Glutaredoxin-3 (PKC-interacting cousin of thioredoxin; PICOT; PKC-theta-interacting protein; PKCq-interacting protein; Thioredoxin-like protein 2)
Glutaredoxin-3 (PKC-interacting cousin of thioredoxin; PICOT; PKC-theta-interacting protein; PKCq-interacting protein; Thioredoxin-like protein 2)
UniProt
O76003
ID GLRX3_HUMAN Reviewed; 335 AA.
AC O76003; B3KMP7; B3KMQ5; D3DRG2; Q5JV01; Q96CE0; Q9P1B0; Q9P1B1;
read moreDT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2003, sequence version 2.
DT 22-JAN-2014, entry version 137.
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; ORFNames=HUSSY-22;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH
RP PRKCQ, 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
RT by PICOT, a novel protein kinase C-interacting protein with a
RT thioredoxin 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>3.3.CO;2-8;
RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B.,
RA Cannata N., Zimbello R., Lanfranchi G., Valle G.;
RT "Characterization of 16 novel human genes showing high similarity to
RT yeast sequences.";
RL Yeast 18:69-80(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-21 AND
RP 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RP 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
RT project: 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
RP 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
RT iron-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.,
RA Buerckstuemmer T., 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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP STRUCTURE BY NMR OF 1-119.
RG RIKEN structural genomics initiative (RSGI);
RT "The solution structure of the thioredoxin domain of human
RT thioredoxin-like protein 2.";
RL Submitted (APR-2007) to the PDB data bank.
CC -!- FUNCTION: Critical negative regulator of cardiac hypertrophy and a
CC positive inotropic regulator (By similarity). May play a role in
CC regulating the function of the thioredoxin system. Does not posses
CC any thyoredoxin activity since it lacks the conserved motif that
CC is essential for catalytic activity.
CC -!- SUBUNIT: Monomer and homodimer; the homodimer is probably linked
CC by 2 2Fe-2S clusters that may serve as a redox sensor. The monomer
CC interacts with other proteins. Interacts (via N-terminus) with
CC PRKCQ/PKC-theta. Interacts (via C-terminus) with CSRP3 (By
CC similarity). Interacts with CSRP2 (By similarity).
CC -!- INTERACTION:
CC Q6FI81:CIAPIN1; NbExp=3; IntAct=EBI-374781, EBI-750511;
CC Q04759:PRKCQ; NbExp=5; IntAct=EBI-374781, EBI-374762;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex. Cytoplasm,
CC myofibril, sarcomere, Z line (By similarity). Note=Under the
CC plasma membrane. After PMA stimulation, GLRX3 and PRKCQ/PKC-theta
CC translocate to a more extended submembrane area. In the Z line,
CC found associated with CSRP3 (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in heart, spleen, testis and, to a
CC lower extent, in thymus and peripheral blood leukocytes. Weakly
CC expressed in lung, placenta, colon and small intestine.
CC -!- DOMAIN: The thioredoxin domain lacks the two redox-active
CC cysteines. This strongly suggests that it lacks thioredoxin
CC activity.
CC -!- SIMILARITY: Contains 2 glutaredoxin domains.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
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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; CAC40691.1; -; 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 RefSeq; NP_001186797.1; NM_001199868.1.
DR RefSeq; NP_006532.2; NM_006541.4.
DR UniGene; Hs.42644; -.
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 ProteinModelPortal; O76003; -.
DR SMR; O76003; 11-125, 132-334.
DR IntAct; O76003; 17.
DR MINT; MINT-5002296; -.
DR STRING; 9606.ENSP00000330836; -.
DR PhosphoSite; O76003; -.
DR REPRODUCTION-2DPAGE; IPI00008552; -.
DR PaxDb; O76003; -.
DR PeptideAtlas; O76003; -.
DR PRIDE; O76003; -.
DR Ensembl; ENST00000331244; ENSP00000330836; ENSG00000108010.
DR Ensembl; ENST00000368644; ENSP00000357633; ENSG00000108010.
DR Ensembl; ENST00000481034; ENSP00000435445; ENSG00000108010.
DR GeneID; 10539; -.
DR KEGG; hsa:10539; -.
DR UCSC; uc001lkm.2; human.
DR CTD; 10539; -.
DR GeneCards; GC10P131934; -.
DR HGNC; HGNC:15987; GLRX3.
DR HPA; HPA028941; -.
DR MIM; 612754; gene.
DR neXtProt; NX_O76003; -.
DR PharmGKB; PA162389829; -.
DR eggNOG; COG0526; -.
DR HOVERGEN; HBG054719; -.
DR InParanoid; O76003; -.
DR OMA; ELPQVSF; -.
DR OrthoDB; EOG7B5WX3; -.
DR PhylomeDB; O76003; -.
DR ChiTaRS; GLRX3; human.
DR EvolutionaryTrace; O76003; -.
DR GeneWiki; GLRX3; -.
DR GenomeRNAi; 10539; -.
DR NextBio; 39985; -.
DR PMAP-CutDB; O76003; -.
DR PRO; PR:O76003; -.
DR Bgee; O76003; -.
DR CleanEx; HS_GLRX3; -.
DR Genevestigator; O76003; -.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0009055; F:electron carrier activity; IEA:InterPro.
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:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:UniProtKB.
DR Gene3D; 3.40.30.10; -; 3.
DR InterPro; IPR002109; Glutaredoxin.
DR InterPro; IPR004480; Monothiol_GRX-rel.
DR InterPro; IPR012336; Thioredoxin-like_fold.
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; PS00194; THIOREDOXIN_1; FALSE_NEG.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Iron; Iron-sulfur; Metal-binding;
KW Polymorphism; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 335 Glutaredoxin-3.
FT /FTId=PRO_0000120019.
FT DOMAIN 2 117 Thioredoxin.
FT DOMAIN 144 236 Glutaredoxin 1.
FT DOMAIN 237 335 Glutaredoxin 2.
FT METAL 159 159 Iron-sulfur (2Fe-2S); shared with dimeric
FT partner (Probable).
FT METAL 261 261 Iron-sulfur (2Fe-2S); shared with dimeric
FT partner (Probable).
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 21 21 Q -> H (in dbSNP:rs13991).
FT /FTId=VAR_016875.
FT VARIANT 123 123 P -> S (in dbSNP:rs2274217).
FT /FTId=VAR_016876.
FT MUTAGEN 159 159 C->S: Loss of 2Fe-2S-binding; when
FT associated with S-261.
FT MUTAGEN 261 261 C->S: Loss of 2Fe-2S-binding; when
FT associated with S-159.
FT CONFLICT 2 2 A -> E (in Ref. 2; CAA09375).
FT CONFLICT 67 67 K -> R (in Ref. 3; BAG51067).
FT CONFLICT 210 210 I -> T (in Ref. 3; BAG51059).
FT STRAND 13 16
FT HELIX 19 28
FT TURN 29 31
FT STRAND 34 39
FT HELIX 44 59
FT STRAND 63 69
FT TURN 70 72
FT HELIX 74 79
FT STRAND 84 92
FT STRAND 95 103
FT HELIX 105 115
FT HELIX 133 141
FT STRAND 143 152
FT STRAND 154 159
FT HELIX 160 171
FT STRAND 177 180
FT HELIX 181 183
FT HELIX 185 195
FT STRAND 202 205
FT STRAND 208 211
FT HELIX 213 221
FT HELIX 225 228
FT HELIX 233 243
FT STRAND 245 254
FT STRAND 256 259
FT HELIX 263 273
FT STRAND 279 282
FT HELIX 283 285
FT HELIX 287 297
FT STRAND 304 307
FT STRAND 310 313
FT HELIX 315 323
FT HELIX 327 331
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
//
ID GLRX3_HUMAN Reviewed; 335 AA.
AC O76003; B3KMP7; B3KMQ5; D3DRG2; Q5JV01; Q96CE0; Q9P1B0; Q9P1B1;
read moreDT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2003, sequence version 2.
DT 22-JAN-2014, entry version 137.
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; ORFNames=HUSSY-22;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH
RP PRKCQ, 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
RT by PICOT, a novel protein kinase C-interacting protein with a
RT thioredoxin 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>3.3.CO;2-8;
RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B.,
RA Cannata N., Zimbello R., Lanfranchi G., Valle G.;
RT "Characterization of 16 novel human genes showing high similarity to
RT yeast sequences.";
RL Yeast 18:69-80(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-21 AND
RP 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RP 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
RT project: 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
RP 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
RT iron-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.,
RA Buerckstuemmer T., 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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP STRUCTURE BY NMR OF 1-119.
RG RIKEN structural genomics initiative (RSGI);
RT "The solution structure of the thioredoxin domain of human
RT thioredoxin-like protein 2.";
RL Submitted (APR-2007) to the PDB data bank.
CC -!- FUNCTION: Critical negative regulator of cardiac hypertrophy and a
CC positive inotropic regulator (By similarity). May play a role in
CC regulating the function of the thioredoxin system. Does not posses
CC any thyoredoxin activity since it lacks the conserved motif that
CC is essential for catalytic activity.
CC -!- SUBUNIT: Monomer and homodimer; the homodimer is probably linked
CC by 2 2Fe-2S clusters that may serve as a redox sensor. The monomer
CC interacts with other proteins. Interacts (via N-terminus) with
CC PRKCQ/PKC-theta. Interacts (via C-terminus) with CSRP3 (By
CC similarity). Interacts with CSRP2 (By similarity).
CC -!- INTERACTION:
CC Q6FI81:CIAPIN1; NbExp=3; IntAct=EBI-374781, EBI-750511;
CC Q04759:PRKCQ; NbExp=5; IntAct=EBI-374781, EBI-374762;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex. Cytoplasm,
CC myofibril, sarcomere, Z line (By similarity). Note=Under the
CC plasma membrane. After PMA stimulation, GLRX3 and PRKCQ/PKC-theta
CC translocate to a more extended submembrane area. In the Z line,
CC found associated with CSRP3 (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in heart, spleen, testis and, to a
CC lower extent, in thymus and peripheral blood leukocytes. Weakly
CC expressed in lung, placenta, colon and small intestine.
CC -!- DOMAIN: The thioredoxin domain lacks the two redox-active
CC cysteines. This strongly suggests that it lacks thioredoxin
CC activity.
CC -!- SIMILARITY: Contains 2 glutaredoxin domains.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
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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; CAC40691.1; -; 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 RefSeq; NP_001186797.1; NM_001199868.1.
DR RefSeq; NP_006532.2; NM_006541.4.
DR UniGene; Hs.42644; -.
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 ProteinModelPortal; O76003; -.
DR SMR; O76003; 11-125, 132-334.
DR IntAct; O76003; 17.
DR MINT; MINT-5002296; -.
DR STRING; 9606.ENSP00000330836; -.
DR PhosphoSite; O76003; -.
DR REPRODUCTION-2DPAGE; IPI00008552; -.
DR PaxDb; O76003; -.
DR PeptideAtlas; O76003; -.
DR PRIDE; O76003; -.
DR Ensembl; ENST00000331244; ENSP00000330836; ENSG00000108010.
DR Ensembl; ENST00000368644; ENSP00000357633; ENSG00000108010.
DR Ensembl; ENST00000481034; ENSP00000435445; ENSG00000108010.
DR GeneID; 10539; -.
DR KEGG; hsa:10539; -.
DR UCSC; uc001lkm.2; human.
DR CTD; 10539; -.
DR GeneCards; GC10P131934; -.
DR HGNC; HGNC:15987; GLRX3.
DR HPA; HPA028941; -.
DR MIM; 612754; gene.
DR neXtProt; NX_O76003; -.
DR PharmGKB; PA162389829; -.
DR eggNOG; COG0526; -.
DR HOVERGEN; HBG054719; -.
DR InParanoid; O76003; -.
DR OMA; ELPQVSF; -.
DR OrthoDB; EOG7B5WX3; -.
DR PhylomeDB; O76003; -.
DR ChiTaRS; GLRX3; human.
DR EvolutionaryTrace; O76003; -.
DR GeneWiki; GLRX3; -.
DR GenomeRNAi; 10539; -.
DR NextBio; 39985; -.
DR PMAP-CutDB; O76003; -.
DR PRO; PR:O76003; -.
DR Bgee; O76003; -.
DR CleanEx; HS_GLRX3; -.
DR Genevestigator; O76003; -.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0009055; F:electron carrier activity; IEA:InterPro.
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:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:UniProtKB.
DR Gene3D; 3.40.30.10; -; 3.
DR InterPro; IPR002109; Glutaredoxin.
DR InterPro; IPR004480; Monothiol_GRX-rel.
DR InterPro; IPR012336; Thioredoxin-like_fold.
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; PS00194; THIOREDOXIN_1; FALSE_NEG.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Iron; Iron-sulfur; Metal-binding;
KW Polymorphism; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 335 Glutaredoxin-3.
FT /FTId=PRO_0000120019.
FT DOMAIN 2 117 Thioredoxin.
FT DOMAIN 144 236 Glutaredoxin 1.
FT DOMAIN 237 335 Glutaredoxin 2.
FT METAL 159 159 Iron-sulfur (2Fe-2S); shared with dimeric
FT partner (Probable).
FT METAL 261 261 Iron-sulfur (2Fe-2S); shared with dimeric
FT partner (Probable).
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 21 21 Q -> H (in dbSNP:rs13991).
FT /FTId=VAR_016875.
FT VARIANT 123 123 P -> S (in dbSNP:rs2274217).
FT /FTId=VAR_016876.
FT MUTAGEN 159 159 C->S: Loss of 2Fe-2S-binding; when
FT associated with S-261.
FT MUTAGEN 261 261 C->S: Loss of 2Fe-2S-binding; when
FT associated with S-159.
FT CONFLICT 2 2 A -> E (in Ref. 2; CAA09375).
FT CONFLICT 67 67 K -> R (in Ref. 3; BAG51067).
FT CONFLICT 210 210 I -> T (in Ref. 3; BAG51059).
FT STRAND 13 16
FT HELIX 19 28
FT TURN 29 31
FT STRAND 34 39
FT HELIX 44 59
FT STRAND 63 69
FT TURN 70 72
FT HELIX 74 79
FT STRAND 84 92
FT STRAND 95 103
FT HELIX 105 115
FT HELIX 133 141
FT STRAND 143 152
FT STRAND 154 159
FT HELIX 160 171
FT STRAND 177 180
FT HELIX 181 183
FT HELIX 185 195
FT STRAND 202 205
FT STRAND 208 211
FT HELIX 213 221
FT HELIX 225 228
FT HELIX 233 243
FT STRAND 245 254
FT STRAND 256 259
FT HELIX 263 273
FT STRAND 279 282
FT HELIX 283 285
FT HELIX 287 297
FT STRAND 304 307
FT STRAND 310 313
FT HELIX 315 323
FT HELIX 327 331
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
//
MIM
612754
*RECORD*
*FIELD* NO
612754
*FIELD* TI
*612754 GLUTAREDOXIN 3; GLRX3
;;PROTEIN KINASE C-INTERACTING COUSIN OF THIOREDOXIN; PICOT
read more*FIELD* TX
CLONING
Using protein kinase C (PKC)-theta (PRKCQ, 600448) as bait in a yeast
2-hybrid screen of a Jurkat T-lymphoma cDNA library, Witte et al. (2000)
cloned GLRX3, which they designated PICOT. The deduced 335-amino acid
protein has a calculated molecular mass of 37.5 kD. It has an N-terminal
thioredoxin (TXN; 187700) homology domain followed by tandem repeats of
an 84-amino acid PICOT domain. Human PICOT shares 99% amino acid
identity with the rat and mouse orthologs. The PICOT domain is highly
conserved, and tandem PICOT domains are present in mouse and rat Picot.
However, only a single PICOT domain is present in nematodes, yeast,
bacteria, viruses, and plants. Northern blot analysis detected a 1.5-kb
PICOT transcript in Jurkat cells. RT-PCR detected abundant PICOT
expression in heart, spleen, and testis, with lower expression in other
tissues. Western blot analysis detected PICOT at an apparent molecular
mass of 38 kD. Fractionation of Jurkat cells revealed PICOT in the
cytosolic compartment, with very low amounts in the membrane fraction.
GENE FUNCTION
Using cotransfection and immunoprecipitation analysis with Jurkat cells,
Witte et al. (2000) showed that PICOT interacted with PKC-theta and,
more weakly, with PKC-zeta (PRKCZ; 176982), but not with PKC-alpha
(PRKCA; 176960). Mutation analysis showed that the thioredoxin homology
domain of PICOT was required for the interaction. Transfection of PICOT
in Jurkat cells reduced basal JNK (see MAPK8; 601158) activity and
significantly reduced PKC-theta-induced JNK activation. PICOT also
inhibited the transcription factors AP1 (see 165160) and NF-kappa-B (see
164011).
Jeong et al. (2008) stated that Picot inhibits pressure overload-induced
cardiac hypertrophy in rodents, concomitant with increased ventricular
function and cardiomyocyte contractility. They showed that Picot
colocalized with Mlp (CSRP3; 600824), which anchors calcineurin (see
PPP3CA, 114105) to the Z disc in the sarcomere and is critical for
calcineurin-Nfat (see NFATC1; 600489) signaling. The C-terminal half of
Picot inhibited cardiac hypertrophy, largely by disrupting the
Mlp-calcineurin interaction and thereby negatively regulating
calcineurin-Nfat signaling.
MAPPING
Hartz (2009) mapped the GLRX3 gene to chromosome 10q26.3 based on an
alignment of the GLRX3 sequence (GenBank GENBANK AJ010841) with the
genomic sequence (build 36.1),
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 4/22/2009.
2. Jeong, D.; Kim, J. M.; Cha, H.; Oh, J. G.; Park, J.; Yun, S.-H.;
Ju, E.-S.; Jeon, E.-S.; Hajjar, R. J.; Park, W. J.: PICOT attenuates
cardiac hypertrophy by disrupting calcineurin-NFAT signaling. Circ.
Res. 102: 711-719, 2008.
3. Witte, S.; Villalba, M.; Bi, K.; Liu, Y.; Isakov, N.; Altman, A.
: Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappa-B pathways
by PICOT, a novel protein kinase C-interacting protein with a thioredoxin
homology domain. J. Biol. Chem. 275: 1902-1909, 2000.
*FIELD* CD
Patricia A. Hartz: 4/22/2009
*FIELD* ED
mgross: 04/22/2009
*RECORD*
*FIELD* NO
612754
*FIELD* TI
*612754 GLUTAREDOXIN 3; GLRX3
;;PROTEIN KINASE C-INTERACTING COUSIN OF THIOREDOXIN; PICOT
read more*FIELD* TX
CLONING
Using protein kinase C (PKC)-theta (PRKCQ, 600448) as bait in a yeast
2-hybrid screen of a Jurkat T-lymphoma cDNA library, Witte et al. (2000)
cloned GLRX3, which they designated PICOT. The deduced 335-amino acid
protein has a calculated molecular mass of 37.5 kD. It has an N-terminal
thioredoxin (TXN; 187700) homology domain followed by tandem repeats of
an 84-amino acid PICOT domain. Human PICOT shares 99% amino acid
identity with the rat and mouse orthologs. The PICOT domain is highly
conserved, and tandem PICOT domains are present in mouse and rat Picot.
However, only a single PICOT domain is present in nematodes, yeast,
bacteria, viruses, and plants. Northern blot analysis detected a 1.5-kb
PICOT transcript in Jurkat cells. RT-PCR detected abundant PICOT
expression in heart, spleen, and testis, with lower expression in other
tissues. Western blot analysis detected PICOT at an apparent molecular
mass of 38 kD. Fractionation of Jurkat cells revealed PICOT in the
cytosolic compartment, with very low amounts in the membrane fraction.
GENE FUNCTION
Using cotransfection and immunoprecipitation analysis with Jurkat cells,
Witte et al. (2000) showed that PICOT interacted with PKC-theta and,
more weakly, with PKC-zeta (PRKCZ; 176982), but not with PKC-alpha
(PRKCA; 176960). Mutation analysis showed that the thioredoxin homology
domain of PICOT was required for the interaction. Transfection of PICOT
in Jurkat cells reduced basal JNK (see MAPK8; 601158) activity and
significantly reduced PKC-theta-induced JNK activation. PICOT also
inhibited the transcription factors AP1 (see 165160) and NF-kappa-B (see
164011).
Jeong et al. (2008) stated that Picot inhibits pressure overload-induced
cardiac hypertrophy in rodents, concomitant with increased ventricular
function and cardiomyocyte contractility. They showed that Picot
colocalized with Mlp (CSRP3; 600824), which anchors calcineurin (see
PPP3CA, 114105) to the Z disc in the sarcomere and is critical for
calcineurin-Nfat (see NFATC1; 600489) signaling. The C-terminal half of
Picot inhibited cardiac hypertrophy, largely by disrupting the
Mlp-calcineurin interaction and thereby negatively regulating
calcineurin-Nfat signaling.
MAPPING
Hartz (2009) mapped the GLRX3 gene to chromosome 10q26.3 based on an
alignment of the GLRX3 sequence (GenBank GENBANK AJ010841) with the
genomic sequence (build 36.1),
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 4/22/2009.
2. Jeong, D.; Kim, J. M.; Cha, H.; Oh, J. G.; Park, J.; Yun, S.-H.;
Ju, E.-S.; Jeon, E.-S.; Hajjar, R. J.; Park, W. J.: PICOT attenuates
cardiac hypertrophy by disrupting calcineurin-NFAT signaling. Circ.
Res. 102: 711-719, 2008.
3. Witte, S.; Villalba, M.; Bi, K.; Liu, Y.; Isakov, N.; Altman, A.
: Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappa-B pathways
by PICOT, a novel protein kinase C-interacting protein with a thioredoxin
homology domain. J. Biol. Chem. 275: 1902-1909, 2000.
*FIELD* CD
Patricia A. Hartz: 4/22/2009
*FIELD* ED
mgross: 04/22/2009