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 22-FEB-2012, entry version 120. 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 MEDLINE=20102703; 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 MEDLINE=21064499; 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 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 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. 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; 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 IPI; IPI00008552; -. 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 PDBsum; 2DIY; -. DR PDBsum; 2WZ9; -. DR PDBsum; 2YAN; -. DR ProteinModelPortal; O76003; -. DR SMR; O76003; 11-125, 137-225, 239-335. DR IntAct; O76003; 10. DR MINT; MINT-5002296; -. DR STRING; O76003; -. DR PhosphoSite; O76003; -. DR REPRODUCTION-2DPAGE; IPI00008552; -. DR PeptideAtlas; O76003; -. DR PRIDE; O76003; -. DR Ensembl; ENST00000331244; ENSP00000330836; ENSG00000108010. DR Ensembl; ENST00000368644; ENSP00000357633; ENSG00000108010. DR GeneID; 10539; -. DR KEGG; hsa:10539; -. DR UCSC; uc001lkm.1; human. DR CTD; 10539; -. DR GeneCards; GC10P131934; -. DR H-InvDB; HIX0009315; -. DR HGNC; HGNC:15987; GLRX3. DR HPA; HPA028941; -. DR MIM; 612754; gene. DR neXtProt; NX_O76003; -. DR PharmGKB; PA162389829; -. DR eggNOG; COG0526; -. DR GeneTree; ENSGT00550000075030; -. DR HOVERGEN; HBG054719; -. DR InParanoid; O76003; -. DR OMA; AKCGFSR; -. DR OrthoDB; EOG4V9TR0; -. DR PhylomeDB; O76003; -. DR NextBio; 39985; -. DR PMAP-CutDB; O76003; -. DR ArrayExpress; O76003; -. DR Bgee; O76003; -. DR CleanEx; HS_GLRX3; -. DR Genevestigator; O76003; -. DR GermOnline; ENSG00000108010; Homo sapiens. 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 InterPro; IPR002109; Glutaredoxin. DR InterPro; IPR004480; Monothiol_GRX-rel. DR InterPro; IPR012336; Thioredoxin-like_fold. DR InterPro; IPR013766; Thioredoxin_domain. DR Gene3D; G3DSA:3.40.30.10; Thioredoxin_fold; 3. DR PANTHER; PTHR10293; Glutredox-rel; 1. DR Pfam; PF00462; Glutaredoxin; 2. DR Pfam; PF00085; Thioredoxin; 1. DR SUPFAM; SSF52833; Thiordxn-like_fd; 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 (By similarity). 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 14 16 FT HELIX 19 28 FT STRAND 31 39 FT HELIX 45 59 FT STRAND 63 69 FT TURN 70 72 FT HELIX 74 80 FT STRAND 84 102 FT HELIX 105 116 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 //