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Q9CQM9 (GLRX3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutaredoxin-3
Alternative name(s):
PKC-interacting cousin of thioredoxin
Short name=PICOT
PKC-theta-interacting protein
Short name=PKCq-interacting protein
Thioredoxin-like protein 2
Gene names
Name:Glrx3
Synonyms:Picot, Txnl2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length337 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Critical negative regulator of cardiac hypertrophy and a positive inotropic regulator. May play a role in regulating the function of the thioredoxin system. Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity. Has an essential function in embryogenesis. Ref.5 Ref.6 Ref.7

Subunit structure

Monomer and homodimer; the homodimer is probably linked by 2 2Fe-2S clusters that may serve as a redox sensor. The monomer interacts with other proteins. Interacts (via N-terminus) with PRKCQ/PKC-theta By similarity. Interacts (via C-terminus) with CSRP3. Interacts with CSRP2. Ref.6

Subcellular location

Cytoplasmcell cortex By similarity. CytoplasmmyofibrilsarcomereZ line By similarity. Note: Under the plasma membrane. After PMA stimulation, GLRX3 and PRKCQ/PKC-theta translocate to a more extended submembrane area By similarity. In the Z line, found associated with CSRP3.

Domain

The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.

Disruption phenotype

Homozygous null mutants die in utero sometime between E12.5 and E14.5. E12.5 embryos have a smaller body size and hemorrhage in the head. Heterozygous mutants are fertile and show no abnormalities in growth and development, cardiomyocytes exhibit significantly reduced contractility. Ref.7

Miscellaneous

Transgenic mice with cardiac-specific Glrx3 overexpression show that it is a potent inhibitor of cardiac hypertrophy induced by pressure overload (transverse aortic constriction). In addition, overexpression dramatically increases the ventricular function and cardiomyocyte contractility.

Sequence similarities

Contains 2 glutaredoxin domains.

Contains 1 thioredoxin domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Ciapin1Q8WTY44EBI-4319195,EBI-2943068

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 337336Glutaredoxin-3
PRO_0000120020

Regions

Domain2 – 119118Thioredoxin
Domain144 – 23895Glutaredoxin 1
Domain239 – 33799Glutaredoxin 2

Sites

Metal binding1611Iron-sulfur (2Fe-2S); shared with dimeric partner By similarity
Metal binding2631Iron-sulfur (2Fe-2S); shared with dimeric partner By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Experimental info

Sequence conflict761P → T in AAF28842. Ref.1

Secondary structure

.................... 337
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9CQM9 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 74A1C65621B28FA0

FASTA33737,778
        10         20         30         40         50         60 
MAAGAAEAGE AAVAVVEVGS AQQFEELLRL KTKSLLVVHF WAPWAPQCVQ MNDVMAELAK 

        70         80         90        100        110        120 
EHPHVSFVKL EAEAVPEVSE KYEISSVPTF LFFKNSQKVD RLDGAHAPEL TKKVQRHVSS 

       130        140        150        160        170        180 
GAFPPSTNEH LKEDLSLRLK KLTHAAPCML FMKGTPQEPR CGFSKQMVEI LHKHNIQFSS 

       190        200        210        220        230        240 
FDIFSDEEVR QGLKTYSNWP TYPQLYVSGE LIGGLDIIKE LEASEELDTI CPKAPKLEER 

       250        260        270        280        290        300 
LKVLTNKASV MLFMKGNKQE AKCGFSKQIL EILNSTGVEY ETFDILEDEE VRQGLKTFSN 

       310        320        330 
WPTYPQLYVR GDLVGGLDIV KELKDNGELL PILKGEN 

« Hide

References

« Hide 'large scale' references
[1]"Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain."
Witte S., Villalba M., Bi K., Liu Y., Isakov N., Altman A.
J. Biol. Chem. 275:1902-1909(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6J.
Tissue: Embryo.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Embryonic stem cell and Head.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Czech II.
Tissue: Kidney and Mammary tumor.
[4]Lubec G., Yang J.W., Zigmond M.
Submitted (JUL-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 82-94.
Tissue: Brain.
[5]"PICOT inhibits cardiac hypertrophy and enhances ventricular function and cardiomyocyte contractility."
Jeong D., Cha H., Kim E., Kang M., Yang D.K., Kim J.M., Yoon P.O., Oh J.G., Bernecker O.Y., Sakata S., Le T.T., Cui L., Lee Y.H., Kim do H., Woo S.H., Liao R., Hajjar R.J., Park W.J.
Circ. Res. 99:307-314(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, OVEREXPRESSION.
[6]"PICOT attenuates cardiac hypertrophy by disrupting calcineurin-NFAT signaling."
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.
Circ. Res. 102:711-719(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, OVEREXPRESSION, INTERACTION WITH CSRP2 AND CSRP3.
[7]"PICOT is a critical regulator of cardiac hypertrophy and cardiomyocyte contractility."
Cha H., Kim J.M., Oh J.G., Jeong M.H., Park C.S., Park J., Jeong H.J., Park B.K., Lee Y.-H., Jeong D., Yang D.K., Bernecker O.Y., Kim do H., Hajjar R.J., Park W.J.
J. Mol. Cell. Cardiol. 45:796-803(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[8]"Solution structure of the picot homology 2 domain of the mouse pkc-interacting cousin of thioredoxin protein."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2004) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 241-336.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF118650 mRNA. Translation: AAF28842.1.
AK010354 mRNA. Translation: BAB26874.1.
AK017371 mRNA. Translation: BAB30712.1.
AK147158 mRNA. Translation: BAE27724.1.
AK152446 mRNA. Translation: BAE31225.1.
AK152634 mRNA. Translation: BAE31376.1.
AK155190 mRNA. Translation: BAE33105.1.
AK167672 mRNA. Translation: BAE39721.1.
BC033506 mRNA. Translation: AAH33506.1.
BC087885 mRNA. Translation: AAH87885.1.
CCDSCCDS21948.1.
RefSeqNP_075629.2. NM_023140.4.
UniGeneMm.267692.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WIKNMR-A241-336[»]
ProteinModelPortalQ9CQM9.
SMRQ9CQM9. Positions 20-121, 134-234, 241-337.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9CQM9. 4 interactions.
MINTMINT-4138889.
STRING10090.ENSMUSP00000066621.

PTM databases

PhosphoSiteQ9CQM9.

2D gel databases

REPRODUCTION-2DPAGEIPI00315550.
Q9CQM9.

Proteomic databases

MaxQBQ9CQM9.
PaxDbQ9CQM9.
PRIDEQ9CQM9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000064404; ENSMUSP00000066621; ENSMUSG00000031068.
GeneID30926.
KEGGmmu:30926.
UCSCuc009kew.1. mouse.

Organism-specific databases

CTD10539.
MGIMGI:1353653. Glrx3.

Phylogenomic databases

eggNOGCOG0526.
GeneTreeENSGT00550000075030.
HOGENOMHOG000165751.
HOVERGENHBG054719.
InParanoidQ9CQM9.
OMAYPQLYLD.
OrthoDBEOG7B5WX3.
PhylomeDBQ9CQM9.
TreeFamTF314151.

Gene expression databases

BgeeQ9CQM9.
CleanExMM_GLRX3.
GenevestigatorQ9CQM9.

Family and domain databases

Gene3D3.40.30.10. 3 hits.
InterProIPR002109. Glutaredoxin.
IPR004480. Monothiol_GRX-rel.
IPR012336. Thioredoxin-like_fold.
IPR013766. Thioredoxin_domain.
[Graphical view]
PANTHERPTHR10293. PTHR10293. 1 hit.
PfamPF00462. Glutaredoxin. 2 hits.
PF00085. Thioredoxin. 1 hit.
[Graphical view]
SUPFAMSSF52833. SSF52833. 3 hits.
TIGRFAMsTIGR00365. TIGR00365. 1 hit.
PROSITEPS51354. GLUTAREDOXIN_2. 2 hits.
PS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9CQM9.
NextBio307324.
PROQ9CQM9.
SOURCESearch...

Entry information

Entry nameGLRX3_MOUSE
AccessionPrimary (citable) accession number: Q9CQM9
Secondary accession number(s): Q5I0V8, Q9JLZ2
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot