Q9CQM9 (GLRX3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	337 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Cytoplasm › cell cortex By similarity. Cytoplasm › myofibril › sarcomere › Z 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Domain	Repeat
Ligand	Iron Iron-sulfur Metal-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro negative regulation of cardiac muscle hypertrophy Inferred from mutant phenotype Ref.6. Source: UniProtKB regulation of the force of heart contraction Inferred from mutant phenotype Ref.6. Source: UniProtKB
Cellular_component	Z disc Inferred from direct assay Ref.6. Source: UniProtKB cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro iron-sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ciapin1	Q8WTY4	4	EBI-4319195,EBI-2943068

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 337

336

Glutaredoxin-3

PRO_0000120020

Regions

Domain

2 – 119

118

Thioredoxin

Domain

144 – 238

95

Glutaredoxin 1

Domain

239 – 337

99

Glutaredoxin 2

Sites

Metal binding

161

1

Iron-sulfur (2Fe-2S); shared with dimeric partner By similarity

Metal binding

263

1

Iron-sulfur (2Fe-2S); shared with dimeric partner By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Experimental info

Sequence conflict

76

1

P → T in AAF28842. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

337

Helix Strand Turn

Details...

Helix

241 – 245

5

Beta strand

248 – 256

9

Turn

257 – 259

3

Helix

266 – 275

10

Beta strand

280 – 287

8

Helix

289 – 299

11

Beta strand

306 – 308

3

Beta strand

310 – 315

6

Helix

317 – 326

10

Helix

330 – 334

5

Sequences

	Sequence		Length	Mass (Da)
	Q9CQM9 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 74A1C65621B28FA0	FASTA	337	37,778
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00315550.

RefSeq

NP_075629.2. NM_023140.4.

UniGene

Mm.267692.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WIK	NMR	-	A	241-336	[»]

ProteinModelPortal

Q9CQM9.

SMR

Q9CQM9. Positions 20-121, 134-234, 241-337.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9CQM9. 1 interaction.

MINT

MINT-4138889.

STRING

10090.ENSMUSP00000066621.

PTM databases

PhosphoSite

Q9CQM9.

2D gel databases

REPRODUCTION-2DPAGE

IPI00315550.
Q9CQM9.

Proteomic databases

PaxDb

Q9CQM9.

PRIDE

Q9CQM9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000064404; ENSMUSP00000066621; ENSMUSG00000031068.

GeneID

30926.

KEGG

mmu:30926.

UCSC

uc009kew.1. mouse.

Organism-specific databases

CTD

10539.

MGI

MGI:1353653. Glrx3.

Phylogenomic databases

eggNOG

COG0526.

GeneTree

ENSGT00550000075030.

HOGENOM

HOG000165751.

HOVERGEN

HBG054719.

InParanoid

Q9CQM9.

OMA

PQLYLDG.

OrthoDB

EOG4V9TR0.

Gene expression databases

Bgee

Q9CQM9.

CleanEx

MM_GLRX3.

Genevestigator

Q9CQM9.

GermOnline

ENSMUSG00000031068. Mus musculus.

Family and domain databases

Gene3D

3.40.30.10. 3 hits.

InterPro

IPR002109. Glutaredoxin.
IPR004480. Monothiol_GRX-rel.
IPR012336. Thioredoxin-like_fold.
IPR013766. Thioredoxin_domain.
[Graphical view]

PANTHER

PTHR10293. PTHR10293. 1 hit.

Pfam

PF00462. Glutaredoxin. 2 hits.
PF00085. Thioredoxin. 1 hit.
[Graphical view]

SUPFAM

SSF52833. Thiordxn-like_fd. 3 hits.

TIGRFAMs

TIGR00365. TIGR00365. 1 hit.

PROSITE

PS51354. GLUTAREDOXIN_2. 2 hits.
PS00194. THIOREDOXIN_1. False negative.
PS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9CQM9.

NextBio

307324.

SOURCE

Search...

Entry information

Entry name

GLRX3_MOUSE

Accession

Primary (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:	May 29, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program