O76003 (GLRX3_HUMAN) 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
ORF Names:	HUSSY-22

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	335 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 By similarity. May play a role in regulating the function of the thioredoxin system. Does not posses any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity.
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. Interacts (via C-terminus) with CSRP3 By similarity. Interacts with CSRP2 By similarity. Ref.1 Ref.8
Subcellular location	Cytoplasm › cell cortex. 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. In the Z line, found associated with CSRP3 By similarity. Ref.1
Tissue specificity	Expressed in heart, spleen, testis and, to a lower extent, in thymus and peripheral blood leukocytes. Weakly expressed in lung, placenta, colon and small intestine.
Domain	The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.
Sequence similarities	Contains 2 glutaredoxin domains. Contains 1 thioredoxin domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
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 sequence or structural similarity. Source: UniProtKB regulation of the force of heart contraction Inferred from sequence or structural similarity PubMed 18258855. Source: UniProtKB
Cellular_component	Z disc Inferred from electronic annotation. Source: UniProtKB-SubCell 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
PRKCQ	Q04759	5	EBI-374781,EBI-374762

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 335

334

Glutaredoxin-3

PRO_0000120019

Regions

Domain

2 – 117

116

Thioredoxin

Domain

144 – 236

93

Glutaredoxin 1

Domain

237 – 335

99

Glutaredoxin 2

Sites

Metal binding

159

1

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

Metal binding

261

1

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

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Natural variations

Natural variant

21

1

Q → H. Ref.1 Ref.3 Ref.6
Corresponds to variant rs13991 [ dbSNP | Ensembl ].

VAR_016875

Natural variant

123

1

P → S. Ref.1 Ref.3 Ref.6
Corresponds to variant rs2274217 [ dbSNP | Ensembl ].

VAR_016876

Experimental info

Mutagenesis

159

1

C → S: Loss of 2Fe-2S-binding; when associated with S-261. Ref.8

Mutagenesis

261

1

C → S: Loss of 2Fe-2S-binding; when associated with S-159. Ref.8

Sequence conflict

2

1

A → E in CAA09375. Ref.2

Sequence conflict

67

1

K → R in BAG51067. Ref.3

Sequence conflict

210

1

I → T in BAG51059. Ref.3

Secondary structure

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335

Helix Strand Turn

Details...

Beta strand

13 – 16

4

Helix

19 – 28

10

Turn

29 – 31

3

Beta strand

34 – 39

6

Helix

44 – 59

16

Beta strand

63 – 69

7

Turn

70 – 72

3

Helix

74 – 79

6

Beta strand

84 – 92

9

Beta strand

95 – 103

9

Helix

105 – 115

11

Helix

133 – 141

9

Beta strand

143 – 152

10

Beta strand

154 – 159

6

Helix

160 – 171

12

Beta strand

177 – 180

4

Helix

181 – 183

3

Helix

185 – 195

11

Beta strand

202 – 205

4

Beta strand

208 – 211

4

Helix

213 – 221

9

Helix

225 – 228

4

Helix

233 – 243

11

Beta strand

245 – 254

10

Beta strand

256 – 259

4

Helix

263 – 273

11

Beta strand

279 – 282

4

Helix

283 – 285

3

Helix

287 – 297

11

Beta strand

304 – 307

4

Beta strand

310 – 313

4

Helix

315 – 323

9

Helix

327 – 331

5

Sequences

	Sequence		Length	Mass (Da)
	O76003 [UniParc]. Last modified September 26, 2003. Version 2. Checksum: 46D644413D9EDFDA	FASTA	335	37,432
	10 20 30 40 50 60 MAAGAAEAAV AAVEEVGSAG QFEELLRLKA KSLLVVHFWA PWAPQCAQMN EVMAELAKEL 70 80 90 100 110 120 PQVSFVKLEA EGVPEVSEKY EISSVPTFLF FKNSQKIDRL DGAHAPELTK KVQRHASSGS 130 140 150 160 170 180 FLPSANEHLK EDLNLRLKKL THAAPCMLFM KGTPQEPRCG FSKQMVEILH KHNIQFSSFD 190 200 210 220 230 240 IFSDEEVRQG LKAYSSWPTY PQLYVSGELI GGLDIIKELE ASEELDTICP KAPKLEERLK 250 260 270 280 290 300 VLTNKASVML FMKGNKQEAK CGFSKQILEI LNSTGVEYET FDILEDEEVR QGLKAYSNWP 310 320 330 TYPQLYVKGE LVGGLDIVKE LKENGELLPI LRGEN

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], SUBCELLULAR LOCATION, INTERACTION WITH PRKCQ, VARIANTS HIS-21 AND SER-123. Tissue: Liver, Spleen and T-cell lymphoma.
[2]	"Characterization of 16 novel human genes showing high similarity to yeast sequences." Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., Zimbello R., Lanfranchi G., Valle G. Yeast 18:69-80(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Melanocyte.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS HIS-21 AND SER-123.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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], VARIANTS HIS-21 AND SER-123. Tissue: Bone marrow and Urinary bladder.
[7]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 59-79; 115-130; 218-231; 246-253; 309-319 AND 323-332. Tissue: Fetal brain cortex.
[8]	"Characterization of the human monothiol glutaredoxin 3 (PICOT) as iron-sulfur protein." Haunhorst P., Berndt C., Eitner S., Godoy J.R., Lillig C.H. Biochem. Biophys. Res. Commun. 394:372-376(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF CYS-159 AND CYS-261, METAL.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"The solution structure of the thioredoxin domain of human thioredoxin-like protein 2." RIKEN structural genomics initiative (RSGI) Submitted (APR-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-119.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF118649 mRNA. Translation: AAF28841.1.
AF118652 mRNA. Translation: AAF28844.1.
AJ010841 mRNA. Translation: CAA09375.1.
AK022131 mRNA. Translation: BAG51067.1.
AK021926 mRNA. Translation: BAG51059.1.
AL139123 Genomic DNA. Translation: CAC40691.1.
CH471066 Genomic DNA. Translation: EAW49152.1.
CH471066 Genomic DNA. Translation: EAW49154.1.
CH471066 Genomic DNA. Translation: EAW49155.1.
BC005289 mRNA. Translation: AAH05289.1.
BC014372 mRNA. Translation: AAH14372.2.

IPI

IPI00008552.

RefSeq

NP_001186797.1. NM_001199868.1.
NP_006532.2. NM_006541.4.

UniGene

Hs.42644.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DIY	NMR	-	A	1-117	[»]
2WZ9	X-ray	1.55	A	1-125	[»]
2YAN	X-ray	1.90	A/B	232-334	[»]
3ZYW	X-ray	1.84	A/B	130-232	[»]

ProteinModelPortal

O76003.

ModBase

Search...

Protein-protein interaction databases

IntAct

O76003. 12 interactions.

MINT

MINT-5002296.

STRING

9606.ENSP00000330836.

PTM databases

PhosphoSite

O76003.

2D gel databases

REPRODUCTION-2DPAGE

IPI00008552.

Proteomic databases

PaxDb

O76003.

PeptideAtlas

O76003.

PRIDE

O76003.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331244; ENSP00000330836; ENSG00000108010.
ENST00000368644; ENSP00000357633; ENSG00000108010.
ENST00000481034; ENSP00000435445; ENSG00000108010.

GeneID

10539.

KEGG

hsa:10539.

UCSC

uc001lkm.2. human.

Organism-specific databases

CTD

10539.

GeneCards

GC10P131934.

HGNC

HGNC:15987. GLRX3.

HPA

HPA028941.

MIM

612754. gene.

neXtProt

NX_O76003.

PharmGKB

PA162389829.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0526.

HOVERGEN

HBG054719.

InParanoid

O76003.

OMA

ELPQVSF.

OrthoDB

EOG4V9TR0.

PhylomeDB

O76003.

Gene expression databases

Bgee

O76003.

CleanEx

HS_GLRX3.

Genevestigator

O76003.

GermOnline

ENSG00000108010. Homo sapiens.

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

ChiTaRS

GLRX3. human.

EvolutionaryTrace

O76003.

GenomeRNAi

10539.

NextBio

39985.

PMAP-CutDB

O76003.

SOURCE

Search...

Entry information

Entry name

GLRX3_HUMAN

Accession

Primary (citable) accession number: O76003
Secondary accession number(s): B3KMP7 , B3KMQ5, D3DRG2, Q5JV01, Q96CE0, Q9P1B0, Q9P1B1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	September 26, 2003
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.