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O76003 (GLRX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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
ORF Names:HUSSY-22
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length335 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 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

Cytoplasmcell cortex. CytoplasmmyofibrilsarcomereZ 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CIAPIN1Q6FI813EBI-374781,EBI-750511
PRKCQQ047595EBI-374781,EBI-374762

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10
Chain2 – 335334Glutaredoxin-3
PRO_0000120019

Regions

Domain2 – 117116Thioredoxin
Domain144 – 23693Glutaredoxin 1
Domain237 – 33599Glutaredoxin 2

Sites

Metal binding1591Iron-sulfur (2Fe-2S); shared with dimeric partner Probable
Metal binding2611Iron-sulfur (2Fe-2S); shared with dimeric partner Probable

Amino acid modifications

Modified residue21N-acetylalanine Ref.10 Ref.11

Natural variations

Natural variant211Q → H. Ref.1 Ref.3 Ref.6
Corresponds to variant rs13991 [ dbSNP | Ensembl ].
VAR_016875
Natural variant1231P → S. Ref.1 Ref.3 Ref.6
Corresponds to variant rs2274217 [ dbSNP | Ensembl ].
VAR_016876

Experimental info

Mutagenesis1591C → S: Loss of 2Fe-2S-binding; when associated with S-261. Ref.8
Mutagenesis2611C → S: Loss of 2Fe-2S-binding; when associated with S-159. Ref.8
Sequence conflict21A → E in CAA09375. Ref.2
Sequence conflict671K → R in BAG51067. Ref.3
Sequence conflict2101I → T in BAG51059. Ref.3

Secondary structure

.............................................................. 335
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O76003 [UniParc].

Last modified September 26, 2003. Version 2.
Checksum: 46D644413D9EDFDA

FASTA33537,432
        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 

« 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], 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"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.
RefSeqNP_001186797.1. NM_001199868.1.
NP_006532.2. NM_006541.4.
UniGeneHs.42644.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DIYNMR-A1-117[»]
2WZ9X-ray1.55A1-125[»]
2YANX-ray1.90A/B232-334[»]
3ZYWX-ray1.84A/B130-232[»]
ProteinModelPortalO76003.
SMRO76003. Positions 11-125, 132-334.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115793. 29 interactions.
IntActO76003. 17 interactions.
MINTMINT-5002296.
STRING9606.ENSP00000330836.

PTM databases

PhosphoSiteO76003.

2D gel databases

REPRODUCTION-2DPAGEIPI00008552.

Proteomic databases

PaxDbO76003.
PeptideAtlasO76003.
PRIDEO76003.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000331244; ENSP00000330836; ENSG00000108010.
ENST00000368644; ENSP00000357633; ENSG00000108010.
ENST00000481034; ENSP00000435445; ENSG00000108010.
GeneID10539.
KEGGhsa:10539.
UCSCuc001lkm.2. human.

Organism-specific databases

CTD10539.
GeneCardsGC10P131934.
HGNCHGNC:15987. GLRX3.
HPAHPA028941.
MIM612754. gene.
neXtProtNX_O76003.
PharmGKBPA162389829.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0526.
HOVERGENHBG054719.
InParanoidO76003.
OMAELPQVSF.
OrthoDBEOG7B5WX3.
PhylomeDBO76003.
TreeFamTF314151.

Gene expression databases

BgeeO76003.
CleanExHS_GLRX3.
GenevestigatorO76003.

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

ChiTaRSGLRX3. human.
EvolutionaryTraceO76003.
GeneWikiGLRX3.
GenomeRNAi10539.
NextBio39985.
PMAP-CutDBO76003.
PROO76003.
SOURCESearch...

Entry information

Entry nameGLRX3_HUMAN
AccessionPrimary (citable) accession number: O76003
Secondary accession number(s): B3KMP7 expand/collapse secondary AC list , B3KMQ5, D3DRG2, Q5JV01, Q96CE0, Q9P1B0, Q9P1B1
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: September 26, 2003
Last modified: April 16, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM