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Protein

Glutaredoxin-3

Gene

GLRX3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (By similarity). Required for hemoglobin maturation (PubMed:23615448). Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity.By similarity3 Publications

Miscellaneous

Silencing of Grx3 in HeLa cells decreases the activities of several cytosolic Fe/S proteins, such as ACO1, a major component of post-transcriptional iron regulation. As a consequence, Grx3-depleted cells show decreased levels of ferritin and increased levels of transferrin receptor, features characteristic of cellular iron starvation (PubMed:23615448).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi159Iron-sulfur (2Fe-2S); shared with dimeric partner2 Publications1
Metal bindingi261Iron-sulfur (2Fe-2S); shared with dimeric partner2 Publications1

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandIron, Iron-sulfur, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-917937 Iron uptake and transport

Names & Taxonomyi

Protein namesi
Recommended name:
Glutaredoxin-3
Alternative name(s):
PKC-interacting cousin of thioredoxin1 Publication
Short name:
PICOT1 Publication
PKC-theta-interacting protein
Short name:
PKCq-interacting protein
Thioredoxin-like protein 2
Gene namesi
Name:GLRX3
Synonyms:PICOT1 Publication, TXNL2
ORF Names:HUSSY-22
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000108010.11
HGNCiHGNC:15987 GLRX3
MIMi612754 gene
neXtProtiNX_O76003

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi159C → S: Loss of 2Fe-2S-binding; when associated with S-261. Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with 197-D-A-198. 2 Publications1
Mutagenesisi197 – 198WP → DA: Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with S-159. 1 Publication2
Mutagenesisi261C → S: Loss of 2Fe-2S-binding; when associated with S-159. Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with 299-D-A-300. 2 Publications1
Mutagenesisi299 – 300WP → DA: Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with S-261. 1 Publication2

Organism-specific databases

DisGeNETi10539
OpenTargetsiENSG00000108010
PharmGKBiPA162389829

Polymorphism and mutation databases

BioMutaiGLRX3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001200192 – 335Glutaredoxin-3Add BLAST334

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei117PhosphoserineCombined sources1
Modified residuei120PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO76003
MaxQBiO76003
PaxDbiO76003
PeptideAtlasiO76003
PRIDEiO76003
ProteomicsDBi50341

2D gel databases

REPRODUCTION-2DPAGEiIPI00008552

PTM databases

iPTMnetiO76003
PhosphoSitePlusiO76003

Miscellaneous databases

PMAP-CutDBiO76003

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000108010 Expressed in 224 organ(s), highest expression level in testis
CleanExiHS_GLRX3
ExpressionAtlasiO76003 baseline and differential
GenevisibleiO76003 HS

Organism-specific databases

HPAiHPA028941

Interactioni

Subunit structurei

Homodimer; the homodimer is independent of 2Fe-2S clusters (PubMed:27519415). Heterotrimer; forms a heterotrimeric complex composed by two BOLA2 molecules and one GLRX3 molecule; linked by [2Fe-2S] clusters (PubMed:22309771, PubMed:26613676, PubMed:27519415). Interacts (via N-terminus) with PRKCQ/PKC-theta (PubMed:10636891). Interacts (via C-terminus) with CSRP3 (By similarity). Interacts with CSRP2 (By similarity).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115793, 101 interactors
DIPiDIP-31306N
IntActiO76003, 98 interactors
MINTiO76003
STRINGi9606.ENSP00000330836

Structurei

Secondary structure

1335
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO76003
SMRiO76003
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO76003

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 117ThioredoxinPROSITE-ProRule annotationAdd BLAST116
Domaini144 – 236Glutaredoxin 1PROSITE-ProRule annotationAdd BLAST93
Domaini237 – 335Glutaredoxin 2PROSITE-ProRule annotationAdd BLAST99

Domaini

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0911 Eukaryota
COG0278 LUCA
GeneTreeiENSGT00550000075030
HOVERGENiHBG054719
InParanoidiO76003
OMAiAKCGFSR
OrthoDBiEOG091G0YN0
PhylomeDBiO76003
TreeFamiTF314151

Family and domain databases

CDDicd03028 GRX_PICOT_like, 2 hits
InterProiView protein in InterPro
IPR002109 Glutaredoxin
IPR033658 GRX_PICOT-like
IPR004480 Monothiol_GRX-rel
IPR036249 Thioredoxin-like_sf
IPR013766 Thioredoxin_domain
PANTHERiPTHR10293 PTHR10293, 1 hit
PfamiView protein in Pfam
PF00462 Glutaredoxin, 2 hits
PF00085 Thioredoxin, 1 hit
SUPFAMiSSF52833 SSF52833, 3 hits
TIGRFAMsiTIGR00365 TIGR00365, 1 hit
PROSITEiView protein in PROSITE
PS51354 GLUTAREDOXIN_2, 2 hits
PS51352 THIOREDOXIN_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O76003-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAAGAAEAAV AAVEEVGSAG QFEELLRLKA KSLLVVHFWA PWAPQCAQMN
60 70 80 90 100
EVMAELAKEL PQVSFVKLEA EGVPEVSEKY EISSVPTFLF FKNSQKIDRL
110 120 130 140 150
DGAHAPELTK KVQRHASSGS FLPSANEHLK EDLNLRLKKL THAAPCMLFM
160 170 180 190 200
KGTPQEPRCG FSKQMVEILH KHNIQFSSFD IFSDEEVRQG LKAYSSWPTY
210 220 230 240 250
PQLYVSGELI GGLDIIKELE ASEELDTICP KAPKLEERLK VLTNKASVML
260 270 280 290 300
FMKGNKQEAK CGFSKQILEI LNSTGVEYET FDILEDEEVR QGLKAYSNWP
310 320 330
TYPQLYVKGE LVGGLDIVKE LKENGELLPI LRGEN
Length:335
Mass (Da):37,432
Last modified:September 26, 2003 - v2
Checksum:i46D644413D9EDFDA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2A → E in CAA09375 (PubMed:11124703).Curated1
Sequence conflicti67K → R in BAG51067 (PubMed:14702039).Curated1
Sequence conflicti210I → T in BAG51059 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01687521Q → H3 PublicationsCorresponds to variant dbSNP:rs13991Ensembl.1
Natural variantiVAR_016876123P → S3 PublicationsCorresponds to variant dbSNP:rs2274217Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
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
CCDSiCCDS7661.1
RefSeqiNP_001186797.1, NM_001199868.1
NP_006532.2, NM_006541.4
UniGeneiHs.42644

Genome annotation databases

EnsembliENST00000331244; ENSP00000330836; ENSG00000108010
ENST00000368644; ENSP00000357633; ENSG00000108010
ENST00000481034; ENSP00000435445; ENSG00000108010
GeneIDi10539
KEGGihsa:10539
UCSCiuc001lkm.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
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
CCDSiCCDS7661.1
RefSeqiNP_001186797.1, NM_001199868.1
NP_006532.2, NM_006541.4
UniGeneiHs.42644

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DIYNMR-A1-117[»]
2WZ9X-ray1.55A1-125[»]
2YANX-ray1.90A/B232-334[»]
3ZYWX-ray1.84A/B130-232[»]
ProteinModelPortaliO76003
SMRiO76003
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115793, 101 interactors
DIPiDIP-31306N
IntActiO76003, 98 interactors
MINTiO76003
STRINGi9606.ENSP00000330836

PTM databases

iPTMnetiO76003
PhosphoSitePlusiO76003

Polymorphism and mutation databases

BioMutaiGLRX3

2D gel databases

REPRODUCTION-2DPAGEiIPI00008552

Proteomic databases

EPDiO76003
MaxQBiO76003
PaxDbiO76003
PeptideAtlasiO76003
PRIDEiO76003
ProteomicsDBi50341

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331244; ENSP00000330836; ENSG00000108010
ENST00000368644; ENSP00000357633; ENSG00000108010
ENST00000481034; ENSP00000435445; ENSG00000108010
GeneIDi10539
KEGGihsa:10539
UCSCiuc001lkm.3 human

Organism-specific databases

CTDi10539
DisGeNETi10539
EuPathDBiHostDB:ENSG00000108010.11
GeneCardsiGLRX3
HGNCiHGNC:15987 GLRX3
HPAiHPA028941
MIMi612754 gene
neXtProtiNX_O76003
OpenTargetsiENSG00000108010
PharmGKBiPA162389829
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0911 Eukaryota
COG0278 LUCA
GeneTreeiENSGT00550000075030
HOVERGENiHBG054719
InParanoidiO76003
OMAiAKCGFSR
OrthoDBiEOG091G0YN0
PhylomeDBiO76003
TreeFamiTF314151

Enzyme and pathway databases

ReactomeiR-HSA-917937 Iron uptake and transport

Miscellaneous databases

ChiTaRSiGLRX3 human
EvolutionaryTraceiO76003
GeneWikiiGLRX3
GenomeRNAii10539
PMAP-CutDBiO76003
PROiPR:O76003
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108010 Expressed in 224 organ(s), highest expression level in testis
CleanExiHS_GLRX3
ExpressionAtlasiO76003 baseline and differential
GenevisibleiO76003 HS

Family and domain databases

CDDicd03028 GRX_PICOT_like, 2 hits
InterProiView protein in InterPro
IPR002109 Glutaredoxin
IPR033658 GRX_PICOT-like
IPR004480 Monothiol_GRX-rel
IPR036249 Thioredoxin-like_sf
IPR013766 Thioredoxin_domain
PANTHERiPTHR10293 PTHR10293, 1 hit
PfamiView protein in Pfam
PF00462 Glutaredoxin, 2 hits
PF00085 Thioredoxin, 1 hit
SUPFAMiSSF52833 SSF52833, 3 hits
TIGRFAMsiTIGR00365 TIGR00365, 1 hit
PROSITEiView protein in PROSITE
PS51354 GLUTAREDOXIN_2, 2 hits
PS51352 THIOREDOXIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGLRX3_HUMAN
AccessioniPrimary (citable) accession number: O76003
Secondary accession number(s): B3KMP7
, B3KMQ5, D3DRG2, Q5JV01, Q96CE0, Q9P1B0, Q9P1B1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: September 26, 2003
Last modified: November 7, 2018
This is version 186 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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