O76003 · GLRX3_HUMAN
- ProteinGlutaredoxin-3
- GeneGLRX3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids335 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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
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
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).
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell cortex | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | dendrite | |
Cellular Component | iron-sulfur cluster assembly complex | |
Cellular Component | nucleus | |
Cellular Component | Z disc | |
Molecular Function | identical protein binding | |
Molecular Function | iron-sulfur cluster binding | |
Molecular Function | metal ion binding | |
Molecular Function | protein kinase C binding | |
Molecular Function | RNA binding | |
Biological Process | [2Fe-2S] cluster assembly | |
Biological Process | cell redox homeostasis | |
Biological Process | intracellular iron ion homeostasis | |
Biological Process | iron-sulfur cluster assembly | |
Biological Process | negative regulation of cardiac muscle hypertrophy | |
Biological Process | protein maturation by iron-sulfur cluster transfer | |
Biological Process | regulation of the force of heart contraction |
Keywords
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGlutaredoxin-3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO76003
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Under the plasma membrane (By similarity).
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 (By similarity).
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 (By similarity).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_016875 | 21 | in dbSNP:rs13991 | |||
Sequence: Q → H | ||||||
Natural variant | VAR_016876 | 123 | in dbSNP:rs2274217 | |||
Sequence: P → S | ||||||
Mutagenesis | 159 | 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. | ||||
Sequence: C → S | ||||||
Mutagenesis | 197-198 | Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with S-159. | ||||
Sequence: WP → DA | ||||||
Mutagenesis | 261 | 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. | ||||
Sequence: C → S | ||||||
Mutagenesis | 299-300 | Loss of 2Fe-2S-binding and interaction with BOLA2; when associated with S-261. | ||||
Sequence: WP → DA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 418 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000120019 | 2-335 | UniProt | Glutaredoxin-3 | |||
Sequence: AAGAAEAAVAAVEEVGSAGQFEELLRLKAKSLLVVHFWAPWAPQCAQMNEVMAELAKELPQVSFVKLEAEGVPEVSEKYEISSVPTFLFFKNSQKIDRLDGAHAPELTKKVQRHASSGSFLPSANEHLKEDLNLRLKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKAYSSWPTYPQLYVSGELIGGLDIIKELEASEELDTICPKAPKLEERLKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKAYSNWPTYPQLYVKGELVGGLDIVKELKENGELLPILRGEN | |||||||
Modified residue | 117 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 117 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 120 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 120 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
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.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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).
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).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 2-117 | Thioredoxin | ||||
Sequence: AAGAAEAAVAAVEEVGSAGQFEELLRLKAKSLLVVHFWAPWAPQCAQMNEVMAELAKELPQVSFVKLEAEGVPEVSEKYEISSVPTFLFFKNSQKIDRLDGAHAPELTKKVQRHAS | ||||||
Domain | 144-236 | Glutaredoxin 1 | ||||
Sequence: APCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKAYSSWPTYPQLYVSGELIGGLDIIKELEASEELDTICPKAPKLE | ||||||
Domain | 237-335 | Glutaredoxin 2 | ||||
Sequence: ERLKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKAYSNWPTYPQLYVKGELVGGLDIVKELKENGELLPILRGEN |
Domain
The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length335
- Mass (Da)37,432
- Last updated2003-09-26 v2
- Checksum46D644413D9EDFDA
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 2 | in Ref. 2; CAA09375 | ||||
Sequence: A → E | ||||||
Sequence conflict | 67 | in Ref. 3; BAG51067 | ||||
Sequence: K → R | ||||||
Sequence conflict | 210 | in Ref. 3; BAG51059 | ||||
Sequence: I → T |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF118649 EMBL· GenBank· DDBJ | AAF28841.1 EMBL· GenBank· DDBJ | mRNA | ||
AF118652 EMBL· GenBank· DDBJ | AAF28844.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ010841 EMBL· GenBank· DDBJ | CAA09375.1 EMBL· GenBank· DDBJ | mRNA | ||
AK022131 EMBL· GenBank· DDBJ | BAG51067.1 EMBL· GenBank· DDBJ | mRNA | ||
AK021926 EMBL· GenBank· DDBJ | BAG51059.1 EMBL· GenBank· DDBJ | mRNA | ||
AL139123 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471066 EMBL· GenBank· DDBJ | EAW49152.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471066 EMBL· GenBank· DDBJ | EAW49154.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471066 EMBL· GenBank· DDBJ | EAW49155.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005289 EMBL· GenBank· DDBJ | AAH05289.1 EMBL· GenBank· DDBJ | mRNA | ||
BC014372 EMBL· GenBank· DDBJ | AAH14372.2 EMBL· GenBank· DDBJ | mRNA |