UniProt functional annotation for Q16881



	UniProt functional annotation for Q16881

UniProt code: Q16881.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid. {ECO:0000269|PubMed:15199063, ECO:0000269|PubMed:18042542, ECO:0000269|PubMed:8577704, ECO:0000269|PubMed:9774665}.

Catalytic activity: Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide + H(+) + NADPH; Xref=Rhea:RHEA:20345, Rhea:RHEA-COMP:10698, Rhea:RHEA- COMP:10700, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.9;

Cofactor: Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD per subunit.;

Subunit: Homodimer. Isoform 4 interacts with ESR1 and ESR2. Interacts with HERC5. {ECO:0000269|PubMed:15199063, ECO:0000269|PubMed:16815975}.

Subcellular location: Cytoplasm {ECO:0000250}.

Subcellular location: [Isoform 4]: Cytoplasm. Nucleus.

Subcellular location: [Isoform 5]: Cytoplasm.

Tissue specificity: Isoform 1 is expressed predominantly in Leydig cells (at protein level). Also expressed in ovary, spleen, heart, liver, kidney and pancreas and in a number of cancer cell lines. Isoform 4 is widely expressed with highest levels in kidney, testis, uterus, ovary, prostate, placenta and fetal liver. {ECO:0000269|PubMed:18042542, ECO:0000269|PubMed:8999974}.

Induction: Isoform 5 is induced by a combination of interferon-beta and retinoic acid (at protein level). Isoform 1 is induced by estradiol or testosterone in HeLa cells. {ECO:0000269|PubMed:9774665}.

Domain: The N-terminal glutaredoxin domain found in isoform 1 does not contain the C-P-Y-C redox-active motif normally found in glutaredoxins and has been found to be inactive in classical glutaredoxin assays. {ECO:0000269|PubMed:15379556}.

Ptm: The N-terminus of isoform 5 is blocked.

Ptm: ISGylated. {ECO:0000305|PubMed:16815975}.

Miscellaneous: The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity.

Miscellaneous: [Isoform 1]: Minor isoform.

Miscellaneous: [Isoform 5]: Major isoform. The N-terminus of the sequence is processed into a mature form that lacks residues Met-151 and Asn-152 at the N-terminus. {ECO:0000305}.

Similarity: Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. {ECO:0000305}.

Sequence caution: Sequence=AAB35418.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAC69621.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAF15900.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAV38446.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAZ67916.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAA13674.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAH11490.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAH12374.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAH14140.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=CAA04503.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=CAA62629.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=CAG38744.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=EAW97745.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid. {ECO:0000269\|PubMed:15199063, ECO:0000269\|PubMed:18042542, ECO:0000269\|PubMed:8577704, ECO:0000269\|PubMed:9774665}.


Catalytic activity:		Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide + H(+) + NADPH; Xref=Rhea:RHEA:20345, Rhea:RHEA-COMP:10698, Rhea:RHEA- COMP:10700, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.9;
Cofactor:		Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD per subunit.;
Subunit:		Homodimer. Isoform 4 interacts with ESR1 and ESR2. Interacts with HERC5. {ECO:0000269\|PubMed:15199063, ECO:0000269\|PubMed:16815975}.
Subcellular location:		Cytoplasm {ECO:0000250}.
Subcellular location:		[Isoform 4]: Cytoplasm. Nucleus.
Subcellular location:		[Isoform 5]: Cytoplasm.
Tissue specificity:		Isoform 1 is expressed predominantly in Leydig cells (at protein level). Also expressed in ovary, spleen, heart, liver, kidney and pancreas and in a number of cancer cell lines. Isoform 4 is widely expressed with highest levels in kidney, testis, uterus, ovary, prostate, placenta and fetal liver. {ECO:0000269\|PubMed:18042542, ECO:0000269\|PubMed:8999974}.
Induction:		Isoform 5 is induced by a combination of interferon-beta and retinoic acid (at protein level). Isoform 1 is induced by estradiol or testosterone in HeLa cells. {ECO:0000269\|PubMed:9774665}.
Domain:		The N-terminal glutaredoxin domain found in isoform 1 does not contain the C-P-Y-C redox-active motif normally found in glutaredoxins and has been found to be inactive in classical glutaredoxin assays. {ECO:0000269\|PubMed:15379556}.
Ptm:		The N-terminus of isoform 5 is blocked.
Ptm:		ISGylated. {ECO:0000305\|PubMed:16815975}.
Miscellaneous:		The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity.
Miscellaneous:		[Isoform 1]: Minor isoform.
Miscellaneous:		[Isoform 5]: Major isoform. The N-terminus of the sequence is processed into a mature form that lacks residues Met-151 and Asn-152 at the N-terminus. {ECO:0000305}.
Similarity:		Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. {ECO:0000305}.
Sequence caution:		Sequence=AAB35418.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAC69621.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAF15900.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAV38446.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=AAZ67916.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAA13674.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAH11490.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAH12374.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAH14140.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=CAA04503.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=CAA62629.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=CAG38744.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=EAW97745.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};