UniProt functional annotation for P10599



	UniProt functional annotation for P10599

UniProt code: P10599.

Organism: Homo sapiens (Human).

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

Function: Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:2176490, PubMed:17182577, PubMed:19032234). Plays a role in the reversible S- nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity (PubMed:16408020, PubMed:17606900). Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity (PubMed:9108029, PubMed:11118054). {ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:16408020, ECO:0000269|PubMed:17182577, ECO:0000269|PubMed:17606900, ECO:0000269|PubMed:19032234, ECO:0000269|PubMed:2176490, ECO:0000269|PubMed:9108029}.

Function: ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).

Subunit: Homodimer; disulfide-linked (PubMed:9369469, PubMed:17260951). Interacts with TXNIP through the redox-active site (PubMed:17260951). Interacts with MAP3K5 and CASP3 (PubMed:15246877). In case of infection, interacts with S.typhimurium protein slrP (PubMed:19690162). Interacts with APEX1; the interaction stimulates the FOS/JUN AP-1 DNA- binding activity in a redox-dependent manner (PubMed:9108029). {ECO:0000269|PubMed:15246877, ECO:0000269|PubMed:17260951, ECO:0000269|PubMed:19690162, ECO:0000269|PubMed:9108029, ECO:0000269|PubMed:9369469}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:9108029}. Cytoplasm {ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:9108029}. Secreted {ECO:0000269|PubMed:1332947}. Note=Translocates from the cytoplasm into the nucleus after phorbol 12- myristate 13-acetate induction (PMA) (PubMed:9108029). Predominantly in the cytoplasm in non irradiated cells (PubMed:11118054). Radiation induces translocation of TRX from the cytoplasm to the nucleus (PubMed:11118054). Secreted by a leaderless secretory pathway (PubMed:1332947). {ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:1332947, ECO:0000269|PubMed:9108029}.

Induction: Up-regulated by ionizing radiation. {ECO:0000269|PubMed:11118054}.

Ptm: In the fully reduced protein, both Cys-69 and Cys-73 are nitrosylated in response to nitric oxide (NO). When two disulfide bonds are present in the protein, only Cys-73 is nitrosylated. Cys-73 can serve as donor for nitrosylation of target proteins. {ECO:0000269|PubMed:15246877, ECO:0000269|PubMed:16408020, ECO:0000269|PubMed:17260951, ECO:0000269|PubMed:17606900}.

Ptm: In case of infection, ubiquitinated by S.typhimurium protein slrP, leading to its degradation. {ECO:0000269|PubMed:19690162}.

Allergen: Causes an allergic reaction in human (PubMed:17182577, PubMed:19032234, PubMed:21489611). Recombinant protein binds to IgE in atopic eczema-suffering patients allergic to opportunistic skin- colonizing yeast M.sympodialis. Intermediate cross-reactivity is detected between the recombinant thioredoxin from M.sympodialis (Mala s 13) and recombinant form of this protein. Skin-prick test (SPT) and atopy patch test (APT) with 5 patients confirm cross-reactivity between the two proteins (PubMed:17182577). Recombinant protein binds to IgE of patients suffering from allergic bronchopulmonary aspergillosis (ABPA) and cross-reacts extensively with recombinant thioredoxin proteins from A.fumigatus (Asp f 28 and Asp f 29) and Mala s 13. Causes a positive skin reaction and induces proliferation of the human peripheral blood mononuclear cells in ABPA patients allergic to this protein. Acts as an IgE-binding self-antigen in ABPA patients allergic to fungal thioredoxin (PubMed:19032234). In atopic dermatitis (AD)-suffering patients allergic to M.sympodialis, a cross-reactivity between Mala s 13 and this protein can be detected in T-cells of the peripheral blood and skin. Keratinocytes stimulated by interferon (IFN)-alpha and tumor necrosis factor (TNF)-alpha release thioredoxin, which then becomes available for cross-reactivity with Mala s 13-specific T cells. The autoreactive T cells identified include T-helper 1 (Th1), T-helper 2 (Th2), T-helper 17 (Th17) and T-helper 22 (Th22) phenotypes. Skinhoming T cells autoreactive to this protein may be relevant for cutaneous inflammation in patients with AD (PubMed:21489611). {ECO:0000269|PubMed:17182577, ECO:0000269|PubMed:19032234, ECO:0000269|PubMed:21489611}.

Similarity: Belongs to the thioredoxin family. {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:		Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:2176490, PubMed:17182577, PubMed:19032234). Plays a role in the reversible S- nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity (PubMed:16408020, PubMed:17606900). Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity (PubMed:9108029, PubMed:11118054). {ECO:0000269\|PubMed:11118054, ECO:0000269\|PubMed:16408020, ECO:0000269\|PubMed:17182577, ECO:0000269\|PubMed:17606900, ECO:0000269\|PubMed:19032234, ECO:0000269\|PubMed:2176490, ECO:0000269\|PubMed:9108029}.



Function:		ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).


Subunit:		Homodimer; disulfide-linked (PubMed:9369469, PubMed:17260951). Interacts with TXNIP through the redox-active site (PubMed:17260951). Interacts with MAP3K5 and CASP3 (PubMed:15246877). In case of infection, interacts with S.typhimurium protein slrP (PubMed:19690162). Interacts with APEX1; the interaction stimulates the FOS/JUN AP-1 DNA- binding activity in a redox-dependent manner (PubMed:9108029). {ECO:0000269\|PubMed:15246877, ECO:0000269\|PubMed:17260951, ECO:0000269\|PubMed:19690162, ECO:0000269\|PubMed:9108029, ECO:0000269\|PubMed:9369469}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11118054, ECO:0000269\|PubMed:9108029}. Cytoplasm {ECO:0000269\|PubMed:11118054, ECO:0000269\|PubMed:9108029}. Secreted {ECO:0000269\|PubMed:1332947}. Note=Translocates from the cytoplasm into the nucleus after phorbol 12- myristate 13-acetate induction (PMA) (PubMed:9108029). Predominantly in the cytoplasm in non irradiated cells (PubMed:11118054). Radiation induces translocation of TRX from the cytoplasm to the nucleus (PubMed:11118054). Secreted by a leaderless secretory pathway (PubMed:1332947). {ECO:0000269\|PubMed:11118054, ECO:0000269\|PubMed:1332947, ECO:0000269\|PubMed:9108029}.
Induction:		Up-regulated by ionizing radiation. {ECO:0000269\|PubMed:11118054}.
Ptm:		In the fully reduced protein, both Cys-69 and Cys-73 are nitrosylated in response to nitric oxide (NO). When two disulfide bonds are present in the protein, only Cys-73 is nitrosylated. Cys-73 can serve as donor for nitrosylation of target proteins. {ECO:0000269\|PubMed:15246877, ECO:0000269\|PubMed:16408020, ECO:0000269\|PubMed:17260951, ECO:0000269\|PubMed:17606900}.
Ptm:		In case of infection, ubiquitinated by S.typhimurium protein slrP, leading to its degradation. {ECO:0000269\|PubMed:19690162}.
Allergen:		Causes an allergic reaction in human (PubMed:17182577, PubMed:19032234, PubMed:21489611). Recombinant protein binds to IgE in atopic eczema-suffering patients allergic to opportunistic skin- colonizing yeast M.sympodialis. Intermediate cross-reactivity is detected between the recombinant thioredoxin from M.sympodialis (Mala s 13) and recombinant form of this protein. Skin-prick test (SPT) and atopy patch test (APT) with 5 patients confirm cross-reactivity between the two proteins (PubMed:17182577). Recombinant protein binds to IgE of patients suffering from allergic bronchopulmonary aspergillosis (ABPA) and cross-reacts extensively with recombinant thioredoxin proteins from A.fumigatus (Asp f 28 and Asp f 29) and Mala s 13. Causes a positive skin reaction and induces proliferation of the human peripheral blood mononuclear cells in ABPA patients allergic to this protein. Acts as an IgE-binding self-antigen in ABPA patients allergic to fungal thioredoxin (PubMed:19032234). In atopic dermatitis (AD)-suffering patients allergic to M.sympodialis, a cross-reactivity between Mala s 13 and this protein can be detected in T-cells of the peripheral blood and skin. Keratinocytes stimulated by interferon (IFN)-alpha and tumor necrosis factor (TNF)-alpha release thioredoxin, which then becomes available for cross-reactivity with Mala s 13-specific T cells. The autoreactive T cells identified include T-helper 1 (Th1), T-helper 2 (Th2), T-helper 17 (Th17) and T-helper 22 (Th22) phenotypes. Skinhoming T cells autoreactive to this protein may be relevant for cutaneous inflammation in patients with AD (PubMed:21489611). {ECO:0000269\|PubMed:17182577, ECO:0000269\|PubMed:19032234, ECO:0000269\|PubMed:21489611}.
Similarity:		Belongs to the thioredoxin family. {ECO:0000305}.