Q9H3N1 · TMX1_HUMAN
- ProteinThioredoxin-related transmembrane protein 1
- GeneTMX1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids280 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Thiredoxin domain-containing protein that participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyze dithiol-disulfide exchange reactions (PubMed:11152479, PubMed:37648867).
Acts as a key inhibitor of the alternative triglyceride biosynthesis pathway by inhibiting the activity of TMEM68/DIESL at the endoplasmic reticulum, thereby restricting accumulation of triacylglycerol (PubMed:37648867).
The alternative triglyceride biosynthesis pathway mediates formation of triacylglycerol from diacylglycerol and membrane phospholipids (PubMed:37648867).
Acts as a protein disulfide isomerase by catalyzing formation or reduction of disulfide bonds (PubMed:22228764, PubMed:29932915).
Specifically mediates formation of disulfide bonds of transmembrane proteins at the endoplasmic reticulum membrane (PubMed:22228764).
Involved in endoplasmic reticulum-associated degradation (ERAD) via its protein disulfide isomerase activity by acting on folding-defective polypeptides at the endoplasmic reticulum membrane (PubMed:29932915).
Acts as a negative regulator of platelet aggregation following secretion in the extracellular space (PubMed:30425049).
Acts as a regulator of endoplasmic reticulum-mitochondria contact sites via its ability to regulate redox signals (PubMed:27502484, PubMed:31304984).
Regulates endoplasmic reticulum-mitochondria Ca2+ flux (PubMed:27502484).
Acts as a key inhibitor of the alternative triglyceride biosynthesis pathway by inhibiting the activity of TMEM68/DIESL at the endoplasmic reticulum, thereby restricting accumulation of triacylglycerol (PubMed:37648867).
The alternative triglyceride biosynthesis pathway mediates formation of triacylglycerol from diacylglycerol and membrane phospholipids (PubMed:37648867).
Acts as a protein disulfide isomerase by catalyzing formation or reduction of disulfide bonds (PubMed:22228764, PubMed:29932915).
Specifically mediates formation of disulfide bonds of transmembrane proteins at the endoplasmic reticulum membrane (PubMed:22228764).
Involved in endoplasmic reticulum-associated degradation (ERAD) via its protein disulfide isomerase activity by acting on folding-defective polypeptides at the endoplasmic reticulum membrane (PubMed:29932915).
Acts as a negative regulator of platelet aggregation following secretion in the extracellular space (PubMed:30425049).
Acts as a regulator of endoplasmic reticulum-mitochondria contact sites via its ability to regulate redox signals (PubMed:27502484, PubMed:31304984).
Regulates endoplasmic reticulum-mitochondria Ca2+ flux (PubMed:27502484).
Miscellaneous
Mediates reduction of intermolecular disulfide bonds between chain A and B of Ricin toxin (Ricin A chain and Ricin B chain, respectively), thereby releasing and activating Ricin A chain.
Catalytic activity
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 56 | Nucleophile | ||||
Sequence: C | ||||||
Active site | 59 | Nucleophile | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endomembrane system | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | extracellular region | |
Cellular Component | mitochondria-associated endoplasmic reticulum membrane contact site | |
Cellular Component | mitochondrial membrane | |
Molecular Function | disulfide oxidoreductase activity | |
Molecular Function | enzyme inhibitor activity | |
Molecular Function | protein disulfide isomerase activity | |
Molecular Function | protein-disulfide reductase activity | |
Biological Process | negative regulation of platelet aggregation | |
Biological Process | negative regulation of triglyceride biosynthetic process | |
Biological Process | positive regulation of ERAD pathway | |
Biological Process | regulation of calcium ion transport | |
Biological Process | response to endoplasmic reticulum stress |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameThioredoxin-related transmembrane protein 1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H3N1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass type I membrane protein
Mitochondrion membrane ; Single-pass type I membrane protein
Note: Predominantly found in the endoplasmic reticulum (PubMed:11152479).
Secreted in the extracellular space following thrombin stimulation (PubMed:30425049).
Localizes to mitochondria-associated endoplasmic reticulum membrane (MAM); palmitoylation is required for MAM localization (PubMed:22045338, PubMed:27502484, PubMed:31304984).
Secreted in the extracellular space following thrombin stimulation (PubMed:30425049).
Localizes to mitochondria-associated endoplasmic reticulum membrane (MAM); palmitoylation is required for MAM localization (PubMed:22045338, PubMed:27502484, PubMed:31304984).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 27-180 | Extracellular | ||||
Sequence: RRSNVRVITDENWRELLEGDWMIEFYAPWCPACQNLQPEWESFAEWGEDLEVNIAKVDVTEQPGLSGRFIITALPTIYHCKDGEFRRYQGPRTKKDFINFISDKEWKSIEPVSSWFGPGSVLMSSMSALFQLSMWIRTCHNYFIEDLGLPVWGS | ||||||
Transmembrane | 181-203 | Helical | ||||
Sequence: YTVFALATLFSGLLLGLCMIFVA | ||||||
Topological domain | 204-280 | Cytoplasmic | ||||
Sequence: DCLCPSKRRRPQPYPYPSKKLLSESAQPLKKVEEEQEADEEDVSEEEAESKEGTNKDFPQNAIRQRSLGPSLATDKS |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 56 | Loss of reductase activity and ability to inhibit TMEM68/DIESL; when associated with S-59. | ||||
Sequence: C → S | ||||||
Mutagenesis | 59 | Loss of reductase activity and ability to inhibit TMEM68/DIESL; when associated with S-56. | ||||
Sequence: C → S | ||||||
Mutagenesis | 205-207 | Abolished palmitoylation, leading to decreased localization to mitochondria-associated endoplasmic reticulum membrane (MAM). | ||||
Sequence: CLC → ALA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 355 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, lipidation, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-26 | UniProt | |||||
Sequence: MAPSGSLAVPLAVLVLLLWGAPWTHG | |||||||
Chain | PRO_0000034153 | 27-280 | UniProt | Thioredoxin-related transmembrane protein 1 | |||
Sequence: RRSNVRVITDENWRELLEGDWMIEFYAPWCPACQNLQPEWESFAEWGEDLEVNIAKVDVTEQPGLSGRFIITALPTIYHCKDGEFRRYQGPRTKKDFINFISDKEWKSIEPVSSWFGPGSVLMSSMSALFQLSMWIRTCHNYFIEDLGLPVWGSYTVFALATLFSGLLLGLCMIFVADCLCPSKRRRPQPYPYPSKKLLSESAQPLKKVEEEQEADEEDVSEEEAESKEGTNKDFPQNAIRQRSLGPSLATDKS | |||||||
Disulfide bond | 56↔59 | UniProt | Redox-active | ||||
Sequence: CPAC | |||||||
Lipidation | 205 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Lipidation | 207 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Modified residue (large scale data) | 226 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 228 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 228 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 247 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 247 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 253 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 257 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 270 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 270 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 274 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 274 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 280 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 280 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Palmitoylated; palmitoylation is required for localization to mitochondria-associated endoplasmic reticulum membrane (MAM).
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with ATP2A2.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9H3N1 | BCL2L2 Q92843 | 3 | EBI-1051115, EBI-707714 | |
BINARY | Q9H3N1 | CCR1 P32246 | 3 | EBI-1051115, EBI-608322 | |
BINARY | Q9H3N1 | FKBP8 Q14318 | 3 | EBI-1051115, EBI-724839 | |
BINARY | Q9H3N1 | GET3 O43681 | 3 | EBI-1051115, EBI-2515857 | |
BINARY | Q9H3N1 | GIMAP1 Q8WWP7 | 3 | EBI-1051115, EBI-11991950 | |
BINARY | Q9H3N1 | GIMAP5 Q96F15 | 3 | EBI-1051115, EBI-6166686 | |
BINARY | Q9H3N1 | LHFPL5 Q8TAF8 | 3 | EBI-1051115, EBI-2820517 | |
BINARY | Q9H3N1 | PMP22 Q01453 | 3 | EBI-1051115, EBI-2845982 | |
BINARY | Q9H3N1 | SOD1 P00441 | 3 | EBI-1051115, EBI-990792 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 27-132 | Thioredoxin | ||||
Sequence: RRSNVRVITDENWRELLEGDWMIEFYAPWCPACQNLQPEWESFAEWGEDLEVNIAKVDVTEQPGLSGRFIITALPTIYHCKDGEFRRYQGPRTKKDFINFISDKEW | ||||||
Region | 218-280 | Disordered | ||||
Sequence: PYPSKKLLSESAQPLKKVEEEQEADEEDVSEEEAESKEGTNKDFPQNAIRQRSLGPSLATDKS | ||||||
Compositional bias | 258-280 | Polar residues | ||||
Sequence: NKDFPQNAIRQRSLGPSLATDKS |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length280
- Mass (Da)31,791
- Last updated2001-03-01 v1
- ChecksumA57E222481A997DE
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
G3V448 | G3V448_HUMAN | TMX1 | 105 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 14-16 | in Ref. 8; AAH36460 | ||||
Sequence: LVL → MVP | ||||||
Sequence conflict | 98 | in Ref. 8; AAH36460 | ||||
Sequence: T → N | ||||||
Sequence conflict | 177 | in Ref. 4; BAC11593 | ||||
Sequence: V → A | ||||||
Compositional bias | 258-280 | Polar residues | ||||
Sequence: NKDFPQNAIRQRSLGPSLATDKS |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB048246 EMBL· GenBank· DDBJ | BAB20629.1 EMBL· GenBank· DDBJ | mRNA | ||
AY358640 EMBL· GenBank· DDBJ | AAQ89003.1 EMBL· GenBank· DDBJ | mRNA | ||
AK075395 EMBL· GenBank· DDBJ | BAC11593.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312905 EMBL· GenBank· DDBJ | BAG35751.1 EMBL· GenBank· DDBJ | mRNA | ||
AL080080 EMBL· GenBank· DDBJ | CAB45700.2 EMBL· GenBank· DDBJ | mRNA | ||
AL591807 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471078 EMBL· GenBank· DDBJ | EAW65678.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC036460 EMBL· GenBank· DDBJ | AAH36460.1 EMBL· GenBank· DDBJ | mRNA | ||
BC056874 EMBL· GenBank· DDBJ | AAH56874.2 EMBL· GenBank· DDBJ | mRNA |