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Details on Person UniProt:P07237 P4HB
| Class:Id | ReferenceGeneProduct:61444 |
|---|---|
| _chainChangeLog | signal peptide:1-17 added on Fri February 6 2015;chain:18-508 added on Fri February 6 2015 |
| _displayName | UniProt:P07237 P4HB |
| _timestamp | 2024-11-03 19:57:54 |
| chain | signal peptide:1-17 chain:18-508 |
| checksum | 906CE6D9900B8FCE |
| comment | FUNCTION This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307).CATALYTIC ACTIVITY Catalyzes the rearrangement of -S-S- bonds in proteins.SUBUNIT Heterodimer; heterodimerizes with the protein microsomal triglyceride transfer MTTP (PubMed:16478722, PubMed:23475612, PubMed:26224785). Homodimer. Monomers and homotetramers may also occur. Interacts with P4HA2, forming a heterotetramer consisting of 2 alpha subunits (P4HA2) and 2 beta (P4HB), where P4HB plays the role of a structural subunit; this tetramer catalyzes the formation of 4-hydroxyproline in collagen (PubMed:7753822). Also constitutes the structural subunit of the microsomal triacylglycerol transfer protein MTTP in mammalian cells. Stabilizes both enzymes and retain them in the ER without contributing to the catalytic activity (By similarity). Binds UBQLN1 (PubMed:12095988). Interacts with ERO1B (PubMed:11707400). Binds to CD4, and upon HIV-1 binding to the cell membrane, is part of a P4HB/PDI-CD4-CXCR4-gp120 complex. Interacts with ILDR2 (By similarity). Interacts with ERN1/IRE1A (via N-terminus); the interaction is enhanced by phosphorylation of P4HB by FAM20C in response to endoplasmic reticulum stress and results in attenuation of ERN1 activity (PubMed:32149426).INTERACTION Highly abundant. In some cell types, seems to be also secreted or associated with the plasma membrane, where it undergoes constant shedding and replacement from intracellular sources (Probable). Localizes near CD4-enriched regions on lymphoid cell surfaces (PubMed:11181151). Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:10636893). Colocalizes with MTTP in the endoplasmic reticulum (PubMed:23475612).PTM Phosphorylation of Ser-357 by FAM20C is induced by endoplasmic reticulum stress and results in a functional switch from oxidoreductase to molecular chaperone (PubMed:32149426). It also promotes interaction with ERN1 (PubMed:32149426).DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Reduces and may activate fusogenic properties of HIV-1 gp120 surface protein, thereby enabling HIV-1 entry into the cell.SIMILARITY Belongs to the protein disulfide isomerase family. |
| description | recommendedName: Protein disulfide-isomerase shortName: PDI ecNumber evidence="20"5.3.4.1 alternativeName: Cellular thyroid hormone-binding protein alternativeName: Prolyl 4-hydroxylase subunit beta alternativeName: p55 |
| geneName | P4HB ERBA2L PDI PDIA1 PO4DB |
| identifier | P07237 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Cell membrane Chaperone Craniosynostosis Direct protein sequencing Disease variant Disulfide bond Endoplasmic reticulum Isomerase Membrane Osteogenesis imperfecta Phosphoprotein Proteomics identification Redox-active center Reference proteome Repeat Signal |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | P4HB |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8957561] ENSEMBL:ENSG00000185624 P4HB [Homo sapiens] |
| secondaryIdentifier | PDIA1_HUMAN B2RDQ2 P30037 P32079 Q15205 Q6LDE5 |
| sequenceLength | 508 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:174692] P4HB [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:3341287] HC53,56-P4HB [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:5358298] HC-P4HB(DHH) [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:5358311] HC-P4HB(IHH) [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:5358313] HC-P4HB(SHH) [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:8956902] p-P4HB [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:8958468] P4HB [extracellular region] [Homo sapiens] |
| (referenceSequence) | [IntraChainCrosslinkedResidue:3341345] Intra-chain Crosslink via L-cystine (cross-link) at 53 and 56 [InterChainCrosslinkedResidue:5358301] Inter-chain Crosslink via L-cystine (cross-link) at 53 and 343 [InterChainCrosslinkedResidue:5358303] Inter-chain Crosslink via L-cystine (cross-link) at 53 and 363 [InterChainCrosslinkedResidue:5358306] Inter-chain Crosslink via L-cystine (cross-link) at 53 and 347 [ModifiedResidue:8956941] phosphorylated residue at unknown position |
| (secondReferenceSequence) | [InterChainCrosslinkedResidue:5358300] Inter-chain Crosslink via L-cystine (cross-link) at 343 and 53 [InterChainCrosslinkedResidue:5358304] Inter-chain Crosslink via L-cystine (cross-link) at 363 and 53 [InterChainCrosslinkedResidue:5358309] Inter-chain Crosslink via L-cystine (cross-link) at 347 and 53 |
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No pathways have been reviewed or authored by UniProt:P07237 P4HB (61444)
