| IED ID | IndEnz0002013778 |
| Enzyme Type ID | protease013778 |
| Protein Name |
Protein disulfide-isomerase PDI EC 5.3.4.1 Cellular thyroid hormone-binding protein Prolyl 4-hydroxylase subunit beta p55 |
| Gene Name | P4HB ERBA2L PDI PDIA1 PO4DB |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MLRRALLCLAVAALVRADAPEEEDHVLVLRKSNFAEALAAHKYLLVEFYAPWCGHCKALAPEYAKAAGKLKAEGSEIRLAKVDATEESDLAQQYGVRGYPTIKFFRNGDTASPKEYTAGREADDIVNWLKKRTGPAATTLPDGAAAESLVESSEVAVIGFFKDVESDSAKQFLQAAEAIDDIPFGITSNSDVFSKYQLDKDGVVLFKKFDEGRNNFEGEVTKENLLDFIKHNQLPLVIEFTEQTAPKIFGGEIKTHILLFLPKSVSDYDGKLSNFKTAAESFKGKILFIFIDSDHTDNQRILEFFGLKKEECPAVRLITLEEEMTKYKPESEELTAERITEFCHRFLEGKIKPHLMSQELPEDWDKQPVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVKVHSFPTLKFFPASADRTVIDYNGERTLDGFKKFLESGGQDGAGDDDDLEDLEEAEEPDMEEDDDQKAVKDEL |
| Enzyme Length | 508 |
| Uniprot Accession Number | P07237 |
| Absorption | |
| Active Site | ACT_SITE 53; /note=Nucleophile; ACT_SITE 56; /note=Nucleophile; ACT_SITE 397; /note=Nucleophile; /evidence=ECO:0000250; ACT_SITE 400; /note=Nucleophile; /evidence=ECO:0000250 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.; EC=5.3.4.1; |
| DNA Binding | |
| EC Number | 5.3.4.1 |
| Enzyme Function | 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, functions as a chaperone that inhibits aggregation of misfolded proteins. 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 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). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (4); Beta strand (29); Chain (1); Compositional bias (1); Disulfide bond (2); Domain (2); Helix (18); Modified residue (4); Motif (1); Natural variant (1); Region (1); Sequence conflict (12); Signal peptide (1); Site (6); Turn (8) |
| Keywords | 3D-structure;Acetylation;Cell membrane;Chaperone;Craniosynostosis;Direct protein sequencing;Disease variant;Disulfide bond;Endoplasmic reticulum;Isomerase;Membrane;Osteogenesis imperfecta;Phosphoprotein;Redox-active center;Reference proteome;Repeat;Signal |
| Interact With | Q9NU02; Q96RK4; O43521; P17655; Q8TAB7; Q8TAP6; Q494V2-2; Q9Y6H1; Q8NE01; P09228; Q96D03; Q96HE7; Q8NEG0; Q53R41; Q9ULW2; P62873; P28799; Q8TCT9; Q8N4N3-2; Q9P2K6; P02538; P60328; Q52LG2; Q9BYQ6; P26371; Q9BYQ0; Q5T7P3; Q5TA82; Q5TA78; P80188; Q6PJG9; Q92692-2; O94818-2; Q9P121-3; Q14990; O15534; Q63HM9; O00444; Q13162; Q09028; Q96B97; Q86WV1-2; Q8WUG5; Q03518; Q5T0J7-2; P01137; Q9UC07-2; Q2GL86 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000269|PubMed:23475612}. Endoplasmic reticulum lumen {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:23475612}. Melanosome {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}. Cell membrane {ECO:0000269|PubMed:21670307}; Peripheral membrane protein {ECO:0000305}. Note=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). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:11181151, ECO:0000269|PubMed:23475612, ECO:0000305}. |
| Modified Residue | MOD_RES 200; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P09103; MOD_RES 222; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:P09103; MOD_RES 271; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:P09103; MOD_RES 357; /note=Phosphoserine; by FAM20C; /evidence=ECO:0000269|PubMed:26091039 |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..17; /evidence="ECO:0000269|PubMed:12665801, ECO:0000269|PubMed:2079031, ECO:0000269|PubMed:9150948, ECO:0000269|Ref.10, ECO:0007744|PubMed:25944712" |
| Structure 3D | NMR spectroscopy (5); X-ray crystallography (6) |
| Cross Reference PDB | 1BJX; 1MEK; 1X5C; 2BJX; 2K18; 3BJ5; 3UEM; 4EKZ; 4EL1; 4JU5; 6I7S; |
| Mapped Pubmed ID | 10436013; 10899108; 10970843; 11054122; 11114383; 11369260; 12518019; 1323838; 1347984; 14500733; 14732096; 15161933; 15163793; 15175163; 15292211; 15358778; 15590633; 15611098; 15695804; 15720785; 16169070; 16282375; 16591531; 16611729; 17055437; 17126548; 17170699; 17215532; 17353931; 17507410; 17620599; 18801374; 19081070; 19187238; 19603532; 19805454; 19890397; 19913121; 19942855; 20000738; 20195357; 20360068; 20562859; 20628086; 20668226; 20711500; 20802462; 21057456; 21215271; 21257310; 21299467; 21357747; 21373848; 21988832; 22045338; 22090031; 22106087; 22190034; 22304920; 22657537; 22665516; 22936677; 23141538; 23167757; 23337974; 23414517; 23444257; 23454490; 23663784; 23861867; 23902751; 24098548; 24549644; 25258311; 25259790; 2543975; 25575667; 25604459; 25609649; 26000911; 26496610; 26607804; 26638075; 26670633; 26752685; 26869642; 27142583; 27703014; 28034831; 28052026; 28257787; 28364042; 28598864; 29191937; 29207176; 29521097; 29904245; 29924999; 30431122; 30760703; 30958660; 30996048; 31005252; 31395737; 31467922; 31640086; 3173483; 32149426; 32452761; 33125139; 33148170; 33637669; 33707149; 33732415; 34111473; 7527811; 7803401; 7885476; 7985023; 8626595; 8689684; 8824192; 9545296; 9560306; 9593755; |
| Motif | MOTIF 505..508; /note=Prevents secretion from ER |
| Gene Encoded By | |
| Mass | 57,116 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 5.3.4.1; |