| IED ID | IndEnz0002000298 |
| Enzyme Type ID | protease000298 |
| Protein Name |
Prohibitin 1 |
| Gene Name | PHB1 PHB |
| 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 | MAAKVFESIGKFGLALAVAGGVVNSALYNVDAGHRAVIFDRFRGVQDIVVGEGTHFLIPWVQKPIIFDCRSRPRNVPVITGSKDLQNVNITLRILFRPVASQLPRIFTSIGEDYDERVLPSITTEILKSVVARFDAGELITQRELVSRQVSDDLTERAATFGLILDDVSLTHLTFGKEFTEAVEAKQVAQQEAERARFVVEKAEQQKKAAIISAEGDSKAAELIANSLATAGDGLIELRKLEAAEDIAYQLSRSRNITYLPAGQSVLLQLPQ |
| Enzyme Length | 272 |
| Uniprot Accession Number | P35232 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus (PubMed:11302691, PubMed:20959514, PubMed:28017329, PubMed:31522117). Plays a role in adipose tissue and glucose homeostasis in a sex-specific manner (By similarity). Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells (By similarity). {ECO:0000250|UniProtKB:P67778, ECO:0000250|UniProtKB:P67779, ECO:0000269|PubMed:11302691, ECO:0000269|PubMed:20959514, ECO:0000269|PubMed:28017329, ECO:0000269|PubMed:31522117}.; FUNCTION: In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner (By similarity). Regulates mitochondrial respiration activity playing a role in cellular aging (PubMed:11302691). The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:28017329). Involved in mitochondrial-mediated antiviral innate immunity, activates DDX58/RIG-I-mediated signal transduction and production of IFNB1 and proinflammatory cytokine IL6 (PubMed:31522117). {ECO:0000250|UniProtKB:P67778, ECO:0000269|PubMed:11302691, ECO:0000269|PubMed:28017329, ECO:0000269|PubMed:31522117, ECO:0000305}.; FUNCTION: In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses (PubMed:14500729). Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells (PubMed:31899195). {ECO:0000269|PubMed:14500729, ECO:0000269|PubMed:31899195}.; FUNCTION: In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates (By similarity). Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (By similarity). {ECO:0000250|UniProtKB:P67778}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (1); Chain (1); Coiled coil (1); Initiator methionine (1); Modified residue (7); Natural variant (2) |
| Keywords | Acetylation;Alternative splicing;Cell membrane;Coiled coil;Cytoplasm;DNA synthesis;Direct protein sequencing;Host-virus interaction;Membrane;Mitochondrion;Mitochondrion inner membrane;Nucleus;Phosphoprotein;Proto-oncogene;Reference proteome |
| Interact With | Q496Y0; Q99623; Q96IW7; Q13309-2; Q9NS68; P04637; O14980; Q9JLL3 |
| Induction | INDUCTION: Expression increases approximately 3-fold upon entry into G1 phase compared with other phases of the cell cycle. Also induced following inhibition of mitochondrial protein synthesis by thiamphenicol. {ECO:0000269|PubMed:11302691}. |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:14500729, ECO:0000269|PubMed:20959514}. Nucleus {ECO:0000269|PubMed:14500729, ECO:0000269|PubMed:20959514, ECO:0000269|PubMed:31899195}. Cytoplasm {ECO:0000269|PubMed:14500729, ECO:0000269|PubMed:31899195}. Cell membrane {ECO:0000269|PubMed:22997079, ECO:0000269|PubMed:24003225}. |
| Modified Residue | MOD_RES 2; /note=N-acetylalanine; /evidence=ECO:0007744|PubMed:25944712; MOD_RES 91; /note=Phosphothreonine; /evidence=ECO:0007744|PubMed:24275569; MOD_RES 128; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P67778; MOD_RES 186; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P67778; MOD_RES 202; /note=N6-acetyllysine; alternate; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 202; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:P67778; MOD_RES 249; /note=Phosphotyrosine; /evidence=ECO:0007744|PubMed:24275569 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10205168; 11325826; 11377649; 12065415; 12068308; 12085232; 12354477; 12466959; 12821355; 12932319; 12932339; 14637159; 14743216; 15035987; 15047060; 15141164; 15250827; 15614618; 15823758; 16041367; 16294014; 16319068; 16364920; 16426920; 16705168; 16918502; 16951178; 16964284; 17004108; 17018604; 17043753; 17284347; 17544200; 17873902; 17932104; 17932509; 18183577; 18258228; 18397521; 18494604; 18676680; 18709484; 18763282; 18789835; 19034380; 19071013; 19170196; 19207009; 19238206; 19327358; 19430483; 19463016; 19497338; 19591124; 19615732; 19625176; 19664078; 19692168; 19710421; 19725029; 19725052; 19738201; 19854158; 20069396; 20130576; 20133800; 20134482; 20141835; 20179705; 20186120; 20186755; 20195357; 20360068; 20391533; 20516557; 20562859; 20596663; 20638487; 20830747; 20856874; 20877624; 21061155; 21152868; 21155232; 21209023; 21275458; 21296110; 21318481; 21441910; 21514245; 21783252; 21879722; 21896168; 21903368; 21911578; 21993244; 22043453; 22124450; 22179832; 22190034; 22212092; 22238093; 22292133; 22304787; 22304920; 22324369; 22410782; 22505583; 22510884; 22537547; 22589270; 22623428; 22669161; 22711522; 22728421; 22904065; 22949832; 22994754; 23098474; 23244120; 23327602; 23352452; 23416715; 23453624; 23587357; 23715748; 23752268; 23870455; 23993095; 24023253; 24133204; 24133587; 24166496; 24189400; 24202393; 24247619; 24347342; 24376711; 24380853; 24388982; 24470505; 24568222; 24651010; 24725412; 24732013; 24879411; 24937142; 24966933; 24975845; 24983503; 25344214; 25435214; 25444511; 25609649; 25640309; 25719244; 25777779; 25907612; 25932630; 26064897; 26496610; 26496733; 26752685; 27025967; 27084680; 27327778; 27485113; 27557820; 27642048; 27687727; 27812762; 27939217; 27981602; 28102850; 28272969; 28294412; 28404970; 28440457; 29126391; 29222040; 29242126; 29324904; 30049713; 30185797; 30396985; 30523154; 30998507; 31009148; 31391345; 31558419; 31684984; 32169072; 32306962; 32665357; 32859869; 33259040; 33548975; 34140524; 7744815; 9020159; |
| Motif | |
| Gene Encoded By | |
| Mass | 29,804 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |