{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q99623","secondaryAccessions":["B4DP75","Q2YDA4","Q7KYU3","Q92978"],"uniProtkbId":"PHB2_HUMAN","entryAudit":{"firstPublicDate":"2005-09-27","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1997-07-01","entryVersion":216,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Prohibitin-2"}},"alternativeNames":[{"fullName":{"value":"B-cell receptor-associated protein BAP37"}},{"fullName":{"value":"D-prohibitin"}},{"fullName":{"value":"Repressor of estrogen receptor activity"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAH14766.1"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:30306"}],"value":"PHB2"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAB51324.1"}],"value":"BAP"},{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAD38042.1"}],"value":"REA"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10359819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11302691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20959514"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24003225"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28017329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31522117"}],"value":"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 and sex steroid hormones in the nucleus"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O35129"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11302691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20959514"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28017329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31522117"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"25904163"}],"value":"In the mitochondria, together with PHB1, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as a 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). Also regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration (PubMed:11302691, PubMed:20959514). Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity (PubMed:11302691, PubMed:20959514). Has a key role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:28017329). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (PubMed:31522117)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O35129"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"25904163"}],"value":"In the nucleus, serves as transcriptional co-regulator (Probable). Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases. Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O35129"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24003225"}],"value":"In the plasma membrane, is involved in IGFBP6-induced cell migration (PubMed:24003225). Cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32276428"}],"value":"(Microbial infection) Involved in human enterovirus 71/EV-71 infection by enhancing the autophagy mechanism during the infection"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O35129"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10359819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11302691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19496786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20959514"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21328542"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21746876"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24003225"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28017329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31522117"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"41398051"}],"value":"The mitochondrial prohibitin complex consists of two subunits (PHB1 and PHB2), assembled into a membrane-associated ring-shaped supercomplex of approximately 1 mDa (PubMed:20959514, PubMed:28017329, PubMed:31522117). Interacts with ESR1, HDAC1 and HDAC5 (By similarity). Interacts with ZNF703 (PubMed:21328542). Interacts with STOML2 (PubMed:21746876). Interacts with ARFGEF3 (PubMed:19496786). Interacts with SPHK2. Interacts with COX4I1; the interaction associates PHB2 with COX (By similarity). Interacts with MAP1LC3B (membrane-bound form LC3-II); the interaction is direct and upon mitochondrial depolarization and proteasome-dependent outer membrane rupture (PubMed:28017329). Interacts with IGFBP6 (via C-terminal domain) (PubMed:24003225). Interacts with CLPB (PubMed:31522117). Interacts with CD86 (via cytoplasmic domain); the interactions increases after priming with CD40 (By similarity). Interacts with AFG3L2 (By similarity). Interacts with DNAJC19 (By similarity). Interacts with AKT2; this interaction may be important for myogenic differentiation (By similarity). Interacts with MISO1; the interaction promotes PHB2 recruitment to mitochondrial subdomains called small MTFP1-enriched mitochondria (SMEM) (PubMed:41398051)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19640993"}],"value":"(Microbial infection) Interacts with SARS coronavirus/SARS-CoV nsp2 protein"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32276428"}],"value":"(Microbial infection) Interacts with human enterovirus 71/EV-71 capsid protein VP1; the interaction is required for induction of autophagy and the infectivity of EV-71"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19906925"}],"value":"(Microbial infection) Interaction with human immunodeficiency virus type 1/HIV-1 envelope glycoprotein GP160"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q99623","intActId":"EBI-358348"},"interactantTwo":{"uniProtKBAccession":"Q16828","geneName":"DUSP6","intActId":"EBI-746870"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99623","intActId":"EBI-358348"},"interactantTwo":{"uniProtKBAccession":"P03372","geneName":"ESR1","intActId":"EBI-78473"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99623","intActId":"EBI-358348"},"interactantTwo":{"uniProtKBAccession":"Q9BR81","geneName":"PCDHGC3","intActId":"EBI-22012354"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q99623","intActId":"EBI-358348"},"interactantTwo":{"uniProtKBAccession":"P35232","geneName":"PHB1","intActId":"EBI-354213"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17565718"}],"value":"Localizes within both nucleus and cytoplasm in proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20959514"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28017329"}],"value":"Mitochondrion inner membrane","id":"SL-0168"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17565718"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19496786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32276428"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17565718"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19496786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20959514"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22997079"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24003225"}],"value":"Cell membrane","id":"SL-0039"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform 1","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"31522117"}],"value":"Mitochondrion inner membrane","id":"SL-0168"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform 2","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"31522117"}],"value":"Mitochondrion inner membrane","id":"SL-0168"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31522117"}],"value":"V1"}],"isoformIds":["Q99623-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"31522117"}],"value":"V3"}],"isoformIds":["Q99623-2"],"sequenceIds":["VSP_045311"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17565718"}],"value":"Expressed in myoblasts"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11302691"}],"value":"Levels of expression in fibroblasts decrease heterogeneously during cellular aging"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11302691"}],"value":"Expression increases approximately 3-fold upon entry into G1 phase compared to other phases of the cell cycle. 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The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner. Also regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration. Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity. Has a key role of mitophagy receptor involved in targeting mitochondria for autophagic degradation. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00045769"}],"value":"In the nucleus, serves as transcriptional co-regulator. Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases. 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The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner. Also regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration. Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity. Has a key role of mitophagy receptor involved in targeting mitochondria for autophagic degradation. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00045769"}],"value":"In the nucleus, serves as transcriptional co-regulator. Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases. Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00046073"}],"value":"In the plasma membrane, is involved in IGFBP6-induced cell migration. Cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. 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