PHB2_HUMAN
ID PHB2_HUMAN Reviewed; 299 AA.
AC Q99623; B4DP75; Q2YDA4; Q7KYU3; Q92978;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Prohibitin-2;
DE AltName: Full=B-cell receptor-associated protein BAP37;
DE AltName: Full=D-prohibitin;
DE AltName: Full=Repressor of estrogen receptor activity;
GN Name=PHB2 {ECO:0000312|EMBL:AAH14766.1, ECO:0000312|HGNC:HGNC:30306};
GN Synonyms=BAP {ECO:0000312|EMBL:AAB51324.1},
GN REA {ECO:0000312|EMBL:AAD38042.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC51639.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=9074930; DOI=10.1101/gr.7.3.268;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAD38042.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH
RP ESR1.
RC TISSUE=Mammary cancer {ECO:0000312|EMBL:AAD38042.1};
RX PubMed=10359819; DOI=10.1073/pnas.96.12.6947;
RA Montano M.M., Ekena K., Delage-Mourroux R., Chang W., Martini P.,
RA Katzenellenbogen B.S.;
RT "An estrogen receptor-selective coregulator that potentiates the
RT effectiveness of antiestrogens and represses the activity of estrogens.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6947-6952(1999).
RN [3] {ECO:0000312|EMBL:AAF44345.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Dendritic cell;
RA Zhang W., Wan T., Chen T., Cao X.;
RT "Identification of a novel D-prohibitin from dendritic cells.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAF17231.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus {ECO:0000312|EMBL:AAF17231.1};
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7] {ECO:0000312|EMBL:AAH14766.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta {ECO:0000312|EMBL:AAH14766.1}, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8] {ECO:0000312|EMBL:AAF44345.1}
RP PROTEIN SEQUENCE OF 2-11; 108-131; 148-157; 172-191; 210-216; 225-236 AND
RP 271-289, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Lilla S., Zebisch A., Kolch W.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9] {ECO:0000305}
RP FUNCTION, INTERACTION WITH PHB, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=11302691; DOI=10.1006/excr.2001.5166;
RA Coates P.J., Nenutil R., McGregor A., Picksley S.M., Crouch D.H.,
RA Hall P.A., Wright E.G.;
RT "Mammalian prohibitin proteins respond to mitochondrial stress and decrease
RT during cellular senescence.";
RL Exp. Cell Res. 265:262-273(2001).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-128, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP INTERACTION WITH ARFGEF3, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19496786; DOI=10.1111/j.1349-7006.2009.01209.x;
RA Kim J.W., Akiyama M., Park J.H., Lin M.L., Shimo A., Ueki T., Daigo Y.,
RA Tsunoda T., Nishidate T., Nakamura Y., Katagiri T.;
RT "Activation of an estrogen/estrogen receptor signaling by BIG3 through its
RT inhibitory effect on nuclear transport of PHB2/REA in breast cancer.";
RL Cancer Sci. 100:1468-1478(2009).
RN [14]
RP INTERACTION WITH SARS-COV NSP2.
RX PubMed=19640993; DOI=10.1128/jvi.00842-09;
RA Cornillez-Ty C.T., Liao L., Yates J.R., Kuhn P., Buchmeier M.J.;
RT "Severe acute respiratory syndrome coronavirus nonstructural protein 2
RT interacts with a host protein complex involved in mitochondrial biogenesis
RT and intracellular signaling.";
RL J. Virol. 83:10314-10318(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-250, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP INTERACTION WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 ENVELOPE GLYCOPROTEIN
RP GP160.
RX PubMed=19906925; DOI=10.1128/jvi.01641-09;
RA Emerson V., Holtkotte D., Pfeiffer T., Wang I.H., Schnoelzer M., Kempf T.,
RA Bosch V.;
RT "Identification of the cellular prohibitin 1/prohibitin 2 heterodimer as an
RT interaction partner of the C-terminal cytoplasmic domain of the HIV-1
RT glycoprotein.";
RL J. Virol. 84:1355-1365(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP INTERACTION WITH ZNF703, AND SUBCELLULAR LOCATION.
RX PubMed=21328542; DOI=10.1002/emmm.201100121;
RA Sircoulomb F., Nicolas N., Ferrari A., Finetti P., Bekhouche I.,
RA Rousselet E., Lonigro A., Adelaide J., Baudelet E., Esteyries S.,
RA Wicinski J., Audebert S., Charafe-Jauffret E., Jacquemier J., Lopez M.,
RA Borg J.P., Sotiriou C., Popovici C., Bertucci F., Birnbaum D.,
RA Chaffanet M., Ginestier C.;
RT "ZNF703 gene amplification at 8p12 specifies luminal B breast cancer.";
RL EMBO Mol. Med. 3:153-166(2011).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PHB.
RX PubMed=20959514; DOI=10.1096/fj.10-167502;
RA Strub G.M., Paillard M., Liang J., Gomez L., Allegood J.C., Hait N.C.,
RA Maceyka M., Price M.M., Chen Q., Simpson D.C., Kordula T., Milstien S.,
RA Lesnefsky E.J., Spiegel S.;
RT "Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria
RT interacts with prohibitin 2 to regulate complex IV assembly and
RT respiration.";
RL FASEB J. 25:600-612(2011).
RN [20]
RP INTERACTION WITH STOML2.
RX PubMed=21746876; DOI=10.1128/mcb.05393-11;
RA Christie D.A., Lemke C.D., Elias I.M., Chau L.A., Kirchhof M.G., Li B.,
RA Ball E.H., Dunn S.D., Hatch G.M., Madrenas J.;
RT "Stomatin-like protein 2 binds cardiolipin and regulates mitochondrial
RT biogenesis and function.";
RL Mol. Cell. Biol. 31:3845-3856(2011).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=22997079; DOI=10.1002/jmv.23403;
RA Wintachai P., Wikan N., Kuadkitkan A., Jaimipuk T., Ubol S.,
RA Pulmanausahakul R., Auewarakul P., Kasinrerk W., Weng W.Y.,
RA Panyasrivanit M., Paemanee A., Kittisenachai S., Roytrakul S., Smith D.R.;
RT "Identification of prohibitin as a Chikungunya virus receptor protein.";
RL J. Med. Virol. 84:1757-1770(2012).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [23]
RP FUNCTION, INTERACTION WITH IGFBP6, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION.
RX PubMed=24003225; DOI=10.1074/jbc.m113.510826;
RA Fu P., Yang Z., Bach L.A.;
RT "Prohibitin-2 binding modulates insulin-like growth factor-binding protein-
RT 6 (IGFBP-6)-induced rhabdomyosarcoma cell migration.";
RL J. Biol. Chem. 288:29890-29900(2013).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP REVIEW OF FUNCTION.
RX PubMed=25904163; DOI=10.1002/iub.1366;
RA Bavelloni A., Piazzi M., Raffini M., Faenza I., Blalock W.L.;
RT "Prohibitin 2: At a communications crossroads.";
RL IUBMB Life 67:239-254(2015).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [28]
RP FUNCTION, INTERACTION WITH PHB1 AND MAP1LC3B, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF TYR-77; 121-TYR--LEU-124 AND 175-PHE--ILE-178.
RX PubMed=28017329; DOI=10.1016/j.cell.2016.11.042;
RA Wei Y., Chiang W.C., Sumpter R. Jr., Mishra P., Levine B.;
RT "Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor.";
RL Cell 168:224.e10-238.e10(2017).
RN [29]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HUMAN ENTEROVIRUS 71
RP CAPSID PROTEIN VP1, AND SUBCELLULAR LOCATION.
RX PubMed=32276428; DOI=10.3390/v12040414;
RA Su W., Huang S., Zhu H., Zhang B., Wu X.;
RT "Interaction between PHB2 and Enterovirus A71 VP1 Induces Autophagy and
RT Affects EV-A71 Infection.";
RL Viruses 12:0-0(2020).
RN [30] {ECO:0007744|PDB:6IQE}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 188-265, ALTERNATIVE SPLICING,
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, MUTAGENESIS OF ILE-225 AND
RP 229-GLU--GLU-233, AND INTERACTION WITH PHB1 AND CLPB.
RX PubMed=31522117; DOI=10.1016/j.isci.2019.08.056;
RA Yoshinaka T., Kosako H., Yoshizumi T., Furukawa R., Hirano Y., Kuge O.,
RA Tamada T., Koshiba T.;
RT "Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes:
RT Insight into a Role of the Coiled-Coil Region.";
RL IScience 19:1065-1078(2019).
CC -!- FUNCTION: Protein with pleiotropic attributes mediated in a cell-
CC compartment- and tissue-specific manner, which include the plasma
CC membrane-associated cell signaling functions, mitochondrial chaperone,
CC and transcriptional co-regulator of transcription factors and sex
CC steroid hormones in the nucleus. {ECO:0000269|PubMed:10359819,
CC ECO:0000269|PubMed:11302691, ECO:0000269|PubMed:20959514,
CC ECO:0000269|PubMed:24003225, ECO:0000269|PubMed:28017329,
CC ECO:0000269|PubMed:31522117}.
CC -!- FUNCTION: In the mitochondria, together with PHB, forms large ring
CC complexes (prohibitin complexes) in the inner mitochondrial membrane
CC (IMM) and functions as chaperone protein that stabilizes mitochondrial
CC respiratory enzymes and maintains mitochondrial integrity in the IMM,
CC which is required for mitochondrial morphogenesis, neuronal survival,
CC and normal lifespan (Probable). The prohibitin complex, with DNAJC19,
CC regulates cardiolipin remodeling and the protein turnover of OMA1 in a
CC cardiolipin-binding manner (By similarity). Also regulates cytochrome-c
CC oxidase assembly (COX) and mitochondrial respiration (PubMed:20959514,
CC PubMed:11302691). Binding to sphingoid 1-phosphate (SPP) modulates its
CC regulator activity (PubMed:20959514, PubMed:11302691). Has a key role
CC of mitophagy receptor involved in targeting mitochondria for autophagic
CC degradation (PubMed:28017329). Involved in mitochondrial-mediated
CC antiviral innate immunity, activates DDX58/RIG-I-mediated signal
CC transduction and production of IFNB1 and pro-inflammatory cytokine IL6
CC (PubMed:31522117). {ECO:0000250|UniProtKB:O35129,
CC ECO:0000269|PubMed:11302691, ECO:0000269|PubMed:20959514,
CC ECO:0000269|PubMed:28017329, ECO:0000269|PubMed:31522117,
CC ECO:0000305|PubMed:25904163}.
CC -!- FUNCTION: In the nucleus, serves as transcriptional co-regulator
CC (Probable). Acts as a mediator of transcriptional repression by nuclear
CC hormone receptors via recruitment of histone deacetylases. Functions as
CC an estrogen receptor (ER)-selective coregulator that potentiates the
CC inhibitory activities of antiestrogens and represses the activity of
CC estrogens. Competes with NCOA1 for modulation of ER transcriptional
CC activity (By similarity). {ECO:0000250|UniProtKB:O35129,
CC ECO:0000305|PubMed:25904163}.
CC -!- FUNCTION: In the plasma membrane, is involved in IGFBP6-induced cell
CC migration (PubMed:24003225). Cooperates with CD86 to mediate CD86-
CC signaling in B lymphocytes that regulates the level of IgG1 produced
CC through the activation of distal signaling intermediates. Upon CD40
CC engagement, required to activate NF-kappa-B signaling pathway via
CC phospholipase C and protein kinase C activation (By similarity).
CC {ECO:0000250|UniProtKB:O35129, ECO:0000269|PubMed:24003225}.
CC -!- FUNCTION: (Microbial infection) Involved in human enterovirus 71/EV-71
CC infection by enhancing the autophagy mechanism during the infection.
CC {ECO:0000269|PubMed:32276428}.
CC -!- SUBUNIT: The mitochondrial prohibitin complex consists of two subunits
CC (PHB1 and PHB2), assembled into a membrane-associated ring-shaped
CC supercomplex of approximately 1 mDa (PubMed:20959514, PubMed:28017329,
CC PubMed:31522117). Interacts with ESR1, HDAC1 and HDAC5 (By similarity).
CC Interacts with ZNF703 (PubMed:21328542). Interacts with STOML2
CC (PubMed:21746876). Interacts with ARFGEF3 (PubMed:19496786). Interacts
CC with SPHK2. Interacts with COX4I1; the interaction associates PHB2 with
CC COX (By similarity). Interacts with MAP1LC3B (membrane-bound form LC3-
CC II); the interaction is direct and upon mitochondrial depolarization
CC and proteasome-dependent outer membrane rupture (PubMed:28017329).
CC Interacts with IGFBP6 (via C-terminal domain) (PubMed:24003225).
CC Interacts with CLPB (PubMed:31522117). Interacts with CD86 (via
CC cytoplasmic domain); the interactions increases after priming with CD40
CC (By similarity). Interacts with AFG3L2 (By similarity). Interacts with
CC DNAJC19 (By similarity). {ECO:0000250|UniProtKB:O35129,
CC ECO:0000269|PubMed:10359819, ECO:0000269|PubMed:11302691,
CC ECO:0000269|PubMed:19496786, ECO:0000269|PubMed:20959514,
CC ECO:0000269|PubMed:21328542, ECO:0000269|PubMed:21746876,
CC ECO:0000269|PubMed:24003225, ECO:0000269|PubMed:28017329,
CC ECO:0000269|PubMed:31522117}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SARS coronavirus/SARS-CoV
CC nsp2 protein. {ECO:0000269|PubMed:19640993}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human enterovirus 71/EV-
CC 71 capsid protein VP1; the interaction is required for induction of
CC autophagy and the infectivity of EV-71. {ECO:0000269|PubMed:32276428}.
CC -!- SUBUNIT: (Microbial infection) Interaction with human immunodeficiency
CC virus type 1/HIV-1 envelope glycoprotein GP160.
CC {ECO:0000269|PubMed:19906925}.
CC -!- INTERACTION:
CC Q99623; Q16828: DUSP6; NbExp=3; IntAct=EBI-358348, EBI-746870;
CC Q99623; P03372: ESR1; NbExp=4; IntAct=EBI-358348, EBI-78473;
CC Q99623; Q9BR81: PCDHGC3; NbExp=3; IntAct=EBI-358348, EBI-22012354;
CC Q99623; P35232: PHB; NbExp=3; IntAct=EBI-358348, EBI-354213;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:20959514, ECO:0000269|PubMed:28017329}. Cytoplasm
CC {ECO:0000269|PubMed:19496786, ECO:0000269|PubMed:32276428}. Nucleus
CC {ECO:0000269|PubMed:19496786, ECO:0000269|PubMed:20959514}. Cell
CC membrane {ECO:0000269|PubMed:22997079, ECO:0000269|PubMed:24003225}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:31522117}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:31522117}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=V1 {ECO:0000303|PubMed:31522117};
CC IsoId=Q99623-1; Sequence=Displayed;
CC Name=2; Synonyms=V3 {ECO:0000303|PubMed:31522117};
CC IsoId=Q99623-2; Sequence=VSP_045311;
CC -!- DEVELOPMENTAL STAGE: Levels of expression in fibroblasts decrease
CC heterogeneously during cellular aging. {ECO:0000269|PubMed:11302691}.
CC -!- INDUCTION: Expression increases approximately 3-fold upon entry into G1
CC phase compared to other phases of the cell cycle. Also induced
CC following inhibition of mitochondrial protein synthesis by
CC thiamphenicol. {ECO:0000269|PubMed:11302691}.
CC -!- DOMAIN: LC3-interaction region (LIR) is required for interaction with
CC MAP1LC3B/LC3-II and for Parkin-mediated mitophagy.
CC {ECO:0000269|PubMed:28017329}.
CC -!- PTM: Phosphorylated. Tyrosine phosphorylation is indirectly stimulated
CC by IGFBP6. {ECO:0000269|PubMed:24003225}.
CC -!- SIMILARITY: Belongs to the prohibitin family. {ECO:0000255}.
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DR EMBL; U72511; AAC51639.1; -; mRNA.
DR EMBL; AF150962; AAD38042.1; -; mRNA.
DR EMBL; AF178980; AAF44345.1; -; mRNA.
DR EMBL; AF126021; AAF17231.1; -; mRNA.
DR EMBL; AK298217; BAG60487.1; -; mRNA.
DR EMBL; U47924; AAB51324.1; -; Genomic_DNA.
DR EMBL; BC014766; AAH14766.1; -; mRNA.
DR EMBL; BC110322; AAI10323.1; -; mRNA.
DR CCDS; CCDS53741.1; -. [Q99623-1]
DR CCDS; CCDS58207.1; -. [Q99623-2]
DR RefSeq; NP_001138303.1; NM_001144831.1. [Q99623-1]
DR RefSeq; NP_001254629.1; NM_001267700.1. [Q99623-2]
DR PDB; 6IQE; X-ray; 1.70 A; A=188-265.
DR PDBsum; 6IQE; -.
DR AlphaFoldDB; Q99623; -.
DR SMR; Q99623; -.
DR BioGRID; 116459; 493.
DR ComplexPortal; CPX-5741; Prohibitin complex.
DR CORUM; Q99623; -.
DR IntAct; Q99623; 143.
DR MINT; Q99623; -.
DR STRING; 9606.ENSP00000441875; -.
DR ChEMBL; CHEMBL4295931; -.
DR DrugBank; DB06774; Capsaicin.
DR DrugBank; DB15496; Didesmethylrocaglamide.
DR DrugBank; DB15495; Rocaglamide.
DR CarbonylDB; Q99623; -.
DR GlyGen; Q99623; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q99623; -.
DR MetOSite; Q99623; -.
DR PhosphoSitePlus; Q99623; -.
DR SwissPalm; Q99623; -.
DR BioMuta; PHB2; -.
DR DMDM; 74752151; -.
DR OGP; Q99623; -.
DR EPD; Q99623; -.
DR jPOST; Q99623; -.
DR MassIVE; Q99623; -.
DR MaxQB; Q99623; -.
DR PaxDb; Q99623; -.
DR PeptideAtlas; Q99623; -.
DR PRIDE; Q99623; -.
DR ProteomicsDB; 4765; -.
DR ProteomicsDB; 78364; -. [Q99623-1]
DR TopDownProteomics; Q99623-1; -. [Q99623-1]
DR TopDownProteomics; Q99623-2; -. [Q99623-2]
DR Antibodypedia; 4444; 477 antibodies from 39 providers.
DR DNASU; 11331; -.
DR Ensembl; ENST00000440277.6; ENSP00000412856.1; ENSG00000215021.10. [Q99623-2]
DR Ensembl; ENST00000535923.6; ENSP00000441875.1; ENSG00000215021.10. [Q99623-1]
DR GeneID; 11331; -.
DR KEGG; hsa:11331; -.
DR MANE-Select; ENST00000535923.6; ENSP00000441875.1; NM_001144831.2; NP_001138303.1.
DR UCSC; uc058kpb.1; human. [Q99623-1]
DR CTD; 11331; -.
DR DisGeNET; 11331; -.
DR GeneCards; PHB2; -.
DR HGNC; HGNC:30306; PHB2.
DR HPA; ENSG00000215021; Low tissue specificity.
DR MIM; 610704; gene.
DR neXtProt; NX_Q99623; -.
DR OpenTargets; ENSG00000215021; -.
DR PharmGKB; PA142671181; -.
DR VEuPathDB; HostDB:ENSG00000215021; -.
DR eggNOG; KOG3090; Eukaryota.
DR GeneTree; ENSGT00950000183070; -.
DR InParanoid; Q99623; -.
DR OMA; IKYTRLG; -.
DR OrthoDB; 1089994at2759; -.
DR PhylomeDB; Q99623; -.
DR TreeFam; TF354230; -.
DR PathwayCommons; Q99623; -.
DR Reactome; R-HSA-8949664; Processing of SMDT1.
DR SignaLink; Q99623; -.
DR SIGNOR; Q99623; -.
DR BioGRID-ORCS; 11331; 808 hits in 1081 CRISPR screens.
DR ChiTaRS; PHB2; human.
DR GeneWiki; PHB2; -.
DR GenomeRNAi; 11331; -.
DR Pharos; Q99623; Tbio.
DR PRO; PR:Q99623; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q99623; protein.
DR Bgee; ENSG00000215021; Expressed in mammalian vulva and 207 other tissues.
DR ExpressionAtlas; Q99623; baseline and differential.
DR Genevisible; Q99623; HS.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0071944; C:cell periphery; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0035632; C:mitochondrial prohibitin complex; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0048786; C:presynaptic active zone; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0033218; F:amide binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; NAS:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0046625; F:sphingolipid binding; IDA:UniProtKB.
DR GO; GO:0007202; P:activation of phospholipase C activity; ISS:UniProtKB.
DR GO; GO:1990051; P:activation of protein kinase C activity; ISS:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProtKB.
DR GO; GO:0042113; P:B cell activation; ISS:UniProtKB.
DR GO; GO:0023035; P:CD40 signaling pathway; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0060749; P:mammary gland alveolus development; IEA:Ensembl.
DR GO; GO:0060744; P:mammary gland branching involved in thelarche; IEA:Ensembl.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0000423; P:mitophagy; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; IMP:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0031536; P:positive regulation of exit from mitosis; IMP:UniProtKB.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:ComplexPortal.
DR GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; IEA:Ensembl.
DR GO; GO:1900208; P:regulation of cardiolipin metabolic process; ISS:UniProtKB.
DR GO; GO:1904959; P:regulation of cytochrome-c oxidase activity; IMP:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0039529; P:RIG-I signaling pathway; IDA:UniProtKB.
DR GO; GO:0007062; P:sister chromatid cohesion; IDA:UniProtKB.
DR CDD; cd03401; SPFH_prohibitin; 1.
DR Gene3D; 3.30.479.30; -; 1.
DR InterPro; IPR001107; Band_7.
DR InterPro; IPR036013; Band_7/SPFH_dom_sf.
DR InterPro; IPR000163; Prohibitin.
DR PANTHER; PTHR23222; PTHR23222; 1.
DR Pfam; PF01145; Band_7; 1.
DR PRINTS; PR00679; PROHIBITIN.
DR SMART; SM00244; PHB; 1.
DR SUPFAM; SSF117892; SSF117892; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane;
KW Coiled coil; Cytoplasm; Direct protein sequencing; Host-virus interaction;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:22814378"
FT CHAIN 2..299
FT /note="Prohibitin-2"
FT /id="PRO_0000213884"
FT REGION 19..49
FT /note="Necessary for transcriptional repression"
FT /evidence="ECO:0000269|PubMed:10359819"
FT REGION 121..124
FT /note="LC3-interaction region"
FT /evidence="ECO:0000269|PubMed:28017329"
FT REGION 150..174
FT /note="Necessary for transcriptional repression"
FT /evidence="ECO:0000269|PubMed:10359819"
FT COILED 190..238
FT /evidence="ECO:0000269|PubMed:28017329,
FT ECO:0007744|PDB:6IQE"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:22814378"
FT MOD_RES 128
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 147
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35129"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 200
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35129"
FT MOD_RES 236
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35129"
FT MOD_RES 250
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 262
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35129"
FT VAR_SEQ 203..240
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045311"
FT MUTAGEN 77
FT /note="Y->K: No effect on interaction wiht MAP1LC3B."
FT /evidence="ECO:0000269|PubMed:28017329"
FT MUTAGEN 121..124
FT /note="YQRL->AQRA: Abolishes interaction with MAP1LC3B. No
FT effect on interaction with PHB. No effect on mitochondrial
FT location. Abolishes rescue of Parkin-mediated mitophagy."
FT /evidence="ECO:0000269|PubMed:28017329"
FT MUTAGEN 175..178
FT /note="FSLI->ASLA: Decreases interaction with MAP1LC3B."
FT /evidence="ECO:0000269|PubMed:28017329"
FT MUTAGEN 225
FT /note="I->P: Reduces helicity. Decreases homodimerization
FT and interaction with PHB. Disrupts mitochondrial dynamics.
FT Disrupts mitochondrial-mediated antiviral innate immune
FT response."
FT /evidence="ECO:0000269|PubMed:31522117"
FT MUTAGEN 229..233
FT /note="EGEAE->KGKAK: No effect on homodimerization or
FT interaction with PHB. Decreases mitochondrial dynamics.
FT Disrupts mitochondrial-mediated antiviral innate immune
FT response."
FT /evidence="ECO:0000269|PubMed:31522117"
FT HELIX 188..244
FT /evidence="ECO:0007829|PDB:6IQE"
SQ SEQUENCE 299 AA; 33296 MW; A887CC982BF85C80 CRC64;
MAQNLKDLAG RLPAGPRGMG TALKLLLGAG AVAYGVRESV FTVEGGHRAI FFNRIGGVQQ
DTILAEGLHF RIPWFQYPII YDIRARPRKI SSPTGSKDLQ MVNISLRVLS RPNAQELPSM
YQRLGLDYEE RVLPSIVNEV LKSVVAKFNA SQLITQRAQV SLLIRRELTE RAKDFSLILD
DVAITELSFS REYTAAVEAK QVAQQEAQRA QFLVEKAKQE QRQKIVQAEG EAEAAKMLGE
ALSKNPGYIK LRKIRAAQNI SKTIATSQNR IYLTADNLVL NLQDESFTRG SDSLIKGKK
