Full text data of PHB2
PHB2
(BAP, REA)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Prohibitin-2 (B-cell receptor-associated protein BAP37; D-prohibitin; Repressor of estrogen receptor activity)
Prohibitin-2 (B-cell receptor-associated protein BAP37; D-prohibitin; Repressor of estrogen receptor activity)
UniProt
Q99623
ID PHB2_HUMAN Reviewed; 299 AA.
AC Q99623; B4DP75; Q2YDA4; Q7KYU3; Q92978;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 2.
DT 22-JAN-2014, entry version 124.
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; Synonyms=BAP, REA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=9074930;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH
RP ESR1.
RC TISSUE=Mammary cancer;
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
RT estrogens.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6947-6952(1999).
RN [3]
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus;
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.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA 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.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA 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.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-11; 108-131; 148-157; 172-191; 210-216; 225-236
RP AND 271-289, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2,
RP AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Lilla S., Zebisch A., Kolch W.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
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
RT decrease during cellular senescence.";
RL Exp. Cell Res. 265:262-273(2001).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-128, AND MASS
RP SPECTROMETRY.
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
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-250, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [13]
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.,
RA Buerckstuemmer T., 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 [14]
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.,
RA Lopez M., Borg J.P., Sotiriou C., Popovici C., Bertucci F.,
RA Birnbaum D., Chaffanet M., Ginestier C.;
RT "ZNF703 gene amplification at 8p12 specifies luminal B breast
RT cancer.";
RL EMBO Mol. Med. 3:153-166(2011).
RN [15]
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.,
RA Li B., 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Acts as a mediator of transcriptional repression by
CC nuclear hormone receptors via recruitment of histone deacetylases
CC (By similarity). Functions as an estrogen receptor (ER)-selective
CC coregulator that potentiates the inhibitory activities of
CC antiestrogens and represses the activity of estrogens. Competes
CC with NCOA1 for modulation of ER transcriptional activity. Probably
CC involved in regulating mitochondrial respiration activity and in
CC aging.
CC -!- SUBUNIT: Interacts with PHB, ESR1, HDAC1 and HDAC5 (By
CC similarity). Interacts with ZNF703. Interacts with STOML2.
CC -!- INTERACTION:
CC P03372:ESR1; NbExp=4; IntAct=EBI-358348, EBI-78473;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane (By
CC similarity). Cytoplasm (By similarity). Nucleus (By similarity).
CC Note=Also cytoplasmic and nuclear (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99623-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99623-2; Sequence=VSP_045311;
CC -!- DEVELOPMENTAL STAGE: Levels of expression in fibroblasts decrease
CC heterogeneously during cellular aging.
CC -!- INDUCTION: Expression increases approximately 3-fold upon entry
CC into G1 phase compared to other phases of the cell cycle. Also
CC induced following inhibition of mitochondrial protein synthesis by
CC thiamphenicol.
CC -!- SIMILARITY: Belongs to the prohibitin family.
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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 RefSeq; NP_001138303.1; NM_001144831.1.
DR RefSeq; NP_001254629.1; NM_001267700.1.
DR UniGene; Hs.504620; -.
DR ProteinModelPortal; Q99623; -.
DR IntAct; Q99623; 21.
DR MINT; MINT-142400; -.
DR STRING; 9606.ENSP00000382362; -.
DR PhosphoSite; Q99623; -.
DR DMDM; 74752151; -.
DR OGP; Q99623; -.
DR PaxDb; Q99623; -.
DR PeptideAtlas; Q99623; -.
DR PRIDE; Q99623; -.
DR DNASU; 11331; -.
DR Ensembl; ENST00000440277; ENSP00000412856; ENSG00000215021.
DR Ensembl; ENST00000535923; ENSP00000441875; ENSG00000215021.
DR Ensembl; ENST00000607236; ENSP00000475972; ENSG00000269079.
DR Ensembl; ENST00000607454; ENSP00000475555; ENSG00000269079.
DR GeneID; 11331; -.
DR KEGG; hsa:11331; -.
DR UCSC; uc010sft.2; human.
DR CTD; 11331; -.
DR GeneCards; GC12M007074; -.
DR HGNC; HGNC:30306; PHB2.
DR HPA; CAB014889; -.
DR HPA; CAB026335; -.
DR HPA; HPA039874; -.
DR MIM; 610704; gene.
DR neXtProt; NX_Q99623; -.
DR PharmGKB; PA142671181; -.
DR eggNOG; COG0330; -.
DR HOGENOM; HOG000205692; -.
DR HOVERGEN; HBG004457; -.
DR InParanoid; Q99623; -.
DR KO; K17081; -.
DR OMA; TYMTFSP; -.
DR ChiTaRS; PHB2; human.
DR GeneWiki; PHB2; -.
DR GenomeRNAi; 11331; -.
DR NextBio; 43043; -.
DR PRO; PR:Q99623; -.
DR ArrayExpress; Q99623; -.
DR Bgee; Q99623; -.
DR CleanEx; HS_PHB2; -.
DR Genevestigator; Q99623; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0030331; F:estrogen receptor binding; NAS:UniProtKB.
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: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-dependent; IDA:UniProtKB.
DR GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR001107; Band_7.
DR InterPro; IPR000163; Prohibitin.
DR PANTHER; PTHR23222; PTHR23222; 1.
DR Pfam; PF01145; Band_7; 1.
DR PRINTS; PR00679; PROHIBITIN.
DR SMART; SM00244; PHB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Coiled coil; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 299 Prohibitin-2.
FT /FTId=PRO_0000213884.
FT REGION 19 49 Necessary for transcriptional repression.
FT REGION 150 174 Necessary for transcriptional repression.
FT COILED 190 238 Potential.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 128 128 Phosphotyrosine.
FT MOD_RES 147 147 N6-acetyllysine (By similarity).
FT MOD_RES 200 200 N6-acetyllysine (By similarity).
FT MOD_RES 236 236 N6-acetyllysine (By similarity).
FT MOD_RES 250 250 N6-acetyllysine.
FT MOD_RES 262 262 N6-acetyllysine (By similarity).
FT VAR_SEQ 203 240 Missing (in isoform 2).
FT /FTId=VSP_045311.
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
//
ID PHB2_HUMAN Reviewed; 299 AA.
AC Q99623; B4DP75; Q2YDA4; Q7KYU3; Q92978;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 2.
DT 22-JAN-2014, entry version 124.
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; Synonyms=BAP, REA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=9074930;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH
RP ESR1.
RC TISSUE=Mammary cancer;
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
RT estrogens.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6947-6952(1999).
RN [3]
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus;
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.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA 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.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA 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.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-11; 108-131; 148-157; 172-191; 210-216; 225-236
RP AND 271-289, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2,
RP AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Lilla S., Zebisch A., Kolch W.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
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
RT decrease during cellular senescence.";
RL Exp. Cell Res. 265:262-273(2001).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-128, AND MASS
RP SPECTROMETRY.
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
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-250, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [13]
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.,
RA Buerckstuemmer T., 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 [14]
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.,
RA Lopez M., Borg J.P., Sotiriou C., Popovici C., Bertucci F.,
RA Birnbaum D., Chaffanet M., Ginestier C.;
RT "ZNF703 gene amplification at 8p12 specifies luminal B breast
RT cancer.";
RL EMBO Mol. Med. 3:153-166(2011).
RN [15]
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.,
RA Li B., 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Acts as a mediator of transcriptional repression by
CC nuclear hormone receptors via recruitment of histone deacetylases
CC (By similarity). Functions as an estrogen receptor (ER)-selective
CC coregulator that potentiates the inhibitory activities of
CC antiestrogens and represses the activity of estrogens. Competes
CC with NCOA1 for modulation of ER transcriptional activity. Probably
CC involved in regulating mitochondrial respiration activity and in
CC aging.
CC -!- SUBUNIT: Interacts with PHB, ESR1, HDAC1 and HDAC5 (By
CC similarity). Interacts with ZNF703. Interacts with STOML2.
CC -!- INTERACTION:
CC P03372:ESR1; NbExp=4; IntAct=EBI-358348, EBI-78473;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane (By
CC similarity). Cytoplasm (By similarity). Nucleus (By similarity).
CC Note=Also cytoplasmic and nuclear (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99623-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99623-2; Sequence=VSP_045311;
CC -!- DEVELOPMENTAL STAGE: Levels of expression in fibroblasts decrease
CC heterogeneously during cellular aging.
CC -!- INDUCTION: Expression increases approximately 3-fold upon entry
CC into G1 phase compared to other phases of the cell cycle. Also
CC induced following inhibition of mitochondrial protein synthesis by
CC thiamphenicol.
CC -!- SIMILARITY: Belongs to the prohibitin family.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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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 RefSeq; NP_001138303.1; NM_001144831.1.
DR RefSeq; NP_001254629.1; NM_001267700.1.
DR UniGene; Hs.504620; -.
DR ProteinModelPortal; Q99623; -.
DR IntAct; Q99623; 21.
DR MINT; MINT-142400; -.
DR STRING; 9606.ENSP00000382362; -.
DR PhosphoSite; Q99623; -.
DR DMDM; 74752151; -.
DR OGP; Q99623; -.
DR PaxDb; Q99623; -.
DR PeptideAtlas; Q99623; -.
DR PRIDE; Q99623; -.
DR DNASU; 11331; -.
DR Ensembl; ENST00000440277; ENSP00000412856; ENSG00000215021.
DR Ensembl; ENST00000535923; ENSP00000441875; ENSG00000215021.
DR Ensembl; ENST00000607236; ENSP00000475972; ENSG00000269079.
DR Ensembl; ENST00000607454; ENSP00000475555; ENSG00000269079.
DR GeneID; 11331; -.
DR KEGG; hsa:11331; -.
DR UCSC; uc010sft.2; human.
DR CTD; 11331; -.
DR GeneCards; GC12M007074; -.
DR HGNC; HGNC:30306; PHB2.
DR HPA; CAB014889; -.
DR HPA; CAB026335; -.
DR HPA; HPA039874; -.
DR MIM; 610704; gene.
DR neXtProt; NX_Q99623; -.
DR PharmGKB; PA142671181; -.
DR eggNOG; COG0330; -.
DR HOGENOM; HOG000205692; -.
DR HOVERGEN; HBG004457; -.
DR InParanoid; Q99623; -.
DR KO; K17081; -.
DR OMA; TYMTFSP; -.
DR ChiTaRS; PHB2; human.
DR GeneWiki; PHB2; -.
DR GenomeRNAi; 11331; -.
DR NextBio; 43043; -.
DR PRO; PR:Q99623; -.
DR ArrayExpress; Q99623; -.
DR Bgee; Q99623; -.
DR CleanEx; HS_PHB2; -.
DR Genevestigator; Q99623; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0030331; F:estrogen receptor binding; NAS:UniProtKB.
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: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-dependent; IDA:UniProtKB.
DR GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR001107; Band_7.
DR InterPro; IPR000163; Prohibitin.
DR PANTHER; PTHR23222; PTHR23222; 1.
DR Pfam; PF01145; Band_7; 1.
DR PRINTS; PR00679; PROHIBITIN.
DR SMART; SM00244; PHB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Coiled coil; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 299 Prohibitin-2.
FT /FTId=PRO_0000213884.
FT REGION 19 49 Necessary for transcriptional repression.
FT REGION 150 174 Necessary for transcriptional repression.
FT COILED 190 238 Potential.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 128 128 Phosphotyrosine.
FT MOD_RES 147 147 N6-acetyllysine (By similarity).
FT MOD_RES 200 200 N6-acetyllysine (By similarity).
FT MOD_RES 236 236 N6-acetyllysine (By similarity).
FT MOD_RES 250 250 N6-acetyllysine.
FT MOD_RES 262 262 N6-acetyllysine (By similarity).
FT VAR_SEQ 203 240 Missing (in isoform 2).
FT /FTId=VSP_045311.
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
//
MIM
610704
*RECORD*
*FIELD* NO
610704
*FIELD* TI
*610704 PROHIBITIN 2; PHB2
;;REPRESSOR OF ESTROGEN RECEPTOR ACTIVITY; REA
*FIELD* TX
read more
CLONING
Using the C-terminal EF domains of a dominant-negative estrogen receptor
(ER)-alpha (ESR1; 133430) mutant as bait in a yeast 2-hybrid screen of a
breast cancer cell line cDNA library, followed by EST database analysis,
Montano et al. (1999) cloned PHB2, which the called REA. The deduced
299-amino acid protein contains 4 potential phosphorylation sites, a
nuclear receptor interaction box, and a nuclear localization motif.
GENE FUNCTION
Montano et al. (1999) showed that REA enhanced the potency of a
dominant-negative ER-alpha mutant and antiestrogens as suppressors of
ER-alpha activity in Chinese hamster ovary cells. When coexpressed with
wildtype ER-alpha or ER-beta (ESR2; 601663), REA suppressed activation
of a reporter gene in a dose-dependent manner. REA had no effect on
reporter activity in the absence of liganded ER, and it had no effect on
the transcriptional activities of other hormone receptors. Mutation
analysis showed that an N-terminal domain and a central domain of REA
were required for its repressor activity. REA interacted directly with
ER-alpha in an in vitro pull-down assay. REA did not interfere with the
ability of ER-alpha to bind to estrogen response element DNA, but it
competed with the coactivator SRC1 (NCOA1; 602691) for modulation of
ER-alpha transcriptional activity.
By gel filtration, mass spectrometry, coimmunoprecipitation, and Western
blot analysis of HeLa cells, Da Cruz et al. (2008) showed that
prohibitin-1 (PHB; 176705) and prohibitin-2 interacted in a 250-kD
complex with SLP2 (STOML2; 608292). Knockdown of SLP2 in HeLa cells or
mouse embryonic fibroblasts via RNA interference led to increased
proteolysis of the prohibitins and other mitochondrial proteins.
Using coimmunoprecipitation analysis, Christie et al. (2011) confirmed
that SLP2 interacted with PHB1 and PHB2. Elevated SLP2 content increased
the association of PHB1 with mitochondrial membranes.
MAPPING
Hartz (2013) mapped the PHB2 gene to chromosome 12p13.31 based on an
alignment of the PHB2 sequence (GenBank GENBANK AF150962) with the
genomic sequence (GRCh37).
ANIMAL MODEL
Mussi et al. (2006) reported that Rea deletion in mice was embryonic
lethal. They found that, compared with wildtype mice, virgin Rea +/-
mice exhibited faster mammary ductal elongation, and Rea +/- mice showed
increased lobuloalveolar development during pregnancy and delayed
mammary gland involution after weaning. These phenotypes of Rea +/- mice
were associated with significantly increased cell proliferation and ER
transcriptional activities. Rea repressed ER transcriptional activity in
mouse mammary gland under natural conditions, as well as following
ovariectomy and after estrogen replacement.
Using conditional gene targeting, Merkwirth et al. (2008) restricted
expression of mouse Phb2 to mitochondria and identified processing of
the dynamin (see 602377)-like GTPase Opa1 (605290), an essential
component of the mitochondrial fusion machinery, as the central cellular
process controlled by prohibitins. Deletion of Phb2 led to selective
loss of long isoforms of Opa1, resulting in aberrant cristae
morphogenesis, impaired cellular proliferation, and resistance to
apoptosis. Expression of a long Opa1 isoform in Phb2-deficient cells
suppressed these defects, identifying impaired Opa1 processing as the
primary cellular defect in the absence of prohibitins. Merkwirth et al.
(2008) concluded that prohibitins are essential for formation of
mitochondrial cristae and suggested that cell proliferation is coupled
with mitochondrial morphogenesis.
*FIELD* RF
1. Christie, D. A.; Lemke, C. D.; Elias, I. M.; Chau, L. A.; Kirchhof,
M. G.; Li, B.; Ball, E. H.; Dunn, S. D.; Hatch, G. M.; Madrenas, J.
: Stomatin-like protein 2 binds cardiolipin and regulates mitochondrial
biogenesis and function. Molec. Cell. Biol. 31: 3845-3856, 2011.
2. Da Cruz, S.; Parone, P. A.; Gonzalo, P.; Bienvenut, W. V.; Tondera,
D.; Jourdain, A.; Quadroni, M.; Martinou, J.-C.: SLP-2 interacts
with prohibitins in the mitochondrial inner membrane and contributes
to their stability. Biochim. Biophys. Acta 1783: 904-911, 2008.
3. Hartz, P. A.: Personal Communication. Baltimore, Md. 2/20/2013.
4. Merkwirth, C.; Dargazanli, S.; Tatsuta, T.; Geimer, S.; Lower,
B.; Wunderlich, F. T.; von Kleist-Retzow, J.-C.; Waisman, A.; Westermann,
B.; Langer, T.: Prohibitins control cell proliferation and apoptosis
by regulating OPA1-dependent cristae morphogenesis in mitochondria. Genes
Dev. 22: 476-488, 2008.
5. Montano, M. M.; Ekena, K.; Delage-Mourroux, R.; Chang, W.; Martini,
P.; Katzenellenbogen, B. S.: An estrogen receptor-selective coregulator
that potentiates the effectiveness of antiestrogens and represses
the activity of estrogens. Proc. Nat. Acad. Sci. 96: 6947-6952,
1999.
6. Mussi, P.; Liao, L.; Park, S.-E.; Ciana, P.; Maggi, A.; Katzenellenbogen,
B. S.; Xu, J.; O'Malley, B. W.: Haploinsufficiency of the corepressor
of estrogen receptor activity (REA) enhances estrogen receptor function
in the mammary gland. Proc. Nat. Acad. Sci. 103: 16716-16721, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 02/20/2013
Patricia A. Hartz - updated: 3/21/2008
*FIELD* CD
Patricia A. Hartz: 1/16/2007
*FIELD* ED
mgross: 02/20/2013
mgross: 3/24/2008
terry: 3/21/2008
mgross: 1/16/2007
*RECORD*
*FIELD* NO
610704
*FIELD* TI
*610704 PROHIBITIN 2; PHB2
;;REPRESSOR OF ESTROGEN RECEPTOR ACTIVITY; REA
*FIELD* TX
read more
CLONING
Using the C-terminal EF domains of a dominant-negative estrogen receptor
(ER)-alpha (ESR1; 133430) mutant as bait in a yeast 2-hybrid screen of a
breast cancer cell line cDNA library, followed by EST database analysis,
Montano et al. (1999) cloned PHB2, which the called REA. The deduced
299-amino acid protein contains 4 potential phosphorylation sites, a
nuclear receptor interaction box, and a nuclear localization motif.
GENE FUNCTION
Montano et al. (1999) showed that REA enhanced the potency of a
dominant-negative ER-alpha mutant and antiestrogens as suppressors of
ER-alpha activity in Chinese hamster ovary cells. When coexpressed with
wildtype ER-alpha or ER-beta (ESR2; 601663), REA suppressed activation
of a reporter gene in a dose-dependent manner. REA had no effect on
reporter activity in the absence of liganded ER, and it had no effect on
the transcriptional activities of other hormone receptors. Mutation
analysis showed that an N-terminal domain and a central domain of REA
were required for its repressor activity. REA interacted directly with
ER-alpha in an in vitro pull-down assay. REA did not interfere with the
ability of ER-alpha to bind to estrogen response element DNA, but it
competed with the coactivator SRC1 (NCOA1; 602691) for modulation of
ER-alpha transcriptional activity.
By gel filtration, mass spectrometry, coimmunoprecipitation, and Western
blot analysis of HeLa cells, Da Cruz et al. (2008) showed that
prohibitin-1 (PHB; 176705) and prohibitin-2 interacted in a 250-kD
complex with SLP2 (STOML2; 608292). Knockdown of SLP2 in HeLa cells or
mouse embryonic fibroblasts via RNA interference led to increased
proteolysis of the prohibitins and other mitochondrial proteins.
Using coimmunoprecipitation analysis, Christie et al. (2011) confirmed
that SLP2 interacted with PHB1 and PHB2. Elevated SLP2 content increased
the association of PHB1 with mitochondrial membranes.
MAPPING
Hartz (2013) mapped the PHB2 gene to chromosome 12p13.31 based on an
alignment of the PHB2 sequence (GenBank GENBANK AF150962) with the
genomic sequence (GRCh37).
ANIMAL MODEL
Mussi et al. (2006) reported that Rea deletion in mice was embryonic
lethal. They found that, compared with wildtype mice, virgin Rea +/-
mice exhibited faster mammary ductal elongation, and Rea +/- mice showed
increased lobuloalveolar development during pregnancy and delayed
mammary gland involution after weaning. These phenotypes of Rea +/- mice
were associated with significantly increased cell proliferation and ER
transcriptional activities. Rea repressed ER transcriptional activity in
mouse mammary gland under natural conditions, as well as following
ovariectomy and after estrogen replacement.
Using conditional gene targeting, Merkwirth et al. (2008) restricted
expression of mouse Phb2 to mitochondria and identified processing of
the dynamin (see 602377)-like GTPase Opa1 (605290), an essential
component of the mitochondrial fusion machinery, as the central cellular
process controlled by prohibitins. Deletion of Phb2 led to selective
loss of long isoforms of Opa1, resulting in aberrant cristae
morphogenesis, impaired cellular proliferation, and resistance to
apoptosis. Expression of a long Opa1 isoform in Phb2-deficient cells
suppressed these defects, identifying impaired Opa1 processing as the
primary cellular defect in the absence of prohibitins. Merkwirth et al.
(2008) concluded that prohibitins are essential for formation of
mitochondrial cristae and suggested that cell proliferation is coupled
with mitochondrial morphogenesis.
*FIELD* RF
1. Christie, D. A.; Lemke, C. D.; Elias, I. M.; Chau, L. A.; Kirchhof,
M. G.; Li, B.; Ball, E. H.; Dunn, S. D.; Hatch, G. M.; Madrenas, J.
: Stomatin-like protein 2 binds cardiolipin and regulates mitochondrial
biogenesis and function. Molec. Cell. Biol. 31: 3845-3856, 2011.
2. Da Cruz, S.; Parone, P. A.; Gonzalo, P.; Bienvenut, W. V.; Tondera,
D.; Jourdain, A.; Quadroni, M.; Martinou, J.-C.: SLP-2 interacts
with prohibitins in the mitochondrial inner membrane and contributes
to their stability. Biochim. Biophys. Acta 1783: 904-911, 2008.
3. Hartz, P. A.: Personal Communication. Baltimore, Md. 2/20/2013.
4. Merkwirth, C.; Dargazanli, S.; Tatsuta, T.; Geimer, S.; Lower,
B.; Wunderlich, F. T.; von Kleist-Retzow, J.-C.; Waisman, A.; Westermann,
B.; Langer, T.: Prohibitins control cell proliferation and apoptosis
by regulating OPA1-dependent cristae morphogenesis in mitochondria. Genes
Dev. 22: 476-488, 2008.
5. Montano, M. M.; Ekena, K.; Delage-Mourroux, R.; Chang, W.; Martini,
P.; Katzenellenbogen, B. S.: An estrogen receptor-selective coregulator
that potentiates the effectiveness of antiestrogens and represses
the activity of estrogens. Proc. Nat. Acad. Sci. 96: 6947-6952,
1999.
6. Mussi, P.; Liao, L.; Park, S.-E.; Ciana, P.; Maggi, A.; Katzenellenbogen,
B. S.; Xu, J.; O'Malley, B. W.: Haploinsufficiency of the corepressor
of estrogen receptor activity (REA) enhances estrogen receptor function
in the mammary gland. Proc. Nat. Acad. Sci. 103: 16716-16721, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 02/20/2013
Patricia A. Hartz - updated: 3/21/2008
*FIELD* CD
Patricia A. Hartz: 1/16/2007
*FIELD* ED
mgross: 02/20/2013
mgross: 3/24/2008
terry: 3/21/2008
mgross: 1/16/2007