PHB2_RAT
ID PHB2_RAT Reviewed; 299 AA.
AC Q5XIH7; P70629; P70630;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Prohibitin-2 {ECO:0000305};
DE AltName: Full=B-cell receptor-associated protein BAP37;
DE Short=BAP-37;
GN Name=Phb2 {ECO:0000312|RGD:620203};
GN Synonyms=Bcap37 {ECO:0000312|EMBL:AAH83705.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [2] {ECO:0000305, ECO:0000312|EMBL:AAB18746.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-110 AND 274-299.
RC STRAIN=Wistar Kyoto {ECO:0000312|EMBL:AAB18746.1};
RC TISSUE=Aortic smooth muscle {ECO:0000312|EMBL:AAB18746.1};
RX PubMed=10559001; DOI=10.1161/01.atv.19.11.2600;
RA Adams L.D., Lemire J.M., Schwartz S.M.;
RT "A systematic analysis of 40 random genes in cultured vascular smooth
RT muscle subtypes reveals a heterogeneity of gene expression and identifies
RT the tight junction gene zonula occludens 2 as a marker of epithelioid 'pup'
RT smooth muscle cells and a participant in carotid neointimal formation.";
RL Arterioscler. Thromb. Vasc. Biol. 19:2600-2608(1999).
RN [3] {ECO:0000312|EMBL:AAH83705.1}
RP PROTEIN SEQUENCE OF 148-157, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [4] {ECO:0000305}
RP INTERACTION WITH PHB, AND SUBCELLULAR LOCATION.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:0000250|UniProtKB:O35129}.
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. The prohibitin complex, with DNAJC19, regulates
CC cardiolipin remodeling and the protein turnover of OMA1 in a
CC cardiolipin-binding manner.Also regulates cytochrome-c oxidase assembly
CC (COX) and mitochondrial respiration. Binding to sphingoid 1-phosphate
CC (SPP) modulates its regulator activity. Has a key role of mitophagy
CC receptor involved in targeting mitochondria for autophagic degradation.
CC Involved in mitochondrial-mediated antiviral innate immunity, activates
CC DDX58/RIG-I-mediated signal transduction and production of IFNB1 and
CC pro-inflammatory cytokine IL6. {ECO:0000250|UniProtKB:O35129}.
CC -!- FUNCTION: In the nucleus, serves as transcriptional co-regulator. Acts
CC as a mediator of transcriptional repression by nuclear hormone
CC receptors via recruitment of histone deacetylases. Functions as an
CC 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. {ECO:0000250|UniProtKB:O35129}.
CC -!- FUNCTION: In the plasma membrane, is involved in IGFBP6-induced cell
CC migration (By similarity). 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:0000250|UniProtKB:Q99623}.
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:11302691). Interacts with
CC ESR1, HDAC1 and HDAC5 (By similarity). Interacts with ZNF703. Interacts
CC with STOML2. Interacts with ARFGEF3 (By similarity). Interacts with
CC SPHK2. Interacts with COX4I1; the interaction associates PHB2 with COX
CC (By similarity). Interacts with MAP1LC3B (membrane-bound form LC3-II);
CC the interaction is direct and upon mitochondrial depolarization and
CC proteasome-dependent outer membrane rupture. Interacts with IGFBP6 (via
CC C-terminal domain). Interacts with CLPB (By similarity). Interacts with
CC CD86 (via cytoplasmic domain); the interactions increases after priming
CC with CD40. Interacts with AFG3L2. Interacts with DNAJC19 (By
CC similarity). {ECO:0000250|UniProtKB:O35129,
CC ECO:0000250|UniProtKB:Q99623, ECO:0000269|PubMed:11302691}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:11302691}. Cytoplasm {ECO:0000269|PubMed:11302691}.
CC Nucleus {ECO:0000269|PubMed:11302691}. Cell membrane
CC {ECO:0000250|UniProtKB:Q99623}.
CC -!- DOMAIN: LC3-interaction region (LIR) is required for interaction with
CC MAP1LC3B/LC3-II and for Parkin-mediated mitophagy.
CC {ECO:0000250|UniProtKB:Q99623}.
CC -!- PTM: Phosphorylated. Tyrosine phosphorylation is indirectly stimulated
CC by IGFBP6. {ECO:0000250|UniProtKB:Q99623}.
CC -!- SIMILARITY: Belongs to the prohibitin family. {ECO:0000255}.
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DR EMBL; BC083705; AAH83705.1; -; mRNA.
DR EMBL; U75391; AAB18746.1; -; mRNA.
DR EMBL; U75392; AAB18747.1; -; mRNA.
DR RefSeq; NP_001013053.1; NM_001013035.1.
DR AlphaFoldDB; Q5XIH7; -.
DR SMR; Q5XIH7; -.
DR BioGRID; 250411; 9.
DR IntAct; Q5XIH7; 7.
DR MINT; Q5XIH7; -.
DR STRING; 10116.ENSRNOP00000017472; -.
DR CarbonylDB; Q5XIH7; -.
DR iPTMnet; Q5XIH7; -.
DR PhosphoSitePlus; Q5XIH7; -.
DR jPOST; Q5XIH7; -.
DR PaxDb; Q5XIH7; -.
DR PRIDE; Q5XIH7; -.
DR Ensembl; ENSRNOT00000091464; ENSRNOP00000075668; ENSRNOG00000012999.
DR GeneID; 114766; -.
DR KEGG; rno:114766; -.
DR UCSC; RGD:620203; rat.
DR CTD; 11331; -.
DR RGD; 620203; Phb2.
DR eggNOG; KOG3090; Eukaryota.
DR GeneTree; ENSGT00950000183070; -.
DR InParanoid; Q5XIH7; -.
DR OMA; IKYTRLG; -.
DR OrthoDB; 1089994at2759; -.
DR PhylomeDB; Q5XIH7; -.
DR TreeFam; TF354230; -.
DR Reactome; R-RNO-8949664; Processing of SMDT1.
DR PRO; PR:Q5XIH7; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000012999; Expressed in heart and 18 other tissues.
DR ExpressionAtlas; Q5XIH7; baseline and differential.
DR Genevisible; Q5XIH7; RN.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0098800; C:inner mitochondrial membrane protein complex; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:RGD.
DR GO; GO:0035632; C:mitochondrial prohibitin complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0048786; C:presynaptic active zone; IDA:SynGO.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0033218; F:amide binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0046625; F:sphingolipid binding; ISS: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; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEP:RGD.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0060749; P:mammary gland alveolus development; ISO:RGD.
DR GO; GO:0060744; P:mammary gland branching involved in thelarche; ISO:RGD.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0000423; P:mitophagy; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISO:RGD.
DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0031536; P:positive regulation of exit from mitosis; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; ISO:RGD.
DR GO; GO:1900208; P:regulation of cardiolipin metabolic process; ISS:UniProtKB.
DR GO; GO:1904959; P:regulation of cytochrome-c oxidase activity; ISS:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEP:RGD.
DR GO; GO:0039529; P:RIG-I signaling pathway; ISO:RGD.
DR GO; GO:0007062; P:sister chromatid cohesion; ISO:RGD.
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 Acetylation; Cell membrane; Coiled coil; Cytoplasm;
KW Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q99623"
FT CHAIN 2..299
FT /note="Prohibitin-2"
FT /id="PRO_0000213886"
FT REGION 19..49
FT /note="Necessary for transcriptional repression"
FT /evidence="ECO:0000250|UniProtKB:Q99623"
FT REGION 150..174
FT /note="Necessary for transcriptional repression"
FT /evidence="ECO:0000250|UniProtKB:Q99623"
FT COILED 190..238
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q99623"
FT MOD_RES 128
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q99623"
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:22673903"
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:0000250|UniProtKB:Q99623"
FT MOD_RES 262
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35129"
FT CONFLICT 87
FT /note="P -> T (in Ref. 2; AAB18746)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="V -> F (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 287..288
FT /note="FT -> LI (in Ref. 2; AAB18747)"
FT /evidence="ECO:0000305"
FT CONFLICT 294
FT /note="L -> F (in Ref. 2; AAB18747)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 299 AA; 33312 MW; E7699DDD31FCCB69 CRC64;
MAQNLKDLAG RLPSGPRGMG 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
