PHB1_RAT
ID PHB1_RAT Reviewed; 272 AA.
AC P67779; P24142; Q4V8M6;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Prohibitin 1;
GN Name=Phb1 {ECO:0000312|RGD:3322}; Synonyms=Phb;
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 [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=1996099; DOI=10.1128/mcb.11.3.1372-1381.1991;
RA Nuell M.J., Stewart D.A., Walker L., Friedman V., Wood C.M., Owens G.A.,
RA Smith J.R., Schneider E.L., Dell'Orco R., Lumpkin C.K., Danner D.B.,
RA McClung J.K.;
RT "Prohibitin, an evolutionarily conserved intracellular protein that blocks
RT DNA synthesis in normal fibroblasts and HeLa cells.";
RL Mol. Cell. Biol. 11:1372-1381(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart, and Placenta;
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 [3]
RP PROTEIN SEQUENCE OF 12-35; 94-105; 158-177 AND 220-253, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [4]
RP INTERACTION WITH PHB2, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
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 IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RX PubMed=19423663; DOI=10.1530/rep-09-0052;
RA Khan S.A., Suryawanshi A.R., Ranpura S.A., Jadhav S.V., Khole V.V.;
RT "Identification of novel immunodominant epididymal sperm proteins using
RT combinatorial approach.";
RL Reproduction 138:81-93(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-249, 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).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY PGF.
RX PubMed=32173312; DOI=10.1016/j.lfs.2020.117548;
RA Cao Y.Y., Ba H.X., Li Y., Tang S.Y., Luo Z.Q., Li X.H.;
RT "Regulatory effects of Prohibitin 1 on proliferation and apoptosis of
RT pulmonary arterial smooth muscle cells. in monocrotaline-induced PAH
RT rats.";
RL Life Sci. 250:117548-117548(2020).
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 in the
CC nucleus. Plays a role in adipose tissue and glucose homeostasis in a
CC sex-specific manner (By similarity) (PubMed:1996099). Contributes to
CC pulmonary vascular remodeling by accelerating proliferation of
CC pulmonary arterial smooth muscle cells (PubMed:32173312).
CC {ECO:0000250|UniProtKB:P67778, ECO:0000269|PubMed:1996099,
CC ECO:0000269|PubMed:32173312}.
CC -!- FUNCTION: In the mitochondria, together with PHB2, 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. Regulates mitochondrial respiration
CC activity playing a role in cellular aging. The prohibitin complex plays
CC a role of mitophagy receptor involved in targeting mitochondria for
CC autophagic degradation (By similarity). Involved in mitochondrial-
CC mediated antiviral innate immunity, activates DDX58/RIG-I-mediated
CC signal transduction and production of IFNB1 and pro-inflammatory
CC cytokine IL6 (By similarity). {ECO:0000250|UniProtKB:P35232,
CC ECO:0000250|UniProtKB:P67778}.
CC -!- FUNCTION: In the nucleus, acts as a transcription coregulator, enhances
CC promoter binding by TP53, a transcription factor it activates, but
CC reduces the promoter binding by E2F1, a transcription factor it
CC represses. Interacts with STAT3 to affect IL17 secretion in T-helper
CC Th17 cells. {ECO:0000250|UniProtKB:P35232}.
CC -!- FUNCTION: In the plasma membrane, 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.
CC {ECO:0000250|UniProtKB:P67778}.
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. Interacts with STOML2. Interacts
CC with MAP1LC3B (membrane-bound form LC3-II); the interaction requires
CC PHB2 and takes place upon Parkin-mediated mitochondrial damage.
CC Interacts with STAT3 (unphosphorylated or phosphorylated at 'Ser-727').
CC Interacts with CLPB (By similarity). Interacts with CD86 (via
CC cytoplasmic domain); the interactions increases after priming with CD40
CC (By similarity). {ECO:0000250|UniProtKB:P35232,
CC ECO:0000250|UniProtKB:P67778}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:11302691}. Nucleus {ECO:0000250|UniProtKB:P35232}.
CC Cytoplasm {ECO:0000250|UniProtKB:P35232}. Cell membrane
CC {ECO:0000250|UniProtKB:P35232}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, intestine, kidney,
CC liver, skeletal muscle. Highest levels in heart, liver, kidney and
CC intestine. Also expressed in flagella of epididymal sperm. Expressed in
CC lung tissue and pulmonary artery smooth muscle (at protein level)
CC (PubMed:32173312). {ECO:0000269|PubMed:19423663,
CC ECO:0000269|PubMed:1996099, ECO:0000269|PubMed:32173312}.
CC -!- DEVELOPMENTAL STAGE: Throughout gestation, highly expressed in brown
CC fat, heart, liver, developing renal tubules and neurons, and detected
CC at lower levels in tissues such as lung and exocrine pancreas.
CC {ECO:0000269|PubMed:11302691}.
CC -!- INDUCTION: Induced by PDGF. {ECO:0000269|PubMed:32173312}.
CC -!- SIMILARITY: Belongs to the prohibitin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M61219; AAA63500.1; -; mRNA.
DR EMBL; BC072518; AAH72518.1; -; mRNA.
DR EMBL; BC097304; AAH97304.1; -; mRNA.
DR PIR; A39682; A39682.
DR RefSeq; NP_114039.1; NM_031851.2.
DR AlphaFoldDB; P67779; -.
DR SMR; P67779; -.
DR BioGRID; 247383; 6.
DR IntAct; P67779; 4.
DR MINT; P67779; -.
DR STRING; 10116.ENSRNOP00000066502; -.
DR iPTMnet; P67779; -.
DR PhosphoSitePlus; P67779; -.
DR World-2DPAGE; 0004:P67779; -.
DR jPOST; P67779; -.
DR PaxDb; P67779; -.
DR PRIDE; P67779; -.
DR DNASU; 25344; -.
DR Ensembl; ENSRNOT00000075733; ENSRNOP00000066502; ENSRNOG00000046799.
DR GeneID; 25344; -.
DR KEGG; rno:25344; -.
DR CTD; 5245; -.
DR RGD; 3322; Phb.
DR eggNOG; KOG3083; Eukaryota.
DR GeneTree; ENSGT00950000183070; -.
DR HOGENOM; CLU_047969_0_0_1; -.
DR InParanoid; P67779; -.
DR OMA; QKMQFVL; -.
DR OrthoDB; 1089994at2759; -.
DR PhylomeDB; P67779; -.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-8949664; Processing of SMDT1.
DR PRO; PR:P67779; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000046799; Expressed in heart and 20 other tissues.
DR Genevisible; P67779; RN.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0031315; C:extrinsic component of mitochondrial outer membrane; IDA:RGD.
DR GO; GO:0098891; C:extrinsic component of presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0030061; C:mitochondrial crista; IDA:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:RGD.
DR GO; GO:0035632; C:mitochondrial prohibitin complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; ISO:RGD.
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:0001850; F:complement component C3a binding; ISO:RGD.
DR GO; GO:0001851; F:complement component C3b binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase 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:0031871; F:proteinase activated receptor binding; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
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:0031100; P:animal organ regeneration; IEP:RGD.
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:0071354; P:cellular response to interleukin-6; ISO:RGD.
DR GO; GO:0071897; P:DNA biosynthetic process; ISO:RGD.
DR GO; GO:0016575; P:histone deacetylation; ISO:RGD.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0044830; P:modulation by host of viral RNA genome replication; ISO:RGD.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; ISO:RGD.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0001552; P:ovarian follicle atresia; IEP:RGD.
DR GO; GO:0001541; P:ovarian follicle development; IEP:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:RGD.
DR GO; GO:0045917; P:positive regulation of complement activation; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:UniProtKB.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0039529; P:RIG-I signaling pathway; ISO:RGD.
DR GO; GO:0072538; P:T-helper 17 type immune response; ISS:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; 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; DNA synthesis; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P35232"
FT CHAIN 2..272
FT /note="Prohibitin 1"
FT /id="PRO_0000213880"
FT COILED 177..211
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P35232"
FT MOD_RES 91
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35232"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P67778"
FT MOD_RES 186
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P67778"
FT MOD_RES 202
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35232"
FT MOD_RES 202
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P67778"
FT MOD_RES 249
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 272 AA; 29820 MW; 6B26073E169C2FFC CRC64;
MAAKVFESIG KFGLALAVAG GVVNSALYNV DAGHRAVIFD RFRGVQDIVV GEGTHFLIPW
VQKPIIFDCR SRPRNVPVIT GSKDLQNVNI TLRILFRPVA SQLPRIYTSI GEDYDERVLP
SITTEILKSV VARFDAGELI TQRELVSRQV SDDLTERAAT FGLILDDVSL THLTFGKEFT
EAVEAKQVAQ QEAERARFVV EKAEQQKKAA IISAEGDSKA AELIANSLAT AGDGLIELRK
LEAAEDIAYQ LSRSRNITYL PAGQSVLLQL PQ
