RBCC

Full text data of PHB

PHB [Confidence: high (present in two of the MS resources)]
Prohibitin

hRBCD IPI00017334
IPI00017334 Prohibitin Prohibitin inhibits DNA synthesis. It has a role in regulating proliferation, as yet it is unclear if the protein or the mRNA exhibits this effect soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight

UniProt P35232
ID PHB_HUMAN Reviewed; 272 AA.
AC P35232; Q4VBQ0;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1994, sequence version 1.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Prohibitin;
GN Name=PHB;
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 [MRNA], AND VARIANTS ALA-88 AND HIS-105.
RC TISSUE=Mammary gland;
RX PubMed=1540973;
RA Sato T., Saito H., Swensen J., Olifant A., Wood C., Danner D.,
RA Sakamoto T., Takita K., Kasumi F., Miki Y., Skolnick M., Nakamura Y.;
RT "The human prohibitin gene located on chromosome 17q21 is mutated in
RT sporadic breast cancer.";
RL Cancer Res. 52:1643-1646(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8244394; DOI=10.1006/geno.1993.1402;
RA Sato T., Sakamoto T., Takita K., Saito H., Okui K., Nakamura Y.;
RT "The human prohibitin (PHB) gene family and its somatic mutations in
RT human tumors.";
RL Genomics 17:762-764(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Muscle;
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 [5]
RP PROTEIN SEQUENCE OF 5-11; 84-93; 106-128; 134-143; 178-186 AND
RP 209-219, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 75-83; 94-117; 134-143; 158-177; 220-253 AND
RP 256-272, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP FUNCTION, INTERACTION WITH PHB2, 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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-202, 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 [9]
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 [10]
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).
CC -!- FUNCTION: Prohibitin inhibits DNA synthesis. It has a role in
CC regulating proliferation. As yet it is unclear if the protein or
CC the mRNA exhibits this effect. May play a role in regulating
CC mitochondrial respiration activity and in aging.
CC -!- SUBUNIT: Interacts with PHB2. Interacts with STOML2.
CC -!- INTERACTION:
CC Q496Y0:LONRF3; NbExp=2; IntAct=EBI-354213, EBI-2690768;
CC Q13309-2:SKP2; NbExp=2; IntAct=EBI-354213, EBI-7791408;
CC O14980:XPO1; NbExp=2; IntAct=EBI-354213, EBI-355867;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane (By
CC similarity).
CC -!- TISSUE SPECIFICITY: Widely expressed in different tissues.
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 with 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; S85655; AAB21614.1; -; mRNA.
DR EMBL; L14272; AAO18340.1; -; Genomic_DNA.
DR EMBL; BT007411; AAP36079.1; -; mRNA.
DR EMBL; BC013401; AAH13401.1; -; mRNA.
DR EMBL; BC095460; AAH95460.1; -; mRNA.
DR PIR; I52690; I52690.
DR RefSeq; NP_001268425.1; NM_001281496.1.
DR RefSeq; NP_001268644.1; NM_001281715.1.
DR RefSeq; NP_002625.1; NM_002634.3.
DR UniGene; Hs.514303; -.
DR PDB; 1LU7; Model; -; A=1-272.
DR PDBsum; 1LU7; -.
DR ProteinModelPortal; P35232; -.
DR SMR; P35232; 61-194.
DR DIP; DIP-24248N; -.
DR IntAct; P35232; 53.
DR MINT; MINT-1158239; -.
DR STRING; 9606.ENSP00000300408; -.
DR PhosphoSite; P35232; -.
DR DMDM; 464371; -.
DR DOSAC-COBS-2DPAGE; P35232; -.
DR OGP; P35232; -.
DR REPRODUCTION-2DPAGE; IPI00017334; -.
DR REPRODUCTION-2DPAGE; P35232; -.
DR SWISS-2DPAGE; P35232; -.
DR UCD-2DPAGE; P35232; -.
DR PaxDb; P35232; -.
DR PeptideAtlas; P35232; -.
DR PRIDE; P35232; -.
DR DNASU; 5245; -.
DR Ensembl; ENST00000300408; ENSP00000300408; ENSG00000167085.
DR GeneID; 5245; -.
DR KEGG; hsa:5245; -.
DR UCSC; uc002iox.1; human.
DR CTD; 5245; -.
DR GeneCards; GC17M047481; -.
DR HGNC; HGNC:8912; PHB.
DR HPA; HPA003280; -.
DR MIM; 176705; gene.
DR neXtProt; NX_P35232; -.
DR PharmGKB; PA33251; -.
DR eggNOG; COG0330; -.
DR HOGENOM; HOG000205692; -.
DR HOVERGEN; HBG004457; -.
DR InParanoid; P35232; -.
DR KO; K17080; -.
DR OMA; IIFDVRS; -.
DR OrthoDB; EOG7V4B04; -.
DR PhylomeDB; P35232; -.
DR GeneWiki; Prohibitin; -.
DR GenomeRNAi; 5245; -.
DR NextBio; 20266; -.
DR PRO; PR:P35232; -.
DR ArrayExpress; P35232; -.
DR Bgee; P35232; -.
DR CleanEx; HS_PHB; -.
DR Genevestigator; P35232; -.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:HGNC.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0000981; F:sequence-specific DNA binding RNA polymerase II transcription factor activity; IEA:Ensembl.
DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
DR GO; GO:0071354; P:cellular response to interleukin-6; IDA:BHF-UCL.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0016575; P:histone deacetylation; IDA:UniProtKB.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:BHF-UCL.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
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 3D-structure; Acetylation; Coiled coil; Complete proteome;
KW Direct protein sequencing; DNA synthesis; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Polymorphism;
KW Proto-oncogene; Reference proteome.
FT CHAIN 1 272 Prohibitin.
FT /FTId=PRO_0000213878.
FT COILED 177 211 Potential.
FT MOD_RES 128 128 N6-acetyllysine (By similarity).
FT MOD_RES 186 186 N6-acetyllysine (By similarity).
FT MOD_RES 202 202 N6-acetyllysine.
FT MOD_RES 249 249 Phosphotyrosine (By similarity).
FT VARIANT 88 88 V -> A (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_006479.
FT VARIANT 105 105 R -> H (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_006480.
FT STRAND 14 18
FT TURN 19 21
FT STRAND 22 27
FT STRAND 29 33
FT STRAND 50 52
FT STRAND 54 60
FT STRAND 65 67
FT TURN 87 89
FT HELIX 99 110
FT HELIX 115 118
FT HELIX 123 144
FT HELIX 146 155
FT STRAND 157 159
FT STRAND 165 167
FT HELIX 172 191
FT HELIX 194 211
FT HELIX 212 214
FT TURN 217 222
FT HELIX 224 240
FT TURN 242 246
FT HELIX 247 252
SQ SEQUENCE 272 AA; 29804 MW; 915494273E342C76 CRC64;
MAAKVFESIG KFGLALAVAG GVVNSALYNV DAGHRAVIFD RFRGVQDIVV GEGTHFLIPW
VQKPIIFDCR SRPRNVPVIT GSKDLQNVNI TLRILFRPVA SQLPRIFTSI GEDYDERVLP
SITTEILKSV VARFDAGELI TQRELVSRQV SDDLTERAAT FGLILDDVSL THLTFGKEFT
EAVEAKQVAQ QEAERARFVV EKAEQQKKAA IISAEGDSKA AELIANSLAT AGDGLIELRK
LEAAEDIAYQ LSRSRNITYL PAGQSVLLQL PQ
//

MIM 176705
*RECORD*
*FIELD* NO
176705
*FIELD* TI
*176705 PROHIBITIN; PHB
;;PHB1
*FIELD* TX

DESCRIPTION

Prohibitin is a 30-kD intracellular, antiproliferative protein (White et
read moreal., 1991).

MAPPING

White et al. (1991) mapped the PHB gene to chromosome 17 by analysis of
human-mouse somatic cell hybrid cell lines using a genomic fragment of
human prohibitin DNA isolated from a library using the rat prohibitin
cDNA clone. By a study of cell lines containing portions of human
chromosome 17, they determined that the PHB gene was located in the
17q11.2-q23 region. By in situ hybridization, they localized the gene to
17q21. Sato et al. (1992) isolated the human homolog of the rat
prohibitin gene and mapped it to 17q12-q21 by in situ hybridization.

GENE FAMILY

Sato et al. (1993) showed that the human prohibitin gene family consists
of 1 functional PHB gene on 17q21 and 4 processed pseudogenes, each on a
different chromosome: PHBP1 on 6q25, PHBP2 on 11p11.2, PHBP3 on 1p31.3,
and PHBP4 on 2q21.

GENE FUNCTION

Proliferation of tumor cells depends on new blood vessel formation
(angiogenesis) that accompanies malignant progression. Anticancer
therapies using angiogenesis inhibitors or cytotoxic agents targeted to
the vasculature of tumors have been evaluated in clinical trials.
Although white fat is a nonmalignant tissue, it has the capability to
quickly proliferate and expand. Furthermore, it is highly vascularized.
Rupnick et al. (2002) showed that nonspecific angiogenesis inhibitors
can prevent the development of obesity of mice. Kolonin et al. (2004)
used in vivo phage display to isolate a peptide motif (amino sequence
CKGGRAKDC) that homes to white fat vasculature. They showed that the
CKGGRAKDC peptide associates with prohibitin, a multifunctional membrane
protein, and thus established prohibitin as a vascular marker of adipose
tissue. Targeting a proapoptotic peptide to prohibitin in the adipose
vasculature caused ablation of white fat in mice. Resorption of
established white adipose tissue and normalization of metabolism
resulted in rapid obesity reversal without detectable adverse effects.
Because prohibitin is also expressed in blood vessels of human white
fat, the work suggested the development of targeted drugs for treatment
of obese patients.

Prohibitins form a ring-like, high-molecular-mass complex at the inner
membrane of mitochondria. Artal-Sanz and Tavernarakis (2009)
demonstrated that the mitochondrial prohibitin complex promotes
longevity by modulating mitochondrial function and fat metabolism in C.
elegans. They found that prohibitin deficiency shortened the life span
of otherwise wildtype animals. Knockdown of prohibitin promoted
longevity in diapause mutants or under conditions of dietary
restriction. In addition, prohibitin deficiency extended the life span
of animals with compromised mitochondrial functions or fat metabolism.
Depletion of prohibitin influenced ATP levels, animal fat content, and
mitochondrial proliferation in a genetic-background- and age-specific
manner. Artal-Sanz and Tavernarakis (2009) concluded that their findings
revealed a novel mechanism regulating mitochondrial biogenesis and
function, with opposing effects on energy metabolism, fat utilization,
and aging in C. elegans.

By gel filtration, mass spectrometry, coimmunoprecipitation, and Western
blot analysis of HeLa cells, Da Cruz et al. (2008) showed that
prohibitin-1 and prohibitin-2 (PHB2; 610704) 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.

MOLECULAR GENETICS

By DNA sequence analysis of 2 exons in the PHB gene in 23 sporadic
breast cancers that showed loss of heterozygosity on 17q or developed in
patients 35 years old or younger, Sato et al. (1993) identified 4 cases
of somatic mutation: 2 of these were missense mutations, 1 showed a 2-bp
deletion resulting in truncation of the gene product due to frameshift,
and the fourth was a splice site mutation. Sato et al. (1993) found no
mutations in the PHB gene in other forms of tumors, namely, those of
ovary, liver, and lung.

In breast cancer cell lines, Jupe et al. (1996) identified a point
mutation at position 729 in the prohibitin 3-prime untranslated region
(base 1630 in the full-length transcript). The change was identified as
a single-nucleotide polymorphism (SNP), 729C-T (176705.0001), in which
the variant T allele lacked the antiproliferative activity of the more
common functional C allele. The observation led to the hypothesis that
women carrying the prohibitin T allele have increased susceptibility to
breast cancer. Jupe et al. (2001) found an association between the T
allele and breast cancer in women who reported a first-degree relative
with the disease, and an even stronger association in a subset of women
diagnosed at or before age 50 years. They suggested that prohibitin
genotyping has value in assessing risk of breast cancer in women aged 50
years or younger with at least 1 first-degree relative with the disease.

*FIELD* AV
.0001
BREAST CANCER, SUSCEPTIBILITY TO
PHB, 729C-T, 3-PRIME UTR

In breast cancer cell lines, Jupe et al. (1996) identified a point
mutation at position 729 in the prohibitin 3-prime untranslated region
(base 1630 in the full-length transcript). The change was identified as
a 729C-T transition in which the variant T allele lacked the
antiproliferative activity of the more common functional C allele. The
observation led to the hypothesis that women carrying the prohibitin T
allele have increased susceptibility to breast cancer.

Jupe et al. (2001) performed a case-control study of prohibitin genotype
in 205 women with breast cancer and 1,046 healthy controls. The results
showed an association between the T allele and breast cancer in women
who reported a first-degree relative with the disease (odds ratio 2.5, p
= 0.005). An even stronger association was found in a subset of women
diagnosed at or before age 50 years (4.8, p = 0.003). Jupe et al. (2001)
suggested that prohibitin genotyping has value in assessing risk of
breast cancer in women aged 50 years or younger with at least 1
first-degree relative with the disease.

*FIELD* RF
1. Artal-Sanz, M.; Tavernarakis, N.: Prohibitin couples diapause
signalling to mitochondrial metabolism during ageing in C. elegans. Nature 461:
793-797, 2009.

2. 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.

3. 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.

4. Jupe, E. R.; Badgett, A. A.; Neas, B. R.; Craft, M. A.; Mitchell,
D. S.; Resta, R.; Mulvihill, J. J.; Aston, C. E.; Thompson, L. F.
: Single nucleotide polymorphism in prohibitin 3-prime untranslated
region and breast-cancer susceptibility. Lancet 357: 1588-1589,
2001.

5. Jupe, E. R.; Liu, X. T.; Kiehlbauch, J. L.; McClung, J. K.; Dell'Orco,
R. T.: Prohibitin in breast cancer cell lines: loss of antiproliferative
activity is linked to 3-prime untranslated region mutations. Cell
Growth Diff. 7: 871-878, 1996.

6. Kolonin, M. G.; Saha, P. K.; Chan, L.; Pasqualini, R.; Arap, W.
: Reversal of obesity by targeted ablation of adipose tissue. Nature
Med. 10: 625-632, 2004.

7. Rupnick, M. A.; Panigrahy, D.; Zhang, C.-Y.; Dallabrida, S. M.;
Lowell, B. B.; Langer, R.; Folkman, M. J.: Adipose tissue mass can
be regulated through the vasculature. Proc. Nat. Acad. Sci. 99:
10730-10735, 2002.

8. Sato, T.; Saito, H.; Swensen, J.; Olifant, A.; Wood, C.; Danner,
D.; Sakamoto, T.; Takita, K.; Kasumi, F.; Miki, Y.; Skolnick, M.;
Nakamura, Y.: The human prohibitin gene located on chromosome 17q21
is mutated in sporadic breast cancer. Cancer Res. 52: 1643-1646,
1992.

9. Sato, T.; Sakamoto, T.; Takita, K.-I.; Saito, H.; Okui, K.; Nakamura,
Y.: The human prohibitin (PHB) gene family and its somatic mutations
in human tumors. Genomics 17: 762-764, 1993.

10. White, J. J.; Ledbetter, D. H.; Eddy, R. L., Jr.; Shows, T. B.;
Stewart, D. A.; Nuell, M. J.; Friedman, V.; Wood, C. M.; Owens, G.
A.; McClung, J. K.; Danner, D. B.; Morton, C. C.: Assignment of the
human prohibitin gene (PHB) to chromosome 17 and identification of
a DNA polymorphism. Genomics 11: 228-230, 1991. Note: Erratum: Genomics
11: 732 only, 1991.

*FIELD* CN
Patricia A. Hartz - updated: 2/20/2013
Ada Hamosh - updated: 11/5/2009
Victor A. McKusick - updated: 5/13/2004
Victor A. McKusick - updated: 5/31/2002

*FIELD* CD
Victor A. McKusick: 8/6/1991

*FIELD* ED
mgross: 02/20/2013
terry: 2/20/2013
carol: 9/24/2012
carol: 3/19/2010
wwang: 1/21/2010
alopez: 11/9/2009
terry: 11/5/2009
mgross: 1/16/2007
terry: 11/2/2004
alopez: 6/28/2004
terry: 5/20/2004
alopez: 5/13/2004
terry: 5/13/2004
terry: 1/2/2003
alopez: 6/18/2002
terry: 5/31/2002
mimadm: 2/25/1995
carol: 9/21/1993
carol: 7/13/1993
carol: 5/28/1993
carol: 5/27/1993
supermim: 3/16/1992

RBCC Red Blood Cell Collection

Full text data of PHB