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FLASH GENE

Symbol

PHB

contributors: mct/npt - updated : 24-10-2017

HGNC name	prohibitin
HGNC id	8912

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	10.82 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002634 7 - 1826 NP_002625 - 272 - Schleicher (2008)

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel       highly Digestive liver       highly Lymphoid/Immune thymus       highly Reproductive female system uterus cervix   highly Skin/Tegument skin       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	binding domain having the potential to fold into a coiled-coil structure
	a PHB domain

conjugated

PhosphoP

HOMOLOGY

interspecies

homolog to murine Phb (99,63 pc)

Homologene

FAMILY

prohibitin family

CATEGORY

tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus,nucleoplasm
text	mainly localized to the inner mitochondrial membrane (Schleicher 2008)

basic FUNCTION	potential tumor suppressor regulating E2F1 function
	playing a role in the activation of the Ras-Raf signaling pathway and in modulating epithelial cell adhesion and migration
	required for growth suppression by estrogen antagonists
	having potential roles as a tumor suppressor, an anti-proliferative protein, a regulator of cell-cycle progression and in apoptosis
	regulating membrane protein function by binding sterols, perhaps by altering their local lipid environment (Ross 2008)
	important for mitochondrial function and prevents reactive oxygen species-induced senescence and thereby maintains the angiogenic capacity of endothelial cells (Schleicher 2008)
	having diverse functions, such as the regulation of apoptosis and the maintenance of mitochondrial morphology (Matsuda 2008)
	having a mitochondrial function that regulates the organization and maintenance of mitochondrial DNA (mtDNA)(Kasashima 2008)
	membrane protein that is essential for cell proliferation and development in higher eukaryotes (Osman 2009)

CELLULAR PROCESS	cell cycle, progression
	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

prohibitin-1 (PHB) and prohibitin-2 (PHB2), form large, multimeric ring complexes in the inner membrane of mitochondria (Osman 2009)

INTERACTION

DNA

RNA

small molecule

protein	PHB2
	binding to the Rb protein as well as E2F and this binding was necessary to suppress cell proliferation
	binding cholesterol
	interacting with TFAM (maintains the organization and copy number of the mtDNA through both TFAM-independent and -dependent pathways) (Kasashima 2008)
	PHB/PHB2 and the CD86 cytoplasmic domain cooperate to mediate CD86 signaling in a B cell through differential phosphorylation of distal signaling intermediates required to increase IGHG1
	SIGLEC9 bound to prohibitins PHB, PHB2, in a sialic acid-independent manner
	PHB can act as a signalling scaffold protein to assist in KDELR1, KDELR2-dependent Src activation
	PHB in spermatocytes regulates the expression of STAG3, a key component of the meiotic cohesin complex, via a non-canonical JAK/STAT pathway

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in breast cancer tumoral     --over   in invasive adenocarcinoma constitutional         silencing of PHB blocks the formation of functional blood vessels (Schleicher 2008) constitutional     --low   loss of PHB in spermatocytes resulted in complete male infertility, associated with not only meiotic pachytene arrest with accompanying apoptosis, but also apoptosis resulting from mitochondrial morphology and function impairment

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target	represent previously unrecognized therapeutic targets for regulating T cell activation, differentiation, viability, and function (Ross 2008)

ANIMAL & CELL MODELS