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FLASH GENE

Symbol

RHBDF2

contributors: mct - updated : 17-02-2016

HGNC name	rhomboid 5 homolog 2 (Drosophila)
HGNC id	20788

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	TOC tylosis with esophageal cancer
Location	17q25.1      Physical location : 74.466.974 - 74.497.509
Synonym name	iRhom2
	inactive rhomboid protein 2
	rhomboid veinlet-like 5
	rhomboid veinlet-like protein 6
Synonym symbol(s)	RHBDL5, RHBDL6, iRhom2

DNA

TYPE	functioning gene
STRUCTURE	30.53 kb     19 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_024599 19 - 3615 - 856 - 2012 22265016 NM_001005498 15 - 3453 - 827 - 2012 22265016

EXPRESSION

Type

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 Skin/Tegument skin         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining epidermis     Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

seven transmembrane domains

HOMOLOGY

Homologene

FAMILY

rhomboid family

CATEGORY

immunity/defense

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
text	strong localization to the cell membrane, but localization is mostly cytoplasmic in skin sections from patients with tylosis

basic FUNCTION	regulate rhomboid-dependent proteolysis (and thus EGF signaling) by targeting specific client proteins like EGF for proteosomal removal by ER-associated degradation (ERAD)
	critical for ADAM17 maturation and trafficking to the cell surface in hematopoietic cells
	regulator of innate immunity that may be an important target for modulating sepsis and pathogen defense
	binds ADAM17 and promotes its exit from the endoplasmic reticulum
	a proteolytically inactive member of the rhomboid family, required for TNF release
	role in growth-factor signaling in esophageal cancer will help to determine whether targeting this pathway in chemotherapy for this and other squamous cell carcinomas will be effective

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacted with ADAM17 and regulated TNF shedding
	serine intramembrane proteases linked with epidermal growth factor receptor (EGFR) signaling and mitochondrial remodeling
	RHBDF2 controls multiple aspects of ADAM17 biology, including stimulated shedding on the cell surface
	FRMD8 binds to RHBDF1, RHBDF2, enhancing the cell surface stability of RHBDF1, RHBDF2 and ADAM17, preventing their degradation in lysosome (
	FRMD8 binds to the cytoplasmic N-terminus of RHBDF1, RHBDF2 and is necessary to stabilise RHBDF1, RHBDF2 and ADAM17 at the cell surface

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

TOC

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   might be dysregulated in sporadic esophageal squamous cell carcinomas, in which case these tumors might be resistant to treatment with EGFR inhibitors

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive oesophagus developing chemotherapies targeted to RHBDF2-regulated pathways could be more effective in reducing the hyperproliferative and invasive aspects of esophageal cancers immunology inflammatory   may represent an attractive therapeutic target in autoimmune and inflammatory diseases

ANIMAL & CELL MODELS

	iRhom2-deficient mice failed to control the replication of Listeria monocytogenes