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FLASH GENE

Symbol

ITGB4

contributors: mct - updated : 05-11-2013

HGNC name	integrin, beta 4
HGNC id	6158

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	36.38 kb     40 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	five alternatively spliced (mutation at branch point), expressed in tissu specific, unknown function (Chavanas)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000213 40 - 5925 NP_000204 202.1 1822 - 2006 16713569 also called ITGB4C a 27 amino acids signal peptide (2.7 kDa) a 40 exons variant containing exon 2a (longer than 2b) lacking exon 35 encoding for the longest product NM_001005619 39 - 5695 NP_001005619 201.7 1805 - 2006 16713569 also called ITGB4B a 27 amino acids signal peptide (2.7 kDa) a 39 exons variant containing exon 2b (shorter than 2a) lacking exons 1 & 33 NM_001005731 39 - 5715 NP_001005731 195 1752 - 2006 16713569 also called ITGB4A a 27 amino acids signal peptide (2.7 kDa) a 39 exons variant containing exon 2a (longer than 2b) lacking exons 33 & 35 variant 4 - - - isoform 4 - 1745 - - also called ITGB4D variant 5 - - - isoform 5 - 964 - - also called ITGB4E

EXPRESSION

Type

widely

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 artery     highly Homo sapiens Digestive intestine large intestine colon   highly Nervous brain         Homo sapiens Reproductive female system ovary     highly   female system breast mammary gland   highly   female system uterus cervix   moderately   female system placenta     moderately   male system prostate     moderately Respiratory lung       moderately   respiratory tract larynx     highly Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective         Epithelial barrier lining retinal pigment epithelium (RPE)   lowly Nervous       highly Homo sapiens skin tegument dermis

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens Skin/Tegument keratinocyte

cell lineage
cell lines	Schwannomas
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a 27 AAs signal peptide (2.7 kDa)
	a globular domain
	a stalk region with four EGF-like repeat domains each with eight cysteine residues
	a single transmembrane (1TM) segment
	a cytoplasmic tail, highly homolog to the EGF-calcium binding motif
	a very large cytoplasmic domain, with three serine residues that play a critical role in the regulation of hemidesmosomes disassembly

mono polymer

heteromer , dimer

isoforms

Precursor

a 1795 amino acids mature peptide (199.4 kDa)

HOMOLOGY

interspecies	homolog to rattus Itgb4 (87.80 pc)
	homolog to murine Itgb4 (88.78 pc)

Homologene

FAMILY

integrin Bêta chain family

CATEGORY

adhesion , receptor

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	cell surface adhesion receptor mediating cell-adhesion to extra cellular matrix or to other cells, through hetero dimerization and connecting to the cytoskeleton and various signaling molecules within cells
	promotes epidermal growth and wound healing through a previously unrecognized effect on nuclear translocation of NF-kappaB and mitogen-activated protein kinases
	important role of ITGB4 phosphorylation on residues Ser-1356 and Ser-1364 in the formation and/or stability of hemidesmosomes
	promotes carcinoma invasion through its ability to promote directed migration and polarization of carcinoma cells
	receptor for laminins that promotes carcinoma invasion through its ability to regulate key signaling pathways and cytoskeletal dynamics
	play an important role in matrix remodeling and invasion
	is a master regulator of transcription and translation of other integrin subunits and underscore its pivotal role in wound healing and cancer
	hemidesmosome component, that attach epithelia to basal lamina and disassemble during migration and carcinoma invasion
	endothelial ITGB4 is predominantly expressed in arterioles, where it promotes vascular remodeling in the hypoxic brain

CELLULAR PROCESS

cell communication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

dimerizing with ITGA6, laminin receptor, also constituent of hemi-desmosomes, beta 4 receptor of laminins

INTERACTION

DNA

RNA

small molecule

protein	ITGA6, laminin receptor
	interacting with ARRDC3 (binds ITGB4 after ubiquitination, and seems likely to have a role in targeting ITGB4 for degradation)
	ITGB4 associates with MMP9 and its ectodomain is a target for cleavage by MMP9
	SPARC is an effector of ITGB4-mediated invasion
	ITGB4 has the ability to regulate the expression of specific miRNAs and that such miRNAs can influence ITGB4-mediated migration and invasion
	calcium/calcineurin pathway promotes hemidesmosome stability through inhibition of ITGB4 phosphorylation
	ITGB4 and SRC activation is important early signaling events to lead MTOR activation and cap-dependent translation of VEGFA
	important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4

cell & other

REGULATION

Other

calcineurin, a serine-threonine protein phosphatase, regulates ITGB4 phosphorylation

ASSOCIATED DISORDERS

corresponding disease(s)

EBJPAB , EBJ2D

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   altered in agressive behavior of cancers

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast ARRCD3-ITGB4 pathway is a new therapeutic target in breast cancer cardiovascular aquired   might be a potential target for therapy in cardiovascular diseases

ANIMAL & CELL MODELS