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FLASH GENE

Symbol

LTBP4

contributors: mct/npt - updated : 31-03-2015

HGNC name	latent transforming growth factor beta binding protein 4
HGNC id	6717

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ARCL1C cutis laxa, autosomal recessive, type IC CPVS craniofacial anomalies, severe pulmonary and visceral involvement, and skin laxity
Location	19q13.2      Physical location : 41.099.071 - 41.135.725
Synonym name	latent transforming growth factor-beta binding protein 4L
Synonym symbol(s)	FLJ46318, FLJ90018, LTBP-4, LTBP-4L, ARCL1C,

DNA

TYPE	functioning gene
STRUCTURE	36.93 kb     33 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	at least four different forms (Saharinen)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003573 33 - 5052 NP_003564 170 1587 - 2010 20175115 NM_001042545 30 - 4979 NP_001036010 - 1557 major form of LTBP4 in lung and intestine 2010 20175115 also called LTBP4S majority of LTBP4S was secreted in a free form NM_001042544 33 - 5163 NP_001036009 - 1624 liver expressed mainly LTBP4L 2010 20175115 also called LTBP4L N terminal extended including a RGD during secretion, LTBP-4L was complexed with TGF-beta1

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 heart         Homo sapiens   vessels aorta       Digestive intestine small intestine       Homo sapiens   liver         Homo sapiens Lymphoid/Immune tonsils       highly Nervous nerve cranial nerve     highly Reproductive female system ovary     highly Respiratory lung         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal     Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	possess heparin binding activity, especially in its N-terminal region
	36 EGF-like motifs (18 calcium-binding cbEGF)
	three 8 cysteine residues motif, one of F type(two of LT type)
	seven ANK repeats
	three LNR (lin/notch) repeats
	C-terminal domain associated with the matrix structures, domain supported fibroblast adhesion, a property reduced by soluble heparin (Kantola 2008)

mono polymer

homomer

HOMOLOGY

Homologene

FAMILY	fibrillin superfamily
	NOTCH family
	LTBP family

CATEGORY

signaling growth factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytoskeleton,microfilament
	intracellular,nucleus
text	microfibrillar
	FBLN5 specifically colocalized with LTBP4 on microfibrils

basic FUNCTION	functioning as a receptor for membrane- bound ligands delta and serrate to regulate cell-fate determination
	playing an essential role for proper differentiation of ectoderm
	having functions as an adhesion molecule (Kantola 2008)
	may contribute to Abdominal Aortic Aneurysm progression (Thompson 2009)
	LTBP4 functions are modified by tissue-specific expression of the two N-terminally distinct variants, which in addition exhibit significant differences in cellular processing and targeting
	unique function for LTBP4 during elastic fibrogenesis
	orchestrates elastin deposition onto microfibrils by binding with FBLN5, which is bound to tropoelastin
	elastogenic activity of LTBP4 is not dependent on associated TGFB1, but is attributed to LTBP4 itself
	promoted elastic fiber assembly by facilitating tropoelastin deposition on microfibrils
	increases elastic fibers by promoting elastin deposition on microfibrils could be an approach toward regenerative treatment for diseases caused by elastic fiber degradation
	role in regulating FBLN5 dependent elastic fiber assembly

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

extracellular matrix constituent likely bound to TGFB1 complex

INTERACTION

DNA

RNA

small molecule

protein	regulating the bioavailability of TGF-betas
	binds directly to fibronectin (FN), which was indispensable for the matrix assembly of LTBP4 (Kantola 2008)
	LTBP4 is necessary for linear deposition of FBLN5 to microfibrils

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CPVS , ARCL1C

Susceptibility

to Abdominal Aortic Aneurysm to variation of age of ambulatory loss in Duchenne muscular dystrophy

Variant & Polymorphism SNP	significant association with the LTBP4 21011A>T genotype in Abdominal Aortic Aneurysm (Thompson 2009)
	in Duchenne muscular dystrophy, individuals homozygous for the IAAM LTBP4 haplotype remained ambulatory significantly longer than those heterozygous or homozygous for the VTTT haplotype

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed dermatology skin   potential therapeutic target for elastic fiber regeneration

ANIMAL & CELL MODELS

mice deficient in Ltbp4 display a defect in lung septation and elastogenesis