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FLASH GENE

Symbol

LTBP2

contributors: mct/npt - updated : 25-05-2018

HGNC name	latent transforming growth factor beta binding protein 2
HGNC id	6715

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	GLC3D glaucoma, primary 3D, congenital (buphtalmos) MSPKA microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma WMS3 Weill-Marchesani syndrome 3
Location	14q24.3      Physical location : 74.964.888 - 75.079.034
Synonym name	chromosome 14 open reading frame 141
	latent transforming growth factor beta binding protein 2
Synonym symbol(s)	LTBP3, MSTP031, C14orf141

DNA

TYPE	functioning gene
STRUCTURE	114.15 kb     36 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

provisional

Map	cen - D14S63 - D14S268 - D14S1036 - LTBP2 - D14S74 - D14S68 - qter
Authors	Cheung (2008)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000428 36 - 8568 NP_000419 195 1821 - 2008 18697872

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 Endocrine thyroid       highly Nervous nerve       highly Respiratory lung       highly

tissue

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

cell lineage
cell lines	melanoma
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal fibrillin 4-cys motif
	a non cbEGF-like motif
	a proline-rich linker
	a LT 4-cys motif
	a second non cbEGF, 18 other EGF-like motifs (one each)
	four cystine repeats (one of F, three of LT type)
	RGD putative integrin recognition site
	C-terminal fragment could block the interaction of the LTBP1 fragment with the fibrillin (Hirani 2007)

mono polymer

homomer

HOMOLOGY

intraspecies	homolog to LTBP1
	homolog to fibrillin

Homologene

FAMILY	fibrillin/LTBP extracellular matrix glycoprotein superfamily
	LTBP family

CATEGORY

adhesion , structural protein , signaling growth factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
text	extracellular matrix
	showed extensive co-localization with fibrillin-1 and elastic lamellae (Hirani 2007)

basic FUNCTION	TGF-beta is released from the extracellular matrix by proteases, localized to cell surfaces
	may play an integral structural role in elastic-fiber architectural organization and/or assembly
	targeting latent TGF-beta to the matrix
	having possibility to compete with LTBP1 for binding to fibrillin-containing microfibrils throughout the aortic wall but particularly in the outer medial region where the LTBP1 is predominantly located (Hirani 2007)
	may be an indirect negative modulator for storage of the large latent TGF-beta complex on microfibrils in aorta and other fibrillin-rich tissues (Hirani 2007)
	essential for normal development of the anterior chamber of the eye, where it may have a structural role in maintaining ciliary muscle tone (Ali 2009)
	may have a negative regulatory role during elastic fiber assembly, perhaps in displacing elastin microassemblies from complexes with FBLN5 and/or cell surface heparan sulfate proteoglycans
	prominent pericellular component of annular fibrochondrocytes in the posterior annulus fibrosus (AF), interstitial matrix adjacent to nucleus pulposus (NP) cells
	is an essential component for the formation of microfibril bundles in ciliary zonules
	LTBP1 and LTBP2 are involved in the keratinization of oral epithelium
	is a potent inhibitor of FGF2 that may influence FGF2 bioactivity during wound repair particularly in fibrotic tissues
	plays vital roles in tumorigenesis through regulating TGFB1 activity, elastogenesis and maintenance of the extracellular matrix (ECM) structure
	acts as an oncogene in head and neck squamous cell carcinoma development and progression

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	not bound to latent TGFB1 independent component of microfibrils
	component of LAP which is a homodimer formed from the propeptide TGF-beta

INTERACTION

DNA

RNA

small molecule

protein	specifically binds to the amino-terminal region of fibrillin-1, but not to fibrillin-2 (Hirani 2007)
	LTBP2, LTBP3 inhibit the proprotein convertase PCSK5
	in response to tension stress, may negatively control the function of FBLN5, thereby modulating the mechanism of oxytalan fiber coalescence
	LTBP2 is a potent inhibitor of FGF2 that may influence FGF2 bioactivity during wound repair particularly in fibrotic tissues

cell & other

has widespread association with fibrillin-containing microfibrils in developing aorta and other tissues (Hirani 2007)

REGULATION

activated by

cell-associated plasmin

ASSOCIATED DISORDERS

corresponding disease(s)

GLC3D , MSPKA , WMS3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in Marfan syndrome tumoral     --over   in pancreatic ductal adenocarcinoma (PDAC) tissue

Susceptibility

to BMD variation (bone mineral density) in trochanter and total hip

Variant & Polymorphism other	strong genetic association between LTBP2 gene locus and total hip BMD variation

Candidate gene
Marker	LTBP2 powerfully predicted early pulmonary death (LTBP2 levels were significantly higher in patients dying from pulmonary causes)
	serum LTBP2 levels might act as a promising biomarker in heart failure with reduced ejection fraction (HFREF)
	is a novel biomarker for the diagnosis of Pancreatic cancer
Therapy target
	System Type Disorder Pubmed cancer endocrine pancreas may be a potential target for PDAC clinical therapy

ANIMAL & CELL MODELS