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FLASH GENE

Symbol

LTBP1

contributors: mct - updated : 23-06-2021

HGNC name	latent transforming growth factor beta binding protein 1
HGNC id	6714

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CLCDSF cutis laxa and inguinal hernia, craniofacial dysmorphology, prominent skeletal features
Location	2p22.3      Physical location : 33.172.368 - 33.624.573
Synonym name	TGF-beta1-BP-1
Synonym symbol(s)	LTBP-1, MGC163161, TGF-beta1-BP-1

DNA

TYPE	functioning gene
STRUCTURE	497.38 kb     34 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	LTBP1S and LTBP1L are derived from different promoters (PMID: 27956181)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000627 30 - 5298 NP_000618 - 1396 - 2011 21161366 LTBP-1S a N terminal non cbEGF and 16 cbEGF-like repeats each with six cysteine residues forming disulfide bonds, four 8 cysteine repeats among them three LT specific, and two proline-rich regions NM_001166264 29 - 5168 NP_001159736 - 1353 in fibroblasts 2011 21161366 NM_206943 34 - 6502 NP_996826 - 1721 - 2011 21161366 LTBP-1L is a major regulator of TGFB1 activity during valvulogenesis since its absence results in a perturbed TGFB1 pathway that causes all LTBP1L(-/-) valvular defects (PMID: 21181942) NM_001394905 34 - 6343 NP_001381834 - 1668 - 2011 21161366 NM_001394916 31 - 5234 NP_001381845 - 1314 - 2011 21161366 NM_001394921 29 - 5006 NP_001381850 - 1299 - 2011 21161366 NM_001394913 30 - 5132 NP_001381842 - 1341 - 2011 21161366 NM_001394923 28 - 4889 NP_001381852 - 1260 - 2011 21161366 NM_001394927 27 - 4739 NP_001381856 - 1210 - 2011 21161366 NM_001394924 28 - 4883 NP_001381853 - 1258 - 2011 21161366 NM_001394926 28 - 4865 NP_001381855 - 1252 - 2011 21161366 NM_001394920 29 - 5009 NP_001381849 - 1300 - 2011 21161366 NM_001394925 28 - 4865 NP_001381854 - 1252 - 2011 21161366 NM_001166266 29 - 5009 NP_001159738 - 1300 - 2011 21161366 NM_001166265 30 - 5135 NP_001159737 - 1342 - 2011 21161366 NM_001394907 30 - 5207 NP_001381836 - 1366 - 2011 21161366 NM_001394914 29 - 5084 NP_001381843 - 1325 - 2011 21161366 NM_001394910 29 - 5165 NP_001381839 - 1352 - 2011 21161366 NM_001394915 29 - 5084 NP_001381844 - 1325 - 2011 21161366 NM_001394911 29 - 5165 NP_001381840 - 1352 - 2011 21161366 NM_001394919 28 - 5021 NP_001381848 - 1304 - 2011 21161366 NM_001394912 29 - 5150 NP_001381841 - 1347 - 2011 21161366 NM_001394908 29 - 5174 NP_001381837 - 1355 - 2011 21161366 NM_001394906 30 - 5291 NP_001381835 - 1394 - 2011 21161366 NM_001394917 28 - 5042 NP_001381846 - 1311 - 2011 21161366 NM_001394918 28 - 5024 NP_001381847 - 1305 - 2011 21161366

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 blood / hematopoietic spleen       highly Cardiovascular heart       highly Hearing/Equilibrium ear inner cochlea   highly Reproductive male system prostate     highly Urinary kidney       highly

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol   digestive Blood/Hematopoietic platelet

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	16 EGF-like domains
	2 EGF domains
	a binding site within three domains of the C terminus
	C terminus of LTBP1 interacts with the N terminus of fibrillin-1 and fibrillin-2 , and flanking regions, together forming a 12 kDa protein fragment at the C-terminus of LTBP1 is likely involved in interactions with fibrillin microfibrils

isoforms

Precursor

fibroblast precursor 170-190kDa

HOMOLOGY

intraspecies	homolog to LTBP family
	homolog to fibrillin

Homologene

FAMILY	fibrillin superfamily
	latent TGF-beta binding proteins (LTBPs)

CATEGORY

signaling growth factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
text	localizes to extracellular fibrillar structures resembling fibronectin-collagen matrix (Taipale 1996)
	strong localization only in the outer medial layer (Hirani 2007)

basic FUNCTION	regulator of TGFB1 metabolism independent structural protein of ECM
	may be involved in the assembly, secretion and targeting of TGFB1 to sites at which it is stored and/or activated
	may play critical roles in controlling and directing the activity of TGFB1
	mediates the extracellular matrix (ECM) targeting and accumulation of most TGF-beta in the bone (Koli 2008)
	differentially regulating TGF-beta activation and extracellular matrix accumulation during osteogenic differentiation (Koli 2008)
	compete with LTBP2 for binding to fibrillin-containing microfibrils throughout the aortic wall but particularly in the outer medial region where it is predominantly located (Hirani 2007)
	LTBP1 and LTBP2 are involved in the keratinization of oral epithelium
	potential function of LTBP1 in female reproduction
	LTBP1 function is crucial for skin and bone extracellular matrix (ECM)assembly and homeostasis
	microfibril-associated multidomain protein essential for the sequestration of TGFB1 in the extracellular matrix (ECM)
	LTBP1 has dual functions in humans and zebrafish affecting cutaneous and skeletal development

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	fibrillin-associated microfibrils
	component of the extracellular matrix and alterations of the pericellular matrix could result in aberrant TGF-beta signaling (Taipale 1996)

INTERACTION

DNA

RNA

small molecule

protein	binding the small TGFB1 complex through its latency associated polypeptide (LAP)
	implicated in the control of secretion, localization, and activation of TGFB1
	has also been demonstrated to interact with a number of insoluble extracellular matrix components, such as fibrillin, which may play a role in TGFB1 regulation
	N-terminal region of FBLN1 mediates a bipartite interaction with LTBP1
	FBLN1c may be a novel driver of TGFB1-induced fibrosis involving LTBP1 and may be an upstream therapeutic target

cell & other

REGULATION

Other

released from the TGFB complex by plasmin,leading to activation of TGFB

ASSOCIATED DISORDERS

corresponding disease(s)

CLCDSF

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in association with TGFB1 in ovarian cancer

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	mice lacking Ltbp1L only or both Ltbp1S and Ltbp1L show a persistent truncus arteriosus and an interrupted aortic arch that associates with perinatal lethality
	ltbp1 deficiency in zebrafish confirms a prominent role for Ltbp1 in skeletal morphogenesis