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FLASH GENE

Symbol

COL1A1

contributors: mct/npt/shn - updated : 14-04-2015

HGNC name	collagen, type I, alpha 1
HGNC id	2197

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	EDS1C Ehlers-Danlos syndrome, type Ic EDS7A1 Ehlers-Danlos syndrome, type VIIA ICHO infantile cortical hyperostosis OI1A osteogenesis imperfecta, types I et IA OI2A osteogenesis imperfecta, type II OI3A osteogenesis imperfecta, type III OI4A osteogenesis imperfecta, type IV OIEDS osteogenesis imperfecta with Ehlers-Danlos syndrome
Location	17q21.33      Physical location : 48.261.458 - 48.279.000
Synonym name	collagen alpha-1
	I chain precursor
	collagen of skin, tendon and bone, alpha-1 chain
Synonym symbol(s)	OI4

DNA

TYPE	functioning gene
STRUCTURE	17.54 kb     51 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	proximal region of COL1A1 harbors a functional 67/ 61-bp DNA-binding site for ZBTB7B in dermal fibroblasts
	TGFbeta-responsive activating sequences regarding the promoter of COL1A1 are located between 174 and 84 bp from the transcription start site in a region containing a binding site for the transcription factor SP1 (specific protein-1) and an element with the canonical NF-1 (nuclear factor-1) binding motif

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D17S943 - D17S1795 - COL1A1 - D17S1869 - D17S1815 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000088 51 - 5927 NP_000079 - 1464 - -

EXPRESSION

Type	restricted

constitutive of

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

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Connective cartilage       Connective dense ligament     Connective dense tendon

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	bone, cochlea

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a rope-like structure
	a long stretch of uninterupted GLY-XY triplets
	a VWFC domain

conjugated

GlycoP

mono polymer

heteromer , trimer

isoforms

Precursor

preprocollagen

HOMOLOGY

interspecies	ortholog to Col1a1, Mus musculus
	ortholog to Col1a1, Rattus norvegicus
	ortholog to COL1A1, Pan troglodytes

Homologene

FAMILY

fibrillar collagen family

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	extracellular
text	extracellular matrix

basic FUNCTION

main source of mechanical strength, template for mineral deposition in bones, involved in determination of bone density

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development , ossification

text	forms the fibrils of tendon, ligaments and bones (in bones the fibrils are mineralized with calcium hydroxyapatite)

PATHWAY

metabolism

signaling

a component

component of fibrillar collagen of type I heterotrimerizing with COL1A2 (two alpha, one alpha chains)

INTERACTION

DNA

RNA

small molecule

protein	secreted protein, acidic, cysteine-rich (osteonectin), SPARC (Termine et al, 1981)
	von Willebrand factor, VWF (Pareti et al, 1986)
	integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor), ITGA2 (Staatz et al, 1990)
	biglycan, BGN (Schönherr et al, 1995)
	matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase), MMP9 (Mäkelä et al, 1998)
	Nidogen-2, NID2 (Kohfeldt et al, 1998)
	platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog), PDGFB (Shimizu et al, 1999)
	metalloproteinase-2, MMP-2 (Ellerbroek et al, 2001)
	Matrilin-2, MATN2 (Piecha et al, 2002)
	Thioredoxin, TRX (Matsumoto et al, 2002)
	NFKB is a strong inhibitor of collagen synthesis and of COL1A1 transcription in healthy and scleroderma fibroblasts, and RELA subunit of NFKB being responsible for the inhibitory action
	COL1A1 and ITM2A genes both regulate the expressions of calcium channel genes

cell & other

REGULATION

induced by	CREB3L1 (Murakami 2009)
		SP7 inducing COL1A1 gene expression through binding to SP1 sites in the bone enhancer and proximal promoter regions

Other

regulation of its transcription in human dermal fibroblasts involves a multimolecular complex implying at least three trans-activators, SP1, SP3, and ZBTB7B, which could act in concert to up-regulate COL1A1 transcription activity or down-regulate promoter activity

ASSOCIATED DISORDERS

corresponding disease(s)

EDS7A1 , OI1A , OI2A , OI3A , OI4A , EDS1C , ICHO , OIEDS

related resource

Collagen Type I & III

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   translocation     with PDGFB t(17;22) (q22;q13) in dermatofibrosarcoma protuberans and in giant cell fibroblastoma constitutional   deletion     of GPATCH8 and COL1A1 in mild osteogenesis imperfecta with hyperuricemia (

Susceptibility

to reduced bone density, osteoporosis (senile, postmenopausal) to otosclerosis to myopia (MYP5) to osteoporosis

Variant & Polymorphism SNP , other	polymorphic binding site sp1
	SNP in the regulatory regions are associated with otosclerosis
	three common polymorphisms in the 5prime flank of COLIA1 interact to regulate COL1A1 transcription by affecting binding affinity of several critical regulatory factors including NMP4, Osterix and Sp1(Jin 2009)
	three SNPs increasing the risk of myopia

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	mice expressing a partially deleted COL1A1 gene have bones significantly shorter in length, a decrease in wet weight, mineral content and collagen content (Pereira et al, 1993)
	mouse Aga2, with a dominant frameshift mutation in the Col1a1 C-propeptide domain, have OI phenotypic changes and endoplasmatic reticulum (ER) stress-related apoptosis in bone tissue
	mice expressing a mutated COL1A1 gene exhibit phenotypic variability and incomplete penetrance of Osteogenesis imperfecta (Pereira et al, 1994)
	transgenic mice with a targeted mutation in COL1A1 gene display ocular hypertension (Aihara et al, 2003)