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FLASH GENE

Symbol

FREM1

contributors: mct/pg - updated : 23-02-2016

HGNC name	FRAS1 related extracellular matrix 1
HGNC id	23399

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	BNAR bifid nose and anorectal and renal anomalies
Location	9p22.3      Physical location : 14.734.663 - 14.910.993
Synonym name	extracellular matrix protein QBRICK
	FRAS1 related extracellular matrix protein 1
	chromosome 9 open reading frame 154
	Toll-like/interleukin-1 receptor regulator
	protein QBRICK
Synonym symbol(s)	C9orf145, FLJ25461, QBRICK, RP11-439N12.3, DKFZp686M16108, C9orf154, C9orf143, TILRR, BNAR

DNA

TYPE	functioning gene
STRUCTURE	176.98 kb     37 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	encoded by an alternatively spliced mRNA (Zhang 2010)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_144966 37 - 7387 NP_659403 - 2179 - 2014 24746155 NM_001177704 14 - 4967 NP_001171175 75 715 - 2014 24746155 TILRR isoform is a co-receptor that enhances pro-inflammatory IL1R1 signal transduction

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 Digestive intestine small intestine       Endocrine pancreas           parathyroid         Hearing/Equilibrium ear inner cochlea   highly Nervous nerve       highly Reproductive female system uterus       Skin/Tegument skin appendages hair

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	predominantly expressed at the tip of developing hair follicles (Kiyozumi 2005)

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a novel N-terminal domain containing an Arg-Gly-Asp cell-adhesive motif
	twelve chondroitin sulfate proteoglycan repeats, tandem repeats of approximately 120 AAs
	one Calx-beta domain
	GAG attachment sites at residues 112 and 417
	a series of putative N-linked glycosylation sites
	a C-terminal C-type lectin domain

conjugated

GlycoP

HOMOLOGY

Homologene

FAMILY

Fras1/Frem family of extracellular matrix proteins

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	extracellular
text	secreted protein
	localized at the basement membrane zone of embryonic epidermis and hair follicles, in which it was more enriched at the tip rather than the stalk region (Kiyozumi 2005)
	FRAS1 and FREM2 were colocalized with FREM3 in the basement membrane of certain skin parts, underlying the thin-layer, of rapidly proliferating keratinocytes, whereas FREM1 was detected only in the basement membrane of the tail

basic FUNCTION	playing a role in epidermal differentiation and required for epidermal adhesion during embryonic development
	adhesive ligand of basement membrane distinctively recognized by cells in the embryonic skin and hair follicles through different types of integrins directed to the Arg-Gly-Asp motif
	involved in the structural adhesion of the skin epithelium to its underlying mesenchyme
	playing a role in human craniofacial and renal development
	controls MYD88-dependent signaling and MYD88 association
	cell surface proteoglycan, associating with IL1RI to potentiate NF-KB activation and inflammatory responses by increasing ligand binding and receptor expression
	IL1RI co-receptor, which associates with the signaling receptor complex to enhance recruitment of MYD88 and control Ras-dependent amplification of NF-kappaB and inflammatory responses
	having a role in the structure and function of basement membrane
	plays a critical role in the development of the diaphragm
	is required for epidermal adhesion during embryogenesis
	extracellular matrix protein that is essential for the formation of the epithelial basement membrane during embryonic development
	FREM1 plays a critical role in the development of the fetal diaphragm

CELLULAR PROCESS

cell migration & motility

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

part of a ternary complex that includes FRAS1 and FREM2

INTERACTION

DNA

RNA

small molecule	metal binding,
	ion Ca2+

protein	interacting with FRAS1 and FREM2 (are simultaneously stabilized at the lowermost region of the basement membrane by forming a macromolecular ternary complex)
	enhancer of IL1-regulated inflammatory responses
	associates with the extracellular domain of IL1RI and magnifies NF-KB-regulated inflammatory responses by potentiating recruitment of MYD88 and linking TIR activation with mechanotransduction by controlling induction of the Ras GTPase
	binds to PDGFC and this interaction regulates signalling downstream of PDGFRA

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

BNAR

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       identified in a significant percentage of people with metopic craniosynostosis, with or without midface hypoplasia constitutional germinal mutation       in isolated Congenital anomalies of the kidney and urinary tract (CAKUT) constitutional germinal mutation       recessive FREM1 mutations can cause isolated Congenital diaphragmatic hernia (CDH)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Frem1 mutant mice is the first bona fide mouse model of human metopic craniosynostosis and a new model for midfacial hypoplasia