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FLASH GENE

Symbol

NELL1

contributors: mct/npt/pgu - updated : 04-03-2014

HGNC name	NEL-like 1 (chicken)
HGNC id	7750

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	11p15.1      Physical location : 20.691.116 - 21.597.227
Synonym name	neural epidermal growth factor like 1
	isocitrate dehydrogenase 3 (NAD+) gamma-like
	Nel-related protein 1
Synonym symbol(s)	IDH3GL, NRP1, NELL-1, FLJ45906, NEL

DNA

TYPE	functioning gene
STRUCTURE	906.14 kb     20 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	three OSE2 (three osteoblast specific binding elements 2 ) in the promoter that are directly bound and transactivated by RUNX2

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_201551 19 - 3114 NP_963845 84.4 763 - 2001 11803583 NM_006157 20 - 3255 NP_006148 89.6 810 - 2001 11803583 NM_001288713 21 - 3354 NP_001275642 92.8 838 - 2001 11803583 NM_001288714 19 - 3099 NP_001275643 83 753 - 2001 11803583

EXPRESSION

Type	restricted

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 mouth tooth       Mus musculus Fetal Endocrine neuroendocrine pituitary     highly Nervous brain diencephalon amygdala   predominantly Homo sapiens Urinary kidney       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Muscular striatum skeletal   highly Nervous central     predominantly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Digestive odontoblast Mus musculus Adult Digestive odontoblast Mus musculus Fetal

cell lineage	transiently in hematopoietic cells during pre B cell development
cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text

brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal signal peptide, with six epidermal growth factor-like motifs, containing signal peptides, and a N-terminal thrombospondin-1 domain involved in multimer formation and heparin- and retinal axon-binding
	a thrombospondin-1 (TSP-1)-like domain (TSPN)
	five von Willebrand factor C domains (VWC)
	six calcium binding EGF-like repeats, lacking the transmembrane domain of chicken nel
	five cysteine-rich domains
	C-terminal cysteine-rich region is critical for cell adhesion activity of NELL1

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to chicken nel-like 1

Homologene

FAMILY

laminin G/TSP-N/pentraxin supergene family, the chordin-like cysteine-rich domain family and the EGF-like domain family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm
	intracellular,nuclear envelope

basic FUNCTION	playing a potential oncogenic role in neural cells
	involved in cell growth regulation and differentiation of neural cells
	craniosynostosis-related gene
	modulating calvarial osteoblast differentiation and apoptosis pathways
	extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells
	plays a key role as a regulator of craniofacial skeletal morphogenesis, especially in committed chondrogenic and osteogenic differentiation
	NELL1 signaling may inhibit adipogenic differentiation via a Hedgehog dependent mechanism
	in addition to the well-recognized role of NELL1 in promotion of osteogenic differentiation and bone formation, NELL1 significantly represses adipogenic differentiation
	osteoinductive molecule associated with premature calvarial suture closure
	role on osteoblastic differentiation and proliferation are partly through binding to APR3
	is an important growth factor for regulation of osteochondral differentiation, by regulating both RUNX2 and SOX9 expression within the calvarium
	is required for normal craniofacial membranous and endochondral skeletal development
	plays an important role in osteoblast differentiation, bone formation, and bone regeneration
	does contribute to the enhanced constructive remodeling of skeletal muscle
	large oligomeric secretory glycoprotein that functions as an osteoinductive factor

CELLULAR PROCESS	cell life, differentiation
	cell life, proliferation/growth
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

text	neurogenesis

PATHWAY

metabolism

signaling

a component

NELL2 and and NELL1 can form hetero-oligomer when co-expressed in the same cells (pMID: 22157752)

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	interacting with RUNX2 (RUNX2 directly binds to the OSE2 elements and transactivates the promoter)
	with PRKCB1
	transiently activates the MAPK signaling cascade, induces the phosphorylation of RUNX2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins
	NFATC2 is a primary response gene of NELL1
	binding to APR3
	SP7 is a direct transcriptional regulator with repressive effect on NELL1 gene expression, contributing to a delicate balance of regulatory effects on NELL1 transcription with RUNX2, and may play a crucial role in osteoblast differentiation and mineralization
	interacts with a range of molecules through its different domains and exerts distinct functions
	increases pre-osteoblast mineralization using both phosphate transporter SLC20A1, SLC20A2
	NELL1 binds to extracellular ITGB1 and induces cell focal adhesion

cell & other

REGULATION

activated by

upregulated during unilateral premature closure of the coronal suture

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in craniofacial anomalies, premature suture closure tumoral     --low   by promoter hypermethylation in early-stage esophageal adenocarcinoma, occuring early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC tumoral     --other   expressed mainly in tumors in the neuronal cell lineage

Susceptibility

Variant & Polymorphism

Candidate gene	candidate growth factor able to induce human perivascular stem cells osteogenesis
Marker
Therapy target
	System Type Disorder Pubmed osteoarticular bone   future therapeutic utility of NELL1 for either skeletal or soft-tissue regenerative medicine

ANIMAL & CELL MODELS

Nell-1 overexpressing mice demonstrate calvarial bone overgrowth and inappropriate cranial suture fusion