Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

ACVRL1

contributors: mct/pgu - updated : 27-02-2015

HGNC name	activin A receptor type II-like 1
HGNC id	175

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	Variants 1 and 2 encode the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000020 10 - 4263 NP_000011 56 503 - 1996 8640225 NM_001077401 9 - 4126 NP_001070869 56 503 - 1996 8640225

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 Cardiovascular vessels         Mus musculus Fetal Digestive intestine           liver         Homo sapiens Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective loose submucosal layer     Epithelial absorptive excretory digestive epithelium     Muscular smooth       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Homo sapiens Cardiovascular endothelial cell Mus musculus Fetal Lymphoid/Immune macrophage Homo sapiens not specific chondrocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	placenta, mesenchyme of the lung

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a small cysteine-rich extracellular region
	a single transmembrane segment (TM)
	a GS domain
	a cytoplasmic serine/threonine kinase domain with three ligands (TGFB1, TGFB3 and one unknown)

secondary structure

a beta-strand framework highly similar to BMPR1A, yet there are significant differences in loops shown previously to be important for binding

HOMOLOGY

interspecies

homolog to murine Acvrl1

Homologene

FAMILY	protein kinase superfamily
	TKL Ser/Thr protein kinase family
	TGFB receptor subfamily

CATEGORY

enzyme , receptor

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	modulator of TGFB1 signaling in the regulation of
	contributing with BMPR2 to growth inhibition of human pulmonary artery endothelial cells
	plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and through interaction with blood flow is involved in the development of arteriovenous malformations
	TGFBR1/ACVRL1 balance regulates leptin expression in mesenchymal stem cells (MSC)
	TMEM100 may play indispensable roles downstream of GDF2/BMP10-ACVRL1 signaling during endothelial differentiation and vascular morphogenesis
	play an important role in cardiovascular remodeling
	ENG and and ACVRL1 contribute to several novel networks, including TGFB1 dependent and independent ones, critical for vascular function and potentially defective in hereditary hemorrhagic telangiectasia
	ACVRL1 and TGFBR1 play antagonistic roles in transforming growth factor beta-induced podosome formation in aortic endothelial cells
	type I BMP/TGFBR that mediates signalling in endothelial cells via phosphorylation of SMAD1/5/8

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

TGFB signaling pathway

a component

component of a complex with TGFB1 and TGFB3

INTERACTION

DNA

RNA

small molecule

protein	GDF2 and BMP10 are specific ligands for ACVRL1 that potently inhibit microvascular endothelial cell migration and growth
	ACVRL1/CSNK2B interaction specifically enhanced SMAD1/5/8 phosphorylation
	high specificity of ACVRL1 for GDF2/BMP10 is determined by a novel orientation of ACVRL1 with respect to GDF2, which leads to a unique set of receptor-ligand interactions
	type I cell surface receptor for the transforming growth factor-beta (TGFB) family of proteins
	BMP9 and BMP10 are the physiological, functionally equivalent ligands of ACVRL1 in vascular development
	BMP10 is the crucial ligand for ACVRL1 in embryonic vascular development, and circulating BMP10 acts through endothelial ACVRL1 to limit endothelial cell number in and thereby stabilize the caliber of nascent arteries
	GDF2 inhibits lymphatic vessel formation via ACVRL1 during development and cancer progression
	PPP2R2B protein interacts with the ACVRL1/TGFBR2/ENG complex and recruits PP2A to nitric oxide synthase 3 (NOS3)
	synergises with NOTCH1 in stalk cells to induce expression of the NOTCH1 targets HEY1 and HEY2 and thereby represses tip cell formation and angiogenic sprouting

cell & other

REGULATION

repressed by

UBR5 (negative regulation of ACVRL1 gene expression by UBR5 that is exerted at the promoter)

Other

signaling regulated by NR1H2 (LXRB)

ASSOCIATED DISORDERS

corresponding disease(s)

ORW2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   with EGFL7 showed lower expression in early-onset pre-eclampsia versus late-onset pre-eclampsia

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

deletion of Alk1 in endothelial cell (EC) in adult mice leads to an increased local EC proliferation during brain angiogenesis and de novo brain arteriovenous malformations (AVMs)