ACVRL1 activin A receptor type II-like 1 [Homo sapiens] - Gene

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Summary

Official Symbol: ACVRL1provided by HGNC
Official Full Name: activin A receptor type II-like 1provided by HGNC
Primary source: HGNC:175
See related: Ensembl:ENSG00000139567; HPRD:03181; MIM:601284; Vega:OTTHUMG00000169507
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HHT; ALK1; HHT2; ORW2; SKR3; ALK-1; TSR-I; ACVRLK1
Summary: This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 12q13.13

Sequence :: Chromosome: 12; NC_000012.11 (52301202..52317145)

See ACVRL1 in Epigenomics, MapViewer

Chromosome 12 - NC_000012.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

insight into the potential structure of ALK1(EC) and into the structural effects of type 2 Hereditary Haemorrhagic Telangiectasia associated mutations
Title: Bioinformatic analysis of pathogenic missense mutations of activin receptor like kinase 1 ectodomain.
A novel endoglin mutation (c.1-127C > T); and a novel ACVRL1 mutation (c.252_253insC; p.Val85fsX168). It was shown for the first time that a 5'-UTR mutation can prevent translation of endoglin among hereditary hemorrhagic telangiectasia patients.
Title: Clinical and genetic analyses of three Korean families with hereditary hemorrhagic telangiectasia.
Studies indicate that mutations in at least five genes are thought to result in hereditary hemorrhagic telangiectasia, but mutations in ENG and ACVRL1/ALK1 cause approximately 85% of cases.
Title: Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis.
Study identified 52 unique, novel mutations by sequencing - 25 in ACVRL1 and 27 in ENG.
Title: Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis.
ALK1 may play a role in stabilizing angiogenic vessels and contribute to resistance to anti-VEGF therapies.
Title: Targeting activin receptor-like kinase 1 inhibits angiogenesis and tumorigenesis through a mechanism of action complementary to anti-VEGF therapies.
ALK1-Fc inhibits multiple mediators of angiogenesis and suppresses tumor growth
Title: ALK1-Fc inhibits multiple mediators of angiogenesis and suppresses tumor growth.
Mutations of ACVRL1 fit with a functional haploinsufficiency model affecting BMP9 signaling in Hereditary hemorrhagic telangiectasia.
Title: Functional analysis of the BMP9 response of ALK1 mutants from HHT2 patients: a diagnostic tool for novel ACVRL1 mutations.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
The demethylation of CpG islands, led to an increase in ACVRL1 transcription, whereas in vitro hypermethylation resulted in the abolishment of Sp1-dependent transcriptional activation of ACVRL1.
Title: Characterization of the human Activin-A receptor type II-like kinase 1 (ACVRL1) promoter and its regulation by Sp1.
This report describes the results of molecular diagnosis of mutations in the ENG and ACVRL1 genes in a series of 600 consecutive probands with HHT-related clinical features.
Title: Update on molecular diagnosis of hereditary hemorrhagic telangiectasia.

Submit: New GeneRIF Correction See all (67)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Telangiectasia, hereditary hemorrhagic, type 2

MIM: 600376

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000011.1	NP_001158.2	XIAP	BIND	PubMed	ALK1 interacts with XIAP. This interaction was modeled on a demonstrated interaction between ALK1 from an unspecified species and human XIAP.
P37023	P27037	ACVR2A	HPRD	PubMed
P37023	Q9UNH7	SNX6	HPRD	PubMed
P37023	P01137	TGFB1	HPRD	PubMed
P37023	P10600	TGFB3	HPRD	PubMed
P37023	P36897	TGFBR1	HPRD	PubMed
P37023	P37173	TGFBR2	HPRD	PubMed
P37023	TGF beta receptor associated protein 1	TGFBRAP1	HPRD	PubMed
P37023	P98170	XIAP	HPRD	PubMed
BioGRID:106609	BioGRID:109763	IGSF1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106609	BioGRID:121852	SNX6	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106609	BioGRID:112898	TGFB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106609	BioGRID:114374	TSC22D1	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
SMAD binding	IDA Inferred from Direct Assay more info	PubMed
activin binding	IDA Inferred from Direct Assay more info	PubMed
activin receptor activity, type I	IDA Inferred from Direct Assay more info	PubMed
contributes_to activin receptor activity, type I	TAS Traceable Author Statement more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
receptor activity	IEA Inferred from Electronic Annotation more info
receptor signaling protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
transforming growth factor beta binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to transforming growth factor beta receptor activity, type I	IDA Inferred from Direct Assay more info	PubMed
transforming growth factor beta-activated receptor activity	IDA Inferred from Direct Assay more info	PubMed
transmembrane receptor protein serine/threonine kinase activity	RCA inferred from Reviewed Computational Analysis more info	PubMed

Process	Evidence Code	Pubs
angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
blood circulation	IMP Inferred from Mutant Phenotype more info	PubMed
blood vessel endothelial cell proliferation involved in sprouting angiogenesis	TAS Traceable Author Statement more info
blood vessel maturation	TAS Traceable Author Statement more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
negative regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of endothelial cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
negative regulation of endothelial cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of focal adhesion assembly	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of endothelial cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of endothelial cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
protein heterooligomerization	IEA Inferred from Electronic Annotation more info
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of DNA replication	TAS Traceable Author Statement more info
regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of blood vessel endothelial cell migration	TAS Traceable Author Statement more info
regulation of endothelial cell proliferation	TAS Traceable Author Statement more info
regulation of transcription, DNA-dependent	IMP Inferred from Mutant Phenotype more info	PubMed
signal transduction	IDA Inferred from Direct Assay more info	PubMed
transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
transmembrane receptor protein serine/threonine kinase signaling pathway	RCA inferred from Reviewed Computational Analysis more info	PubMed
wound healing, spreading of epidermal cells	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
cell surface	IDA Inferred from Direct Assay more info	PubMed
dendrite	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
membrane	IEA Inferred from Electronic Annotation more info
neuronal cell body	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: serine/threonine-protein kinase receptor R3

Names: serine/threonine-protein kinase receptor R3; activin receptor-like kinase 1; TGF-B superfamily receptor type I; activin A receptor, type II-like kinase 1

NP_000011.2

EC 2.7.11.30

NP_001070869.1

EC 2.7.11.30

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009549.1 RefSeqGene

Range

5001..20944

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000020.2 → NP_000011.2 serine/threonine-protein kinase receptor R3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 encode the same isoform.

Source sequence(s)

AC025259, DN999570, Z22533

Consensus CDS

CCDS31804.1

UniProtKB/Swiss-Prot

P37023

Related

ENSP00000373574, OTTHUMP00000241377, ENST00000388922, OTTHUMT00000404520

Conserved Domains (5) summary

cd00180
Location:208 – 408
Blast Score: 380

PKc; Catalytic domain of Protein Kinases

pfam01064
Location:32 – 103
Blast Score: 119

Activin_recp; Activin types I and II receptor domain

cl02621
Location:182 – 200
Blast Score: 118

TGF_beta_GS; Transforming growth factor beta type I GS-motif

pfam00069
Location:204 – 487
Blast Score: 495

Pkinase; Protein kinase domain

cl09925
Location:328 – 492
Blast Score: 131

PKc_like; Protein Kinases, catalytic domain
NM_001077401.1 → NP_001070869.1 serine/threonine-protein kinase receptor R3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform.

Source sequence(s)

AC025259, BC042637

Consensus CDS

CCDS31804.1

UniProtKB/Swiss-Prot

P37023

Related

ENSP00000447884, OTTHUMP00000241379, ENST00000550683, OTTHUMT00000404523

Conserved Domains (5) summary

cd00180
Location:208 – 408
Blast Score: 380

PKc; Catalytic domain of Protein Kinases

pfam01064
Location:32 – 103
Blast Score: 119

Activin_recp; Activin types I and II receptor domain

cl02621
Location:182 – 200
Blast Score: 118

TGF_beta_GS; Transforming growth factor beta type I GS-motif

pfam00069
Location:204 – 487
Blast Score: 495

Pkinase; Protein kinase domain

cl09925
Location:328 – 492
Blast Score: 131

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000012.11 Reference GRCh37.p5 Primary Assembly

Range

52301202..52317145

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000144.1 Alternate HuRef

Range

49334280..49350228

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	A38805.1	CAA02404.1
genomic	AC025259.49 (160359..171391)	None
genomic	CH471111.1	EAW58211.1
		EAW58212.1
		EAW58213.1
		EAW58214.1
genomic	U77707.1	AAB61900.1
genomic	U77708.1	AAB61900.1
genomic	U77709.1	AAB61900.1
genomic	U77710.1	AAB61900.1
genomic	U77711.1	AAB61900.1
genomic	U77712.1	AAB61900.1
genomic	U77713.1	AAB61900.1
mRNA	AK056725.1	None
mRNA	AK298493.1	BAG60701.1
mRNA	AK300619.1	BAG62312.1
mRNA	AK303331.1	BAG64396.1
mRNA	BC042637.1	AAH42637.1
mRNA	DN999570.1	None
mRNA	HM161905.1	ADJ79922.1
mRNA	HM161906.1	ADJ79923.1
mRNA	L17075.1	AAA16160.1
mRNA	Z22533.1	CAA80255.1
other-genetic	JF432428.1	ADZ15645.1