Human Gene ACVRL1 (ENST00000388922.9) from GENCODE V44
  Description: Homo sapiens activin A receptor like type 1 (ACVRL1), transcript variant 2, mRNA. (from RefSeq NM_001077401)
RefSeq Summary (NM_000020): 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].
Gencode Transcript: ENST00000388922.9
Gencode Gene: ENSG00000139567.13
Transcript (Including UTRs)
   Position: hg38 chr12:51,907,504-51,923,361 Size: 15,858 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg38 chr12:51,912,475-51,920,893 Size: 8,419 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:51,907,504-51,923,361)mRNA (may differ from genome)Protein (503 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ACVL1_HUMAN
DESCRIPTION: RecName: Full=Serine/threonine-protein kinase receptor R3; Short=SKR3; EC=2.7.11.30; AltName: Full=Activin receptor-like kinase 1; Short=ALK-1; AltName: Full=TGF-B superfamily receptor type I; Short=TSR-I; Flags: Precursor;
FUNCTION: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for TGF-beta. May bind activin as well.
CATALYTIC ACTIVITY: ATP + [receptor-protein] = ADP + [receptor- protein] phosphate.
COFACTOR: Magnesium or manganese (By similarity).
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
DISEASE: Defects in ACVRL1 are the cause of hereditary hemorrhagic telangiectasia type 2 (HHT2) [MIM:600376]; also known as Osler- Rendu-Weber syndrome 2 (ORW2). HHT2 is an autosomal dominant multisystemic vascular dysplasia, characterized by recurrent epistaxis, muco-cutaneous telangiectases, gastro-intestinal hemorrhage, and pulmonary, cerebral and hepatic arteriovenous malformations; all secondary manifestations of the underlying vascular dysplasia.
SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.
SIMILARITY: Contains 1 GS domain.
SIMILARITY: Contains 1 protein kinase domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ACVRL1";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: ACVRL1
Diseases sorted by gene-association score: telangiectasia, hereditary hemorrhagic, type 2* (1200), acvrl1-related hereditary hemorrhagic telangiectasia* (500), pulmonary hypertension* (317), hereditary hemorrhagic telangiectasia* (226), pulmonary hypertension, familial primary, 1, with or without hht* (179), arteriovenous malformation (31), telangiectasis (30), mixed connective tissue disease (19), pulmonary arteriovenous malformation (18), angiodysplasia (17), weber syndrome (14), tricuspid valve insufficiency (10), pulmonary venoocclusive disease (9), heritable pulmonary arterial hypertension* (9), vascular disease (9), vascular malformation (8), connective tissue disease (7), tricuspid valve disease (7), chronic pulmonary heart disease (6), pericardium disease (5), cardiac tamponade (5), atrial heart septal defect (5), mitral valve stenosis (5), venous malformations, multiple cutaneous and mucosal (5), pericardial effusion (4), inflammatory myofibroblastic tumor (4), acute contagious conjunctivitis (4), heart septal defect (4), autosomal genetic disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 53.83 RPKM in Lung
Total median expression: 455.03 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -110.50197-0.561 Picture PostScript Text
3' UTR -994.702468-0.403 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000333 - Activin_II/TGFBeta-II_recpt
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR008271 - Ser/Thr_kinase_AS
IPR003605 - TGF_beta_rcpt_GS

Pfam Domains:
PF00069 - Protein kinase domain
PF08515 - Transforming growth factor beta type I GS-motif

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2LCR - NMR MuPIT 3MY0 - X-ray MuPIT 4FAO - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P37023
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004675 transmembrane receptor protein serine/threonine kinase activity
GO:0005024 transforming growth factor beta-activated receptor activity
GO:0005025 transforming growth factor beta receptor activity, type I
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016361 activin receptor activity, type I
GO:0016740 transferase activity
GO:0019901 protein kinase binding
GO:0046332 SMAD binding
GO:0046872 metal ion binding
GO:0048185 activin binding
GO:0050431 transforming growth factor beta binding
GO:0098821 BMP receptor activity

Biological Process:
GO:0001525 angiogenesis
GO:0001666 response to hypoxia
GO:0001701 in utero embryonic development
GO:0001936 regulation of endothelial cell proliferation
GO:0001937 negative regulation of endothelial cell proliferation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0001946 lymphangiogenesis
GO:0001955 blood vessel maturation
GO:0001974 blood vessel remodeling
GO:0002043 blood vessel endothelial cell proliferation involved in sprouting angiogenesis
GO:0003203 endocardial cushion morphogenesis
GO:0006275 regulation of DNA replication
GO:0006355 regulation of transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0007162 negative regulation of cell adhesion
GO:0007165 signal transduction
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0008015 blood circulation
GO:0008217 regulation of blood pressure
GO:0008285 negative regulation of cell proliferation
GO:0010596 negative regulation of endothelial cell migration
GO:0010629 negative regulation of gene expression
GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0016310 phosphorylation
GO:0030308 negative regulation of cell growth
GO:0030336 negative regulation of cell migration
GO:0030509 BMP signaling pathway
GO:0030513 positive regulation of BMP signaling pathway
GO:0032332 positive regulation of chondrocyte differentiation
GO:0032924 activin receptor signaling pathway
GO:0035313 wound healing, spreading of epidermal cells
GO:0035912 dorsal aorta morphogenesis
GO:0043535 regulation of blood vessel endothelial cell migration
GO:0043537 negative regulation of blood vessel endothelial cell migration
GO:0045602 negative regulation of endothelial cell differentiation
GO:0045603 positive regulation of endothelial cell differentiation
GO:0045766 positive regulation of angiogenesis
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048514 blood vessel morphogenesis
GO:0051895 negative regulation of focal adhesion assembly
GO:0060836 lymphatic endothelial cell differentiation
GO:0060840 artery development
GO:0060841 venous blood vessel development
GO:0061154 endothelial tube morphogenesis
GO:0061298 retina vasculature development in camera-type eye
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071773 cellular response to BMP stimulus
GO:2000279 negative regulation of DNA biosynthetic process
GO:0090500 endocardial cushion to mesenchymal transition

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030425 dendrite
GO:0043025 neuronal cell body


-  Descriptions from all associated GenBank mRNAs
  LF212648 - JP 2014500723-A/20151: Polycomb-Associated Non-Coding RNAs.
MA448225 - JP 2018138019-A/20151: Polycomb-Associated Non-Coding RNAs.
HM161905 - Homo sapiens activin A receptor type II-like kinase 1 variant 3 (ACVRL1) mRNA, partial cds, alternatively spliced.
HM161906 - Homo sapiens activin A receptor type II-like kinase 1 variant 4 (ACVRL1) mRNA, partial cds, alternatively spliced.
Z22533 - H.sapiens ALK-1 mRNA.
LF385084 - JP 2014500723-A/192587: Polycomb-Associated Non-Coding RNAs.
MA620661 - JP 2018138019-A/192587: Polycomb-Associated Non-Coding RNAs.
JD335753 - Sequence 316777 from Patent EP1572962.
JD190995 - Sequence 172019 from Patent EP1572962.
AK298493 - Homo sapiens cDNA FLJ57074 complete cds, highly similar to Serine/threonine-protein kinase receptor R3 precursor (EC 2.7.11.30).
JD253452 - Sequence 234476 from Patent EP1572962.
JD054419 - Sequence 35443 from Patent EP1572962.
JD387503 - Sequence 368527 from Patent EP1572962.
JD336828 - Sequence 317852 from Patent EP1572962.
AK303331 - Homo sapiens cDNA FLJ50328 complete cds, highly similar to Serine/threonine-protein kinase receptor R3 precursor (EC 2.7.11.30).
L17075 - Human TGF-b superfamily receptor type I mRNA, complete cds.
BC042637 - Homo sapiens activin A receptor type II-like 1, mRNA (cDNA clone MGC:34522 IMAGE:5179243), complete cds.
CU692110 - Synthetic construct Homo sapiens gateway clone IMAGE:100021164 5' read ACVRL1 mRNA.
JF432428 - Synthetic construct Homo sapiens clone IMAGE:100073635 activin A receptor type II-like 1 (ACVRL1) gene, encodes complete protein.
KJ890625 - Synthetic construct Homo sapiens clone ccsbBroadEn_00019 ACVRL1 gene, encodes complete protein.
KJ905134 - Synthetic construct Homo sapiens clone ccsbBroadEn_14531 ACVRL1 gene, encodes complete protein.
KR710995 - Synthetic construct Homo sapiens clone CCSBHm_00018710 ACVRL1 (ACVRL1) mRNA, encodes complete protein.
KR710996 - Synthetic construct Homo sapiens clone CCSBHm_00018745 ACVRL1 (ACVRL1) mRNA, encodes complete protein.
KR710997 - Synthetic construct Homo sapiens clone CCSBHm_00018806 ACVRL1 (ACVRL1) mRNA, encodes complete protein.
KR710998 - Synthetic construct Homo sapiens clone CCSBHm_00018845 ACVRL1 (ACVRL1) mRNA, encodes complete protein.
KU177888 - Homo sapiens activin A receptor type II-like 1 isoform 1 (ACVRL1) mRNA, partial cds.
KU177889 - Homo sapiens activin A receptor type II-like 1 isoform 2 (ACVRL1) mRNA, partial cds, alternatively spliced.
AK300619 - Homo sapiens cDNA FLJ57835 complete cds, highly similar to Serine/threonine-protein kinase receptor R3 precursor (EC 2.7.11.30).
JD103599 - Sequence 84623 from Patent EP1572962.
JD134503 - Sequence 115527 from Patent EP1572962.
JD152101 - Sequence 133125 from Patent EP1572962.
JD142237 - Sequence 123261 from Patent EP1572962.
JD387287 - Sequence 368311 from Patent EP1572962.
AK056725 - Homo sapiens cDNA FLJ32163 fis, clone PLACE6000371.
JD403401 - Sequence 384425 from Patent EP1572962.
JD187760 - Sequence 168784 from Patent EP1572962.
JD372235 - Sequence 353259 from Patent EP1572962.
JD452853 - Sequence 433877 from Patent EP1572962.
JD482819 - Sequence 463843 from Patent EP1572962.
JD188764 - Sequence 169788 from Patent EP1572962.
JD557887 - Sequence 538911 from Patent EP1572962.
JD198826 - Sequence 179850 from Patent EP1572962.
JD154367 - Sequence 135391 from Patent EP1572962.
JD262565 - Sequence 243589 from Patent EP1572962.
JD562264 - Sequence 543288 from Patent EP1572962.
JD085894 - Sequence 66918 from Patent EP1572962.
JD371219 - Sequence 352243 from Patent EP1572962.
JD337466 - Sequence 318490 from Patent EP1572962.
JD252601 - Sequence 233625 from Patent EP1572962.
JD242569 - Sequence 223593 from Patent EP1572962.
JD328241 - Sequence 309265 from Patent EP1572962.
JD354765 - Sequence 335789 from Patent EP1572962.
JD420419 - Sequence 401443 from Patent EP1572962.
JD513970 - Sequence 494994 from Patent EP1572962.
JD379767 - Sequence 360791 from Patent EP1572962.
JD312236 - Sequence 293260 from Patent EP1572962.
JD499043 - Sequence 480067 from Patent EP1572962.
JD238944 - Sequence 219968 from Patent EP1572962.
JD374448 - Sequence 355472 from Patent EP1572962.
JD545922 - Sequence 526946 from Patent EP1572962.
JD069538 - Sequence 50562 from Patent EP1572962.
JD235817 - Sequence 216841 from Patent EP1572962.
JD240124 - Sequence 221148 from Patent EP1572962.
JD354123 - Sequence 335147 from Patent EP1572962.
JD053776 - Sequence 34800 from Patent EP1572962.
JD416062 - Sequence 397086 from Patent EP1572962.
JD391040 - Sequence 372064 from Patent EP1572962.
JD118874 - Sequence 99898 from Patent EP1572962.
JD107104 - Sequence 88128 from Patent EP1572962.
JD357030 - Sequence 338054 from Patent EP1572962.
JD242132 - Sequence 223156 from Patent EP1572962.
JD365426 - Sequence 346450 from Patent EP1572962.
JD194486 - Sequence 175510 from Patent EP1572962.
JD469339 - Sequence 450363 from Patent EP1572962.
JD318512 - Sequence 299536 from Patent EP1572962.
JD180832 - Sequence 161856 from Patent EP1572962.
JD080380 - Sequence 61404 from Patent EP1572962.
JD441650 - Sequence 422674 from Patent EP1572962.
JD141050 - Sequence 122074 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P37023 (Reactome details) participates in the following event(s):

R-HSA-8858369 ACVRL1 binds BMP9,BMP10
R-HSA-201451 Signaling by BMP
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A6NGA8, ACVL1_HUMAN, ACVRLK1, ALK1, ENST00000388922.1, ENST00000388922.2, ENST00000388922.3, ENST00000388922.4, ENST00000388922.5, ENST00000388922.6, ENST00000388922.7, ENST00000388922.8, NM_001077401, P37023, uc001rzj.1, uc001rzj.2, uc001rzj.3, uc001rzj.4, uc001rzj.5
UCSC ID: ENST00000388922.9
RefSeq Accession: NM_000020
Protein: P37023 (aka ACVL1_HUMAN)
CCDS: CCDS31804.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ACVRL1:
hht (Hereditary Hemorrhagic Telangiectasia)
pph (Heritable Pulmonary Arterial Hypertension Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.