Tchem ACVRL1 Serine/threonine-protein kinase receptor R3

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Serine/threonine Protein Kinase Receptor / Serine/threonine-protein Kinase Receptor R3

Protein / Receptor / Protein Kinase Receptor / Serine/threonine Protein Kinase Receptor / Serine/threonine-protein Kinase Receptor R3

Protein / Receptor / Cytokine Receptor / Tgf-beta Receptor / Serine/threonine-protein Kinase Receptor R3

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Stkr Family / Stkr Type 1 Subfamily / Serine/threonine-protein Kinase Receptor R3

Protein Summary

Description

Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. 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. May bind activin as well. 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]

Uniprot Accession IDs

• P37023
• A6NGA8
• SKR3

Gene Name

• ACVRL1

Ensembl ID

• ENST00000388922
• ENSP00000373574
• ENSG00000139567

Symbol

• ACVRLK1
• ALK1
• HHT
• ALK1
• HHT2
• ORW2
• SKR3
• ALK-1
• TSR-I
• ACVRLK1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	1
protein domain	0.92
disease perturbation	0.79
biological term	0.78

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 383.6   (req: < 5)

Gene RIFs: 115   (req: <= 3)

Antibodies: 540   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 383.6   (req: >= 5)

Gene RIFs: 115   (req: > 3)

Antibodies: 540   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 60

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 54

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (54)

Explore Active Ligands

1 – 10 of 54

SID103905531

ACVRL1Tchem Kinase

IC50 : 8.87

AT-9283

ACVRL1Tchem Kinase

Kd : 7.82

PP-242

ACVRL1Tchem Kinase

Kd : 8.54

CHEMBL2385579

ACVRL1Tchem Kinase

IC50 : 7.38000011

CHEMBL2385582

ACVRL1Tchem Kinase

IC50 : 8.30000019

CHEMBL2385596

ACVRL1Tchem Kinase

IC50 : 8.30000019

panulisib

ACVRL1Tchem Kinase

IC50 : 7.32999992

US8822500, [1]

ACVRL1Tchem Kinase

IC50 : 8.33

US8822500, [4]

ACVRL1Tchem Kinase

IC50 : 8.01

CHEMBL513147

ACVRL1Tchem Kinase

IC50 : 7.95

GWAS Traits (23)

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5

1 – 5 of 23

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
neutrophil count	EFO_0004833	3	2	3		84.7
hematocrit	EFO_0004348	4	3	4		84.3
myeloid white cell count	EFO_0007988	2	1	2		78.5
urate measurement	EFO_0004531	4	4	4		75
platelet crit	EFO_0007985	2	1	2		73.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
neutrophil count	EFO_0004833	3		84.7
hematocrit	EFO_0004348	4		84.3
myeloid white cell count	EFO_0007988	2		78.5
urate measurement	EFO_0004531	4		75
platelet crit	EFO_0007985	2		73.7

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Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	activin A receptor like type 1	VGNC:8313	451910
Macaque	activin A receptor like type 1		696471
Mouse	activin A receptor, type II-like 1	MGI:1338946	11482
Rat	activin A receptor like type 1	RGD:2029	25237
Dog	activin A receptor like type 1	VGNC:37566	477603

Species	Name	OMA	EggNOG	Inparanoid
Chimp	activin A receptor like type 1
Macaque	activin A receptor like type 1
Mouse	activin A receptor, type II-like 1
Rat	activin A receptor like type 1
Dog	activin A receptor like type 1

Protein Structure (3 Structures, 1 AlphaFold Model)

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Representation

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Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P37023-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 3 of 3

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (56)

Reactome (3)

KEGG (1)

PathwayCommons (13)

WikiPathways (39)

Signal Transduction (R-HSA-162582)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by BMP	28 targets	R-HSA-201451
Reactome	Signaling by TGF-beta family members	102 targets	R-HSA-9006936

Name	Explore in Pharos	Explore in Source
Signal Transduction	2704 targets	R-HSA-162582
Signaling by BMP	28 targets	R-HSA-201451
Signaling by TGF-beta family members	102 targets	R-HSA-9006936

Gene Ontology Terms (67)

Functions (13)

Components (7)

Processes (47)

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10

1 – 10 of 13

GO Term	Evidence	Assigned by
activin binding	Inferred from Direct Assay (IDA)	UniProtKB
activin receptor activity, type I	Inferred from Direct Assay (IDA)	MGI
ATP binding	Inferred from Direct Assay (IDA)	HGNC
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	HGNC
SMAD binding	Inferred from Direct Assay (IDA)	HGNC
transforming growth factor beta receptor activity, type I	Inferred from Direct Assay (IDA)	UniProtKB
transforming growth factor beta-activated receptor activity	Inferred from Direct Assay (IDA)	MGI
protein kinase binding	Inferred from Physical Interaction (IPI)	BHF-UCL
transforming growth factor beta binding	Inferred from Physical Interaction (IPI)	UniProtKB
BMP receptor activity	Inferred from Mutant Phenotype (IMP)	UniProtKB

Protein-Protein Interactions (103)

Explore Interacting Targets

1 – 10 of 103

• See Interactions on String-DB

PDXDC2P

Tdark

Family:  Enzyme

p_int:  0.982542538

p_ni:  0.016176108

p_wrong:  0.001281354

Data Source:  BioPlex

SLC25A24

Tbio

Family:  Transporter

Novelty:  0.06151955

p_int:  0.958455576

p_ni:  0.036005985

p_wrong:  0.005538439

Score:  0.228

Data Source:  BioPlex,STRINGDB

ACVR1

Tchem

Family:  Kinase

Novelty:  0.00284646

p_int:  0.874917456

p_ni:  8e-9

p_wrong:  0.125082536

Score:  0.546

Data Source:  BioPlex,STRINGDB

GDF2

Tbio

Novelty:  0.00433233

Score:  0.998

Data Source:  Reactome,STRINGDB

ENG

Tbio

Novelty:  0.00036729

Score:  0.993

Data Source:  STRINGDB

BMP10

Tbio

Novelty:  0.01860398

Score:  0.984

Data Source:  Reactome,STRINGDB

ACVR2B

Tchem

Family:  Kinase

Novelty:  0.00555742

Score:  0.976

Data Source:  STRINGDB

SMAD1

Tbio

Family:  TF

Novelty:  0.02348173

Score:  0.97

Data Source:  STRINGDB

SMAD9

Tbio

Family:  TF

Novelty:  0.00285887

Score:  0.969

Data Source:  STRINGDB

TGFB1

Tbio

Novelty:  0.0001299

Score:  0.969

Data Source:  STRINGDB

Publication Statistics

PubMed Score  383.60

PubMed score by year

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PubTator Score  310.99

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Angiogenesis
ATP-binding
Cell membrane
Complete proteome
Disease mutation
Disulfide bond
Glycoprotein
Kinase
Magnesium

GWAS Trait Find Similar Targets

No Header	No Header
CC16 measurement
depressive symptom measurement
energy intake measurement
granulocyte count
hematocrit
hemoglobin measurement
HMG CoA reductase inhibitor use measurement
leukocyte count
lung adenocarcinoma
lung carcinoma

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
craniofacial phenotype
digestive/alimentary phenotype
embryo phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
liver/biliary system phenotype
mortality/aging
muscle phenotype