Serine/threonine-protein kinase receptor R3 is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that in humans is encoded by the ''ACVRL1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. ACVRL1 is a receptor in the

TGF beta signaling pathway The transforming growth factor beta (TGFB) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, cell migration, apoptosis, cellular homeostasis an ...

. It is also known as activin receptor-like kinase 1, or ALK1.

Function

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 hereditary hemorrhagic telangiectasia (HHT) type 2, also known as Rendu-Osler-Weber syndrome 2.

Pathology

Germline mutation A germline mutation, or germinal mutation, is any detectable variation within germ cells (cells that, when fully developed, become sperm and ova). Mutations in these cells are the only mutations that can be passed on to offspring, when either a m ...

s of ACVRL1 are associated with: *

hereditary hemorrhagic telangiectasia Hereditary hemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu disease and Osler–Weber–Rendu syndrome, is a rare autosomal dominant genetic disorder that leads to abnormal blood vessel formation in the skin, mucous membranes, ...

type 2 (Rendu-Osler-Weber syndrome 2) * Pulmonary

arteriovenous malformation Arteriovenous malformation is an abnormal connection between arteries and veins, bypassing the capillary system. This vascular anomaly is widely known because of its occurrence in the central nervous system (usually cerebral AVM), but can app ...

Somatic mosaicism Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized ...

in ACVRL1 are associated with severe pulmonary arterial hypertension. ACVRL1 directly interacts with

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densi ...

(

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

), which implies that it might initiate the early phases of

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...

. Abnormal activity of ACVRL1 has been found to be closely associated with idiopathic pulmonary arterial hypertension.

As a drug target

Dalantercept ALK inhibitors are anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4- ALK translocation. They fall under the category of tyrosine kinase inhibitors, which work by inhibiting proteins involve ...

is an experimental

ALK1 Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ''ACVRL1'' gene. ACVRL1 is a receptor in the TGF beta signaling pathway. It is also known as activin receptor-like kinase 1, or ALK1. Function This ge ...

inhibitor.

Closely/family related kinases

(Not to be confused with

anaplastic lymphoma kinase Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ''ALK'' gene. Identification Anaplastic lymphoma kinase (ALK) was originally d ...

(ALK) )
ALK4 is

ACVR1B Activin receptor type-1B is a protein that in humans is encoded by the ''ACVR1B'' gene. ACVR1B or ALK-4 acts as a transducer of activin or activin-like ligands (e.g., inhibin) signals. Activin binds to either ACVR2A or ACVR2B and then forms a c ...

, ALK7 is

ACVR1C The activin A receptor also known as ACVR1C or ALK-7 is a protein that in humans is encoded by the ACVR1C gene. ACVR1C is a type I receptor for the TGFB family of signaling molecules. ACVR1C transduces signals of Nodal. Nodal binds to ACVR2B ...

, and ALK5 is

art of Art is a diverse range of human behavior, human activity, and resulting product, that involves creative or imagination, imaginative talent expressive of technical proficiency, beauty, emotional power, or conceptual ideas. There is no genera ...

the TGF-β type I receptor.

References

External links

GeneReviews/NCBI/NIH/UW entry on Hereditary Hemorrhagic Telangiectasia
* {{Portal bar, Biology, border=no Human proteins EC 2.7.11