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Identification
HMDB Protein ID HMDBP01222
Secondary Accession Numbers
  • 6518
Name Serine/threonine-protein kinase receptor R3
Synonyms
  1. ALK-1
  2. Activin receptor-like kinase 1
  3. SKR3
  4. TGF-B superfamily receptor type I
  5. TSR-I
Gene Name ACVRL1
Protein Type Unknown
Biological Properties
General Function Involved in receptor signaling protein serine/threonine kinase activity
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
transmembrane receptor protein serine/threonine kinase activity
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
receptor signaling protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
enzyme linked receptor protein signaling pathway
transmembrane receptor protein serine/threonine kinase signaling pathway
metabolic process
cellular metabolic process
protein amino acid phosphorylation
signaling
signaling pathway
cell surface receptor linked signaling pathway
phosphorylation
Cellular Location
  1. Membrane
  2. Single-pass type I membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 12q11-q14
SNPs ACVRL1
Gene Sequence
>1512 bp
ATGACCTTGGGCTCCCCCAGGAAAGGCCTTCTGATGCTGCTGATGGCCTTGGTGACCCAG
GGAGACCCTGTGAAGCCGTCTCGGGGCCCGCTGGTGACCTGCACGTGTGAGAGCCCACAT
TGCAAGGGGCCTACCTGCCGGGGGGCCTGGTGCACAGTAGTGCTGGTGCGGGAGGAGGGG
AGGCACCCCCAGGAACATCGGGGCTGCGGGAACTTGCACAGGGAGCTCTGCAGGGGGCGC
CCCACCGAGTTCGTCAACCACTACTGCTGCGACAGCCACCTCTGCAACCACAACGTGTCC
CTGGTGCTGGAGGCCACCCAACCTCCTTCGGAGCAGCCGGGAACAGATGGCCAGCTGGCC
CTGATCCTGGGCCCCGTGCTGGCCTTGCTGGCCCTGGTGGCCCTGGGTGTCCTGGGCCTG
TGGCATGTCCGACGGAGGCAGGAGAAGCAGCGTGGCCTGCACAGCGAGCTGGGAGAGTCC
AGTCTCATCCTGAAAGCATCTGAGCAGGGCGACACGATGTTGGGGGACCTCCTGGACAGT
GACTGCACCACAGGGAGTGGCTCAGGGCTCCCCTTCCTGGTGCAGAGGACAGTGGCACGG
CAGGTTGCCTTGGTGGAGTGTGTGGGAAAAGGCCGCTATGGCGAAGTGTGGCGGGGCTTG
TGGCACGGTGAGAGTGTGGCCGTCAAGATCTTCTCCTCGAGGGATGAACAGTCCTGGTTC
CGGGAGACTGAGATCTATAACACAGTATTGCTCAGACACGACAACATCCTAGGCTTCATC
GCCTCAGACATGACCTCCCGCAACTCGAGCACGCAGCTGTGGCTCATCACGCACTACCAC
GAGCACGGCTCCCTCTACGACTTTCTGCAGAGACAGACGCTGGAGCCCCATCTGGCTCTG
AGGCTAGCTGTGTCCGCGGCATGCGGCCTGGCGCACCTGCACGTGGAGATCTTCGGTACA
CAGGGCAAACCAGCCATTGCCCACCGCGACTTCAAGAGCCGCAATGTGCTGGTCAAGAGC
AACCTGCAGTGTTGCATCGCCGACCTGGGCCTGGCTGTGATGCACTCACAGGGCAGCGAT
TACCTGGACATCGGCAACAACCCGAGAGTGGGCACCAAGCGGTACATGGCACCCGAGGTG
CTGGACGAGCAGATCCGCACGGACTGCTTTGAGTCCTACAAGTGGACTGACATCTGGGCC
TTTGGCCTGGTGCTGTGGGAGATTGCCCGCCGGACCATCGTGAATGGCATCGTGGAGGAC
TATAGACCACCCTTCTATGATGTGGTGCCCAATGACCCCAGCTTTGAGGACATGAAGAAG
GTGGTGTGTGTGGATCAGCAGACCCCCACCATCCCTAACCGGCTGGCTGCAGACCCGGTC
CTCTCAGGCCTAGCTCAGATGATGCGGGAGTGCTGGTACCCAAACCCCTCTGCCCGACTC
ACCGCGCTGCGGATCAAGAAGACACTACAAAAAATTAGCAACAGTCCAGAGAAGCCTAAA
GTGATTCAATAG
Protein Properties
Number of Residues 503
Molecular Weight 56124.0
Theoretical pI 7.64
Pfam Domain Function
Signals
  • 1-21
Transmembrane Regions
  • 119-141
Protein Sequence
>Serine/threonine-protein kinase receptor R3
MTLGSPRKGLLMLLMALVTQGDPVKPSRGPLVTCTCESPHCKGPTCRGAWCTVVLVREEG
RHPQEHRGCGNLHRELCRGRPTEFVNHYCCDSHLCNHNVSLVLEATQPPSEQPGTDGQLA
LILGPVLALLALVALGVLGLWHVRRRQEKQRGLHSELGESSLILKASEQGDSMLGDLLDS
DCTTGSGSGLPFLVQRTVARQVALVECVGKGRYGEVWRGLWHGESVAVKIFSSRDEQSWF
RETEIYNTVLLRHDNILGFIASDMTSRNSSTQLWLITHYHEHGSLYDFLQRQTLEPHLAL
RLAVSAACGLAHLHVEIFGTQGKPAIAHRDFKSRNVLVKSNLQCCIADLGLAVMHSQGSD
YLDIGNNPRVGTKRYMAPEVLDEQIRTDCFESYKWTDIWAFGLVLWEIARRTIVNGIVED
YRPPFYDVVPNDPSFEDMKKVVCVDQQTPTIPNRLAADPVLSGLAQMMRECWYPNPSARL
TALRIKKTLQKISNSPEKPKVIQ
GenBank ID Protein 402197
UniProtKB/Swiss-Prot ID P37023
UniProtKB/Swiss-Prot Entry Name ACVL1_HUMAN
PDB IDs Not Available
GenBank Gene ID Z22533
GeneCard ID ACVRL1
GenAtlas ID ACVRL1
HGNC ID HGNC:175
References
General References
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  3. ten Dijke P, Ichijo H, Franzen P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K: Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity. Oncogene. 1993 Oct;8(10):2879-87. [PubMed:8397373 ]
  4. Attisano L, Carcamo J, Ventura F, Weis FM, Massague J, Wrana JL: Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors. Cell. 1993 Nov 19;75(4):671-80. [PubMed:8242742 ]
  5. Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA: The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet. 1997 Jul;61(1):60-7. [PubMed:9245985 ]
  6. Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA: Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996 Jun;13(2):189-95. [PubMed:8640225 ]
  7. Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA: Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online. Hum Mutat. 1998;12(2):137. [PubMed:10694922 ]
  8. Abdalla SA, Pece-Barbara N, Vera S, Tapia E, Paez E, Bernabeu C, Letarte M: Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2. Hum Mol Genet. 2000 May 1;9(8):1227-37. [PubMed:10767348 ]
  9. Kjeldsen AD, Brusgaard K, Poulsen L, Kruse T, Rasmussen K, Green A, Vase P: Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families. Am J Med Genet. 2001 Feb 1;98(4):298-302. [PubMed:11170071 ]
  10. Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L: Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2001 Aug 2;345(5):325-34. [PubMed:11484689 ]
  11. Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Kermeen F, Halme M, Raisanen-Sokolowski A, Laitinen T, Morrell NW, Trembath RC: Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet. 2003 Dec;40(12):865-71. [PubMed:14684682 ]
  12. Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Riviere S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S: Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004 Apr;23(4):289-99. [PubMed:15024723 ]
  13. Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M: Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations. Hum Mutat. 2005 Mar;25(3):320. [PubMed:15712270 ]