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Reviewed, UniProtKB/Swiss-Prot P37023 (ACVL1_HUMAN)

Last modified September 23, 2008. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Serine/threonine-protein kinase receptor R3
      Short name=SKR3
    EC=2.7.11.30
Alternative name(s):
    Activin receptor-like kinase 1
      Short name=ALK-1
    TGF-B superfamily receptor type I
      Short name=TSR-I
Gene names
Name: ACVRL1
Synonyms: ACVRLK1, ALK1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

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.

Involvement in 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.

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

Contains 1 GS domain.

Contains 1 protein kinase domain.

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Ontologies

Keywords

   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal
Transmembrane
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Serine/threonine-protein kinase
Transferase
   PTMGlycoprotein

Gene Ontology (GO)

   Biological processangiogenesis

Inferred from mutant phenotype. Source: HGNC

negative regulation of cell growth

Inferred from direct assay. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype. Source: HGNC

negative regulation of endothelial cell migration

Inferred from direct assay. Source: UniProtKB

negative regulation of focal adhesion formation

Inferred from mutant phenotype. Source: HGNC

positive regulation of BMP signaling pathway

Inferred from direct assay. Source: UniProtKB

positive regulation of transcription

Inferred from direct assay. Source: HGNC

protein amino acid phosphorylation

Inferred from direct assay. Source: HGNC

regulation of blood pressure Ref.12

Inferred from mutant phenotype. Source: HGNC

transforming growth factor beta receptor signaling pathway

Inferred from direct assay. Source: HGNC

wound healing, spreading of epidermal cells

Inferred from mutant phenotype. Source: HGNC

   Cellular componentintegral to plasma membrane Ref.2

Inferred from direct assay. Source: UniProtKB

   Molecular functionATP binding

Inferred from direct assay. Source: HGNC

SMAD binding

Inferred from direct assay. Source: HGNC

activin binding Ref.2

Inferred from direct assay. Source: UniProtKB

transforming growth factor beta binding Ref.2

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 503482Serine/threonine-protein kinase receptor R3

Regions

Topological domain22 – 11897Extracellular Potential
Transmembrane119 – 14123 Potential
Topological domain142 – 503362Cytoplasmic Potential
Domain172 – 20130GS
Domain202 – 492291Protein kinase
Nucleotide binding208 – 2169ATP By similarity

Sites

Active site3301Proton acceptor By similarity
Binding site2291ATP By similarity

Amino acid modifications

Glycosylation981N-linked (GlcNAc...) Potential

Natural variations

Natural variant48 – 492GA → EP in HHT2.
Natural variant481G → R in HHT2.
Natural variant501W → C in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant511C → Y in HHT2.
Natural variant671R → Q in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant671R → W in HHT2.
Natural variant771C → W in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant961N → D in HHT2.
Natural variant1791D → A in HHT2; mutant protein is capable of targeting the cell surface appropriately.
Natural variant2111G → D in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant2151E → K in HHT2.
Natural variant2231G → R in HHT2.
Natural variant2291K → R in HHT2.
Natural variant2321Missing in HHT2; mutant protein is capable of targeting the cell surface appropriately.
Natural variant2331Missing in HHT2.
Natural variant2451I → N: dbSNP rs1804508.
Natural variant2541Missing in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant2851L → F in HHT2.
Natural variant3061A → P in HHT2.
Natural variant3141H → Y in HHT2.
Natural variant3331S → I in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant3371L → P in HHT2.
Natural variant3441C → Y in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant3471A → P in HHT2.
Natural variant3741R → Q in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant3741R → W in HHT2.
Natural variant3761M → R in HHT2.
Natural variant3761M → V in HHT2.
Natural variant3781P → L in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant3791E → K in HHT2.
Natural variant3971D → G in HHT2.
Natural variant3981I → N in HHT2.
Natural variant3991W → S in HHT2.
Natural variant4071E → D in HHT2.
Natural variant4111R → P in HHT2.
Natural variant4111R → Q in HHT2; retained in the cell cytoplasm in the endoplasmic reticulum.
Natural variant4111R → W in HHT2.
Natural variant4241P → T in HHT2.
Natural variant4251F → L in HHT2.
Natural variant4251F → V in HHT2.
Natural variant4251Missing in HHT2.
Natural variant4791R → L in HHT2.
Natural variant4821A → V in HHT2.
Natural variant4841R → W in HHT2.
Natural variant4871K → T in HHT2; mutant protein is capable of targeting the cell surface appropriately.

Experimental info

Sequence conflict1721S → T in CAA80255. Ref.1

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Sequences

Sequence LengthMass (Da)Tools
P37023-1 [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: 074522AA802325DD

FASTA50356,124
        10         20         30         40         50         60 
MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG 

        70         80         90        100        110        120 
RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA 

       130        140        150        160        170        180 
LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS 

       190        200        210        220        230        240 
DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGESVAVKI FSSRDEQSWF 

       250        260        270        280        290        300 
RETEIYNTVL LRHDNILGFI ASDMTSRNSS TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL 

       310        320        330        340        350        360 
RLAVSAACGL AHLHVEIFGT QGKPAIAHRD FKSRNVLVKS NLQCCIADLG LAVMHSQGSD 

       370        380        390        400        410        420 
YLDIGNNPRV GTKRYMAPEV LDEQIRTDCF ESYKWTDIWA FGLVLWEIAR RTIVNGIVED 

       430        440        450        460        470        480 
YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT IPNRLAADPV LSGLAQMMRE CWYPNPSARL 

       490        500 
TALRIKKTLQ KISNSPEKPK VIQ

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References

« Hide 'large scale' references
[1]"Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity."
ten Dijke P., Ichijo H., Franzen P., Schulz P., Saras J., Toyoshima H., Heldin C.-H., Miyazono K.
Oncogene 8:2879-2887(1993) [PubMed: 8397373] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[2]"Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors."
Attisano L., Carcamo J., Ventura F., Weis F.M., Massague J., Wrana J.L.
Cell 75:671-680(1993) [PubMed: 8242742] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2."
Berg J.N., Gallione C.J., Stenzel T.T., Johnson D.W., Allen W.P., Schwartz C.E., Jackson C.E., Porteous M.E.M., Marchuk D.A.
Am. J. Hum. Genet. 61:60-67(1997) [PubMed: 9245985] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HHT2 CYS-50; GLN-67; ILE-333; TRP-374 AND THR-424.
[4]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed: 16541075] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2."
Johnson D.W., Berg J.N., Baldwin M.A., Gallione C.J., Marondel I., Yoon S.-J., Stenzel T.T., Speer M., Pericak-Vance M.A., Diamond A., Guttmacher A.E., Jackson C.E., Attisano L., Kucherlapati R., Porteous M.E.M., Marchuk D.A.
Nat. Genet. 13:189-194(1996) [PubMed: 8640225] [Abstract]
Cited for: VARIANTS HHT2 SER-232 DEL; ARG-376 AND GLN-411.
[8]"Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia."