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P37023 (ACVL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 161. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

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) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

General annotation (Comments)

Function

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. Ref.7 Ref.8

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

Telangiectasia, hereditary hemorrhagic, 2 (HHT2) [MIM:600376]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20

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.

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Serine/threonine-protein kinase
Transferase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from mutant phenotype PubMed 19366699. Source: BHF-UCL

activin receptor signaling pathway

Inferred from direct assay Ref.2. Source: GOC

angiogenesis

Inferred from mutant phenotype Ref.18. Source: HGNC

artery development

Inferred from sequence or structural similarity. Source: BHF-UCL

blood circulation

Inferred from mutant phenotype Ref.18. Source: HGNC

blood vessel endothelial cell proliferation involved in sprouting angiogenesis

Traceable author statement PubMed 20406889. Source: DFLAT

blood vessel maturation

Traceable author statement PubMed 20406889. Source: DFLAT

blood vessel remodeling

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to BMP stimulus

Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL

cellular response to transforming growth factor beta stimulus

Inferred from direct assay PubMed 19494318. Source: BHF-UCL

endothelial tube morphogenesis

Inferred from mutant phenotype PubMed 19592636. Source: BHF-UCL

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

lymphangiogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

lymphatic endothelial cell differentiation

Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL

negative regulation of DNA biosynthetic process

Inferred from mutant phenotype PubMed 19366699. Source: BHF-UCL

negative regulation of blood vessel endothelial cell migration

Inferred from mutant phenotype PubMed 19592636. Source: BHF-UCL

negative regulation of cell adhesion

Inferred from mutant phenotype PubMed 12453878. Source: HGNC

negative regulation of cell growth

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

negative regulation of cell migration

Inferred from mutant phenotype PubMed 12453878. Source: HGNC

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 12453878. Source: HGNC

negative regulation of endothelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of endothelial cell migration

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

negative regulation of endothelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of focal adhesion assembly

Inferred from mutant phenotype PubMed 12453878. Source: HGNC

positive regulation of BMP signaling pathway

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

positive regulation of chondrocyte differentiation

Traceable author statement PubMed 19494318. Source: BHF-UCL

positive regulation of endothelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from mutant phenotype PubMed 19366699. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19366699. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12393874. Source: HGNC

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 12065756. Source: HGNC

regulation of DNA replication

Traceable author statement PubMed 20406889. Source: DFLAT

regulation of blood pressure

Inferred from mutant phenotype Ref.14. Source: HGNC

regulation of blood vessel endothelial cell migration

Traceable author statement PubMed 20406889. Source: DFLAT

regulation of endothelial cell proliferation

Traceable author statement PubMed 20406889. Source: DFLAT

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 15702480. Source: HGNC

retina vasculature development in camera-type eye

Inferred from sequence or structural similarity. Source: BHF-UCL

signal transduction

Inferred from direct assay PubMed 15702480. Source: HGNC

transforming growth factor beta receptor signaling pathway

Inferred from direct assay PubMed 15702480. Source: HGNC

venous blood vessel development

Inferred from sequence or structural similarity. Source: BHF-UCL

wound healing, spreading of epidermal cells

Inferred from mutant phenotype PubMed 12453878. Source: HGNC

   Cellular_componentcell surface

Inferred from direct assay Ref.2. Source: MGI

dendrite

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Inferred from direct assay Ref.2. Source: UniProtKB

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from direct assay PubMed 12065756. Source: HGNC

SMAD binding

Inferred from direct assay PubMed 12065756. Source: HGNC

activin binding

Inferred from direct assay Ref.2. Source: UniProtKB

activin receptor activity, type I

Inferred from direct assay Ref.2. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase binding

Inferred from physical interaction PubMed 19592636. Source: BHF-UCL

protein serine/threonine kinase activity

Inferred from direct assay PubMed 12065756PubMed 12393874. Source: HGNC

receptor signaling protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta binding

Inferred from physical interaction Ref.2. Source: UniProtKB

transforming growth factor beta receptor activity, type I

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta-activated receptor activity

Inferred from direct assay Ref.2. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 503482Serine/threonine-protein kinase receptor R3
PRO_0000024420

Regions

Topological domain22 – 11897Extracellular Potential
Transmembrane119 – 14123Helical; Potential
Topological domain142 – 503362Cytoplasmic Potential
Domain172 – 20130GS
Domain202 – 492291Protein kinase
Nucleotide binding208 – 2169ATP By similarity
Region73 – 764Mediates specificity for BMP ligand

Sites

Active site3301Proton acceptor By similarity
Binding site2291ATP By similarity

Amino acid modifications

Modified residue1551Phosphoserine By similarity
Glycosylation981N-linked (GlcNAc...) Potential
Disulfide bond34 ↔ 51 Ref.7 Ref.8
Disulfide bond36 ↔ 41 Ref.7 Ref.8
Disulfide bond46 ↔ 69 Ref.7 Ref.8
Disulfide bond77 ↔ 89 Ref.7 Ref.8
Disulfide bond90 ↔ 95 Ref.7 Ref.8

Natural variations

Natural variant301P → S Found in a patient with hereditary hemorrhagic talagiectasia; unknown pathological significance. Ref.18
VAR_070308
Natural variant341C → Y in HHT2. Ref.18
VAR_070309
Natural variant381S → C. Ref.20
VAR_070310
Natural variant48 – 492GA → EP in HHT2.
VAR_026784
Natural variant481G → R in HHT2. Ref.16
VAR_026785
Natural variant501W → C in HHT2; retained in the endoplasmic reticulum. Ref.3 Ref.11 Ref.14
VAR_006204
Natural variant501W → G in HHT2. Ref.19
VAR_070311
Natural variant511C → Y in HHT2. Ref.10
VAR_006205
Natural variant521T → A in HHT2. Ref.18
VAR_070312
Natural variant661H → P in HHT2. Ref.19
VAR_070313
Natural variant671R → Q in HHT2; retained in the endoplasmic reticulum. Ref.3 Ref.14
VAR_006206
Natural variant671R → W in HHT2. Ref.17
VAR_026786
Natural variant691C → R in HHT2. Ref.19
VAR_070314
Natural variant771C → W in HHT2; retained in the endoplasmic reticulum. Ref.10 Ref.14
VAR_006207
Natural variant961N → D in HHT2. Ref.10
VAR_006208
Natural variant961N → S in HHT2. Ref.20
VAR_070315
Natural variant1381L → P. Ref.20
VAR_070316
Natural variant1761D → Y in HHT2. Ref.19
VAR_070317
Natural variant1791D → A in HHT2; mutant protein is capable of targeting the cell surface appropriately. Ref.14
VAR_026787
Natural variant1971T → I in HHT2. Ref.18
VAR_070318
Natural variant2111G → D in HHT2; retained in the endoplasmic reticulum. Ref.14
Corresponds to variant rs28936687 [ dbSNP | Ensembl ].
VAR_026788
Natural variant2151E → K in HHT2. Ref.16
VAR_026789
Natural variant2171W → G in HHT2. Ref.20
VAR_070319
Natural variant2191G → D in HHT2. Ref.18
VAR_070320
Natural variant2231G → R in HHT2. Ref.16
VAR_026790
Natural variant2261V → E in HHT2. Ref.20
VAR_070321
Natural variant2291K → R in HHT2. Ref.16
VAR_026791
Natural variant2321Missing in HHT2; mutant protein is capable of targeting the cell surface appropriately. Ref.9 Ref.11 Ref.14
VAR_006209
Natural variant2331S → L in HHT2. Ref.19
VAR_070322
Natural variant2331Missing in HHT2. Ref.16
VAR_026792
Natural variant2371Q → K in HHT2. Ref.18
VAR_070323
Natural variant2451I → N.
Corresponds to variant rs1804508 [ dbSNP | Ensembl ].
VAR_011717
Natural variant2541Missing in HHT2; retained in the endoplasmic reticulum. Ref.13 Ref.14
VAR_026793
Natural variant2601I → L in HHT2. Ref.18
VAR_070324
Natural variant2651T → P in HHT2. Ref.19
VAR_070325
Natural variant2771T → K Found in a patient with hereditary hemorrhagic talagiectasia; unknown pathological significance. Ref.20
VAR_070326
Natural variant2801H → R in HHT2. Ref.20
VAR_070327
Natural variant2851L → F in HHT2. Ref.16
VAR_026794
Natural variant2891L → P in HHT2. Ref.18
VAR_070328
Natural variant2941L → R in HHT2. Ref.20
VAR_070329
Natural variant3061A → P in HHT2. Ref.16
VAR_026795
Natural variant3141H → Y in HHT2. Ref.16
VAR_026796
Natural variant3281H → Q in HHT2. Ref.20
VAR_070330
Natural variant3331S → I in HHT2; retained in the endoplasmic reticulum. Ref.3 Ref.11 Ref.14
VAR_006210
Natural variant3351N → H in HHT2. Ref.20
VAR_070331
Natural variant3371L → P in HHT2. Ref.16
VAR_026797
Natural variant3421L → P. Ref.20
VAR_070332
Natural variant3441C → R in HHT2. Ref.18
VAR_070333
Natural variant3441C → Y in HHT2; retained in the endoplasmic reticulum. Ref.11 Ref.14
Corresponds to variant rs28936688 [ dbSNP | Ensembl ].
VAR_026798
Natural variant3471A → D in HHT2. Ref.20
VAR_070334
Natural variant3471A → P in HHT2. Ref.16
VAR_026799
Natural variant3741R → Q in HHT2; retained in the endoplasmic reticulum. Ref.14 Ref.16
VAR_026800
Natural variant3741R → W in HHT2. Ref.3 Ref.12 Ref.14 Ref.17
Corresponds to variant rs28936401 [ dbSNP | Ensembl ].
VAR_006211
Natural variant3761M → R in HHT2. Ref.9
Corresponds to variant rs28936399 [ dbSNP | Ensembl ].
VAR_006212
Natural variant3761M → V in HHT2. Ref.16
VAR_026801
Natural variant3781P → L in HHT2; retained in the endoplasmic reticulum. Ref.14
VAR_026802
Natural variant3781P → S in HHT2. Ref.20
VAR_070335
Natural variant3791E → K in HHT2. Ref.16 Ref.17
VAR_026803
Natural variant3971D → G in HHT2. Ref.16
VAR_026804
Natural variant3981I → N in HHT2. Ref.12
Corresponds to variant rs28936400 [ dbSNP | Ensembl ].
VAR_026805
Natural variant3991W → S in HHT2. Ref.14
Corresponds to variant rs28936402 [ dbSNP | Ensembl ].
VAR_026806
Natural variant4001A → T Found in a patient with hereditary hemorrhagic talagiectasia; unknown pathological significance. Ref.20
VAR_070336
Natural variant4031L → P in HHT2. Ref.19
VAR_070337
Natural variant4071E → D in HHT2. Ref.11 Ref.17
VAR_026807
Natural variant4111R → P in HHT2. Ref.16
VAR_026808
Natural variant4111R → Q in HHT2; retained in the endoplasmic reticulum. Ref.9 Ref.14 Ref.16
Corresponds to variant rs28936398 [ dbSNP | Ensembl ].
VAR_006213
Natural variant4111R → W in HHT2. Ref.13 Ref.16 Ref.17
VAR_026809
Natural variant4161G → S in HHT2. Ref.19
VAR_070338
Natural variant4241P → R in HHT2. Ref.20
VAR_070339
Natural variant4241P → T in HHT2. Ref.3
VAR_006214
Natural variant4251F → L in HHT2. Ref.16
VAR_026810
Natural variant4251F → V in HHT2. Ref.17
VAR_026811
Natural variant4251Missing in HHT2. Ref.17
VAR_026812
Natural variant4261Y → C in HHT2. Ref.18
VAR_070340
Natural variant4331P → R in HHT2. Ref.18
VAR_070341
Natural variant4491P → S in HHT2. Ref.20
VAR_070342
Natural variant4791R → L in HHT2. Ref.16
VAR_026813
Natural variant4791R → P in HHT2. Ref.20
VAR_070343
Natural variant4821A → V in HHT2. Ref.16
Corresponds to variant rs139142865 [ dbSNP | Ensembl ].
VAR_026814
Natural variant4841R → W in HHT2. Ref.13 Ref.16
VAR_026815
Natural variant4861K → E Found in a patient with hereditary hemorrhagic talagiectasia; unknown pathological significance. Ref.20
VAR_070344
Natural variant4871K → T in HHT2; mutant protein is capable of targeting the cell surface appropriately. Ref.14
VAR_026816

Experimental info

Mutagenesis74 – 763REL → DFQ: Affinity for BMP9 decreased by 200-fold. Ref.7
Sequence conflict1721S → T in CAA80255. Ref.1

Secondary structure

................................................................ 503
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P37023 [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 

« Hide

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties."
Mahlawat P., Ilangovan U., Biswas T., Sun L.Z., Hinck A.P.
Biochemistry 51:6328-6341(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 19-118, FUNCTION AS BMP9 RECEPTOR, DISULFIDE BONDS, MUTAGENESIS OF 74-ARG--LEU-76.
[8]"Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex."
Townson S.A., Martinez-Hackert E., Greppi C., Lowden P., Sako D., Liu J., Ucran J.A., Liharska K., Underwood K.W., Seehra J., Kumar R., Grinberg A.V.
J. Biol. Chem. 287:27313-27325(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.36 ANGSTROMS) OF 22-118 IN COMPLEX WITH BMP9 AND ACVR2B, FUNCTION AS BMP9 AND BMP10 RECEPTOR, DISULFIDE BONDS.
[9]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 SER-232 DEL; ARG-376 AND GLN-411.
[10]"Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia."
Klaus D.J., Gallione C.J., Anthony K., Yeh E.Y., Yu J., Lux A., Johnson D.W., Marchuk D.A.
Hum. Mutat. 12:137-137(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 TYR-51; TRP-77 AND ASP-96.
[11]"Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2."
Abdalla S.A., Pece-Barbara N., Vera S., Tapia E., Paez E., Bernabeu C., Letarte M.
Hum. Mol. Genet. 9:1227-1237(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 GLY-48-49-ALA DELINS EP; CYS-50; SER-232 DEL; ILE-333; TYR-344 AND ASP-407.
[12]"Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families."
Kjeldsen A.D., Brusgaard K., Poulsen L., Kruse T., Rasmussen K., Green A., Vase P.
Am. J. Med. Genet. 98:298-302(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 TRP-374 AND ASN-398.
[13]"Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia."
Trembath R.C., Thomson J.R., Machado R.D., Morgan N.V., Atkinson C., Winship I., Simonneau G., Galie N., Loyd J.E., Humbert M., Nichols W.C., Berg J., Manes A., McGaughran J., Pauciulo M., Wheeler L., Morrell N.W.
N. Engl. J. Med. 345:325-334(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 ASP-254 DEL; TRP-411 AND TRP-484.
[14]"Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia."
Harrison R.E., Flanagan J.A., Sankelo M., Abdalla S.A., Rowell J., Machado R.D., Elliott C.G., Robbins I.M., Olschewski H., McLaughlin V., Gruenig E., Kermeen F., Halme M., Raeisaenen-Sokolowski A., Laitinen T., Morrell N.W., Trembath R.C.
J. Med. Genet. 40:865-871(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 ALA-179; ASP-211; TYR-344; TRP-374; GLN-374; SER-399; GLN-411 AND THR-487, CHARACTERIZATION OF VARIANTS HHT2 CYS-50; GLN-67; TRP-77; ALA-179; ASP-211; SER-232 DEL; ASP-254 DEL; ILE-333; TYR-344; GLN-374; LEU-378; GLN-411 AND THR-487.
[15]Erratum
Harrison R.E., Flanagan J.A., Sankelo M., Abdalla S.A., Rowell J., Machado R.D., Elliott C.G., Robbins I.M., Olschewski H., McLaughlin V., Gruenig E., Kermeen F., Halme M., Raeisaenen-Sokolowski A., Laitinen T., Morrell N.W., Trembath R.C.
J. Med. Genet. 41:576-576(2004)
[16]"Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France."
French Rendu-Osler network
Lesca G., Plauchu H., Coulet F., Lefebvre S., Plessis G., Odent S., Riviere S., Leheup B., Goizet C., Carette M.-F., Cordier J.-F., Pinson S., Soubrier F., Calender A., Giraud S.
Hum. Mutat. 23:289-299(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 ARG-48; LYS-215; ARG-223; ARG-229; SER-233 DEL; PHE-285; PRO-306; TYR-314; PRO-337; PRO-347; GLN-374; VAL-376; LYS-379; GLY-397; TRP-411; PRO-411; GLN-411; LEU-425; LEU-479; VAL-482 AND TRP-484.
[17]"Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations."
Kuehl H.K.A., Caselitz M., Hasenkamp S., Wagner S., El-Harith E.-H.A., Manns M.P., Stuhrmann M.
Hum. Mutat. 25:320-320(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 TRP-67; TRP-374; LYS-379; ASP-407; TRP-411; VAL-425 AND PHE-425 DEL.
[18]"Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype."
Bossler A.D., Richards J., George C., Godmilow L., Ganguly A.
Hum. Mutat. 27:667-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-30, VARIANTS HHT2 TYR-34; ALA-52; ILE-197; ASP-219; LYS-237; LEU-260; PRO-289; ARG-344; CYS-426 AND ARG-433.
[19]"Novel mutations in the ENG and ACVRL1 genes causing hereditary hemorrhagic teleangiectasia."
Argyriou L., Twelkemeyer S., Panchulidze I., Wehner L.E., Teske U., Engel W., Nayernia K.
Int. J. Mol. Med. 17:655-659(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT2 GLY-50; PRO-66; ARG-69; TYR-176; LEU-233; PRO-265; PRO-403 AND SER-416.
[20]"Update on molecular diagnosis of hereditary hemorrhagic telangiectasia."
Richards-Yutz J., Grant K., Chao E.C., Walther S.E., Ganguly A.
Hum. Genet. 128:61-77(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYS-38; PRO-138; LYS-277; PRO-342; THR-400 AND GLU-486, VARIANTS HHT2 SER-96; GLY-217; GLU-226; ARG-280; ARG-294; GLN-328; HIS-335; ASP-347; SER-378; ARG-424; SER-449 AND PRO-479.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z22533 mRNA. Translation: CAA80255.1.
L17075 mRNA. Translation: AAA16160.1.
U77713 expand/collapse EMBL AC list , U77707, U77708, U77709, U77710, U77711, U77712 Genomic DNA. Translation: AAB61900.1.
AC025259 Genomic DNA. No translation available.
CH471111 Genomic DNA. Translation: EAW58213.1.
BC042637 mRNA. Translation: AAH42637.1.
PIRA49431.
RefSeqNP_000011.2. NM_000020.2.
NP_001070869.1. NM_001077401.1.
XP_005269292.1. XM_005269235.2.
UniGeneHs.591026.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LCRNMR-A19-118[»]
3MY0X-ray2.65A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X195-497[»]
4FAOX-ray3.36C/D/I/J/O/P/U/V/c/d/i/j22-118[»]
ProteinModelPortalP37023.
SMRP37023. Positions 170-493.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106609. 15 interactions.
DIPDIP-5938N.
IntActP37023. 1 interaction.
STRING9606.ENSP00000267008.

Chemistry

BindingDBP37023.
ChEMBLCHEMBL5311.
DrugBankDB00171. Adenosine triphosphate.
GuidetoPHARMACOLOGY1784.

PTM databases

PhosphoSiteP37023.

Polymorphism databases

DMDM3915750.

Proteomic databases

PaxDbP37023.
PRIDEP37023.

Protocols and materials databases

DNASU94.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000388922; ENSP00000373574; ENSG00000139567.
GeneID94.
KEGGhsa:94.
UCSCuc001rzj.3. human.

Organism-specific databases

CTD94.
GeneCardsGC12P052300.
HGNCHGNC:175. ACVRL1.
HPAHPA007041.
MIM600376. phenotype.
601284. gene.
neXtProtNX_P37023.
Orphanet774. Hereditary hemorrhagic telangiectasia.
275777. Heritable pulmonary arterial hypertension.
PharmGKBPA24496.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000230587.
HOVERGENHBG054502.
InParanoidP37023.
KOK13594.
PhylomeDBP37023.
TreeFamTF314724.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
SignaLinkP37023.

Gene expression databases

ArrayExpressP37023.
BgeeP37023.
CleanExHS_ACVRL1.
GenevestigatorP37023.

Family and domain databases

InterProIPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR003605. TGF_beta_rcpt_GS.
IPR000333. TGFB_receptor.
[Graphical view]
PfamPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
PRINTSPR00653. ACTIVIN2R.
SMARTSM00467. GS. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSACVRL1. human.
GeneWikiACVRL1.
GenomeRNAi94.
NextBio355.
PROP37023.
SOURCESearch...

Entry information

Entry nameACVL1_HUMAN
AccessionPrimary (citable) accession number: P37023
Secondary accession number(s): A6NGA8
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: December 15, 1998
Last modified: April 16, 2014
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM