P37023 (ACVL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	503 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Hereditary hemorrhagic telangiectasia 2 (HHT2) [MIM:600376]: 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. 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
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 process	Angiogenesis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from mutant phenotype PubMed 19366699. Source: BHF-UCL artery development Inferred from sequence or structural similarity. Source: BHF-UCL 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 endothelial tube morphogenesis Inferred from mutant phenotype PubMed 19592636. Source: BHF-UCL in utero embryonic development Inferred from electronic annotation. Source: Compara 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 growth Inferred from direct assay PubMed 17068149. Source: BHF-UCL negative regulation of cell proliferation Inferred from mutant phenotype PubMed 12453878. Source: HGNC negative regulation of endothelial cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of endothelial cell proliferation Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of endothelial cell proliferation Inferred from electronic annotation. Source: Compara 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 protein heterooligomerization Inferred from electronic annotation. Source: Compara 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 endothelial cell proliferation Traceable author statement PubMed 20406889. Source: DFLAT retina vasculature development in camera-type eye Inferred from sequence or structural similarity. Source: BHF-UCL 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_component	cell surface Inferred from direct assay Ref.2. Source: MGI dendrite Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from direct assay Ref.2. Source: UniProtKB neuronal cell body Inferred from electronic annotation. Source: Compara
Molecular_function	ATP 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 receptor signaling protein serine/threonine kinase activity Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor activity, type I Inferred from electronic annotation. Source: Compara transforming growth factor beta-activated receptor activity Inferred from direct assay Ref.2. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 503

482

Serine/threonine-protein kinase receptor R3

PRO_0000024420

Regions

Topological domain

22 – 118

97

Extracellular Potential

Transmembrane

119 – 141

23

Helical; Potential

Topological domain

142 – 503

362

Cytoplasmic Potential

Domain

172 – 201

30

GS

Domain

202 – 492

291

Protein kinase

Nucleotide binding

208 – 216

9

ATP By similarity

Region

73 – 76

4

Mediates specificity for BMP ligand

Sites

Active site

330

1

Proton acceptor By similarity

Binding site

229

1

ATP By similarity

Amino acid modifications

Modified residue

155

1

Phosphoserine By similarity

Glycosylation

98

1

N-linked (GlcNAc...) Potential

Disulfide bond

34 ↔ 51

Ref.7 Ref.8

Disulfide bond

36 ↔ 41

Ref.7 Ref.8

Disulfide bond

46 ↔ 69

Ref.7 Ref.8

Disulfide bond

77 ↔ 89

Ref.7 Ref.8

Disulfide bond

90 ↔ 95

Ref.7 Ref.8

Natural variations

Natural variant

48 – 49

2

GA → EP in HHT2.

VAR_026784

Natural variant

48

1

G → R in HHT2. Ref.16

VAR_026785

Natural variant

50

1

W → C in HHT2; retained in the endoplasmic reticulum. Ref.3 Ref.11 Ref.14

VAR_006204

Natural variant

51

1

C → Y in HHT2. Ref.10

VAR_006205

Natural variant

67

1

R → Q in HHT2; retained in the endoplasmic reticulum. Ref.3 Ref.14

VAR_006206

Natural variant

67

1

R → W in HHT2. Ref.17

VAR_026786

Natural variant

77

1

C → W in HHT2; retained in the endoplasmic reticulum. Ref.10 Ref.14

VAR_006207

Natural variant

96

1

N → D in HHT2. Ref.10

VAR_006208

Natural variant

179

1

D → A in HHT2; mutant protein is capable of targeting the cell surface appropriately. Ref.14

VAR_026787

Natural variant

211

1

G → D in HHT2; retained in the endoplasmic reticulum. Ref.14
Corresponds to variant rs28936687 [ dbSNP | Ensembl ].

VAR_026788

Natural variant

215

1

E → K in HHT2. Ref.16

VAR_026789

Natural variant

223

1

G → R in HHT2. Ref.16

VAR_026790

Natural variant

229

1

K → R in HHT2. Ref.16

VAR_026791

Natural variant

232

1

Missing in HHT2; mutant protein is capable of targeting the cell surface appropriately. Ref.9 Ref.11 Ref.14

VAR_006209

Natural variant

233

1

Missing in HHT2. Ref.16

VAR_026792

Natural variant

245

1

I → N.
Corresponds to variant rs1804508 [ dbSNP | Ensembl ].

VAR_011717

Natural variant

254

1

Missing in HHT2; retained in the endoplasmic reticulum. Ref.13 Ref.14

VAR_026793

Natural variant

285

1

L → F in HHT2. Ref.16

VAR_026794

Natural variant

306

1

A → P in HHT2. Ref.16

VAR_026795

Natural variant

314

1

H → Y in HHT2. Ref.16

VAR_026796

Natural variant

333

1

S → I in HHT2; retained in the endoplasmic reticulum. Ref.3 Ref.11 Ref.14

VAR_006210

Natural variant

337

1

L → P in HHT2. Ref.16

VAR_026797

Natural variant

344

1

C → Y in HHT2; retained in the endoplasmic reticulum. Ref.11 Ref.14
Corresponds to variant rs28936688 [ dbSNP | Ensembl ].

VAR_026798

Natural variant

347

1

A → P in HHT2. Ref.16

VAR_026799

Natural variant

374

1

R → Q in HHT2; retained in the endoplasmic reticulum. Ref.14 Ref.16

VAR_026800

Natural variant

374

1

R → W in HHT2. Ref.3 Ref.12 Ref.14 Ref.17
Corresponds to variant rs28936401 [ dbSNP | Ensembl ].

VAR_006211

Natural variant

376

1

M → R in HHT2. Ref.9
Corresponds to variant rs28936399 [ dbSNP | Ensembl ].

VAR_006212

Natural variant

376

1

M → V in HHT2. Ref.16

VAR_026801

Natural variant

378

1

P → L in HHT2; retained in the endoplasmic reticulum. Ref.14

VAR_026802

Natural variant

379

1

E → K in HHT2. Ref.16 Ref.17

VAR_026803

Natural variant

397

1

D → G in HHT2. Ref.16

VAR_026804

Natural variant

398

1

I → N in HHT2. Ref.12
Corresponds to variant rs28936400 [ dbSNP | Ensembl ].

VAR_026805

Natural variant

399

1

W → S in HHT2. Ref.14
Corresponds to variant rs28936402 [ dbSNP | Ensembl ].

VAR_026806

Natural variant

407

1

E → D in HHT2. Ref.11 Ref.17

VAR_026807

Natural variant

411

1

R → P in HHT2. Ref.16

VAR_026808

Natural variant

411

1

R → Q in HHT2; retained in the endoplasmic reticulum. Ref.9 Ref.14 Ref.16
Corresponds to variant rs28936398 [ dbSNP | Ensembl ].

VAR_006213

Natural variant

411

1

R → W in HHT2. Ref.13 Ref.16 Ref.17

VAR_026809

Natural variant

424

1

P → T in HHT2. Ref.3

VAR_006214

Natural variant

425

1

F → L in HHT2. Ref.16

VAR_026810

Natural variant

425

1

F → V in HHT2. Ref.17

VAR_026811

Natural variant

425

1

Missing in HHT2. Ref.17

VAR_026812

Natural variant

479

1

R → L in HHT2. Ref.16

VAR_026813

Natural variant

482

1

A → V in HHT2. Ref.16

VAR_026814

Natural variant

484

1

R → W in HHT2. Ref.13 Ref.16

VAR_026815

Natural variant

487

1

K → T in HHT2; mutant protein is capable of targeting the cell surface appropriately. Ref.14

VAR_026816

Experimental info

Mutagenesis

74 – 76

3

REL → DFQ: Affinity for BMP9 decreased by 200-fold. Ref.7

Sequence conflict

172

1

S → T in CAA80255. Ref.1

Secondary structure

1

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503

Helix Strand Turn

Details...

Helix

26 – 28

3

Beta strand

32 – 35

4

Beta strand

42 – 56

15

Beta strand

59 – 61

3

Beta strand

64 – 68

5

Helix

74 – 78

5

Beta strand

83 – 90

8

Turn

93 – 96

4

Helix

198 – 201

4

Beta strand

203 – 211

9

Beta strand

214 – 221

8

Beta strand

224 – 231

8

Helix

233 – 235

3

Helix

236 – 248

13

Beta strand

259 – 265

7

Beta strand

272 – 278

7

Helix

285 – 291

7

Helix

296 – 314

19

Beta strand

325 – 327

3

Beta strand

335 – 338

4

Beta strand

344 – 346

3

Beta strand

353 – 355

3

Beta strand

357 – 359

3

Helix

373 – 375

3

Helix

378 – 381

4

Helix

390 – 410

21

Turn

424 – 428

5

Helix

435 – 442

8

Beta strand

455 – 459

5

Turn

460 – 462

3

Helix

463 – 469

7

Helix

476 – 478

3

Helix

482 – 491

10

Sequences

	Sequence		Length	Mass (Da)
	P37023 [UniParc]. Last modified December 15, 1998. Version 2. Checksum: 074522AA802325DD	FASTA	503	56,124
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z22533 mRNA. Translation: CAA80255.1.
L17075 mRNA. Translation: AAA16160.1.
U77713 , 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.

IPI

IPI01013348.

PIR

A49431.

RefSeq

NP_000011.2. NM_000020.2.
NP_001070869.1. NM_001077401.1.

UniGene

Hs.591026.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LCR	NMR	-	A	19-118	[»]
3MY0	X-ray	2.65	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X	195-497	[»]
4FAO	X-ray	3.36	C/D/I/J/O/P/U/V/c/d/i/j	22-118	[»]

ProteinModelPortal

P37023.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-423N.
DIP-5938N.

STRING

9606.ENSP00000267008.

PTM databases

PhosphoSite

P37023.

Polymorphism databases

DMDM

3915750.

Proteomic databases

PaxDb

P37023.

PRIDE

P37023.

Protocols and materials databases

DNASU

94.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000388922; ENSP00000373574; ENSG00000139567.

GeneID

94.

KEGG

hsa:94.

UCSC

uc001rzj.3. human.

Organism-specific databases

CTD

94.

GeneCards

GC12P052300.

HGNC

HGNC:175. ACVRL1.

HPA

HPA007041.

MIM

600376. phenotype.
601284. gene.

neXtProt

NX_P37023.

Orphanet

275777. Heritable pulmonary arterial hypertension.
275766. Idiopathic pulmonary arterial hypertension.
774. Rendu-Osler-Weber disease.

PharmGKB

PA24496.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000230587.

HOVERGEN

HBG054502.

InParanoid

P37023.

KO

K13594.

OrthoDB

EOG4HDSTB.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Gene expression databases

ArrayExpress

P37023.

Bgee

P37023.

CleanEx

HS_ACVRL1.

Genevestigator

P37023.

GermOnline

ENSG00000139567. Homo sapiens.

Family and domain databases

InterPro

IPR000333. Activin_II/TGFBeta-II_recpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR003605. TGF_beta_rcpt_GS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]

PRINTS

PR00653. ACTIVIN2R.

SMART

SM00467. GS. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P37023.

ChEMBL

CHEMBL5311.

ChiTaRS

ACVRL1. human.

DrugBank

DB00171. Adenosine triphosphate.

GenomeRNAi

94.

NextBio

355.

SOURCE

Search...

Entry information

Entry name

ACVL1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 150 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.