Q04771 (ACVR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Activin receptor type-1
EC=2.7.11.30

Alternative name(s):
Activin receptor type I
Short name=ACTR-I
Activin receptor-like kinase 2
Short name=ALK-2
Serine/threonine-protein kinase receptor R1
Short name=SKR1
TGF-B superfamily receptor type I
Short name=TSR-I

Gene names

Name:	ACVR1
Synonyms:	ACVRLK2

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	509 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	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 activin. May be involved for left-right pattern formation during embryogenesis By similarity.
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Subunit structure	Interacts with FKBP1A. Interacts with FCHO1. Ref.5
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells.
Involvement in disease	Fibrodysplasia ossificans progressiva (FOP) [MIM:135100]: A rare autosomal dominant connective tissue disorder resulting in skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to a debilitating ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.9 Ref.10
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
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	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from direct assay PubMed 18436533. Source: BHF-UCL G1/S transition of mitotic cell cycle Inferred from mutant phenotype PubMed 9884026. Source: HGNC activin receptor signaling pathway Inferred from direct assay PubMed 19506109. Source: BHF-UCL acute inflammatory response Inferred from electronic annotation. Source: Compara atrial septum primum morphogenesis Inferred from mutant phenotype PubMed 19506109. Source: BHF-UCL cardiac muscle cell fate commitment Inferred from mutant phenotype PubMed 19506109. Source: BHF-UCL cellular response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara determination of left/right symmetry Inferred from electronic annotation. Source: Compara embryonic heart tube morphogenesis Inferred from mutant phenotype PubMed 19506109. Source: BHF-UCL endocardial cushion cell fate commitment Inferred from mutant phenotype PubMed 19506109. Source: BHF-UCL gastrulation with mouth forming second Inferred from electronic annotation. Source: Compara germ cell development Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara mesoderm formation Inferred from electronic annotation. Source: Compara mitral valve morphogenesis Inferred from mutant phenotype PubMed 19506109. Source: BHF-UCL negative regulation of activin receptor signaling pathway Inferred from mutant phenotype PubMed 9884026. Source: HGNC negative regulation of apoptotic process Inferred from mutant phenotype PubMed 9884026. Source: HGNC neural crest cell migration Inferred from electronic annotation. Source: Compara pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 19736306. Source: BHF-UCL patterning of blood vessels Inferred from electronic annotation. Source: Compara peptidyl-threonine phosphorylation Inferred from direct assay PubMed 19736306. Source: BHF-UCL pharyngeal system development Inferred from electronic annotation. Source: Compara positive regulation of bone mineralization Inferred from mutant phenotype PubMed 18436533. Source: BHF-UCL positive regulation of determination of dorsal identity Inferred from direct assay PubMed 19506109. Source: BHF-UCL positive regulation of osteoblast differentiation Inferred from mutant phenotype PubMed 18436533. Source: BHF-UCL positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 19506109. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19506109. Source: BHF-UCL regulation of skeletal muscle tissue development Inferred from electronic annotation. Source: Compara smooth muscle cell differentiation Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 8242742. Source: UniProtKB urogenital system development Inferred from electronic annotation. Source: Compara
Cellular_component	activin receptor complex Inferred from direct assay PubMed 8242742. Source: UniProtKB apical part of cell 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 PubMed 8242742. Source: UniProtKB activin receptor activity, type I Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW peptide hormone binding Non-traceable author statement PubMed 12702211. Source: UniProtKB protein homodimerization activity Inferred from direct assay PubMed 18436533. Source: BHF-UCL protein serine/threonine kinase activity Inferred from direct assay PubMed 12065756. Source: HGNC receptor signaling protein serine/threonine kinase activity Inferred from electronic annotation. Source: Compara transforming growth factor beta binding Inferred from direct assay PubMed 8242742. Source: UniProtKB transforming growth factor beta receptor activity, type I Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

By similarity

Chain

21 – 509

489

Activin receptor type-1

PRO_0000024394

Regions

Topological domain

21 – 123

103

Extracellular Potential

Transmembrane

124 – 146

23

Helical; Potential

Topological domain

147 – 509

363

Cytoplasmic Potential

Domain

178 – 207

30

GS

Domain

208 – 502

295

Protein kinase

Nucleotide binding

214 – 222

9

ATP By similarity

Sites

Active site

336

1

Proton acceptor By similarity

Binding site

235

1

ATP By similarity

Amino acid modifications

Modified residue

501

1

Phosphoserine Ref.4

Glycosylation

102

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

15

1

A → G. Ref.8
Corresponds to variant rs13406336 [ dbSNP | Ensembl ].

VAR_041392

Natural variant

41

1

S → F. Ref.8
Corresponds to variant rs55957214 [ dbSNP | Ensembl ].

VAR_041393

Natural variant

47

1

H → Q. Ref.8
Corresponds to variant rs34056189 [ dbSNP | Ensembl ].

VAR_041394

Natural variant

115

1

P → S in a melanoma sample; somatic mutation. Ref.8

VAR_041395

Natural variant

197 – 198

2

PF → L in FOP; variant phenotype.

VAR_058418

Natural variant

202

1

R → I in FOP; with some atypical features. Ref.10

VAR_058419

Natural variant

206

1

R → H in FOP. Ref.7 Ref.9

VAR_028444

Natural variant

207

1

Q → E in FOP; with some atypical features. Ref.9

VAR_058420

Natural variant

328

1

G → E in FOP; variant phenotype. Ref.9 Ref.10

VAR_058421

Natural variant

328

1

G → R in FOP; variant phenotype. Ref.9

VAR_058422

Natural variant

328

1

G → W in FOP; variant phenotype. Ref.9

VAR_058423

Natural variant

356

1

G → D in FOP; variant phenotype. Ref.9

VAR_058424

Natural variant

375

1

R → P in FOP; variant phenotype. Ref.9

VAR_058425

Secondary structure

1

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509

Helix Strand Turn

Details...

Helix

180 – 185

6

Beta strand

194 – 196

3

Helix

205 – 207

3

Beta strand

209 – 216

8

Beta strand

218 – 227

10

Beta strand

230 – 237

8

Helix

239 – 241

3

Helix

242 – 254

13

Beta strand

265 – 273

9

Beta strand

276 – 283

8

Helix

291 – 295

5

Helix

302 – 320

19

Beta strand

325 – 327

3

Beta strand

331 – 333

3

Helix

339 – 341

3

Beta strand

342 – 344

3

Beta strand

350 – 352

3

Beta strand

359 – 362

4

Turn

363 – 366

4

Beta strand

367 – 369

3

Helix

379 – 381

3

Helix

384 – 387

4

Helix

396 – 415

20

Turn

430 – 434

5

Helix

441 – 448

8

Helix

459 – 463

5

Helix

465 – 477

13

Helix

482 – 484

3

Helix

488 – 498

11

Sequences

	Sequence		Length	Mass (Da)
	Q04771 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: E2B0F051D19DD052	FASTA	509	57,153
	10 20 30 40 50 60 MVDGVMILPV LIMIALPSPS MEDEKPKVNP KLYMCVCEGL SCGNEDHCEG QQCFSSLSIN 70 80 90 100 110 120 DGFHVYQKGC FQVYEQGKMT CKTPPSPGQA VECCQGDWCN RNITAQLPTK GKSFPGTQNF 130 140 150 160 170 180 HLEVGLIILS VVFAVCLLAC LLGVALRKFK RRNQERLNPR DVEYGTIEGL ITTNVGDSTL 190 200 210 220 230 240 ADLLDHSCTS GSGSGLPFLV QRTVARQITL LECVGKGRYG EVWRGSWQGE NVAVKIFSSR 250 260 270 280 290 300 DEKSWFRETE LYNTVMLRHE NILGFIASDM TSRHSSTQLW LITHYHEMGS LYDYLQLTTL 310 320 330 340 350 360 DTVSCLRIVL SIASGLAHLH IEIFGTQGKP AIAHRDLKSK NILVKKNGQC CIADLGLAVM 370 380 390 400 410 420 HSQSTNQLDV GNNPRVGTKR YMAPEVLDET IQVDCFDSYK RVDIWAFGLV LWEVARRMVS 430 440 450 460 470 480 NGIVEDYKPP FYDVVPNDPS FEDMRKVVCV DQQRPNIPNR WFSDPTLTSL AKLMKECWYQ 490 500 NPSARLTALR IKKTLTKIDN SLDKLKTDC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A widely expressed transmembrane serine/threonine kinase that does not bind activin, inhibin, transforming growth factor beta, or bone morphogenic factor." Matsuzaki K., McKeehan W.L. J. Biol. Chem. 268:12719-12723(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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.
[3]	"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: Lung.
[4]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501, MASS SPECTROMETRY.
[5]	"Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning." Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B., Tsang M., Traub L.M. Nat. Cell Biol. 14:488-501(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FCHO1.
[6]	"Crystal structure of the kinase domain of type I activin receptor (ACVR1) in complex with FKBP12 and dorsomorphin." Structural genomics consortium (SGC) Submitted (JUN-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 172-499 IN COMPLEX WITH FKBP1A.
[7]	"A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva." Shore E.M., Xu M., Feldman G.J., Fenstermacher D.A., Brown M.A., Kaplan F.S. Nat. Genet. 38:525-527(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FOP HIS-206.
[8]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-15; PHE-41; GLN-47 AND SER-115.
[9]	"Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1." Kaplan F.S., Xu M., Seemann P., Connor J.M., Glaser D.L., Carroll L., Delai P., Fastnacht-Urban E., Forman S.J., Gillessen-Kaesbach G., Hoover-Fong J., Koester B., Pauli R.M., Reardon W., Zaidi S.A., Zasloff M., Morhart R., Mundlos S., Groppe J., Shore E.M. Hum. Mutat. 30:379-390(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FOP 197-PRO-PHE-198 DELINS LEU; HIS-206; GLU-207; ARG-328; TRP-328; GLU-328; ASP-356 AND PRO-375.
[10]	"Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients." Petrie K.A., Lee W.H., Bullock A.N., Pointon J.J., Smith R., Russell R.G., Brown M.A., Wordsworth B.P., Triffitt J.T. PLoS ONE 4:E5005-E5005(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FOP ILE-202 AND GLU-328.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L02911 mRNA. Translation: AAA36614.1.
Z22534 mRNA. Translation: CAA80256.1.
BC033867 mRNA. Translation: AAH33867.1.

IPI

IPI00029219.

PIR

A45992.

RefSeq

NP_001096.1. NM_001105.4.
NP_001104537.1. NM_001111067.2.

UniGene

Hs.470316.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3H9R	X-ray	2.35	A	172-499	[»]
3MTF	X-ray	2.15	A/B	201-499	[»]
3OOM	X-ray	2.00	A	201-499	[»]
3Q4U	X-ray	1.82	A/B/C/D	201-499	[»]
4DYM	X-ray	2.42	A	201-499	[»]

ProteinModelPortal

Q04771.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-212N.

MINT

MINT-1340145.

STRING

9606.ENSP00000263640.

PTM databases

PhosphoSite

Q04771.

Polymorphism databases

DMDM

462447.

Proteomic databases

PaxDb

Q04771.

PRIDE

Q04771.

Protocols and materials databases

DNASU

90.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263640; ENSP00000263640; ENSG00000115170.
ENST00000409283; ENSP00000387273; ENSG00000115170.
ENST00000410057; ENSP00000387127; ENSG00000115170.
ENST00000434821; ENSP00000405004; ENSG00000115170.

GeneID

90.

KEGG

hsa:90.

UCSC

uc002tzm.3. human.

Organism-specific databases

CTD

90.

GeneCards

GC02M158594.

HGNC

HGNC:171. ACVR1.

HPA

HPA007505.

MIM

102576. gene.
135100. phenotype.

neXtProt

NX_Q04771.

Orphanet

337. Fibrodysplasia ossificans progressiva.

PharmGKB

PA24492.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000230587.

HOVERGEN

HBG054502.

InParanoid

Q04771.

KO

K04675.

OMA

VCEGMSC.

OrthoDB

EOG45QHD2.

PhylomeDB

Q04771.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Gene expression databases

ArrayExpress

Q04771.

Bgee

Q04771.

CleanEx

HS_ACVR1.

Genevestigator

Q04771.

GermOnline

ENSG00000115170. Homo sapiens.

Family and domain databases

InterPro

IPR000333. Activin_II/TGFBeta-II_recpt.
IPR000472. Activin_rcpt.
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

PF01064. Activin_recp. 1 hit.
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

Q04771.

ChEMBL

CHEMBL5903.

DrugBank

DB00171. Adenosine triphosphate.

EvolutionaryTrace

Q04771.

GenomeRNAi

90.

NextBio

335.

SOURCE

Search...

Entry information

Entry name

ACVR1_HUMAN

Accession

Primary (citable) accession number: Q04771

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	May 1, 2013
This is version 141 of the entry and version 1 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.