Reviewed, UniProtKB/Swiss-Prot Q04771 (ACVR1_HUMAN)

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
    Serine/threonine-protein kinase receptor R1
      Short name=SKR1
    Activin receptor-like kinase 2
      Short name=ALK-2
    TGF-B superfamily receptor type I
      Short name=TSR-I

Gene names

Name:	ACVR1
Synonyms:	ACVRLK2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
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	Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:135100]. FOP is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification in FOP begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to extra-articular ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible. 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
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
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from direct assay. Source: UniProtKB G1/S transition of mitotic cell cycle Inferred from mutant phenotype. Source: HGNC negative regulation of activin receptor signaling pathway Inferred from mutant phenotype. Source: HGNC negative regulation of apoptosis Inferred from mutant phenotype. Source: HGNC positive regulation of bone mineralization Inferred from mutant phenotype. Source: UniProtKB positive regulation of osteoblast differentiation Inferred from mutant phenotype. Source: UniProtKB positive regulation of transcription Inferred from direct assay. Source: UniProtKB protein amino acid phosphorylation Inferred from direct assay. Source: HGNC transforming growth factor beta receptor signaling pathway Inferred from direct assay. Source: UniProtKB
Cellular component	activin receptor complex Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from direct assay. Source: HGNC SMAD binding Inferred from direct assay. Source: HGNC activin binding Inferred from direct assay. Source: UniProtKB follistatin binding Non-traceable author statement. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein homodimerization activity Inferred from direct assay. Source: UniProtKB transforming growth factor beta binding Inferred from direct assay. Source: UniProtKB
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

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

226

1

Phosphoserine

Modified residue

501

1

Phosphoserine Ref.4

Glycosylation

102

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

15

1

A → G: dbSNP rs13406336. Ref.8

VAR_041392

Natural variant

41

1

S → F: dbSNP rs55957214. Ref.8

VAR_041393

Natural variant

47

1

H → Q: dbSNP rs34056189. Ref.8

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

Helix

198 – 205

8

Beta strand

222 – 224

3

Beta strand

233 – 237

5

Helix

239 – 241

3

Helix

242 – 254

13

Beta strand

267 – 271

5

Beta strand

278 – 283

6

Helix

291 – 297

7

Helix

302 – 313

12

Helix

317 – 320

4

Beta strand

331 – 333

3

Helix

339 – 341

3

Beta strand

342 – 345

4

Beta strand

350 – 352

3

Beta strand

359 – 361

3

Helix

379 – 381

3

Helix

384 – 387

4

Helix

396 – 406

11

Helix

410 – 415

6

Turn

430 – 434

5

Helix

441 – 448

8

Helix

459 – 463

5

Helix

465 – 475

11

Helix

482 – 484

3

Helix

488 – 498

11

Sequences

	Sequence		Length	Mass (Da)
	Q04771-1 [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: 8389764] [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: 8397373] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[4]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501, MASS SPECTROMETRY.
[5]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND SER-501, MASS SPECTROMETRY.
[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: 16642017] [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: 17344846] [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: 19085907] [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: 19330033] [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.
NP_001104537.1.

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	[»]

SMR

Q04771. Positions 33-108.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-212N.

STRING

Q04771.

PTM databases

PhosphoSite

Q04771.

Proteomic databases

PRIDE

Q04771.

Genome annotation databases

Ensembl

ENST00000263640; ENSP00000263640; ENSG00000115170; Homo sapiens. [Genome view]
ENST00000409283; ENSP00000387273; ENSG00000115170; Homo sapiens. [Genome view]
ENST00000410057; ENSP00000387127; ENSG00000115170; Homo sapiens. [Genome view]
ENST00000434821; ENSP00000405004; ENSG00000115170; Homo sapiens. [Genome view]

GeneID

90.

KEGG

hsa:90.

UCSC

uc002tzm.2. human.

Organism-specific databases

CTD

90.

GeneCards

GC02M158301.

H-InvDB

HIX0002524.

HGNC

HGNC:171. ACVR1.

HPA

HPA007505.

MIM

102576. gene.
135100. phenotype.

Orphanet

337. Fibrodysplasia ossificans progressiva.

PharmGKB

PA24492.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09977.

HOGENOM

HBG314718.

HOVERGEN

Q04771.

InParanoid

Q04771.

OMA

GSEDHCE.

OrthoDB

EOG983GQ0.

PhylomeDB

Q04771.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.
2.7.11.30. 247.

Gene expression databases

ArrayExpress

Q04771.

Bgee

Q04771.

CleanEx

HS_ACVR1.

Genevestigator

Q04771.

GermOnline

ENSG00000115170. Homo sapiens.

Family and domain databases

InterPro

IPR000333. Activin_II_recpt.
IPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_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]

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 Resources

DrugBank

DB00171. Adenosine triphosphate.

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:	February 9, 2010
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.