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Q04771 (ACVR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. 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:
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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length509 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 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
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP 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: Ensembl

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: Ensembl

determination of left/right symmetry

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

germ cell development

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

mesoderm formation

Inferred from electronic annotation. Source: Ensembl

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 extrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 9884026. Source: BHF-UCL

negative regulation of signal transduction

Inferred from mutant phenotype PubMed 9884026. Source: HGNC

neural crest cell migration

Inferred from electronic annotation. Source: Ensembl

pathway-restricted SMAD protein phosphorylation

Inferred from direct assay PubMed 19736306. Source: BHF-UCL

patterning of blood vessels

Inferred from electronic annotation. Source: Ensembl

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 19736306. Source: BHF-UCL

pharyngeal system development

Inferred from electronic annotation. Source: Ensembl

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

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 8242742. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 19506109. Source: BHF-UCL

regulation of ossification

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of skeletal muscle tissue development

Inferred from electronic annotation. Source: Ensembl

smooth muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta receptor signaling pathway

Inferred from direct assay PubMed 8242742. Source: UniProtKB

urogenital system development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentactivin receptor complex

Inferred from direct assay PubMed 8242742. Source: UniProtKB

apical part of cell

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Inferred from direct assay PubMed 8242742. Source: UniProtKB

   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 PubMed 8242742. Source: UniProtKB

activin receptor activity, type I

Inferred from electronic annotation. Source: Ensembl

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 kinase activity

Inferred from direct assay PubMed 19736306. 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: Ensembl

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: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 By similarity
Chain21 – 509489Activin receptor type-1
PRO_0000024394

Regions

Topological domain21 – 123103Extracellular Potential
Transmembrane124 – 14623Helical; Potential
Topological domain147 – 509363Cytoplasmic Potential
Domain178 – 20730GS
Domain208 – 502295Protein kinase
Nucleotide binding214 – 2229ATP By similarity

Sites

Active site3361Proton acceptor By similarity
Binding site2351ATP By similarity

Amino acid modifications

Modified residue5011Phosphoserine Ref.4
Glycosylation1021N-linked (GlcNAc...) Potential

Natural variations

Natural variant151A → G. Ref.8
Corresponds to variant rs13406336 [ dbSNP | Ensembl ].
VAR_041392
Natural variant411S → F. Ref.8
Corresponds to variant rs55957214 [ dbSNP | Ensembl ].
VAR_041393
Natural variant471H → Q. Ref.8
Corresponds to variant rs34056189 [ dbSNP | Ensembl ].
VAR_041394
Natural variant1151P → S in a melanoma sample; somatic mutation. Ref.8
VAR_041395
Natural variant197 – 1982PF → L in FOP; variant phenotype.
VAR_058418
Natural variant2021R → I in FOP; with some atypical features. Ref.10
VAR_058419
Natural variant2061R → H in FOP. Ref.7 Ref.9
VAR_028444
Natural variant2071Q → E in FOP; with some atypical features. Ref.9
VAR_058420
Natural variant3281G → E in FOP; variant phenotype. Ref.9 Ref.10
VAR_058421
Natural variant3281G → R in FOP; variant phenotype. Ref.9
VAR_058422
Natural variant3281G → W in FOP; variant phenotype. Ref.9
VAR_058423
Natural variant3561G → D in FOP; variant phenotype. Ref.9
VAR_058424
Natural variant3751R → P in FOP; variant phenotype. Ref.9
VAR_058425

Secondary structure

....................................................... 509
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q04771 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: E2B0F051D19DD052

FASTA50957,153
        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 

« Hide

References

« Hide '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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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. expand/collapse author list , 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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L02911 mRNA. Translation: AAA36614.1.
Z22534 mRNA. Translation: CAA80256.1.
BC033867 mRNA. Translation: AAH33867.1.
PIRA45992.
RefSeqNP_001096.1. NM_001105.4.
NP_001104537.1. NM_001111067.2.
XP_005246996.1. XM_005246939.1.
XP_005246997.1. XM_005246940.1.
UniGeneHs.470316.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3H9RX-ray2.35A172-499[»]
3MTFX-ray2.15A/B201-499[»]
3OOMX-ray2.00A201-499[»]
3Q4UX-ray1.82A/B/C/D201-499[»]
4BGGX-ray2.56A/B/C/D201-499[»]
4C02X-ray2.17A172-499[»]
4DYMX-ray2.42A201-499[»]
ProteinModelPortalQ04771.
SMRQ04771. Positions 143-499.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106605. 59 interactions.
DIPDIP-212N.
IntActQ04771. 1 interaction.
MINTMINT-1340145.
STRING9606.ENSP00000263640.

Chemistry

BindingDBQ04771.
ChEMBLCHEMBL5903.
DrugBankDB00171. Adenosine triphosphate.
GuidetoPHARMACOLOGY1785.

PTM databases

PhosphoSiteQ04771.

Polymorphism databases

DMDM462447.

Proteomic databases

PaxDbQ04771.
PRIDEQ04771.

Protocols and materials databases

DNASU90.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263640; ENSP00000263640; ENSG00000115170.
ENST00000409283; ENSP00000387273; ENSG00000115170.
ENST00000410057; ENSP00000387127; ENSG00000115170.
ENST00000434821; ENSP00000405004; ENSG00000115170.
GeneID90.
KEGGhsa:90.
UCSCuc002tzm.3. human.

Organism-specific databases

CTD90.
GeneCardsGC02M158594.
HGNCHGNC:171. ACVR1.
HPAHPA007505.
HPA046514.
MIM102576. gene.
135100. phenotype.
neXtProtNX_Q04771.
Orphanet337. Fibrodysplasia ossificans progressiva.
PharmGKBPA24492.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000230587.
HOVERGENHBG054502.
InParanoidQ04771.
KOK04675.
OMAVCEGMSC.
OrthoDBEOG7Q8CN3.
PhylomeDBQ04771.
TreeFamTF314724.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
SignaLinkQ04771.

Gene expression databases

ArrayExpressQ04771.
BgeeQ04771.
CleanExHS_ACVR1.
GenevestigatorQ04771.

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

EvolutionaryTraceQ04771.
GeneWikiACVR1.
GenomeRNAi90.
NextBio335.
PROQ04771.
SOURCESearch...

Entry information

Entry nameACVR1_HUMAN
AccessionPrimary (citable) accession number: Q04771
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: April 16, 2014
This is version 151 of the entry and version 1 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 2

Human chromosome 2: entries, gene names and cross-references to MIM