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)

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.
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.5
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
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
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	501	1	Phosphoserine Ref.4
	Glycosylation	102	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	15	1	A → G: dbSNP rs13406336. Ref.6		VAR_041392
	Natural variant	41	1	S → F Ref.6		VAR_041393
	Natural variant	47	1	H → Q Ref.6		VAR_041394
	Natural variant	115	1	P → S in a melanoma sample; somatic mutation. Ref.6		VAR_041395
	Natural variant	206	1	R → H in FOP. Ref.5		VAR_028444

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]	"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.
[6]	"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.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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
HSSP	HSSP built from PDB template 1IAS based on UniProtKB P36897.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:212N.
PTM databases
PhosphoSite	Q04771.
Proteomic databases
PRIDE	Q04771.
Genome annotation databases
Ensembl	ENSG00000115170. Homo sapiens. [Contig view]
GeneID	90.
KEGG	hsa:90.
Organism-specific databases
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
HOGENOM	Q04771.
HOVERGEN	Q04771.
OMA	Q04771. GSEDHCE.
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.
GermOnline	ENSG00000115170. Homo sapiens.
Family and domain databases
InterPro	IPR000333. Activin_II_recpt. IPR000472. Activin_rcpt. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_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.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
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:	June 16, 2009
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)