Reviewed, UniProtKB/Swiss-Prot P27037 (AVR2A_HUMAN)

Names and origin

Protein names

Recommended name:
    Activin receptor type-2A
    EC=2.7.11.30
Alternative name(s):
    Activin receptor type IIA
      Short name=ACTR-IIA
      Short name=ACTRIIA

Gene names

Name:	ACVR2A
Synonyms:	ACVR2

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	513 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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 A, activin B and inhibin A.
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Subunit structure	Interacts with AIP1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from direct assay. Source: UniProtKB activin receptor signaling pathway Inferred from electronic annotation. Source: InterPro positive regulation of activin receptor signaling pathway Inferred from direct assay. Source: HGNC positive regulation of bone mineralization Inferred from mutant phenotype. Source: UniProtKB positive regulation of erythrocyte differentiation Inferred from direct assay. Source: HGNC positive regulation of osteoblast differentiation Inferred from mutant phenotype. Source: UniProtKB positive regulation of protein amino acid phosphorylation Inferred from mutant phenotype. Source: MGI protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HGNC inhibin-betaglycan-ActRII complex Inferred from direct assay. Source: UniProtKB integral to plasma membrane Ref.2 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW activin receptor activity Inferred from electronic annotation. Source: InterPro coreceptor activity Inferred from direct assay. Source: UniProtKB inhibin beta-A binding Inferred from direct assay. Source: HGNC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 513	494	Activin receptor type-2A		PRO_0000024398
Regions
	Topological domain	20 – 135	116	Extracellular Potential
	Transmembrane	136 – 161	26	Potential
	Topological domain	162 – 513	352	Cytoplasmic Potential
	Domain	192 – 485	294	Protein kinase
	Nucleotide binding	198 – 206	9	ATP By similarity
Sites
	Active site	322	1	Proton acceptor By similarity
	Binding site	219	1	ATP By similarity
Amino acid modifications
	Glycosylation	43	1	N-linked (GlcNAc...) Potential
	Glycosylation	66	1	N-linked (GlcNAc...) Potential
	Disulfide bond	30 ↔ 60		By similarity
	Disulfide bond	50 ↔ 78		By similarity
	Disulfide bond	85 ↔ 104		By similarity
	Disulfide bond	91 ↔ 103		By similarity
	Disulfide bond	105 ↔ 110		By similarity
Natural variations
	Natural variant	258	1	S → R Ref.7		VAR_032809
	Natural variant	306	1	D → N in a gastric adenocarcinoma sample; somatic mutation. Ref.7		VAR_032810
Experimental info
	Sequence conflict	13	1	L → V in BAA06548. Ref.4
	Sequence conflict	204 – 206	3	GCV → PSL in BAA06548. Ref.4
	Sequence conflict	348	1	E → V in BAA06548. Ref.4
	Sequence conflict	507	1	P → L in AAH67417. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P27037-1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: A89822E880979618	FASTA	513	57,848
	10 20 30 40 50 60 MGAAAKLAFA VFLISCSSGA ILGRSETQEC LFFNANWEKD RTNQTGVEPC YGDKDKRRHC 70 80 90 100 110 120 FATWKNISGS IEIVKQGCWL DDINCYDRTD CVEKKDSPEV YFCCCEGNMC NEKFSYFPEM 130 140 150 160 170 180 EVTQPTSNPV TPKPPYYNIL LYSLVPLMLI AGIVICAFWV YRHHKMAYPP VLVPTQDPGP 190 200 210 220 230 240 PPPSPLLGLK PLQLLEVKAR GRFGCVWKAQ LLNEYVAVKI FPIQDKQSWQ NEYEVYSLPG 250 260 270 280 290 300 MKHENILQFI GAEKRGTSVD VDLWLITAFH EKGSLSDFLK ANVVSWNELC HIAETMARGL 310 320 330 340 350 360 AYLHEDIPGL KDGHKPAISH RDIKSKNVLL KNNLTACIAD FGLALKFEAG KSAGDTHGQV 370 380 390 400 410 420 GTRRYMAPEV LEGAINFQRD AFLRIDMYAM GLVLWELASR CTAADGPVDE YMLPFEEEIG 430 440 450 460 470 480 QHPSLEDMQE VVVHKKKRPV LRDYWQKHAG MAMLCETIEE CWDHDAEARL SAGCVGERIT 490 500 510 QMQRLTNIIT TEDIVTVVTM VTNVDFPPKE SSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human activin receptor cDNA reveals high evolutionary conservation." Matzuk M.M., Bradley A. Biochim. Biophys. Acta 1130:105-108(1992) [PubMed: 1311955] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"Molecular cloning and binding properties of the human type II activin receptor." Donaldson C.J., Mathews L.S., Vale W.W. Biochem. Biophys. Res. Commun. 184:310-316(1992) [PubMed: 1314589] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[3]	Geiser A.G. Submitted (DEC-1991) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary gland.
[4]	Iimura T., Oida S. Submitted (NOV-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"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 ARG-258 AND ASN-306.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

CGP resequencing studies

Cross-references

Sequence databases
EMBLGenBankDDBJ	X63128 mRNA. Translation: CAA44839.1. M93415 mRNA. Translation: AAA35504.1. X62381 mRNA. Translation: CAA44245.1. D31770 mRNA. Translation: BAA06548.1. BC067418 mRNA. Translation: AAH67418.1. AC009480 Genomic DNA. Translation: AAX93050.1. BC067417 mRNA. Translation: AAH67417.1. BC069707 mRNA. Translation: AAH69707.1.
IPI	IPI00015691.
PIR	JQ1486.
RefSeq	NP_001607.1.
UniGene	Hs.470174
3D structure databases
HSSP	HSSP built from PDB template 1BTE based on UniProtKB P27038.
SMR	P27037. Positions 26-119.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:520N.
IntAct	P27037. 2 interactions.
Proteomic databases
PRIDE	P27037.
Genome annotation databases
Ensembl	ENSG00000121989. Homo sapiens. [Contig view]
GeneID	92.
KEGG	hsa:92.
NMPDR	fig|9606.3.peg.18734.
Organism-specific databases
GeneCards	GC02P148319.
H-InvDB	HIX0029973.
HGNC	HGNC:173. ACVR2A.
MIM	102581. gene.
PharmGKB	PA24494.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P27037.
HOVERGEN	P27037.
Enzyme and pathway databases
BRENDA	2.7.10.2. 247. 2.7.11.30. 247.
Reactome	REACT_12034. Signaling by BMP.
Gene expression databases
ArrayExpress	P27037.
Bgee	P27037.
CleanEx	HS_ACVR2A.
GermOnline	ENSG00000121989. Homo sapiens.
Family and domain databases
InterPro	IPR000333. Activin_II_recpt. IPR015768. Activin_II_recpt_C. IPR000472. Activin_rcpt. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
PANTHER	PTHR23255:SF10. Activin_II_recpt_C. 1 hit.
Pfam	PF01064. Activin_recp. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR00653. ACTIVIN2R.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	347.
SOURCE	Search...

Entry information

Entry name

AVR2A_HUMAN

Accession

Primary (citable) accession number: P27037
Secondary accession number(s): Q53TH4, Q6NWV2, Q92474

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	June 16, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)