P27037 (AVR2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	513 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 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 Transmembrane helix
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Glycoprotein
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 Sertoli cell proliferation Inferred from electronic annotation. Source: Compara anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara determination of left/right symmetry Inferred from electronic annotation. Source: Compara embryonic skeletal system development Inferred from electronic annotation. Source: Compara gastrulation with mouth forming second Inferred from electronic annotation. Source: Compara mesoderm development Inferred from electronic annotation. Source: Compara penile erection Inferred from electronic annotation. Source: Compara positive regulation of activin receptor signaling pathway Inferred from direct assay PubMed 12665502. Source: HGNC positive regulation of bone mineralization Inferred from mutant phenotype PubMed 18436533. Source: BHF-UCL positive regulation of erythrocyte differentiation Inferred from direct assay PubMed 9032295. Source: HGNC positive regulation of osteoblast differentiation Inferred from mutant phenotype PubMed 18436533. Source: BHF-UCL positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from mutant phenotype PubMed 19366699. Source: BHF-UCL regulation of BMP signaling pathway Inferred from electronic annotation. Source: Compara regulation of nitric-oxide synthase activity Inferred from electronic annotation. Source: Compara signal transduction by phosphorylation Inferred from electronic annotation. Source: GOC sperm ejaculation Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay PubMed 14738881. Source: HGNC inhibin-betaglycan-ActRII complex Inferred from direct assay PubMed 10746731. Source: BHF-UCL integral to plasma membrane Traceable author statement Ref.2. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW activin-activated receptor activity Inferred from electronic annotation. Source: InterPro coreceptor activity Inferred from direct assay PubMed 10746731. Source: BHF-UCL metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro transforming growth factor beta-activated receptor activity Inferred from electronic annotation. Source: InterPro transmembrane receptor protein serine/threonine kinase activity Traceable author statement Ref.2. Source: ProtInc
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

Helical; 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.10
Corresponds to variant rs34917571 [ dbSNP | Ensembl ].

VAR_032809

Natural variant

306

1

D → N in a gastric adenocarcinoma sample; somatic mutation. Ref.10

VAR_032810

Natural variant

367

1

A → T Found in a clear cell renal carcinoma case; somatic mutation. Ref.11

VAR_064692

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.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

513

Helix Strand Turn

Details...

Beta strand

191 – 199

9

Beta strand

205 – 211

7

Beta strand

214 – 221

8

Helix

223 – 225

3

Helix

226 – 236

11

Beta strand

249 – 256

8

Beta strand

258 – 268

11

Helix

275 – 281

7

Helix

286 – 303

18

Beta strand

307 – 310

4

Beta strand

313 – 315

3

Beta strand

317 – 319

3

Beta strand

327 – 330

4

Beta strand

336 – 338

3

Beta strand

345 – 347

3

Helix

363 – 365

3

Helix

368 – 371

4

Helix

379 – 398

20

Beta strand

404 – 406

3

Helix

416 – 419

4

Helix

425 – 432

8

Helix

443 – 446

4

Helix

449 – 461

13

Helix

466 – 468

3

Helix

472 – 485

14

Sequences

	Sequence		Length	Mass (Da)
	P27037 [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] [Europe PMC] [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] [Europe PMC] [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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hippocampus.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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].
[9]	"Crystal structure of activin receptor type-IIa (ACVR2A) kinase domain in complex with dorsomorphin." Structural genomics consortium (SGC) Submitted (FEB-2011) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 191-488 IN COMPLEX WITH DORSOMORPHIN.
[10]	"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 ARG-258 AND ASN-306.
[11]	"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma." Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A. Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THR-367.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

CGP resequencing studies

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X63128 mRNA. Translation: CAA44839.1.
M93415 mRNA. Translation: AAA35504.1.
X62381 mRNA. Translation: CAA44245.1.
D31770 mRNA. Translation: BAA06548.1.
AK314124 mRNA. Translation: BAG36815.1.
CH471058 Genomic DNA. Translation: EAX11561.1.
CH471058 Genomic DNA. Translation: EAX11562.1.
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. NM_001616.3.

UniGene

Hs.470174.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3Q4T	X-ray	1.96	A/B	191-488	[»]
3SOC	X-ray	1.95	A/B	191-488	[»]
4ASX	X-ray	2.05	A/B	191-488	[»]

ProteinModelPortal

P27037.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-520N.

IntAct

P27037. 1 interaction.

MINT

MINT-122188.

STRING

9606.ENSP00000241416.

PTM databases

PhosphoSite

P27037.

Polymorphism databases

DMDM

114722.

Proteomic databases

PaxDb

P27037.

PRIDE

P27037.

Protocols and materials databases

DNASU

92.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000241416; ENSP00000241416; ENSG00000121989.
ENST00000404590; ENSP00000384338; ENSG00000121989.

GeneID

92.

KEGG

hsa:92.

UCSC

uc002twg.3. human.

Organism-specific databases

CTD

92.

GeneCards

GC02P148602.

HGNC

HGNC:173. ACVR2A.

HPA

HPA046997.

MIM

102581. gene.

neXtProt

NX_P27037.

PharmGKB

PA24494.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000231495.

HOVERGEN

HBG054502.

InParanoid

P27037.

KO

K04670.

OMA

ERIIQMQ.

OrthoDB

EOG47WNNH.

PhylomeDB

P27037.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.

SignaLink

P27037.

Gene expression databases

ArrayExpress

P27037.

Bgee

P27037.

CleanEx

HS_ACVR2A.

Genevestigator

P27037.

GermOnline

ENSG00000121989. Homo sapiens.

Family and domain databases

InterPro

IPR000333. Activin_II/TGFBeta-II_recpt.
IPR015768. Activin_II_recpt.
IPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

PANTHER

PTHR23255:SF10. PTHR23255:SF10. 1 hit.

Pfam

PF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

PRINTS

PR00653. ACTIVIN2R.

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P27037.

ChEMBL

CHEMBL5616.

EvolutionaryTrace

P27037.

GenomeRNAi

92.

NextBio

347.

SOURCE

Search...

Entry information

Entry name

AVR2A_HUMAN

Accession

Primary (citable) accession number: P27037
Secondary accession number(s): B2RAB8 , D3DP85, Q53TH4, Q6NWV2, Q92474

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	May 29, 2013
This is version 144 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.