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Protein

Activin receptor type-2A

Gene

ACVR2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Mediates induction of adipogenesis by GDF6 (By similarity).By similarity1 Publication

Catalytic activityi

ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei219ATPPROSITE-ProRule annotation1
Active sitei322Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi198 – 206ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • activin receptor signaling pathway Source: BHF-UCL
  • anterior/posterior pattern specification Source: Ensembl
  • BMP signaling pathway Source: BHF-UCL
  • cellular response to BMP stimulus Source: BHF-UCL
  • determination of left/right symmetry Source: Ensembl
  • embryonic skeletal system development Source: Ensembl
  • gastrulation with mouth forming second Source: Ensembl
  • mesoderm development Source: Ensembl
  • penile erection Source: Ensembl
  • positive regulation of activin receptor signaling pathway Source: HGNC
  • positive regulation of bone mineralization Source: BHF-UCL
  • positive regulation of erythrocyte differentiation Source: HGNC
  • positive regulation of osteoblast differentiation Source: BHF-UCL
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of BMP signaling pathway Source: Ensembl
  • regulation of nitric-oxide synthase activity Source: Ensembl
  • Sertoli cell proliferation Source: Ensembl
  • spermatogenesis Source: Ensembl
  • sperm ejaculation Source: Ensembl
  • transmembrane receptor protein serine/threonine kinase signaling pathway Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS04537-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-1181150. Signaling by NODAL.
R-HSA-1433617. Regulation of signaling by NODAL.
R-HSA-1502540. Signaling by Activin.
R-HSA-201451. Signaling by BMP.
SignaLinkiP27037.
SIGNORiP27037.

Names & Taxonomyi

Protein namesi
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 namesi
Name:ACVR2A
Synonyms:ACVR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:173. ACVR2A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 135ExtracellularSequence analysisAdd BLAST116
Transmembranei136 – 161HelicalSequence analysisAdd BLAST26
Topological domaini162 – 513CytoplasmicSequence analysisAdd BLAST352

GO - Cellular componenti

  • cell surface Source: Ensembl
  • cytoplasm Source: HGNC
  • inhibin-betaglycan-ActRII complex Source: BHF-UCL
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
  • receptor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi92.
OpenTargetsiENSG00000121989.
PharmGKBiPA24494.

Chemistry databases

ChEMBLiCHEMBL5616.
GuidetoPHARMACOLOGYi1791.

Polymorphism and mutation databases

DMDMi114722.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000002439820 – 513Activin receptor type-2AAdd BLAST494

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 60By similarity
Glycosylationi43N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi50 ↔ 78By similarity
Glycosylationi66N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi85 ↔ 104By similarity
Disulfide bondi91 ↔ 103By similarity
Disulfide bondi105 ↔ 110By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP27037.
PaxDbiP27037.
PeptideAtlasiP27037.
PRIDEiP27037.

PTM databases

iPTMnetiP27037.
PhosphoSitePlusiP27037.

Expressioni

Gene expression databases

BgeeiENSG00000121989.
CleanExiHS_ACVR2A.
GenevisibleiP27037. HS.

Organism-specific databases

HPAiHPA046997.

Interactioni

Subunit structurei

Interacts with AIP1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 (By similarity).By similarity

Protein-protein interaction databases

BioGridi106607. 32 interactors.
DIPiDIP-520N.
IntActiP27037. 1 interactor.
MINTiMINT-122188.
STRINGi9606.ENSP00000241416.

Chemistry databases

BindingDBiP27037.

Structurei

Secondary structure

1513
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi191 – 199Combined sources9
Beta strandi205 – 211Combined sources7
Beta strandi214 – 221Combined sources8
Helixi223 – 225Combined sources3
Helixi226 – 236Combined sources11
Beta strandi249 – 256Combined sources8
Beta strandi258 – 268Combined sources11
Helixi275 – 281Combined sources7
Helixi286 – 303Combined sources18
Beta strandi307 – 310Combined sources4
Beta strandi313 – 315Combined sources3
Beta strandi317 – 319Combined sources3
Beta strandi327 – 330Combined sources4
Beta strandi336 – 338Combined sources3
Beta strandi345 – 347Combined sources3
Helixi363 – 365Combined sources3
Helixi368 – 371Combined sources4
Helixi379 – 398Combined sources20
Beta strandi404 – 406Combined sources3
Helixi416 – 419Combined sources4
Helixi425 – 432Combined sources8
Helixi443 – 446Combined sources4
Helixi449 – 461Combined sources13
Helixi466 – 468Combined sources3
Helixi472 – 485Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3Q4TX-ray1.96A/B191-488[»]
3SOCX-ray1.95A/B191-488[»]
4ASXX-ray2.05A/B191-488[»]
ProteinModelPortaliP27037.
SMRiP27037.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27037.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini192 – 485Protein kinasePROSITE-ProRule annotationAdd BLAST294

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG054502.
InParanoidiP27037.
KOiK04670.
OMAiSCYGDKD.
OrthoDBiEOG091G03YO.
PhylomeDBiP27037.
TreeFamiTF352876.

Family and domain databases

InterProiIPR000472. Activin_recp.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR00653. ACTIVIN2R.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P27037-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGAAAKLAFA VFLISCSSGA ILGRSETQEC LFFNANWEKD RTNQTGVEPC
60 70 80 90 100
YGDKDKRRHC FATWKNISGS IEIVKQGCWL DDINCYDRTD CVEKKDSPEV
110 120 130 140 150
YFCCCEGNMC NEKFSYFPEM EVTQPTSNPV TPKPPYYNIL LYSLVPLMLI
160 170 180 190 200
AGIVICAFWV YRHHKMAYPP VLVPTQDPGP PPPSPLLGLK PLQLLEVKAR
210 220 230 240 250
GRFGCVWKAQ LLNEYVAVKI FPIQDKQSWQ NEYEVYSLPG MKHENILQFI
260 270 280 290 300
GAEKRGTSVD VDLWLITAFH EKGSLSDFLK ANVVSWNELC HIAETMARGL
310 320 330 340 350
AYLHEDIPGL KDGHKPAISH RDIKSKNVLL KNNLTACIAD FGLALKFEAG
360 370 380 390 400
KSAGDTHGQV GTRRYMAPEV LEGAINFQRD AFLRIDMYAM GLVLWELASR
410 420 430 440 450
CTAADGPVDE YMLPFEEEIG QHPSLEDMQE VVVHKKKRPV LRDYWQKHAG
460 470 480 490 500
MAMLCETIEE CWDHDAEARL SAGCVGERIT QMQRLTNIIT TEDIVTVVTM
510
VTNVDFPPKE SSL
Length:513
Mass (Da):57,848
Last modified:August 1, 1992 - v1
Checksum:iA89822E880979618
GO
Isoform 2 (identifier: P27037-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Note: No experimental confirmation available.
Show »
Length:405
Mass (Da):45,713
Checksum:iF0D4F7B18BD200AB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13L → V in BAA06548 (Ref. 4) Curated1
Sequence conflicti204 – 206GCV → PSL in BAA06548 (Ref. 4) Curated3
Sequence conflicti348E → V in BAA06548 (Ref. 4) Curated1
Sequence conflicti507P → L in AAH67417 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032809258S → R.1 PublicationCorresponds to variant rs34917571dbSNPEnsembl.1
Natural variantiVAR_032810306D → N in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs764255410dbSNPEnsembl.1
Natural variantiVAR_064692367A → T Found in a clear cell renal carcinoma case; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0546891 – 108Missing in isoform 2. 1 PublicationAdd BLAST108

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63128 mRNA. Translation: CAA44839.1.
M93415 mRNA. Translation: AAA35504.1.
X62381 mRNA. Translation: CAA44245.1.
D31770 mRNA. Translation: BAA06548.1.
AK301629 mRNA. Translation: BAG63114.1.
AK314124 mRNA. Translation: BAG36815.1.
AC009480 Genomic DNA. Translation: AAX93050.1.
CH471058 Genomic DNA. Translation: EAX11561.1.
CH471058 Genomic DNA. Translation: EAX11562.1.
BC067418 mRNA. Translation: AAH67418.1.
BC067417 mRNA. Translation: AAH67417.1.
BC069707 mRNA. Translation: AAH69707.1.
CCDSiCCDS33301.1. [P27037-1]
CCDS63030.1. [P27037-2]
PIRiJQ1486.
RefSeqiNP_001265508.1. NM_001278579.1. [P27037-1]
NP_001265509.1. NM_001278580.1. [P27037-2]
NP_001607.1. NM_001616.4. [P27037-1]
UniGeneiHs.470174.

Genome annotation databases

EnsembliENST00000241416; ENSP00000241416; ENSG00000121989. [P27037-1]
ENST00000404590; ENSP00000384338; ENSG00000121989. [P27037-1]
ENST00000535787; ENSP00000439988; ENSG00000121989. [P27037-2]
GeneIDi92.
KEGGihsa:92.
UCSCiuc002twg.5. human. [P27037-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63128 mRNA. Translation: CAA44839.1.
M93415 mRNA. Translation: AAA35504.1.
X62381 mRNA. Translation: CAA44245.1.
D31770 mRNA. Translation: BAA06548.1.
AK301629 mRNA. Translation: BAG63114.1.
AK314124 mRNA. Translation: BAG36815.1.
AC009480 Genomic DNA. Translation: AAX93050.1.
CH471058 Genomic DNA. Translation: EAX11561.1.
CH471058 Genomic DNA. Translation: EAX11562.1.
BC067418 mRNA. Translation: AAH67418.1.
BC067417 mRNA. Translation: AAH67417.1.
BC069707 mRNA. Translation: AAH69707.1.
CCDSiCCDS33301.1. [P27037-1]
CCDS63030.1. [P27037-2]
PIRiJQ1486.
RefSeqiNP_001265508.1. NM_001278579.1. [P27037-1]
NP_001265509.1. NM_001278580.1. [P27037-2]
NP_001607.1. NM_001616.4. [P27037-1]
UniGeneiHs.470174.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3Q4TX-ray1.96A/B191-488[»]
3SOCX-ray1.95A/B191-488[»]
4ASXX-ray2.05A/B191-488[»]
ProteinModelPortaliP27037.
SMRiP27037.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106607. 32 interactors.
DIPiDIP-520N.
IntActiP27037. 1 interactor.
MINTiMINT-122188.
STRINGi9606.ENSP00000241416.

Chemistry databases

BindingDBiP27037.
ChEMBLiCHEMBL5616.
GuidetoPHARMACOLOGYi1791.

PTM databases

iPTMnetiP27037.
PhosphoSitePlusiP27037.

Polymorphism and mutation databases

DMDMi114722.

Proteomic databases

MaxQBiP27037.
PaxDbiP27037.
PeptideAtlasiP27037.
PRIDEiP27037.

Protocols and materials databases

DNASUi92.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000241416; ENSP00000241416; ENSG00000121989. [P27037-1]
ENST00000404590; ENSP00000384338; ENSG00000121989. [P27037-1]
ENST00000535787; ENSP00000439988; ENSG00000121989. [P27037-2]
GeneIDi92.
KEGGihsa:92.
UCSCiuc002twg.5. human. [P27037-1]

Organism-specific databases

CTDi92.
DisGeNETi92.
GeneCardsiACVR2A.
HGNCiHGNC:173. ACVR2A.
HPAiHPA046997.
MIMi102581. gene.
neXtProtiNX_P27037.
OpenTargetsiENSG00000121989.
PharmGKBiPA24494.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG054502.
InParanoidiP27037.
KOiK04670.
OMAiSCYGDKD.
OrthoDBiEOG091G03YO.
PhylomeDBiP27037.
TreeFamiTF352876.

Enzyme and pathway databases

BioCyciZFISH:HS04537-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-1181150. Signaling by NODAL.
R-HSA-1433617. Regulation of signaling by NODAL.
R-HSA-1502540. Signaling by Activin.
R-HSA-201451. Signaling by BMP.
SignaLinkiP27037.
SIGNORiP27037.

Miscellaneous databases

EvolutionaryTraceiP27037.
GeneWikiiACVR2A.
GenomeRNAii92.
PROiP27037.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121989.
CleanExiHS_ACVR2A.
GenevisibleiP27037. HS.

Family and domain databases

InterProiIPR000472. Activin_recp.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR00653. ACTIVIN2R.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAVR2A_HUMAN
AccessioniPrimary (citable) accession number: P27037
Secondary accession number(s): B2RAB8
, B4DWQ2, D3DP85, Q53TH4, Q6NWV2, Q92474
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 2, 2016
This is version 178 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.