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P27040 (AVR2B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Activin receptor type-2B

EC=2.7.11.30
Alternative name(s):
Activin receptor type IIB
Short name=ACTR-IIB
Gene names
Name:Acvr2b
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length536 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin-A/INHA-INHBA). The type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor By similarity.

Catalytic activity

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

Cofactor

Magnesium or manganese By similarity.

Subunit structure

Forms an activin receptor complex with activin type II receptors such as ACVR1B By similarity. Interacts with VPS39 By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity.

Post-translational modification

Phosphorylated. Constitutive phosphorylation is in part catalyzed by its own kinase activity By similarity.

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 componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Serine/threonine-protein kinase
Transferase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

activation of protein kinase activity

Inferred from direct assay PubMed 16806156. Source: MGI

anterior/posterior pattern specification

Inferred from mutant phenotype PubMed 16845371PubMed 16991118PubMed 9242489. Source: MGI

artery development

Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL

blood vessel remodeling

Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL

determination of left/right symmetry

Inferred from mutant phenotype PubMed 9242489. Source: MGI

embryonic foregut morphogenesis

Inferred from mutant phenotype PubMed 10921901. Source: MGI

gastrulation with mouth forming second

Inferred from genetic interaction PubMed 10452853. Source: MGI

heart development

Inferred from mutant phenotype PubMed 9242489. Source: MGI

insulin secretion

Inferred from genetic interaction PubMed 17849440. Source: MGI

kidney development

Inferred from mutant phenotype PubMed 16845371. Source: MGI

lung development

Inferred from genetic interaction PubMed 17849440. Source: MGI

lymphangiogenesis

Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL

lymphatic endothelial cell differentiation

Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL

mesoderm development

Inferred from genetic interaction PubMed 10452853. Source: MGI

odontogenesis of dentin-containing tooth

Inferred from mutant phenotype PubMed 11714685PubMed 16330774. Source: MGI

organ growth

Inferred from genetic interaction PubMed 17849440. Source: MGI

palate development

Inferred from mutant phenotype PubMed 16845371. Source: MGI

pancreas development

Inferred from genetic interaction PubMed 17849440. Source: MGI

pattern specification process

Inferred from genetic interaction PubMed 17849440. Source: MGI

positive regulation of activin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of bone mineralization

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from mutant phenotype PubMed 17849440. Source: MGI

regulation of signal transduction

Inferred from direct assay PubMed 17936261. Source: MGI

response to glucose

Inferred from genetic interaction PubMed 17849440. Source: MGI

retina vasculature development in camera-type eye

Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL

skeletal system development

Inferred from mutant phenotype PubMed 16845371. Source: MGI

skeletal system morphogenesis

Inferred from mutant phenotype PubMed 16991118. Source: MGI

venous blood vessel development

Inferred from mutant phenotype PubMed 19903896. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

protein complex

Inferred from sequence orthology PubMed 24019467. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

activin binding

Inferred from direct assay PubMed 15304227. Source: MGI

growth factor binding

Inferred from mutant phenotype PubMed 12414726. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 11882656PubMed 16845371. Source: MGI

protein serine/threonine kinase activity

Inferred from direct assay PubMed 1326537. Source: MGI

protein serine/threonine/tyrosine kinase activity

Inferred from direct assay PubMed 1326537. Source: MGI

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

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: ActR-IIB1 and ActR-IIB2 have similar but higher affinities for activin A than ActR-II, ActR-IIB3 and ActR-IIB4.
Isoform ActR-IIB1 (identifier: P27040-1)

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.
Isoform ActR-IIB2 (identifier: P27040-2)

The sequence of this isoform differs from the canonical sequence as follows:
     175-198: Missing.
Isoform ActR-IIB3 (identifier: P27040-3)

The sequence of this isoform differs from the canonical sequence as follows:
     124-131: Missing.
Isoform ActR-IIB4 (identifier: P27040-4)

The sequence of this isoform differs from the canonical sequence as follows:
     124-131: Missing.
     175-198: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 536518Activin receptor type-2B
PRO_0000024405

Regions

Topological domain19 – 137119Extracellular Potential
Transmembrane138 – 15821Helical; Potential
Topological domain159 – 536378Cytoplasmic Potential
Domain214 – 504291Protein kinase
Nucleotide binding220 – 2289ATP By similarity

Sites

Active site3451Proton acceptor By similarity
Binding site2411ATP By similarity

Amino acid modifications

Glycosylation421N-linked (GlcNAc...) Potential
Glycosylation651N-linked (GlcNAc...) Potential
Disulfide bond29 ↔ 59
Disulfide bond49 ↔ 77
Disulfide bond84 ↔ 103
Disulfide bond90 ↔ 102
Disulfide bond104 ↔ 109

Natural variations

Alternative sequence124 – 1318Missing in isoform ActR-IIB3 and isoform ActR-IIB4.
VSP_004951
Alternative sequence175 – 19824Missing in isoform ActR-IIB2 and isoform ActR-IIB4.
VSP_004952

Secondary structure

................... 536
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform ActR-IIB1 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: BF1C8CAC974BF5E2

FASTA53660,542
        10         20         30         40         50         60 
MTAPWAALAL LWGSLCAGSG RGEAETRECI YYNANWELER TNQSGLERCE GEQDKRLHCY 

        70         80         90        100        110        120 
ASWRNSSGTI ELVKKGCWLD DFNCYDRQEC VATEENPQVY FCCCEGNFCN ERFTHLPEPG 

       130        140        150        160        170        180 
GPEVTYEPPP TAPTLLTVLA YSLLPIGGLS LIVLLAFWMY RHRKPPYGHV DIHEVRQCQR 

       190        200        210        220        230        240 
WAGRRDGCAD SFKPLPFQDP GPPPPSPLVG LKPLQLLEIK ARGRFGCVWK AQLMNDFVAV 

       250        260        270        280        290        300 
KIFPLQDKQS WQSEREIFST PGMKHENLLQ FIAAEKRGSN LEVELWLITA FHDKGSLTDY 

       310        320        330        340        350        360 
LKGNIITWNE LCHVAETMSR GLSYLHEDVP WCRGEGHKPS IAHRDFKSKN VLLKSDLTAV 

       370        380        390        400        410        420 
LADFGLAVRF EPGKPPGDTH GQVGTRRYMA PEVLEGAINF QRDAFLRIDM YAMGLVLWEL 

       430        440        450        460        470        480 
VSRCKAADGP VDEYMLPFEE EIGQHPSLEE LQEVVVHKKM RPTIKDHWLK HPGLAQLCVT 

       490        500        510        520        530 
IEECWDHDAE ARLSAGCVEE RVSLIRRSVN GTTSDCLVSL VTSVTNVDLL PKESSI 

« Hide

Isoform ActR-IIB2 [UniParc].

Checksum: F8C53AE6D0825D7A
Show »

FASTA51257,738
Isoform ActR-IIB3 [UniParc].

Checksum: 1559B59DEAF7733B
Show »

FASTA52859,657
Isoform ActR-IIB4 [UniParc].

Checksum: 42A315009EE8C17A
Show »

FASTA50456,853

References

« Hide 'large scale' references
[1]"Novel activin receptors: distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors."
Attisano L., Wrana J.L., Cheifetz S., Massague J.
Cell 68:97-108(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ACTR-IIB1; ACTR-IIB2; ACTR-IIB3 AND ACTR-IIB4).
Strain: BALB/c.
[2]"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] (ISOFORM ACTR-IIB2).
Tissue: Jaw.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M84120 mRNA. Translation: AAA37172.1.
BC106189 mRNA. Translation: AAI06190.1.
CCDSCCDS23615.1. [P27040-1]
PIRA40829.
B40829.
C40829.
D40829.
RefSeqNP_031423.1. NM_007397.2. [P27040-1]
XP_006511988.1. XM_006511925.1. [P27040-2]
XP_006511989.1. XM_006511926.1. [P27040-4]
UniGeneMm.390239.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S4YX-ray2.30A/C23-120[»]
2H64X-ray1.92C19-117[»]
ProteinModelPortalP27040.
SMRP27040. Positions 24-116, 214-536.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid197956. 1 interaction.
DIPDIP-5799N.
IntActP27040. 1 interaction.
MINTMINT-2842249.
STRING10090.ENSMUSP00000035093.

PTM databases

PhosphoSiteP27040.

Proteomic databases

PRIDEP27040.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035093; ENSMUSP00000035093; ENSMUSG00000061393. [P27040-3]
ENSMUST00000165044; ENSMUSP00000126108; ENSMUSG00000061393. [P27040-1]
GeneID11481.
KEGGmmu:11481.
UCSCuc009sax.1. mouse. [P27040-1]
uc009say.1. mouse. [P27040-2]

Organism-specific databases

CTD93.
MGIMGI:87912. Acvr2b.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00560000076906.
HOGENOMHOG000231495.
HOVERGENHBG054502.
InParanoidP27040.
KOK13596.
OMAKKMRPAI.
OrthoDBEOG7JHM5B.
PhylomeDBP27040.
TreeFamTF352876.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.
ReactomeREACT_188576. Developmental Biology.

Gene expression databases

BgeeP27040.
CleanExMM_ACVR2B.
GenevestigatorP27040.

Family and domain databases

InterProIPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERPTHR23255. PTHR23255. 1 hit.
PfamPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR00653. ACTIVIN2R.
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP27040.
NextBio278832.
PROP27040.
SOURCESearch...

Entry information

Entry nameAVR2B_MOUSE
AccessionPrimary (citable) accession number: P27040
Secondary accession number(s): Q3KQI1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: July 9, 2014
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot