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Q61271 (ACV1B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Activin receptor type-1B

EC=2.7.11.30
Alternative name(s):
Activin receptor type IB
Short name=ACTR-IB
Activin receptor-like kinase 4
Short name=ALK-4
Serine/threonine-protein kinase receptor R2
Short name=SKR2
Gene names
Name:Acvr1b
Synonyms:Alk4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length505 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-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a 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, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas 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 such as ACVR1B. 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. ACVR1B also phosphorylates TDP2. Ref.2 Ref.3

Catalytic activity

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

Enzyme regulation

Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain By similarity.

Subunit structure

Forms an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Interacts with TDP2 By similarity. Interacts with AIP1, FKBP1A, IGSF1, TDGF1, SMAD2, SMAD3 and SMAD7 By similarity. Ref.3

Subcellular location

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

Domain

The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors By similarity.

Post-translational modification

Autophosphorylated. Phosphorylated by activin receptor type-2 (ACVR2A or ACVR2B) in response to activin-binding at serine and threonine residues in the GS domain. Phosphorylation of ACVR1B by activin receptor type-2 regulates association with SMAD7 By similarity.

Ubiquitinated. Level of ubiquitination is regulated by the SMAD7-SMURF1 complex By similarity.

Ubiquitinated By similarity.

Disruption phenotype

Leads to hair loss. Ref.4

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 componentCell membrane
Membrane
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Serine/threonine-protein kinase
Transferase
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

activin receptor signaling pathway

Inferred from direct assay PubMed 16115198. Source: MGI

cell surface receptor signaling pathway

Traceable author statement PubMed 9512518. Source: MGI

central nervous system development

Inferred from electronic annotation. Source: Ensembl

development of primary female sexual characteristics

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

hair follicle development

Inferred from mutant phenotype PubMed 16127153. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 15485907PubMed 16564040. Source: MGI

mesoderm development

Inferred from sequence alignment PubMed 9012495. Source: MGI

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

nodal signaling pathway

Inferred from electronic annotation. Source: Ensembl

peptidyl-threonine phosphorylation

Inferred from direct assay Ref.3. Source: UniProtKB

positive regulation of activin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of erythrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of trophoblast cell migration

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of signal transduction

Inferred from direct assay PubMed 17936261. Source: MGI

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement PubMed 9512518. Source: MGI

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

activin binding

Inferred from physical interaction Ref.1. Source: MGI

activin-activated receptor activity

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.3. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.3. Source: UniProtKB

receptor signaling protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta-activated receptor activity

Inferred from electronic annotation. Source: InterPro

transmembrane receptor protein serine/threonine kinase activity

Traceable author statement PubMed 9512518. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 505482Activin receptor type-1B
PRO_0000024418

Regions

Topological domain24 – 126103Extracellular Potential
Transmembrane127 – 14923Helical; Potential
Topological domain150 – 505356Cytoplasmic Potential
Domain177 – 20630GS
Domain207 – 497291Protein kinase
Nucleotide binding213 – 2219ATP By similarity

Sites

Active site3351Proton acceptor By similarity
Binding site2341ATP By similarity

Amino acid modifications

Modified residue3801Phosphotyrosine By similarity
Glycosylation431N-linked (GlcNAc...) Potential

Sequences

Sequence LengthMass (Da)Tools
Q61271 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 56E9EEF1607A2517

FASTA50556,700
        10         20         30         40         50         60 
MAESAGASSF FPLVVLLLAG SGGSGPRGIQ ALLCACTSCL QTNYTCETDG ACMVSIFNLD 

        70         80         90        100        110        120 
GVEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYIDF CNKIDLRVPS GHLKEPAHPS 

       130        140        150        160        170        180 
MWGPVELVGI IAGPVFLLFL IIIIVFLVIN YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ 

       190        200        210        220        230        240 
DLVYDLSTSG SGSGLPLFVQ RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE 

       250        260        270        280        290        300 
ERSWFREAEI YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT 

       310        320        330        340        350        360 
IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA IADLGLAVRH 

       370        380        390        400        410        420 
DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC ADIYALGLVY WEIARRCNSG 

       430        440        450        460        470        480 
GVHEDYQLPY YDLVPSDPSI EEMRKVVCDQ KLRPNVPNWW QSYEALRVMG KMMRECWYAN 

       490        500 
GAARLTALRI KKTLSQLSVQ EDVKI 

« Hide

References

[1]"Expression of type I and type IB receptors for activin in midgestation mouse embryos suggests distinct functions in organogensis."
Verschuern K., Dewulf N., Goumans M.J., Lonnoy O., Freijen A., Grimsby S., Vande Spiegle K., ten Dijke P., Moren A., Vanscheeuwijck P., Heldin C.H., Miyazono K., Mummery C., Van Den Eijnden-Van Raaij J., Huylebroeck D.
Mech. Dev. 52:109-123(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: NIH Swiss.
Tissue: Placenta.
[2]"Transgenic mice expressing dominant-negative activin receptor IB in forebrain neurons reveal novel functions of activin at glutamatergic synapses."
Muller M.R., Zheng F., Werner S., Alzheimer C.
J. Biol. Chem. 281:29076-29084(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[3]"Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination."
Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D., Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D., Huylebroeck D.
Development 134:4381-4393(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TDP2.
[4]"Conditional activin receptor type 1B (Acvr1b) knockout mice reveal hair loss abnormality."
Qiu W., Li X., Tang H., Huang A.S., Panteleyev A.A., Owens D.M., Su G.H.
J. Invest. Dermatol. 131:1067-1076(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z31663 mRNA. Translation: CAA83483.1.
CCDSCCDS27846.1.
RefSeqNP_031421.1. NM_007395.3.
UniGeneMm.308467.

3D structure databases

ProteinModelPortalQ61271.
SMRQ61271. Positions 31-104, 149-501.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid197954. 2 interactions.
IntActQ61271. 1 interaction.
MINTMINT-2842316.

PTM databases

PhosphoSiteQ61271.

Proteomic databases

PaxDbQ61271.
PRIDEQ61271.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000000544; ENSMUSP00000000544; ENSMUSG00000000532.
GeneID11479.
KEGGmmu:11479.
UCSCuc007xsr.1. mouse.

Organism-specific databases

CTD91.
MGIMGI:1338944. Acvr1b.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110337.
HOGENOMHOG000230587.
HOVERGENHBG054502.
InParanoidQ61271.
KOK13567.
OMAQCACTSC.
OrthoDBEOG7Q8CN3.
PhylomeDBQ61271.
TreeFamTF314724.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.

Gene expression databases

ArrayExpressQ61271.
BgeeQ61271.
CleanExMM_ACVR1B.
GenevestigatorQ61271.

Family and domain databases

InterProIPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR003605. TGF_beta_rcpt_GS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERPTHR23255. PTHR23255. 1 hit.
PfamPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTSM00467. GS. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio278824.
PROQ61271.
SOURCESearch...

Entry information

Entry nameACV1B_MOUSE
AccessionPrimary (citable) accession number: Q61271
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 126 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

MGD cross-references

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