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Protein

Activin receptor type-1B

Gene

Acvr1b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 TDP2.2 Publications

Catalytic activityi

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

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei234 – 2341ATPPROSITE-ProRule annotation
Active sitei335 – 3351Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi213 – 2219ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. activin binding Source: MGI
  2. activin receptor activity, type I Source: MGI
  3. ATP binding Source: MGI
  4. inhibin binding Source: MGI
  5. metal ion binding Source: UniProtKB-KW
  6. protein serine/threonine kinase activity Source: UniProtKB
  7. receptor signaling protein serine/threonine kinase activity Source: Ensembl
  8. SMAD binding Source: MGI
  9. transforming growth factor beta-activated receptor activity Source: InterPro
  10. transmembrane receptor protein serine/threonine kinase activity Source: MGI

GO - Biological processi

  1. activin receptor signaling pathway Source: MGI
  2. cell surface receptor signaling pathway Source: MGI
  3. central nervous system development Source: Ensembl
  4. development of primary female sexual characteristics Source: Ensembl
  5. extrinsic apoptotic signaling pathway Source: MGI
  6. G1/S transition of mitotic cell cycle Source: MGI
  7. hair follicle development Source: MGI
  8. in utero embryonic development Source: MGI
  9. mesoderm development Source: MGI
  10. negative regulation of cell growth Source: MGI
  11. negative regulation of gene expression Source: MGI
  12. nodal signaling pathway Source: MGI
  13. peptidyl-threonine phosphorylation Source: UniProtKB
  14. positive regulation of activin receptor signaling pathway Source: MGI
  15. positive regulation of erythrocyte differentiation Source: MGI
  16. positive regulation of gene expression Source: MGI
  17. positive regulation of pathway-restricted SMAD protein phosphorylation Source: Ensembl
  18. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  19. positive regulation of trophoblast cell migration Source: MGI
  20. protein autophosphorylation Source: MGI
  21. protein phosphorylation Source: MGI
  22. regulation of signal transduction Source: MGI
  23. regulation of transcription, DNA-templated Source: MGI
  24. signal transduction Source: MGI
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

ReactomeiREACT_331083. Signaling by NODAL.
REACT_347120. Signaling by Activin.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Acvr1b
Synonyms:Alk4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1338944. Acvr1b.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 126103ExtracellularSequence AnalysisAdd
BLAST
Transmembranei127 – 14923HelicalSequence AnalysisAdd
BLAST
Topological domaini150 – 505356CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. activin receptor complex Source: MGI
  2. cell surface Source: MGI
  3. extracellular vesicular exosome Source: MGI
  4. integral component of plasma membrane Source: MGI
  5. plasma membrane Source: Reactome
  6. receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Leads to hair loss.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 505482Activin receptor type-1BPRO_0000024418Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi43 – 431N-linked (GlcNAc...)Sequence Analysis
Modified residuei380 – 3801PhosphotyrosineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ61271.
PaxDbiQ61271.
PRIDEiQ61271.

PTM databases

PhosphoSiteiQ61271.

Expressioni

Gene expression databases

BgeeiQ61271.
CleanExiMM_ACVR1B.
ExpressionAtlasiQ61271. baseline and differential.
GenevestigatoriQ61271.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi197954. 2 interactions.
IntActiQ61271. 1 interaction.
MINTiMINT-2842316.

Structurei

3D structure databases

ProteinModelPortaliQ61271.
SMRiQ61271. Positions 31-104, 149-501.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini177 – 20630GSPROSITE-ProRule annotationAdd
BLAST
Domaini207 – 497291Protein kinasePROSITE-ProRule annotationAdd
BLAST

Domaini

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).By similarity

Sequence similaritiesi

Contains 1 GS domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiQ61271.
KOiK13567.
OMAiNTHCCYE.
OrthoDBiEOG7Q8CN3.
PhylomeDBiQ61271.
TreeFamiTF314724.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR000472. TFB_recept_I/II_C.
IPR003605. TGF_beta_rcpt_GS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTiSM00467. GS. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q61271-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAESAGASSF FPLVVLLLAG SGGSGPRGIQ ALLCACTSCL QTNYTCETDG
60 70 80 90 100
ACMVSIFNLD GVEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYIDF
110 120 130 140 150
CNKIDLRVPS GHLKEPAHPS MWGPVELVGI IAGPVFLLFL IIIIVFLVIN
160 170 180 190 200
YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ DLVYDLSTSG SGSGLPLFVQ
210 220 230 240 250
RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE ERSWFREAEI
260 270 280 290 300
YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT
310 320 330 340 350
IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA
360 370 380 390 400
IADLGLAVRH DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC
410 420 430 440 450
ADIYALGLVY WEIARRCNSG GVHEDYQLPY YDLVPSDPSI EEMRKVVCDQ
460 470 480 490 500
KLRPNVPNWW QSYEALRVMG KMMRECWYAN GAARLTALRI KKTLSQLSVQ

EDVKI
Length:505
Mass (Da):56,700
Last modified:November 1, 1996 - v1
Checksum:i56E9EEF1607A2517
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z31663 mRNA. Translation: CAA83483.1.
CCDSiCCDS27846.1.
RefSeqiNP_031421.1. NM_007395.3.
UniGeneiMm.308467.

Genome annotation databases

EnsembliENSMUST00000000544; ENSMUSP00000000544; ENSMUSG00000000532.
GeneIDi11479.
KEGGimmu:11479.
UCSCiuc007xsr.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z31663 mRNA. Translation: CAA83483.1.
CCDSiCCDS27846.1.
RefSeqiNP_031421.1. NM_007395.3.
UniGeneiMm.308467.

3D structure databases

ProteinModelPortaliQ61271.
SMRiQ61271. Positions 31-104, 149-501.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi197954. 2 interactions.
IntActiQ61271. 1 interaction.
MINTiMINT-2842316.

PTM databases

PhosphoSiteiQ61271.

Proteomic databases

MaxQBiQ61271.
PaxDbiQ61271.
PRIDEiQ61271.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000000544; ENSMUSP00000000544; ENSMUSG00000000532.
GeneIDi11479.
KEGGimmu:11479.
UCSCiuc007xsr.1. mouse.

Organism-specific databases

CTDi91.
MGIiMGI:1338944. Acvr1b.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiQ61271.
KOiK13567.
OMAiNTHCCYE.
OrthoDBiEOG7Q8CN3.
PhylomeDBiQ61271.
TreeFamiTF314724.

Enzyme and pathway databases

ReactomeiREACT_331083. Signaling by NODAL.
REACT_347120. Signaling by Activin.

Miscellaneous databases

NextBioi278824.
PROiQ61271.
SOURCEiSearch...

Gene expression databases

BgeeiQ61271.
CleanExiMM_ACVR1B.
ExpressionAtlasiQ61271. baseline and differential.
GenevestigatoriQ61271.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR000472. TFB_recept_I/II_C.
IPR003605. TGF_beta_rcpt_GS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTiSM00467. GS. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiACV1B_MOUSE
AccessioniPrimary (citable) accession number: Q61271
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: November 1, 1996
Last modified: April 1, 2015
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.