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Q61271

- ACV1B_MOUSE

UniProt

Q61271 - ACV1B_MOUSE

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Protein

Activin receptor type-1B

Gene

Acvr1b

Organism
Mus musculus (Mouse)
Status
Reviewed - 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-activated receptor activity Source: Ensembl
  2. activin binding Source: MGI
  3. ATP binding Source: UniProtKB-KW
  4. metal ion binding Source: UniProtKB-KW
  5. protein serine/threonine kinase activity Source: UniProtKB
  6. receptor signaling protein serine/threonine kinase activity Source: Ensembl
  7. transforming growth factor beta-activated receptor activity Source: InterPro
  8. 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: Ensembl
  6. G1/S transition of mitotic cell cycle Source: Ensembl
  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: Ensembl
  11. negative regulation of gene expression Source: MGI
  12. nodal signaling pathway Source: Ensembl
  13. peptidyl-threonine phosphorylation Source: UniProtKB
  14. positive regulation of activin receptor signaling pathway Source: Ensembl
  15. positive regulation of erythrocyte differentiation Source: Ensembl
  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: Ensembl
  20. protein autophosphorylation Source: Ensembl
  21. regulation of 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_216258. Signaling by Activin.
REACT_220645. Signaling by NODAL.

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: Chromosome 15

Organism-specific databases

MGIiMGI:1338944. Acvr1b.

Subcellular locationi

GO - Cellular componenti

  1. cell surface Source: Ensembl
  2. extracellular vesicular exosome Source: Ensembl
  3. integral component of plasma membrane Source: MGI
  4. plasma membrane Source: Reactome
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...

Topological domain

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

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei127 – 14923HelicalSequence AnalysisAdd
BLAST

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.
OMAiQCACTSC.
OrthoDBiEOG7Q8CN3.
PhylomeDBiQ61271.
TreeFamiTF314724.

Family and domain databases

InterProiIPR000472. 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]
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:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
Z31663 mRNA. Translation: CAA83483.1 .
CCDSi CCDS27846.1.
RefSeqi NP_031421.1. NM_007395.3.
UniGenei Mm.308467.

3D structure databases

ProteinModelPortali Q61271.
SMRi Q61271. Positions 31-104, 149-501.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 197954. 2 interactions.
IntActi Q61271. 1 interaction.
MINTi MINT-2842316.

PTM databases

PhosphoSitei Q61271.

Proteomic databases

MaxQBi Q61271.
PaxDbi Q61271.
PRIDEi Q61271.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000000544 ; ENSMUSP00000000544 ; ENSMUSG00000000532 .
GeneIDi 11479.
KEGGi mmu:11479.
UCSCi uc007xsr.1. mouse.

Organism-specific databases

CTDi 91.
MGIi MGI:1338944. Acvr1b.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118876.
HOGENOMi HOG000230587.
HOVERGENi HBG054502.
InParanoidi Q61271.
KOi K13567.
OMAi QCACTSC.
OrthoDBi EOG7Q8CN3.
PhylomeDBi Q61271.
TreeFami TF314724.

Enzyme and pathway databases

Reactomei REACT_216258. Signaling by Activin.
REACT_220645. Signaling by NODAL.

Miscellaneous databases

NextBioi 278824.
PROi Q61271.
SOURCEi Search...

Gene expression databases

Bgeei Q61271.
CleanExi MM_ACVR1B.
ExpressionAtlasi Q61271. baseline and differential.
Genevestigatori Q61271.

Family and domain databases

InterProi IPR000472. 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 ]
PANTHERi PTHR23255. PTHR23255. 1 hit.
Pfami PF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view ]
SMARTi SM00467. GS. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 129 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