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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)DescriptionActionsGraphical viewLength
Binding sitei234ATPPROSITE-ProRule annotation1
Active sitei335Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi213 – 221ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

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

ReactomeiR-MMU-1181150. Signaling by NODAL.
R-MMU-1502540. 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
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1338944. Acvr1b.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 126ExtracellularSequence analysisAdd BLAST103
Transmembranei127 – 149HelicalSequence analysisAdd BLAST23
Topological domaini150 – 505CytoplasmicSequence analysisAdd BLAST356

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000002441824 – 505Activin receptor type-1BAdd BLAST482

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi43N-linked (GlcNAc...)Sequence analysis1
Modified residuei380PhosphotyrosineBy similarity1

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

iPTMnetiQ61271.
PhosphoSitePlusiQ61271.

Expressioni

Gene expression databases

BgeeiENSMUSG00000000532.
CleanExiMM_ACVR1B.
ExpressionAtlasiQ61271. baseline and differential.
GenevisibleiQ61271. MM.

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

GO - Molecular functioni

  • activin binding Source: MGI
  • inhibin binding Source: MGI
  • SMAD binding Source: MGI

Protein-protein interaction databases

BioGridi197954. 2 interactors.
IntActiQ61271. 1 interactor.
MINTiMINT-2842316.
STRINGi10090.ENSMUSP00000000544.

Chemistry databases

BindingDBiQ61271.

Structurei

3D structure databases

ProteinModelPortaliQ61271.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini177 – 206GSPROSITE-ProRule annotationAdd BLAST30
Domaini207 – 497Protein kinasePROSITE-ProRule annotationAdd BLAST291

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

eggNOGiKOG2052. Eukaryota.
ENOG410XQT0. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiQ61271.
KOiK13567.
OMAiQCACTSC.
OrthoDBiEOG091G0BIU.
PhylomeDBiQ61271.
TreeFamiTF314724.

Family and domain databases

InterProiIPR000472. Activin_recp.
IPR003605. GS_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
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.
SM00220. S_TKc. 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi197954. 2 interactors.
IntActiQ61271. 1 interactor.
MINTiMINT-2842316.
STRINGi10090.ENSMUSP00000000544.

Chemistry databases

BindingDBiQ61271.

PTM databases

iPTMnetiQ61271.
PhosphoSitePlusiQ61271.

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

eggNOGiKOG2052. Eukaryota.
ENOG410XQT0. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiQ61271.
KOiK13567.
OMAiQCACTSC.
OrthoDBiEOG091G0BIU.
PhylomeDBiQ61271.
TreeFamiTF314724.

Enzyme and pathway databases

ReactomeiR-MMU-1181150. Signaling by NODAL.
R-MMU-1502540. Signaling by Activin.

Miscellaneous databases

PROiQ61271.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000000532.
CleanExiMM_ACVR1B.
ExpressionAtlasiQ61271. baseline and differential.
GenevisibleiQ61271. MM.

Family and domain databases

InterProiIPR000472. Activin_recp.
IPR003605. GS_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
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.
SM00220. S_TKc. 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...

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: November 2, 2016
This is version 147 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

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.