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P27040

- AVR2B_MOUSE

UniProt

P27040 - AVR2B_MOUSE

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Protein

Activin receptor type-2B

Gene

Acvr2b

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

Functioni

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).By similarity

Catalytic activityi

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

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei241 – 2411ATPPROSITE-ProRule annotation
Active sitei345 – 3451Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi220 – 2289ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. activin binding Source: MGI
  2. ATP binding Source: UniProtKB-KW
  3. growth factor binding Source: MGI
  4. metal ion binding Source: UniProtKB-KW
  5. protein serine/threonine/tyrosine kinase activity Source: MGI
  6. protein serine/threonine kinase activity Source: MGI
  7. receptor signaling protein serine/threonine kinase activity Source: InterPro
  8. transforming growth factor beta-activated receptor activity Source: InterPro

GO - Biological processi

  1. activation of protein kinase activity Source: MGI
  2. anterior/posterior pattern specification Source: MGI
  3. artery development Source: BHF-UCL
  4. blood vessel remodeling Source: BHF-UCL
  5. BMP signaling pathway Source: Ensembl
  6. determination of left/right symmetry Source: MGI
  7. embryonic foregut morphogenesis Source: MGI
  8. gastrulation with mouth forming second Source: MGI
  9. heart development Source: MGI
  10. insulin secretion Source: MGI
  11. kidney development Source: MGI
  12. lung development Source: MGI
  13. lymphangiogenesis Source: BHF-UCL
  14. lymphatic endothelial cell differentiation Source: BHF-UCL
  15. mesoderm development Source: MGI
  16. odontogenesis of dentin-containing tooth Source: MGI
  17. organ growth Source: MGI
  18. palate development Source: MGI
  19. pancreas development Source: MGI
  20. pattern specification process Source: MGI
  21. positive regulation of activin receptor signaling pathway Source: Ensembl
  22. positive regulation of bone mineralization Source: Ensembl
  23. positive regulation of osteoblast differentiation Source: Ensembl
  24. post-embryonic development Source: MGI
  25. regulation of signal transduction Source: MGI
  26. response to glucose Source: MGI
  27. retina vasculature development in camera-type eye Source: BHF-UCL
  28. skeletal system development Source: MGI
  29. skeletal system morphogenesis Source: MGI
  30. venous blood vessel development Source: BHF-UCL
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

BRENDAi2.7.10.2. 3474.
ReactomeiREACT_216258. Signaling by Activin.
REACT_220505. Signaling by BMP.
REACT_220645. Signaling by NODAL.

Names & Taxonomyi

Protein namesi
Recommended name:
Activin receptor type-2B (EC:2.7.11.30)
Alternative name(s):
Activin receptor type IIB
Short name:
ACTR-IIB
Gene namesi
Name:Acvr2b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:87912. Acvr2b.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 137119ExtracellularSequence AnalysisAdd
BLAST
Transmembranei138 – 15821HelicalSequence AnalysisAdd
BLAST
Topological domaini159 – 536378CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: Reactome
  4. protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 536518Activin receptor type-2BPRO_0000024405Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi29 ↔ 59
Glycosylationi42 – 421N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi49 ↔ 77
Glycosylationi65 – 651N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi84 ↔ 103
Disulfide bondi90 ↔ 102
Disulfide bondi104 ↔ 109

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiP27040.

PTM databases

PhosphoSiteiP27040.

Expressioni

Gene expression databases

BgeeiP27040.
CleanExiMM_ACVR2B.
GenevestigatoriP27040.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi197956. 1 interaction.
DIPiDIP-5799N.
IntActiP27040. 1 interaction.
MINTiMINT-2842249.
STRINGi10090.ENSMUSP00000035093.

Structurei

Secondary structure

1
536
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi28 – 336Combined sources
Turni34 – 407Combined sources
Beta strandi43 – 486Combined sources
Beta strandi57 – 6610Combined sources
Beta strandi69 – 7911Combined sources
Helixi82 – 843Combined sources
Beta strandi88 – 925Combined sources
Beta strandi93 – 964Combined sources
Beta strandi98 – 1069Combined sources
Turni107 – 1104Combined sources
Beta strandi111 – 1155Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1S4YX-ray2.30A/C23-120[»]
2H64X-ray1.92C19-117[»]
ProteinModelPortaliP27040.
SMRiP27040. Positions 24-116, 214-536.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27040.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini214 – 504291Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG054502.
InParanoidiP27040.
KOiK13596.
OMAiKKMRPAI.
OrthoDBiEOG7JHM5B.
PhylomeDBiP27040.
TreeFamiTF352876.

Family and domain databases

InterProiIPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR00653. ACTIVIN2R.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. Align

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) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MTAPWAALAL LWGSLCAGSG RGEAETRECI YYNANWELER TNQSGLERCE
60 70 80 90 100
GEQDKRLHCY ASWRNSSGTI ELVKKGCWLD DFNCYDRQEC VATEENPQVY
110 120 130 140 150
FCCCEGNFCN ERFTHLPEPG GPEVTYEPPP TAPTLLTVLA YSLLPIGGLS
160 170 180 190 200
LIVLLAFWMY RHRKPPYGHV DIHEVRQCQR WAGRRDGCAD SFKPLPFQDP
210 220 230 240 250
GPPPPSPLVG LKPLQLLEIK ARGRFGCVWK AQLMNDFVAV KIFPLQDKQS
260 270 280 290 300
WQSEREIFST PGMKHENLLQ FIAAEKRGSN LEVELWLITA FHDKGSLTDY
310 320 330 340 350
LKGNIITWNE LCHVAETMSR GLSYLHEDVP WCRGEGHKPS IAHRDFKSKN
360 370 380 390 400
VLLKSDLTAV LADFGLAVRF EPGKPPGDTH GQVGTRRYMA PEVLEGAINF
410 420 430 440 450
QRDAFLRIDM YAMGLVLWEL VSRCKAADGP VDEYMLPFEE EIGQHPSLEE
460 470 480 490 500
LQEVVVHKKM RPTIKDHWLK HPGLAQLCVT IEECWDHDAE ARLSAGCVEE
510 520 530
RVSLIRRSVN GTTSDCLVSL VTSVTNVDLL PKESSI
Length:536
Mass (Da):60,542
Last modified:August 1, 1992 - v1
Checksum:iBF1C8CAC974BF5E2
GO
Isoform ActR-IIB2 (identifier: P27040-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:512
Mass (Da):57,738
Checksum:iF8C53AE6D0825D7A
GO
Isoform ActR-IIB3 (identifier: P27040-3) [UniParc]FASTAAdd to Basket

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

Show »
Length:528
Mass (Da):59,657
Checksum:i1559B59DEAF7733B
GO
Isoform ActR-IIB4 (identifier: P27040-4) [UniParc]FASTAAdd to Basket

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

Show »
Length:504
Mass (Da):56,853
Checksum:i42A315009EE8C17A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei124 – 1318Missing in isoform ActR-IIB3 and isoform ActR-IIB4. 1 PublicationVSP_004951
Alternative sequencei175 – 19824Missing in isoform ActR-IIB2 and isoform ActR-IIB4. 2 PublicationsVSP_004952Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84120 mRNA. Translation: AAA37172.1.
BC106189 mRNA. Translation: AAI06190.1.
CCDSiCCDS23615.1. [P27040-1]
PIRiA40829.
B40829.
C40829.
D40829.
RefSeqiNP_031423.1. NM_007397.2. [P27040-1]
XP_006511988.1. XM_006511925.1. [P27040-2]
XP_006511989.1. XM_006511926.1. [P27040-4]
UniGeneiMm.390239.

Genome annotation databases

EnsembliENSMUST00000035093; ENSMUSP00000035093; ENSMUSG00000061393. [P27040-3]
ENSMUST00000165044; ENSMUSP00000126108; ENSMUSG00000061393. [P27040-1]
GeneIDi11481.
KEGGimmu:11481.
UCSCiuc009sax.1. mouse. [P27040-1]
uc009say.1. mouse. [P27040-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84120 mRNA. Translation: AAA37172.1 .
BC106189 mRNA. Translation: AAI06190.1 .
CCDSi CCDS23615.1. [P27040-1 ]
PIRi A40829.
B40829.
C40829.
D40829.
RefSeqi NP_031423.1. NM_007397.2. [P27040-1 ]
XP_006511988.1. XM_006511925.1. [P27040-2 ]
XP_006511989.1. XM_006511926.1. [P27040-4 ]
UniGenei Mm.390239.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1S4Y X-ray 2.30 A/C 23-120 [» ]
2H64 X-ray 1.92 C 19-117 [» ]
ProteinModelPortali P27040.
SMRi P27040. Positions 24-116, 214-536.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 197956. 1 interaction.
DIPi DIP-5799N.
IntActi P27040. 1 interaction.
MINTi MINT-2842249.
STRINGi 10090.ENSMUSP00000035093.

PTM databases

PhosphoSitei P27040.

Proteomic databases

PRIDEi P27040.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000035093 ; ENSMUSP00000035093 ; ENSMUSG00000061393 . [P27040-3 ]
ENSMUST00000165044 ; ENSMUSP00000126108 ; ENSMUSG00000061393 . [P27040-1 ]
GeneIDi 11481.
KEGGi mmu:11481.
UCSCi uc009sax.1. mouse. [P27040-1 ]
uc009say.1. mouse. [P27040-2 ]

Organism-specific databases

CTDi 93.
MGIi MGI:87912. Acvr2b.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118876.
HOGENOMi HOG000231495.
HOVERGENi HBG054502.
InParanoidi P27040.
KOi K13596.
OMAi KKMRPAI.
OrthoDBi EOG7JHM5B.
PhylomeDBi P27040.
TreeFami TF352876.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 3474.
Reactomei REACT_216258. Signaling by Activin.
REACT_220505. Signaling by BMP.
REACT_220645. Signaling by NODAL.

Miscellaneous databases

EvolutionaryTracei P27040.
NextBioi 278832.
PROi P27040.
SOURCEi Search...

Gene expression databases

Bgeei P27040.
CleanExi MM_ACVR2B.
Genevestigatori P27040.

Family and domain databases

InterProi IPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view ]
PANTHERi PTHR23255. PTHR23255. 1 hit.
Pfami PF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR00653. ACTIVIN2R.
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiAVR2B_MOUSE
AccessioniPrimary (citable) accession number: P27040
Secondary accession number(s): Q3KQI1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 26, 2014
This is version 152 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

3D-structure, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3