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Q13705 (AVR2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Activin receptor type-2B

EC=2.7.11.30
Alternative name(s):
Activin receptor type IIB
Short name=ACTR-IIB
Gene names
Name:ACVR2B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length512 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-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. Ref.5

Catalytic activity

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

Cofactor

Magnesium or manganese By similarity.

Subunit structure

Forms an activin receptor complex with activin type II receptors such as ACVR1B. Interacts with VPS39. Ref.5 Ref.6

Subcellular location

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

Post-translational modification

Phosphorylated. Constitutive phosphorylation is in part catalyzed by its own kinase activity. Ref.5

Involvement in disease

Heterotaxy, visceral, 4, autosomal (HTX4) [MIM:613751]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can been associated with variety of congenital defects including cardiac malformations. HTX4 clinical features include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Heterotaxy
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Serine/threonine-protein kinase
Transferase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from direct assay PubMed 18436533. Source: BHF-UCL

activation of protein kinase activity

Inferred from electronic annotation. Source: Ensembl

activin receptor signaling pathway

Traceable author statement Ref.5. Source: GOC

anterior/posterior pattern specification

Inferred from mutant phenotype Ref.3. Source: HGNC

artery development

Inferred from sequence or structural similarity. Source: BHF-UCL

blood vessel remodeling

Inferred from sequence or structural similarity. Source: BHF-UCL

determination of left/right symmetry

Inferred from electronic annotation. Source: Ensembl

embryonic foregut morphogenesis

Inferred from electronic annotation. Source: Ensembl

gastrulation with mouth forming second

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from electronic annotation. Source: Ensembl

insulin secretion

Inferred from electronic annotation. Source: Ensembl

kidney development

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from electronic annotation. Source: Ensembl

lymphangiogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

lymphatic endothelial cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

mesoderm development

Inferred from electronic annotation. Source: Ensembl

odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

organ growth

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from electronic annotation. Source: Ensembl

pancreas development

Inferred from electronic annotation. Source: Ensembl

positive regulation of activin receptor signaling pathway

Inferred from direct assay Ref.5. Source: HGNC

positive regulation of bone mineralization

Inferred from mutant phenotype PubMed 18436533. Source: BHF-UCL

positive regulation of osteoblast differentiation

Inferred from mutant phenotype PubMed 18436533. Source: BHF-UCL

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: HGNC

response to glucose

Inferred from electronic annotation. Source: Ensembl

retina vasculature development in camera-type eye

Inferred from sequence or structural similarity. Source: BHF-UCL

signal transduction

Inferred from direct assay Ref.5. Source: HGNC

skeletal system morphogenesis

Inferred from electronic annotation. Source: Ensembl

transmembrane receptor protein serine/threonine kinase signaling pathway

Traceable author statement Ref.1. Source: ProtInc

venous blood vessel development

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 14738881. Source: HGNC

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

protein complex

Inferred from physical interaction PubMed 24019467. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

growth factor binding

Inferred from physical interaction PubMed 14517293. Source: HGNC

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 11266516PubMed 11278302PubMed 11279102. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from mutant phenotype Ref.5. Source: HGNC

protein serine/threonine/tyrosine kinase activity

Inferred from electronic annotation. Source: Ensembl

receptor signaling protein serine/threonine kinase activity

Inferred from electronic annotation. Source: InterPro

transforming growth factor beta-activated receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MSTNO147934EBI-1383577,EBI-8542977

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]
Isoform ActR-IIB2 (identifier: Q13705-1)

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.
Isoform ActR-IIB1 (identifier: Q13705-2)

The sequence of this isoform is not available.
Note: Produced from the insertion in the transcript of 82 base pairs, leading to frameshift and protein truncation. May be not functional.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 512494Activin receptor type-2B
PRO_0000024404

Regions

Topological domain19 – 137119Extracellular Potential
Transmembrane138 – 15821Helical; Potential
Topological domain159 – 512354Cytoplasmic Potential
Domain190 – 480291Protein kinase
Nucleotide binding196 – 2049ATP By similarity

Sites

Active site3211Proton acceptor By similarity
Binding site2171ATP By similarity

Amino acid modifications

Glycosylation421N-linked (GlcNAc...) Ref.7
Glycosylation651N-linked (GlcNAc...) Ref.7
Disulfide bond29 ↔ 59 Ref.7
Disulfide bond49 ↔ 77 Ref.7
Disulfide bond84 ↔ 103 Ref.7
Disulfide bond90 ↔ 102 Ref.7
Disulfide bond104 ↔ 109 Ref.7

Natural variations

Natural variant401R → H in HTX4. Ref.3
Corresponds to variant rs121434437 [ dbSNP | Ensembl ].
VAR_013281
Natural variant1761P → R. Ref.8
Corresponds to variant rs35882617 [ dbSNP | Ensembl ].
VAR_041396
Natural variant4591E → D. Ref.2
Corresponds to variant rs500611 [ dbSNP | Ensembl ].
VAR_050594
Natural variant4941V → I in HTX4. Ref.3
VAR_013282

Experimental info

Sequence conflict16 – 172CA → WP in CAA54671. Ref.1
Sequence conflict641R → A Ref.1
Sequence conflict641R → A Ref.2
Sequence conflict4591E → A in AAC64515. Ref.3

Secondary structure

..................................................................... 512
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform ActR-IIB2 [UniParc].

Last modified May 16, 2006. Version 3.
Checksum: B377FEF92EF74937

FASTA51257,724
        10         20         30         40         50         60 
MTAPWVALAL LWGSLCAGSG RGEAETRECI YYNANWELER TNQSGLERCE GEQDKRLHCY 

        70         80         90        100        110        120 
ASWRNSSGTI ELVKKGCWLD DFNCYDRQEC VATEENPQVY FCCCEGNFCN ERFTHLPEAG 

       130        140        150        160        170        180 
GPEVTYEPPP TAPTLLTVLA YSLLPIGGLS LIVLLAFWMY RHRKPPYGHV DIHEDPGPPP 

       190        200        210        220        230        240 
PSPLVGLKPL QLLEIKARGR FGCVWKAQLM NDFVAVKIFP LQDKQSWQSE REIFSTPGMK 

       250        260        270        280        290        300 
HENLLQFIAA EKRGSNLEVE LWLITAFHDK GSLTDYLKGN IITWNELCHV AETMSRGLSY 

       310        320        330        340        350        360 
LHEDVPWCRG EGHKPSIAHR DFKSKNVLLK SDLTAVLADF GLAVRFEPGK PPGDTHGQVG 

       370        380        390        400        410        420 
TRRYMAPEVL EGAINFQRDA FLRIDMYAMG LVLWELVSRC KAADGPVDEY MLPFEEEIGQ 

       430        440        450        460        470        480 
HPSLEELQEV VVHKKMRPTI KDHWLKHPGL AQLCVTIEEC WDHDAEARLS AGCVEERVSL 

       490        500        510 
IRRSVNGTTS DCLVSLVTSV TNVDLPPKES SI 

« Hide

Isoform ActR-IIB1 (Sequence not available).

References

« Hide 'large scale' references
[1]"Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB activin receptor."
Hilden K., Tuuri T., Eramaa M., Ritvos O.
Blood 83:2163-2170(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Genomic organization and mapping of the human activin receptor type IIB (hActR-IIB) gene."
Ishikawa S., Kai M., Murata Y., Tamari M., Daigo Y., Murano T., Ogawa M., Nakamura Y.
J. Hum. Genet. 43:132-134(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-459.
[3]"Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB."
Kosaki R., Gebbia M., Kosaki K., Lewin M., Bowers P., Towbin J.A., Casey B.
Am. J. Med. Genet. 82:70-76(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, VARIANTS HTX4 HIS-40 AND ILE-494.
[4]"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].
[5]"Activation of signalling by the activin receptor complex."
Attisano L., Wrana J.L., Montalvo E., Massague J.
Mol. Cell. Biol. 16:1066-1073(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH ACVR1B, FUNCTION IN PHOSPHORYLATION OF ACVR1B.
[6]"TLP, a novel modulator of TGF-beta signaling, has opposite effects on Smad2- and Smad3-dependent signaling."
Felici A., Wurthner J.U., Parks W.T., Giam L.R., Reiss M., Karpova T.S., McNally J.G., Roberts A.B.
EMBO J. 22:4465-4477(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH VPS39.
[7]"Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex."
Townson S.A., Martinez-Hackert E., Greppi C., Lowden P., Sako D., Liu J., Ucran J.A., Liharska K., Underwood K.W., Seehra J., Kumar R., Grinberg A.V.
J. Biol. Chem. 287:27313-27325(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.36 ANGSTROMS) OF 19-134 IN COMPLEX WITH ACVRL1 AND BMP9, DISULFIDE BONDS, GLYCOSYLATION AT ASN-42 AND ASN-65.
[8]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-176.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X77533 mRNA. Translation: CAA54671.1.
AB008681 Genomic DNA. Translation: BAA24180.2.
AF060202 expand/collapse EMBL AC list , AF060199, AF060200, AF060201 Genomic DNA. Translation: AAC64515.1.
BC096243 mRNA. Translation: AAH96243.1.
BC096244 mRNA. Translation: AAH96244.1.
BC099642 mRNA. Translation: AAH99642.1.
CCDSCCDS2679.1. [Q13705-1]
PIRI37134.
RefSeqNP_001097.2. NM_001106.3. [Q13705-1]
UniGeneHs.174273.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2H62X-ray1.85D19-116[»]
2QLUX-ray2.00A190-487[»]
4FAOX-ray3.36E/F/K/L/Q/R/W/X/e/f/k/l19-134[»]
ProteinModelPortalQ13705.
SMRQ13705. Positions 24-116, 190-484.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106608. 22 interactions.
IntActQ13705. 6 interactions.
MINTMINT-3028545.
STRING9606.ENSP00000340361.

Chemistry

BindingDBQ13705.
ChEMBLCHEMBL5466.
GuidetoPHARMACOLOGY1792.

PTM databases

PhosphoSiteQ13705.

Polymorphism databases

DMDM97535735.

Proteomic databases

PaxDbQ13705.
PRIDEQ13705.

Protocols and materials databases

DNASU93.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000352511; ENSP00000340361; ENSG00000114739. [Q13705-1]
GeneID93.
KEGGhsa:93.
UCSCuc003cif.3. human. [Q13705-1]

Organism-specific databases

CTD93.
GeneCardsGC03P038470.
HGNCHGNC:174. ACVR2B.
HPACAB025115.
MIM602730. gene.
613751. phenotype.
neXtProtNX_Q13705.
Orphanet157769. Situs ambiguus.
PharmGKBPA24495.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG054502.
InParanoidQ13705.
KOK13596.
OMAKKMRPAI.
OrthoDBEOG7JHM5B.
PhylomeDBQ13705.
TreeFamTF352876.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
SignaLinkQ13705.

Gene expression databases

ArrayExpressQ13705.
BgeeQ13705.
CleanExHS_ACVR2B.
GenevestigatorQ13705.

Family and domain databases

InterProIPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERPTHR23255. PTHR23255. 1 hit.
PfamPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR00653. ACTIVIN2R.
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13705.
GeneWikiACVR2B.
GenomeRNAi93.
NextBio351.
PROQ13705.
SOURCESearch...

Entry information

Entry nameAVR2B_HUMAN
AccessionPrimary (citable) accession number: Q13705
Secondary accession number(s): Q4VAV0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 16, 2006
Last modified: July 9, 2014
This is version 155 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM