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Protein

Activin receptor type-2B

Gene

ACVR2B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.1 Publication

Catalytic activityi

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

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei217ATPPROSITE-ProRule annotation1
Active sitei321Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi196 – 204ATPPROSITE-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

BioCyciZFISH:HS03794-MONOMER.
ReactomeiR-HSA-1181150. Signaling by NODAL.
R-HSA-1433617. Regulation of signaling by NODAL.
R-HSA-1502540. Signaling by Activin.
R-HSA-201451. Signaling by BMP.
SignaLinkiQ13705.
SIGNORiQ13705.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:174. ACVR2B.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 137ExtracellularSequence analysisAdd BLAST119
Transmembranei138 – 158HelicalSequence analysisAdd BLAST21
Topological domaini159 – 512CytoplasmicSequence analysisAdd BLAST354

GO - Cellular componenti

  • cytoplasm Source: HGNC
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
  • protein complex Source: MGI
  • receptor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Heterotaxy, visceral, 4, autosomal (HTX4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613751
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01328140R → H in HTX4. 1 PublicationCorresponds to variant rs121434437dbSNPEnsembl.1
Natural variantiVAR_013282494V → I in HTX4. 1 PublicationCorresponds to variant rs121434438dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Heterotaxy

Organism-specific databases

DisGeNETi93.
MalaCardsiACVR2B.
MIMi613751. phenotype.
OpenTargetsiENSG00000114739.
Orphaneti157769. Situs ambiguus.
PharmGKBiPA24495.

Chemistry databases

ChEMBLiCHEMBL5466.
GuidetoPHARMACOLOGYi1792.

Polymorphism and mutation databases

BioMutaiACVR2B.
DMDMi97535735.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000002440419 – 512Activin receptor type-2BAdd BLAST494

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi29 ↔ 591 Publication
Glycosylationi42N-linked (GlcNAc...)1 Publication1
Disulfide bondi49 ↔ 771 Publication
Glycosylationi65N-linked (GlcNAc...)1 Publication1
Disulfide bondi84 ↔ 1031 Publication
Disulfide bondi90 ↔ 1021 Publication
Disulfide bondi104 ↔ 1091 Publication

Post-translational modificationi

Phosphorylated. Constitutive phosphorylation is in part catalyzed by its own kinase activity.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ13705.
PaxDbiQ13705.
PeptideAtlasiQ13705.
PRIDEiQ13705.

PTM databases

iPTMnetiQ13705.
PhosphoSitePlusiQ13705.

Expressioni

Gene expression databases

BgeeiENSG00000114739.
CleanExiHS_ACVR2B.
GenevisibleiQ13705. HS.

Organism-specific databases

HPAiCAB025115.
HPA007398.

Interactioni

Subunit structurei

Forms an activin receptor complex with activin type II receptors such as ACVR1B. Interacts with VPS39.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MSTNO147934EBI-1383577,EBI-8542977

GO - Molecular functioni

  • growth factor binding Source: HGNC

Protein-protein interaction databases

BioGridi106608. 47 interactors.
IntActiQ13705. 6 interactors.
MINTiMINT-3028545.
STRINGi9606.ENSP00000340361.

Chemistry databases

BindingDBiQ13705.

Structurei

Secondary structure

1512
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 33Combined sources7
Helixi36 – 39Combined sources4
Beta strandi43 – 49Combined sources7
Beta strandi57 – 66Combined sources10
Beta strandi69 – 79Combined sources11
Helixi82 – 84Combined sources3
Beta strandi88 – 91Combined sources4
Beta strandi98 – 106Combined sources9
Turni107 – 110Combined sources4
Beta strandi111 – 114Combined sources4
Beta strandi191 – 197Combined sources7
Beta strandi200 – 209Combined sources10
Beta strandi212 – 219Combined sources8
Helixi221 – 223Combined sources3
Helixi224 – 235Combined sources12
Beta strandi247 – 253Combined sources7
Turni256 – 258Combined sources3
Beta strandi260 – 266Combined sources7
Helixi273 – 279Combined sources7
Helixi284 – 302Combined sources19
Beta strandi305 – 308Combined sources4
Turni309 – 311Combined sources3
Beta strandi312 – 314Combined sources3
Beta strandi316 – 318Combined sources3
Helixi324 – 326Combined sources3
Beta strandi327 – 329Combined sources3
Beta strandi335 – 337Combined sources3
Beta strandi344 – 346Combined sources3
Helixi362 – 364Combined sources3
Helixi367 – 370Combined sources4
Helixi378 – 398Combined sources21
Turni413 – 417Combined sources5
Helixi424 – 431Combined sources8
Helixi442 – 446Combined sources5
Helixi448 – 460Combined sources13
Helixi465 – 467Combined sources3
Helixi471 – 482Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ13705.
SMRiQ13705.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13705.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini190 – 480Protein kinasePROSITE-ProRule annotationAdd BLAST291

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOVERGENiHBG054502.
InParanoidiQ13705.
KOiK13596.
OMAiILLAFWM.
OrthoDBiEOG091G03YO.
PhylomeDBiQ13705.
TreeFamiTF352876.

Family and domain databases

InterProiIPR000472. Activin_recp.
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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform ActR-IIB2 (identifier: Q13705-1) [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
MTAPWVALAL LWGSLCAGSG RGEAETRECI YYNANWELER TNQSGLERCE
60 70 80 90 100
GEQDKRLHCY ASWRNSSGTI ELVKKGCWLD DFNCYDRQEC VATEENPQVY
110 120 130 140 150
FCCCEGNFCN ERFTHLPEAG GPEVTYEPPP TAPTLLTVLA YSLLPIGGLS
160 170 180 190 200
LIVLLAFWMY RHRKPPYGHV DIHEDPGPPP PSPLVGLKPL QLLEIKARGR
210 220 230 240 250
FGCVWKAQLM NDFVAVKIFP LQDKQSWQSE REIFSTPGMK HENLLQFIAA
260 270 280 290 300
EKRGSNLEVE LWLITAFHDK GSLTDYLKGN IITWNELCHV AETMSRGLSY
310 320 330 340 350
LHEDVPWCRG EGHKPSIAHR DFKSKNVLLK SDLTAVLADF GLAVRFEPGK
360 370 380 390 400
PPGDTHGQVG TRRYMAPEVL EGAINFQRDA FLRIDMYAMG LVLWELVSRC
410 420 430 440 450
KAADGPVDEY MLPFEEEIGQ HPSLEELQEV VVHKKMRPTI KDHWLKHPGL
460 470 480 490 500
AQLCVTIEEC WDHDAEARLS AGCVEERVSL IRRSVNGTTS DCLVSLVTSV
510
TNVDLPPKES SI
Length:512
Mass (Da):57,724
Last modified:May 16, 2006 - v3
Checksum:iB377FEF92EF74937
GO
Isoform ActR-IIB1 (identifier: Q13705-2)
Sequence 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.
Length:
Mass (Da):

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16 – 17CA → WP in CAA54671 (PubMed:8161782).Curated2
Sequence conflicti64R → A (PubMed:8161782).Curated1
Sequence conflicti64R → A (PubMed:9621519).Curated1
Sequence conflicti459E → A in AAC64515 (PubMed:9916847).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01328140R → H in HTX4. 1 PublicationCorresponds to variant rs121434437dbSNPEnsembl.1
Natural variantiVAR_041396176P → R.1 PublicationCorresponds to variant rs35882617dbSNPEnsembl.1
Natural variantiVAR_050594459E → D.1 PublicationCorresponds to variant rs500611dbSNPEnsembl.1
Natural variantiVAR_013282494V → I in HTX4. 1 PublicationCorresponds to variant rs121434438dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X77533 mRNA. Translation: CAA54671.1.
AB008681 Genomic DNA. Translation: BAA24180.2.
AF060202
, AF060199, AF060200, AF060201 Genomic DNA. Translation: AAC64515.1.
BC096243 mRNA. Translation: AAH96243.1.
BC096244 mRNA. Translation: AAH96244.1.
BC099642 mRNA. Translation: AAH99642.1.
CCDSiCCDS2679.1. [Q13705-1]
PIRiI37134.
RefSeqiNP_001097.2. NM_001106.3. [Q13705-1]
UniGeneiHs.174273.

Genome annotation databases

EnsembliENST00000352511; ENSP00000340361; ENSG00000114739. [Q13705-1]
GeneIDi93.
KEGGihsa:93.
UCSCiuc003cif.4. human. [Q13705-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X77533 mRNA. Translation: CAA54671.1.
AB008681 Genomic DNA. Translation: BAA24180.2.
AF060202
, AF060199, AF060200, AF060201 Genomic DNA. Translation: AAC64515.1.
BC096243 mRNA. Translation: AAH96243.1.
BC096244 mRNA. Translation: AAH96244.1.
BC099642 mRNA. Translation: AAH99642.1.
CCDSiCCDS2679.1. [Q13705-1]
PIRiI37134.
RefSeqiNP_001097.2. NM_001106.3. [Q13705-1]
UniGeneiHs.174273.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ13705.
SMRiQ13705.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106608. 47 interactors.
IntActiQ13705. 6 interactors.
MINTiMINT-3028545.
STRINGi9606.ENSP00000340361.

Chemistry databases

BindingDBiQ13705.
ChEMBLiCHEMBL5466.
GuidetoPHARMACOLOGYi1792.

PTM databases

iPTMnetiQ13705.
PhosphoSitePlusiQ13705.

Polymorphism and mutation databases

BioMutaiACVR2B.
DMDMi97535735.

Proteomic databases

EPDiQ13705.
PaxDbiQ13705.
PeptideAtlasiQ13705.
PRIDEiQ13705.

Protocols and materials databases

DNASUi93.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000352511; ENSP00000340361; ENSG00000114739. [Q13705-1]
GeneIDi93.
KEGGihsa:93.
UCSCiuc003cif.4. human. [Q13705-1]

Organism-specific databases

CTDi93.
DisGeNETi93.
GeneCardsiACVR2B.
HGNCiHGNC:174. ACVR2B.
HPAiCAB025115.
HPA007398.
MalaCardsiACVR2B.
MIMi602730. gene.
613751. phenotype.
neXtProtiNX_Q13705.
OpenTargetsiENSG00000114739.
Orphaneti157769. Situs ambiguus.
PharmGKBiPA24495.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOVERGENiHBG054502.
InParanoidiQ13705.
KOiK13596.
OMAiILLAFWM.
OrthoDBiEOG091G03YO.
PhylomeDBiQ13705.
TreeFamiTF352876.

Enzyme and pathway databases

BioCyciZFISH:HS03794-MONOMER.
ReactomeiR-HSA-1181150. Signaling by NODAL.
R-HSA-1433617. Regulation of signaling by NODAL.
R-HSA-1502540. Signaling by Activin.
R-HSA-201451. Signaling by BMP.
SignaLinkiQ13705.
SIGNORiQ13705.

Miscellaneous databases

ChiTaRSiACVR2B. human.
EvolutionaryTraceiQ13705.
GeneWikiiACVR2B.
GenomeRNAii93.
PROiQ13705.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114739.
CleanExiHS_ACVR2B.
GenevisibleiQ13705. HS.

Family and domain databases

InterProiIPR000472. Activin_recp.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiAVR2B_HUMAN
AccessioniPrimary (citable) accession number: Q13705
Secondary accession number(s): Q4VAV0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 16, 2006
Last modified: November 2, 2016
This is version 177 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.