Q13705 (AVR2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	512 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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	Defects in ACVR2B are the cause of visceral heterotaxy autosomal type 4 (HTX4) [MIM:613751]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy type 4 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. 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 component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Heterotaxy
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from direct assay. Source: BHF-UCL activin receptor signaling pathway Inferred from electronic annotation. Source: InterPro anterior/posterior pattern specification Inferred from mutant phenotype Ref.3. Source: HGNC positive regulation of activin receptor signaling pathway Inferred from direct assay Ref.5. Source: HGNC positive regulation of bone mineralization Inferred from mutant phenotype. Source: BHF-UCL positive regulation of osteoblast differentiation Inferred from mutant phenotype. Source: BHF-UCL regulation of transcription, DNA-dependent Inferred from direct assay Ref.5. Source: HGNC
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB cytoplasm Inferred from direct assay. Source: HGNC integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW activin receptor activity, type II Traceable author statement. Source: Reactome growth factor binding Inferred from physical interaction. Source: HGNC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 512

494

Activin receptor type-2B

PRO_0000024404

Regions

Topological domain

19 – 137

119

Extracellular Potential

Transmembrane

138 – 158

21

Helical; Potential

Topological domain

159 – 512

354

Cytoplasmic Potential

Domain

190 – 480

291

Protein kinase

Nucleotide binding

196 – 204

9

ATP By similarity

Sites

Active site

321

1

Proton acceptor By similarity

Binding site

217

1

ATP By similarity

Amino acid modifications

Glycosylation

42

1

N-linked (GlcNAc...) Potential

Glycosylation

65

1

N-linked (GlcNAc...) Potential

Disulfide bond

29 ↔ 59

By similarity

Disulfide bond

49 ↔ 77

By similarity

Disulfide bond

84 ↔ 103

By similarity

Disulfide bond

90 ↔ 102

By similarity

Disulfide bond

104 ↔ 109

By similarity

Natural variations

Natural variant

40

1

R → H in HTX4. Ref.3

VAR_013281

Natural variant

176

1

P → R. Ref.6
Corresponds to variant rs35882617 [ dbSNP | Ensembl ].

VAR_041396

Natural variant

459

1

E → D. Ref.2
Corresponds to variant rs500611 [ dbSNP | Ensembl ].

VAR_050594

Natural variant

494

1

V → I in HTX4. Ref.3

VAR_013282

Experimental info

Sequence conflict

16 – 17

2

CA → WP in CAA54671. Ref.1

Sequence conflict

64

1

R → A Ref.1

Sequence conflict

64

1

R → A Ref.2

Sequence conflict

459

1

E → A in AAC64515. Ref.3

Secondary structure

1

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512

Helix Strand Turn

Details...

Beta strand

27 – 33

7

Helix

36 – 39

4

Beta strand

43 – 49

7

Beta strand

57 – 66

10

Beta strand

69 – 79

11

Helix

82 – 84

3

Beta strand

88 – 91

4

Beta strand

98 – 106

9

Turn

107 – 110

4

Beta strand

111 – 114

4

Beta strand

191 – 197

7

Beta strand

200 – 209

10

Beta strand

212 – 219

8

Helix

221 – 223

3

Helix

224 – 235

12

Beta strand

247 – 253

7

Turn

256 – 258

3

Beta strand

260 – 266

7

Helix

273 – 279

7

Helix

284 – 302

19

Beta strand

305 – 308

4

Turn

309 – 311

3

Beta strand

312 – 314

3

Beta strand

316 – 318

3

Helix

324 – 326

3

Beta strand

327 – 329

3

Beta strand

335 – 337

3

Beta strand

344 – 346

3

Helix

362 – 364

3

Helix

367 – 370

4

Helix

378 – 398

21

Turn

413 – 417

5

Helix

424 – 431

8

Helix

442 – 446

5

Helix

448 – 460

13

Helix

465 – 467

3

Helix

471 – 482

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform ActR-IIB2 [UniParc]. Last modified May 16, 2006. Version 3. Checksum: B377FEF92EF74937	FASTA	512	57,724
	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
	Isoform ActR-IIB1 (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow '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: 8161782] [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: 9621519] [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: 9916847] [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: 15489334] [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: 8622651] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH ACVR1B, FUNCTION IN PHOSPHORYLATION OF ACVR1B.
[6]	"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. , 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: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-176.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00437565.

PIR

I37134.

RefSeq

NP_001097.2. NM_001106.3.

UniGene

Hs.174273.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H62	X-ray	1.85	D	19-116	[»]
2QLU	X-ray	2.00	A	190-487	[»]

ProteinModelPortal

Q13705.

SMR

Q13705. Positions 24-116, 190-484.

ModBase

Search...

Protein-protein interaction databases

STRING

Q13705.

Polymorphism databases

DMDM

97535735.

Proteomic databases

PRIDE

Q13705.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000352511; ENSP00000340361; ENSG00000114739.

GeneID

93.

KEGG

hsa:93.

UCSC

uc003cif.1. human.

Organism-specific databases

CTD

93.

GeneCards

GC03P038470.

H-InvDB

HIX0030708.

HGNC

HGNC:174. ACVR2B.

HPA

CAB025115.

MIM

602730. gene.
613751. phenotype.

neXtProt

NX_Q13705.

Orphanet

157769. Situs ambiguus.

PharmGKB

PA24495.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16481.

HOVERGEN

HBG054502.

InParanoid

Q13705.

OMA

KKMRPAI.

OrthoDB

EOG4XPQFN.

PhylomeDB

Q13705.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q13705.

Bgee

Q13705.

CleanEx

HS_ACVR2B.

Genevestigator

Q13705.

GermOnline

ENSG00000114739. Homo sapiens.

Family and domain databases

InterPro

IPR000333. Activin_II/TGFBeta-II_recpt.
IPR015768. Activin_II_recpt.
IPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

KO

K13596.

PANTHER

PTHR23255:SF10. Activin_II_recpt_C. 1 hit.

Pfam

PF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

PRINTS

PR00653. ACTIVIN2R.

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

351.

SOURCE

Search...

Entry information

Entry name

AVR2B_HUMAN

Accession

Primary (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:	December 14, 2011
This is version 126 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.