Reviewed, UniProtKB/Swiss-Prot Q13705 (AVR2B_HUMAN)

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	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin A, activin B and inhibin A.
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Involvement in disease	Defects in ACVR2B are a cause of left-right axis malformations [MIM:602730]. Th effect is due to the loss of normal left-right asymmetry. Complete left-right asymmetry reversal imparts no deleterious consequences to the affected individual, whereas randomization typically results in complex, often lethal heart malformations as well as abdominal abnormalities.
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	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from direct assay. Source: UniProtKB anterior/posterior pattern formation Ref.3 Inferred from mutant phenotype. Source: HGNC positive regulation of activin receptor signaling pathway Inferred from direct assay. Source: HGNC positive regulation of bone mineralization Inferred from mutant phenotype. Source: UniProtKB positive regulation of osteoblast differentiation Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of transcription Inferred from direct assay. Source: HGNC
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB cytoplasm Inferred from direct assay. Source: HGNC integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro activin receptor activity Inferred from electronic annotation. Source: InterPro growth factor binding Inferred from physical interaction. Source: HGNC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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.

Notes: 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

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 left-right axis malformations.

VAR_013281

Natural variant

176

1

P → R

VAR_041396

Natural variant

494

1

V → I in left-right axis malformations.

VAR_013282

Experimental info

Sequence conflict

16 – 17

2

CA → WP in CAA54671. Ref.1

Sequence conflict

64

1

R → A Ref.1 Ref.2

Sequence conflict

459

1

E → A in AAC64515. Ref.3

Sequence conflict

459

1

E → D in BAA24180. Ref.2

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].
[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 LEFT-RIGHT AXIS MALFORMATIONS 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]	"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
EMBLGenBankDDBJ	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.
PIR	I37134.
RefSeq