P80202 (ACV1B_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Activin receptor type-1B
EC=2.7.11.30

Alternative name(s):
Activin receptor type IB
Short name=ACTR-IB
Activin receptor-like kinase 4
Short name=ALK-4
Serine/threonine-protein kinase receptor R2
Short name=SKR2

Gene names

Name:	Acvr1b
Synonyms:	Acvrlk4, Alk4

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	505 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a 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, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas 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 such as ACVR1B. 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. ACVR1B also phosphorylates TDP2 By similarity.
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Enzyme regulation	Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain By similarity.
Subunit structure	Forms an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Interacts with TDP2 By similarity. Interacts with AIP1, FKBP1A, IGSF1, TDGF1, SMAD2, SMAD3 and SMAD7 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity.
Tissue specificity	Urogenital ridge, testis, ovary, brain and lungs.
Domain	The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors By similarity.
Post-translational modification	Autophosphorylated. Phosphorylated by activin receptor type-2 (ACVR2A or ACVR2B) in response to activin-binding at serine and threonine residues in the GS domain. Phosphorylation of ACVR1B by activin receptor type-2 regulates association with SMAD7 By similarity. Ubiquitinated. Level of ubiquitination is regulated by the SMAD7-SMURF1 complex By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. Contains 1 GS domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from electronic annotation. Source: Compara central nervous system development Inferred from expression pattern PubMed 8854897. Source: RGD development of primary female sexual characteristics Inferred from expression pattern PubMed 11897700. Source: RGD hair follicle development Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from electronic annotation. Source: Compara negative regulation of cell growth Inferred from electronic annotation. Source: Compara nodal signaling pathway Inferred from electronic annotation. Source: Compara peptidyl-threonine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of activin receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of erythrocyte differentiation Inferred from electronic annotation. Source: Compara positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from mutant phenotype PubMed 17040568. Source: RGD positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 17040568. Source: RGD positive regulation of trophoblast cell migration Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW SMAD binding Inferred from mutant phenotype PubMed 12844345. Source: RGD activin receptor activity, type I Inferred from mutant phenotype PubMed 12844345. Source: RGD metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein serine/threonine kinase activity Inferred from mutant phenotype PubMed 12844345. Source: RGD transforming growth factor beta-activated receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 505	482	Activin receptor type-1B		PRO_0000024419
Regions
	Topological domain	24 – 126	103	Extracellular Potential
	Transmembrane	127 – 149	23	Helical; Potential
	Topological domain	150 – 505	356	Cytoplasmic Potential
	Domain	177 – 206	30	GS
	Domain	207 – 497	291	Protein kinase
	Nucleotide binding	213 – 221	9	ATP By similarity
Sites
	Active site	335	1	Proton acceptor By similarity
	Binding site	234	1	ATP By similarity
Amino acid modifications
	Modified residue	380	1	Phosphotyrosine By similarity
	Glycosylation	43	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	P80202 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: 377F4A5C867B3860	FASTA	505	56,805
	10 20 30 40 50 60 MAESAGASSF FPLVVLLLAG SGGSGPRGIQ ALLCACTSCL QTNYTCETDG ACMVSIFNLD 70 80 90 100 110 120 GMEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYIDF CNKIDLRVPS GHLKEPEHPS 130 140 150 160 170 180 MWGPVELVGI IAGPVFLLFL IIIIVFLVIN YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ 190 200 210 220 230 240 DLVYDLSTSG SGSGLPLFVQ RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE 250 260 270 280 290 300 ERSWFREAEI YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT 310 320 330 340 350 360 IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA IADLGLAVRH 370 380 390 400 410 420 DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC ADIYALGLVY WEIARRCNSG 430 440 450 460 470 480 GVHEEYQLPY YDLVPSDPSI EEMRKVVCDQ KLRPNVPNWW QSYEALRVMG KMMRECWYAN 490 500 GAARLTALRI KKTLSQLSVQ EDVKI

References

[1]	"Developmental expression of four novel serine/threonine kinase receptors homologous to the activin/transforming growth factor-beta type II receptor family." He W.-W., Gustafson M.L., Hirobe S., Donahoe P.K. Dev. Dyn. 196:133-142(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Urogenital ridge.
[2]	"Molecular characterization of a type I serine-threonine kinase receptor for TGF-beta and activin in the rat pituitary tumor cell line GH3." Takumi T., Moustakas A., Lin H.Y., Lodish H.F. Exp. Cell Res. 216:208-214(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pituitary.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S76466 mRNA. Translation: AAB33045.1.
IPI	IPI00195456.
RefSeq	NP_954700.1. NM_199230.1.
UniGene	Rn.214018.
3D structure databases
ProteinModelPortal	P80202.
SMR	P80202. Positions 173-501.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000009345.
PTM databases
PhosphoSite	P80202.
Proteomic databases
PaxDb	P80202.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000009345; ENSRNOP00000009345; ENSRNOG00000006934.
GeneID	29381.
KEGG	rno:29381.
UCSC	RGD:735207. rat.
Organism-specific databases
CTD	91.
RGD	735207. Acvr1b.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00560000076615.
HOGENOM	HOG000230587.
HOVERGEN	HBG054502.
InParanoid	P80202.
KO	K13567.
OrthoDB	EOG4FJ88P.
Enzyme and pathway databases
BRENDA	2.7.10.2. 5301.
Gene expression databases
ArrayExpress	P80202.
Genevestigator	P80202.
GermOnline	ENSRNOG00000006934. Rattus norvegicus.
Family and domain databases
InterPro	IPR000472. Activin_rcpt. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. IPR003605. TGF_beta_rcpt_GS. [Graphical view]
Pfam	PF01064. Activin_recp. 1 hit. PF00069. Pkinase. 1 hit. PF08515. TGF_beta_GS. 1 hit. [Graphical view]
SMART	SM00467. GS. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS51256. GS. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	608961.

Entry information

Entry name

ACV1B_RAT

Accession

Primary (citable) accession number: P80202

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	April 3, 2013
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program