ACVR1 activin A receptor type 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACVR1provided by HGNC
Official Full Name: activin A receptor type 1provided by HGNC
Primary source: HGNC:HGNC:171
See related: Ensembl:ENSG00000115170 MIM:102576
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FOP; ALK2; SKR1; TSRI; ACTRI; ACVR1A; ACVRLK2
Summary: Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I ( I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type I receptor which signals a particular transcriptional response in concert with activin type II receptors. Mutations in this gene are associated with fibrodysplasia ossificans progressive. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in thyroid (RPKM 15.1), gall bladder (RPKM 9.4) and 23 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2q24.1

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (157736446..157876330, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (158592958..158732374, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

BMPR2 inhibits ALK2-mediated signaling by preventing ALK2 from oligomerizing with the type 2 receptors ACVR2A and ACVR2B.
Title: BMPR2 inhibits activin and BMP signaling via wild-type ALK2.
AFAP1-AS1 functions as an endogenous RNA by competitively binding to miR-384 to regulate ACVR1, thus conferring inhibitory effects on pancreatic cancer cell stemness and tumorigenicity
Title: Cross-talk among AFAP1-AS1, ACVR1 and microRNA-384 regulates the stemness of pancreatic cancer cells and tumorigenicity in nude mice.
this study characterized the ALK2 mutants R258G, G328V and F246Y, which were identified in patients with severe fibrodysplasia ossificans progressiva, diffuse intrinsic pontine glioma and unusual hereditary skeletal dysplasia, respectively.
Title: Effects of FKBP12 and type II BMP receptors on signal transduction by ALK2 activating mutations associated with genetic disorders.
Identification of small molecule inhibitors of ALK2: a virtual screening, density functional theory, and molecular dynamics simulations study.
Title: Identification of small molecule inhibitors of ALK2: a virtual screening, density functional theory, and molecular dynamics simulations study.
Results showed that ACVR1 was a direct target of miR-384 and was involved in the inhibitory effects of miR-384 on breast cancer progression. Furthermore, the study indicated that ACVR1 activated the Wnt/beta-catenin signaling pathway in breast cancer.
Title: MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1.
Study emphasizes about the role of ACVR1 which encoding a receptor for BMP proteins in fibrodysplasia ossificans progressiva (FOP). Most FOP patients carry the recurrent R206H substitution in the GS domain, whereas a few other mutations are responsible for limited cases. Mutations cause a dysregulation of the downstream BMP-dependent pathway making mutated ACVR1 responsive to a non-canonical ligand, Activin A. [review]
Title: The Horizon of a Therapy for Rare Genetic Diseases: A "Druggable" Future for Fibrodysplasia Ossificans Progressiva.
The role of an ALK2 mutation (R258S) in IRIDA development in a patient also bearing compound heterozygous mutations in TMPRSS6 was demonstrated by reconstructing in vitro the proband's genotype, expressing mutants TMPRSS6 and ACVR1 in the presence of hemojuvelin and assessing hepcidin activation. ALK2(R258S) maintained high hepcidin expression in the presence of MT2(I212T).
Title: A new form of IRIDA due to combined heterozygous mutations of TMPRSS6 and ACVR1A encoding the BMP receptor ALK2.
activation of AMPK upregulated Smad6 and Smurf1 and thereby enhanced their interactions, resulting in its proteosome-dependent degradation of ALK2.
Title: AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation.
the Fibrodysplasia Ossificans Progressiva mutation ACVR1(R206H) is more sensitive to a number of natural ligands.
Title: The Fibrodysplasia Ossificans Progressiva (FOP) mutation p.R206H in ACVR1 confers an altered ligand response.
both bone morphogenetic protein 2 (BMP2) and BMP6 are proangiogenic in vitro and ex vivo and that the BMP type I receptors, activin receptor-like kinase 3 (ALK3) and ALK2, play crucial and distinct roles in this process.
Title: Role of bone morphogenetic proteins in sprouting angiogenesis: differential BMP receptor-dependent signaling pathways balance stalk vs. tip cell competence.

Submit: New GeneRIF Correction See all GeneRIFs (85)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Progressive myositis ossificans MedGen: C0016037 OMIM: 135100 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of activin A receptor, type I (ACVR1) in human B cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D4S2417 (e-PCR), detects polymorphism
- UniSTS:12810

RH69582 (e-PCR)
- UniSTS:13845

SHGC-89211 (e-PCR)
- UniSTS:170531

D2S2000 (e-PCR)
- UniSTS:312

D4S1625 (e-PCR), detects polymorphism
- UniSTS:43591

SHGC-78610 (e-PCR)
- UniSTS:101715

D2S284 (e-PCR)
- UniSTS:21595

D2S1294 (e-PCR)
- UniSTS:17283

D2S284 (e-PCR)
- UniSTS:63137

RH70974 (e-PCR)
- UniSTS:73647

MARC_1909-1910:991931646:1 (e-PCR)
- UniSTS:230886

RH68903 (e-PCR)
- UniSTS:66551

Homology

Homologs of the ACVR1 gene: The ACVR1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 284 organisms have orthologs with human gene ACVR1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
SMAD binding	IDA Inferred from Direct Assay more info	PubMed
activin binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to activin receptor activity, type I	IDA Inferred from Direct Assay more info	PubMed
cadherin binding	IPI Inferred from Physical Interaction more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
peptide hormone binding	NAS Non-traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
transforming growth factor beta binding	IDA Inferred from Direct Assay more info	PubMed
transforming growth factor beta receptor activity, type I	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane receptor protein serine/threonine kinase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
BMP signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
BMP signaling pathway involved in heart development	ISS Inferred from Sequence or Structural Similarity more info
G1/S transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
activin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
activin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acute inflammatory response	IEA Inferred from Electronic Annotation more info
angiogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
atrial septum primum morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
atrial septum primum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
atrioventricular valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
branching involved in blood vessel morphogenesis	IEA Inferred from Electronic Annotation more info
cardiac muscle cell fate commitment	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to BMP stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to growth factor stimulus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
determination of left/right symmetry	IEA Inferred from Electronic Annotation more info
embryonic heart tube morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
endocardial cushion cell fate commitment	IMP Inferred from Mutant Phenotype more info	PubMed
endocardial cushion fusion	ISS Inferred from Sequence or Structural Similarity more info
endocardial cushion morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
gastrulation with mouth forming second	IEA Inferred from Electronic Annotation more info
germ cell development	IEA Inferred from Electronic Annotation more info
heart development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
in utero embryonic development	IEA Inferred from Electronic Annotation more info
mesoderm formation	IEA Inferred from Electronic Annotation more info
mitral valve morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of activin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
neural crest cell migration	IEA Inferred from Electronic Annotation more info
NOT outflow tract septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
pathway-restricted SMAD protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
pharyngeal system development	IEA Inferred from Electronic Annotation more info
positive regulation of bone mineralization	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cell migration	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of determination of dorsal identity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of pathway-restricted SMAD protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of pathway-restricted SMAD protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of peptidyl-tyrosine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of ossification	IMP Inferred from Mutant Phenotype more info	PubMed
smooth muscle cell differentiation	IEA Inferred from Electronic Annotation more info
transforming growth factor beta receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
ventricular septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
BMP receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
activin receptor complex	IDA Inferred from Direct Assay more info	PubMed
apical part of cell	IEA Inferred from Electronic Annotation more info
integral component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: activin receptor type-1

Names: TGF-B superfamily receptor type I; activin A receptor, type I; activin A receptor, type II-like kinase 2; activin receptor type I; activin receptor-like kinase 2; hydroxyalkyl-protein kinase; serine/threonine-protein kinase receptor R1

NP_001096.1

EC 2.7.11.30

NP_001104537.1

EC 2.7.11.30

NP_001334592.1

EC 2.7.11.30

NP_001334593.1

EC 2.7.11.30

NP_001334594.1

EC 2.7.11.30

NP_001334595.1

EC 2.7.11.30

NP_001334596.1

EC 2.7.11.30

XP_006712888.1

EC 2.7.11.30

XP_011510410.1

EC 2.7.11.30

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008004.1 RefSeqGene

Range

5113..143666

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001105.5 → NP_001096.1 activin receptor type-1 precursor

See identical proteins and their annotated locations for NP_001096.1

Status: REVIEWED

Source sequence(s)

AC013731, BC033867, L02911

Consensus CDS

CCDS2206.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Related

ENSP00000263640.3, ENST00000263640.7

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif
NM_001111067.4 → NP_001104537.1 activin receptor type-1 precursor

See identical proteins and their annotated locations for NP_001104537.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 5' UTR compared to variant 1. All seven variants encode the same protein.

Source sequence(s)

AC013731, AK313630, BC033867, KU177885, L02911

Consensus CDS

CCDS2206.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Related

ENSP00000405004.1, ENST00000434821.7

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif
NM_001347663.1 → NP_001334592.1 activin receptor type-1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate 5' UTR compared to variant 1. All seven variants encode the same protein.

Source sequence(s)

AC013731, AC019186

Consensus CDS

CCDS2206.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Related

ENSP00000387273.2, ENST00000409283.6

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif
NM_001347664.1 → NP_001334593.1 activin receptor type-1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) has an alternate 5' UTR compared to variant 1. All seven variants encode the same protein.

Source sequence(s)

AC013731, AC019186

Consensus CDS

CCDS2206.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Related

ENSP00000440091.2, ENST00000539637.6

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif
NM_001347665.1 → NP_001334594.1 activin receptor type-1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5) has an alternate 5' UTR compared to variant 1. All seven variants encode the same protein.

Source sequence(s)

AC013731, AC019186

Consensus CDS

CCDS2206.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Related

ENSP00000400767.2, ENST00000424669.6

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif
NM_001347666.1 → NP_001334595.1 activin receptor type-1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (6) has an alternate 5' UTR compared to variant 1. All seven variants encode the same protein.

Source sequence(s)

AC013731, AC019186

Consensus CDS

CCDS2206.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Related

ENSP00000500605.1, ENST00000672582.1

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif
NM_001347667.2 → NP_001334596.1 activin receptor type-1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (7) has an alternate 5' UTR compared to variant 1. All seven variants encode the same protein.

Source sequence(s)

AC013731, AC019186

Consensus CDS

CCDS2206.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Related

ENSP00000387127.2, ENST00000410057.6

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p13 Primary Assembly

Range

157736446..157876330 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006712825.4 → XP_006712888.1 activin receptor type-1 isoform X1

See identical proteins and their annotated locations for XP_006712888.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif
XM_011512108.3 → XP_011510410.1 activin receptor type-1 isoform X1

See identical proteins and their annotated locations for XP_011510410.1

UniProtKB/Swiss-Prot

Q04771

UniProtKB/TrEMBL

D3DPA4

Conserved Domains (3) summary

cd14142
Location:202 → 499

STKc_ACVR1_ALK1; Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1

pfam01064
Location:33 → 103

Activin_recp; Activin types I and II receptor domain

pfam08515
Location:179 → 206

TGF_beta_GS; Transforming growth factor beta type I GS-motif