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Q5CD18 (TGFR1_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
TGF-beta receptor type-1

Short name=TGFR-1
EC=2.7.11.30
Alternative name(s):
TGF-beta type I receptor
Transforming growth factor-beta receptor type I
Short name=TGF-beta receptor type I
Short name=TbetaR-I
Gene names
Name:TGFBR1
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation By similarity.

Catalytic activity

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

Cofactor

Magnesium or manganese By similarity.

Enzyme regulation

Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor By similarity.

Subunit structure

Homodimer; in the endoplasmic reticulum but also at the cell membrane. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGBRB1 and TGFBR2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Interacts with CD109; inhibits TGF-beta receptor activation in keratinocytes. Interacts with RBPMS. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with SMAD7, NEDD4L, SMURF1 and SMURF2; SMAD7 recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor By similarity. Interacts with USP15 and VPS39 By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Cell junctiontight junction By similarity.

Post-translational modification

Phosphorylated at basal levels in the absence of ligand. Activated upon phosphorylation by TGFBR2, mainly in the GS domain. Phosphorylation in the GS domain abrogates FKBP1A-binding By similarity.

N-Glycosylated By similarity.

Ubiquitinated; undergoes ubiquitination catalyzed by several E3 ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the proteasomal and/or lysosomal degradation of the receptor thereby negatively regulating its activity. Deubiquitinated by USP15, leading to stabilization of the protein and enhanced TGF-beta signal 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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5CD18-1)

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 2 (identifier: Q5CD18-2)

The sequence of this isoform differs from the canonical sequence as follows:
     111-114: Missing.
Note: May be due to a competing donnor splice site.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 By similarity
Chain30 – 503474TGF-beta receptor type-1
PRO_0000260305

Regions

Topological domain30 – 12697Extracellular Potential
Transmembrane127 – 14721Helical; Potential
Topological domain148 – 503356Cytoplasmic Potential
Domain175 – 20430GS
Domain205 – 495291Protein kinase
Nucleotide binding211 – 2199ATP By similarity
Motif193 – 1942FKBP1A-binding

Sites

Active site3331Proton acceptor By similarity
Binding site2321ATP By similarity

Amino acid modifications

Modified residue1651Phosphoserine By similarity
Modified residue1851Phosphothreonine; by TGFBR2 By similarity
Modified residue1861Phosphothreonine; by TGFBR2 By similarity
Modified residue1871Phosphoserine; by TGFBR2 By similarity
Modified residue1891Phosphoserine; by TGFBR2 By similarity
Modified residue1911Phosphoserine; by TGFBR2 By similarity
Glycosylation411N-linked (GlcNAc...) Potential
Cross-link391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence111 – 1144Missing in isoform 2.
VSP_021594
Natural variant81P → S. Ref.1
Natural variant4171I → V. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 12, 2005. Version 1.
Checksum: CFA1EEC793401A4A

FASTA50356,174
        10         20         30         40         50         60 
MEVAAGAPRS RLLLFVLAAT ATLAPEATAF QCFCHLCTKD NFTCVTDGLC FVSVTETTDK 

        70         80         90        100        110        120 
VIHNSMCIAE IDLIPRDRPF VCAPSSKTGS VTTTYCCNQD HCNKIELPTV GPFPGKPPSG 

       130        140        150        160        170        180 
LGPVELAAVI AGPVCFVCIS LMLMVYICHN RTVIHHRVPN EEDPSLDRPF ISEGTTLKDL 

       190        200        210        220        230        240 
IYDMTTSGSG SGLPLLVQRT IARTIVLQES IGKGRFGEVW RGKWRGEEVA VKIFSSREER 

       250        260        270        280        290        300 
SWFREAEIYQ TVMLRHENIL GFIAADNKDN GTWTQLWLVS DYHEHGSLFD YLNRYTVTVE 

       310        320        330        340        350        360 
GMIKLALSTA SGLAHLHMEI VGTQGKPAIA HRDLKSKNIL VKKNGTCCIA DLGLAVRHDS 

       370        380        390        400        410        420 
ATDTIDIAPN HRVGTKRYMA PEVLDDSINM KHFESFKRAD IYAMGLVFWE IARRCSIGGI 

       430        440        450        460        470        480 
HEDYQLPYYD LVPSDPSVEE MRKVVCEQKL RPNIPNRWQS CEALRVMAKI MRECWYANGA 

       490        500 
ARLTALRIKK TLSQLSQQEG IKM 

« Hide

Isoform 2 [UniParc].

Checksum: 208EB1C35ED32918
Show »

FASTA49955,775

References

[1]"Structure and polymorphism analysis of transforming growth factor beta receptor 1 (TGFBR1) in pigs."
Shimanuki S., Mikawa A., Miyake Y., Hamasima N., Mikawa S., Awata T.
Biochem. Genet. 43:491-500(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS SER-8 AND VAL-417.
Tissue: Testis.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB182259 mRNA. Translation: BAD91022.1.
AB182260 mRNA. Translation: BAD91023.1.
RefSeqNP_001033728.1. NM_001038639.1. [Q5CD18-1]
UniGeneSsc.23794.

3D structure databases

ProteinModelPortalQ5CD18.
SMRQ5CD18. Positions 29-107, 171-500.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID396665.
KEGGssc:396665.

Organism-specific databases

CTD7046.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000230587.
HOVERGENHBG054502.
KOK04674.

Family and domain databases

InterProIPR000472. Activin_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR003605. TGF_beta_rcpt_GS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERPTHR23255. PTHR23255. 1 hit.
PfamPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTSM00467. GS. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameTGFR1_PIG
AccessionPrimary (citable) accession number: Q5CD18
Secondary accession number(s): Q5CD19
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: April 12, 2005
Last modified: June 11, 2014
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families