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Q5CD18

- TGFR1_PIG

UniProt

Q5CD18 - TGFR1_PIG

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Protein
TGF-beta receptor type-1
Gene
TGFBR1
Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

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 activityi

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

Cofactori

Magnesium or manganese By similarity.

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei232 – 2321ATP By similarity
Active sitei333 – 3331Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi211 – 2199ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. receptor signaling protein serine/threonine kinase activity Source: InterPro
  4. transforming growth factor beta-activated receptor activity Source: InterPro

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. cell differentiation Source: UniProtKB-KW
  3. regulation of growth Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Differentiation, Growth regulation

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
TGF-beta receptor type-1 (EC:2.7.11.30)
Short name:
TGFR-1
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 namesi
Name:TGFBR1
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini30 – 12697Extracellular Reviewed prediction
Add
BLAST
Transmembranei127 – 14721Helical; Reviewed prediction
Add
BLAST
Topological domaini148 – 503356Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. plasma membrane Source: UniProtKB-SubCell
  3. tight junction Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Tight junction

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929 By similarity
Add
BLAST
Chaini30 – 503474TGF-beta receptor type-1
PRO_0000260305Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi41 – 411N-linked (GlcNAc...) Reviewed prediction
Modified residuei165 – 1651Phosphoserine By similarity
Modified residuei185 – 1851Phosphothreonine; by TGFBR2 By similarity
Modified residuei186 – 1861Phosphothreonine; by TGFBR2 By similarity
Modified residuei187 – 1871Phosphoserine; by TGFBR2 By similarity
Modified residuei189 – 1891Phosphoserine; by TGFBR2 By similarity
Modified residuei191 – 1911Phosphoserine; by TGFBR2 By similarity
Cross-linki391 – 391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Post-translational modificationi

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.

Keywords - PTMi

Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

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.

Structurei

3D structure databases

ProteinModelPortaliQ5CD18.
SMRiQ5CD18. Positions 29-107, 171-500.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini175 – 20430GS
Add
BLAST
Domaini205 – 495291Protein kinase
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi193 – 1942FKBP1A-binding

Sequence similaritiesi

Contains 1 GS domain.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
KOiK04674.

Family and domain databases

InterProiIPR000472. 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]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTiSM00467. GS. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q5CD18-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MEVAAGAPRS RLLLFVLAAT ATLAPEATAF QCFCHLCTKD NFTCVTDGLC    50
FVSVTETTDK VIHNSMCIAE IDLIPRDRPF VCAPSSKTGS VTTTYCCNQD 100
HCNKIELPTV GPFPGKPPSG LGPVELAAVI AGPVCFVCIS LMLMVYICHN 150
RTVIHHRVPN EEDPSLDRPF ISEGTTLKDL IYDMTTSGSG SGLPLLVQRT 200
IARTIVLQES IGKGRFGEVW RGKWRGEEVA VKIFSSREER SWFREAEIYQ 250
TVMLRHENIL GFIAADNKDN GTWTQLWLVS DYHEHGSLFD YLNRYTVTVE 300
GMIKLALSTA SGLAHLHMEI VGTQGKPAIA HRDLKSKNIL VKKNGTCCIA 350
DLGLAVRHDS ATDTIDIAPN HRVGTKRYMA PEVLDDSINM KHFESFKRAD 400
IYAMGLVFWE IARRCSIGGI HEDYQLPYYD LVPSDPSVEE MRKVVCEQKL 450
RPNIPNRWQS CEALRVMAKI MRECWYANGA ARLTALRIKK TLSQLSQQEG 500
IKM 503
Length:503
Mass (Da):56,174
Last modified:April 12, 2005 - v1
Checksum:iCFA1EEC793401A4A
GO
Isoform 2 (identifier: Q5CD18-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:499
Mass (Da):55,775
Checksum:i208EB1C35ED32918
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti8 – 81P → S.1 Publication
Natural varianti417 – 4171I → V.1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei111 – 1144Missing in isoform 2.
VSP_021594

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB182259 mRNA. Translation: BAD91022.1.
AB182260 mRNA. Translation: BAD91023.1.
RefSeqiNP_001033728.1. NM_001038639.1. [Q5CD18-1]
UniGeneiSsc.23794.

Genome annotation databases

GeneIDi396665.
KEGGissc:396665.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB182259 mRNA. Translation: BAD91022.1 .
AB182260 mRNA. Translation: BAD91023.1 .
RefSeqi NP_001033728.1. NM_001038639.1. [Q5CD18-1 ]
UniGenei Ssc.23794.

3D structure databases

ProteinModelPortali Q5CD18.
SMRi Q5CD18. Positions 29-107, 171-500.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 396665.
KEGGi ssc:396665.

Organism-specific databases

CTDi 7046.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000230587.
HOVERGENi HBG054502.
KOi K04674.

Family and domain databases

InterProi IPR000472. 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 ]
PANTHERi PTHR23255. PTHR23255. 1 hit.
Pfami PF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view ]
SMARTi SM00467. GS. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiTGFR1_PIG
AccessioniPrimary (citable) accession number: Q5CD18
Secondary accession number(s): Q5CD19
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: April 12, 2005
Last modified: September 3, 2014
This is version 79 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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