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Protein

TGF-beta receptor type-2

Gene

TGFBR2

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, 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 TGFRB1 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 (By similarity).By similarity

Catalytic activityi

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

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei277 – 2771ATPPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi250 – 2589ATPPROSITE-ProRule annotation

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 receptor activity, type II 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-2 (EC:2.7.11.30)
Short name:
TGFR-2
Alternative name(s):
TGF-beta type II receptor
Transforming growth factor-beta receptor type II
Short name:
TGF-beta receptor type II
Short name:
TbetaR-II
Gene namesi
Name:TGFBR2
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 166143ExtracellularSequence AnalysisAdd
BLAST
Transmembranei167 – 18721HelicalSequence AnalysisAdd
BLAST
Topological domaini188 – ›297›110CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – ›297›274TGF-beta receptor type-2PRO_0000024428Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi51 ↔ 84By similarity
Disulfide bondi54 ↔ 71By similarity
Disulfide bondi61 ↔ 67By similarity
Glycosylationi70 – 701N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi77 ↔ 101By similarity
Glycosylationi94 – 941N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi121 ↔ 136By similarity
Disulfide bondi138 ↔ 143By similarity

Post-translational modificationi

Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Interactioni

Subunit structurei

Homodimer. 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 TGFRB1 and TGFRB2 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 DAXX. Interacts with TCTEX1D4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor (By similarity). Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2 (By similarity). Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliP38551.
SMRiP38551. Positions 38-159.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini244 – ›297›54Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
HOVERGENiHBG104975.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000333. TGFB_receptor.
IPR015013. Transforming_GF_b_rcpt_2_ecto.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF08917. ecTbetaR2. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

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

P38551-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRGLLGGLW PLHVVLWTRI ASTIPPHVPK SVNSDMMVTD SNGAVKLPQL
60 70 80 90 100
CKFCDVRSST CDNQKSCLSN CSITAICEKP QEVCVAVWRK NDENITIETV
110 120 130 140 150
CDDPKIAYHG FVLDDAASSK CIMKERKGSG ETFFMCSCSS DECNDHIIFS
160 170 180 190 200
EEYATNNPDL LLVIFQVTGV SLLPPLGIAI AVIITFYCYR VHRQQKLSPS
210 220 230 240 250
WDSGKPRKLM EFSEHLAIIL EDDRSDISST CANNINHNTE LLPIELDTLV
260 270 280 290
GKGRFAEVYK AKLRQNTSEQ FETVAVKIFP YEEYASWKTE KDIFSDL
Length:297
Mass (Da):33,302
Last modified:September 30, 1994 - v1
Checksum:iF9869D3079B66A15
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei297 – 2971

Cross-referencesi

3D structure databases

ProteinModelPortaliP38551.
SMRiP38551. Positions 38-159.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiCOG0515.
HOVERGENiHBG104975.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000333. TGFB_receptor.
IPR015013. Transforming_GF_b_rcpt_2_ecto.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF08917. ecTbetaR2. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase."
    Lin H.Y., Wang X.-F., Ng-Eaton E., Weinberg R.A., Lodish H.F.
    Cell 68:775-785(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE.

Entry informationi

Entry nameiTGFR2_PIG
AccessioniPrimary (citable) accession number: P38551
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 30, 1994
Last sequence update: September 30, 1994
Last modified: January 6, 2015
This is version 105 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.