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Details on Person UniProt:P37173 TGFBR2
| Class:Id | ReferenceGeneProduct:65971 |
|---|---|
| _chainChangeLog | signal peptide:1-22 added on Fri February 6 2015;chain:23-567 added on Fri February 6 2015 |
| _displayName | UniProt:P37173 TGFBR2 |
| _timestamp | 2025-02-21 19:23:38 |
| chain | signal peptide:1-22 chain:23-567 |
| checksum | C541DA751FFBDBEB |
| comment | FUNCTION 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 thus regulates 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 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.FUNCTION Has transforming growth factor beta-activated receptor activity.FUNCTION Has transforming growth factor beta-activated receptor activity.FUNCTION Binds TGFB1, TGFB2 and TGFB3 in the picomolar affinity range without the participation of additional receptors. Blocks activation of SMAD2 and SMAD3 by TGFB1.CATALYTIC ACTIVITY L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+)CATALYTIC ACTIVITY L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+)COFACTOR 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. Component of a complex composed of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the interaction between TSC22D1 and TGFBR1 is inhibited by SMAD7 and promoted by TGFB1 (PubMed:21791611). Interacts with DAXX. Interacts with DYNLT4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2. Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta. Interacts with CLU (PubMed:8555189).SUBUNIT Homodimer; disulfide-linked.INTERACTION Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry. TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries (PubMed:16027248), they have been considered as LDS2 by the OMIM resource.SIMILARITY Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. |
| description | recommendedName: TGF-beta receptor type-2 shortName: TGFR-2 ecNumber: 2.7.11.30 alternativeName: TGF-beta type II receptor alternativeName: Transforming growth factor-beta receptor type II shortName: TGF-beta receptor type II shortName: TbetaR-II |
| geneName | TGFBR2 |
| identifier | P37173 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Aortic aneurysm Apoptosis ATP-binding Cell membrane Craniosynostosis Differentiation Direct protein sequencing Disease variant Disulfide bond Glycoprotein Growth regulation Hereditary nonpolyposis colorectal cancer Kinase Magnesium Manganese Membrane Metal-binding Nucleotide-binding Phosphoprotein Proteomics identification Receptor Reference proteome Secreted Serine/threonine-protein kinase Signal Transferase Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | TGFBR2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8988716] ENSEMBL:ENSG00000163513 TGFBR2 [Homo sapiens] |
| secondaryIdentifier | TGFR2_HUMAN B4DTV5 Q15580 Q6DKT6 Q99474 |
| sequenceLength | 567 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:251092] UniProt:P37173-2 TGFBR2 [Homo sapiens] [ReferenceIsoform:403902] UniProt:P37173-1 TGFBR2 [Homo sapiens] [ReferenceIsoform:9807374] UniProt:P37173-3 TGFBR2 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:170842] TGFBR2 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:193561] TGFBR2 [Homo sapiens] [EntityWithAccessionedSequence:205971] TGFBR2 [early endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:206008] TGFBR2 [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:3640894] TGFBR2 R528H [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:3640899] TGFBR2 R528C [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:3640905] TGFBR2 Y470D [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:3640907] TGFBR2 D522N [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:3642166] TGFBR2 K128Sfs*35 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:3642173] TGFBR2 K128Afs*3 [cytosol] [Homo sapiens] |
| (referenceSequence) | [ReplacedResidue:3640886] L-arginine 528 replaced with L-histidine [ReplacedResidue:3640896] L-arginine 528 replaced with L-cysteine [ReplacedResidue:3640904] L-aspartic acid 522 replaced with L-asparagine [ReplacedResidue:3640906] L-tyrosine 470 replaced with L-aspartic acid [ReplacedResidue:3642142] L-isoleucine 147 replaced with L-serine [ReplacedResidue:3642143] L-asparagine 146 replaced with L-threonine [ReplacedResidue:3642144] L-methionine 135 replaced with L-cysteine [ReplacedResidue:3642145] L-leucine 161 replaced with L-cysteine [ReplacedResidue:3642146] L-cysteine 138 replaced with L-valine [ReplacedResidue:3642148] L-glutamic acid 142 replaced with L-serine |
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No pathways have been reviewed or authored by UniProt:P37173 TGFBR2 (65971)
