UniProt:P36897 TGFBR1

chain
  • signal peptide:1-33
  • chain:34-503
checksum 179F11404725DDCB
comment
  • 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.ACTIVITY REGULATION Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor.SUBUNIT 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. Interacts with USP15 and VPS39. Interacts with SDCBP (via C-terminus) (PubMed:25893292) Interacts with CAV1 and this interaction is impaired in the presence of SDCBP (PubMed:25893292). Interacts with APPL1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432).TISSUE SPECIFICITY Found in all tissues examined, most abundant in placenta and least abundant in brain and heart. Expressed in a variety of cancer cell lines (PubMed:25893292).PTM 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.PTM N-Glycosylated.PTM 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. Its ubiquitination and proteasome-mediated degradation is negatively regulated by SDCBP (PubMed:25893292).SIMILARITY Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.CAUTION One report originally reported variant Ile-375 (PubMed:22113417). This variant has been subsequently corrected to Arg-375 by the same authors (Ref.49).
crossReference
databaseName UniProt
dbId 65969
description
  • recommendedName: TGF-beta receptor type-1 shortName:TGFR-1 ecNumber2.7.11.30/ecNumber alternativeName: Activin A receptor type II-like protein kinase of 53kD alternativeName: Activin receptor-like kinase 5 shortName:ALK-5 shortName:ALK5 alternativeName: Serine/threonine-protein kinase receptor R4 shortName:SKR4 alternativeName: TGF-beta type I receptor alternativeName: Transforming growth factor-beta receptor type I shortName:TGF-beta receptor type I shortName:TbetaR-I
displayName UniProt:P36897 TGFBR1
geneName
  • TGFBR1
  • ALK5
  • SKR4
identifier P36897
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • Aortic aneurysm
  • Apoptosis
  • ATP-binding
  • Cell junction
  • Cell membrane
  • Craniosynostosis
  • Differentiation
  • Direct protein sequencing
  • Disease variant
  • Disulfide bond
  • Glycoprotein
  • Growth regulation
  • Isopeptide bond
  • Kinase
  • Magnesium
  • Manganese
  • Membrane
  • Metal-binding
  • Nucleotide-binding
  • Phosphoprotein
  • Receptor
  • Reference proteome
  • Serine/threonine-protein kinase
  • Signal
  • Tight junction
  • Transferase
  • Transmembrane
  • Transmembrane helix
  • Ubl conjugation
modified [InstanceEdit:11703684] Shorser, Solomon, 2021-05-28
name
  • TGFBR1
otherIdentifier
  • 0000870154
  • 11739462_a_at
  • 11746441_a_at
  • 11758014_s_at
  • 17087480
  • 1957_s_at
  • 206943_at
  • 224793_s_at
  • 3181729
  • 3181730
  • 3181747
  • 3181748
  • 3181752
  • 3181754
  • 3181756
  • 3181758
  • 3181760
  • 3181762
  • 3181763
  • 3181764
  • 3181765
  • 3181766
  • 3181767
  • 3181768
  • 3181769
  • 3181777
  • 3181779
  • 32903_at
  • 44127_at
  • 49222_at
  • 52307_at
  • 52539_at
  • 7046
  • 8156826
  • A_14_P111822
  • A_23_P123943
  • A_33_P3331451
  • GE80220
  • GO:0000003
  • GO:0000166
  • GO:0000186
  • GO:0001501
  • GO:0001525
  • GO:0001701
  • GO:0001822
  • GO:0001824
  • GO:0001837
  • GO:0001937
  • GO:0001938
  • GO:0002088
  • GO:0002376
  • GO:0003222
  • GO:0003223
  • GO:0003674
  • GO:0004672
  • GO:0004674
  • GO:0004675
  • GO:0005024
  • GO:0005025
  • GO:0005102
  • GO:0005114
  • GO:0005515
  • GO:0005524
  • GO:0005575
  • GO:0005622
  • GO:0005634
  • GO:0005737
  • GO:0005768
  • GO:0005886
  • GO:0005923
  • GO:0006355
  • GO:0006464
  • GO:0006468
  • GO:0006915
  • GO:0006950
  • GO:0007010
  • GO:0007049
  • GO:0007050
  • GO:0007165
  • GO:0007178
  • GO:0007179
  • GO:0007399
  • GO:0007507
  • GO:0008150
  • GO:0008219
  • GO:0008283
  • GO:0008284
  • GO:0008354
  • GO:0008584
  • GO:0009058
  • GO:0009790
  • GO:0009791
  • GO:0009952
  • GO:0009986
  • GO:0010468
  • GO:0010628
  • GO:0010717
  • GO:0010718
  • GO:0010862
  • GO:0016020
  • GO:0016021
  • GO:0016301
  • GO:0016310
  • GO:0016361
  • GO:0016579
  • GO:0016740
  • GO:0018105
  • GO:0018107
  • GO:0019838
  • GO:0022607
  • GO:0030054
  • GO:0030154
  • GO:0030198
  • GO:0030199
  • GO:0030307
  • GO:0030335
  • GO:0030512
  • GO:0031396
  • GO:0031410
  • GO:0032331
  • GO:0032924
  • GO:0032991
  • GO:0034330
  • GO:0034641
  • GO:0035556
  • GO:0040007
  • GO:0040008
  • GO:0040011
  • GO:0042060
  • GO:0042118
  • GO:0043062
  • GO:0043065
  • GO:0043066
  • GO:0043167
  • GO:0043226
  • GO:0043235
  • GO:0043393
  • GO:0043542
  • GO:0045121
  • GO:0045893
  • GO:0046332
  • GO:0046872
  • GO:0048179
  • GO:0048185
  • GO:0048538
  • GO:0048646
  • GO:0048663
  • GO:0048701
  • GO:0048705
  • GO:0048762
  • GO:0048844
  • GO:0048856
  • GO:0048870
  • GO:0050431
  • GO:0051272
  • GO:0051491
  • GO:0051496
  • GO:0051897
  • GO:0060017
  • GO:0060021
  • GO:0060037
  • GO:0060043
  • GO:0060317
  • GO:0060389
  • GO:0060391
  • GO:0060412
  • GO:0060978
  • GO:0060982
  • GO:0070411
  • GO:0070723
  • GO:0071363
  • GO:0071560
  • GO:1905007
  • GO:1905075
  • GO:1905223
  • GO:2001235
  • GO:2001237
  • HMNXSV003047156
  • Hs.28005.0.S1_3p_a_at
  • ILMN_1745927
  • ILMN_1797611
  • L11695_at
  • PH_hs_0022072
  • TC09000500.hg
  • g4759225_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • TGFR1_HUMAN
  • Q6IR47
  • Q706C0
  • Q706C1
sequenceLength 503
species [Species:48887] Homo sapiens
url http://purl.uniprot.org/uniprot/P36897

Referrals

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