TGF-beta receptor type-1

UniProt data

UniProt name: TGFR1_HUMAN (P36897)

Gene name: TGFBR1; Synonyms=ALK5, SKR4

Organism: Homo sapiens (Human).

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. {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9346908}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:9472030}; Single-pass type I membrane protein {ECO:0000269|PubMed:9472030}. Cell junction, tight junction {ECO:0000269|PubMed:15761148}. Cell surface {ECO:0000269|PubMed:25893292}. Membrane raft {ECO:0000269|PubMed:25893292}.

Transmembrane domains:

  1. 127-147, 21 AA, Helical. {ECO:0000255}.

Sequence: 503 AA

10 20 30 40 50 60 MEAAVAAPRP RLLLLVLAAA AAAAAALLPG ATALQCFCHL CTKDNFTCVT DGLCFVSVTE 70 80 90 100 110 120 TTDKVIHNSM CIAEIDLIPR DRPFVCAPSS KTGSVTTTYC CNQDHCNKIE LPTTVKSSPG 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

CATM prediction

The sequence of TGFR1_HUMAN returned 1 potential models

The positions at the dimer's interface are highlighted in yellow. The position at the crossing point is highlighted in orange.

# Sequence and interface d θ Z' ω' Score
        130       140       1
 +    |    +    |    +    |		 (Å) (°) (Å) (°)  
Model 1 VELAAVIAGAVCFVCISLMLMVYICHN 7.2 -55.2° 2.4 48.0 -7.0
Prolines* VELAAVIAGPVCFVCISLMLMVYICHN          

* Note: this sequence contains Pro residues. CATM substituted them with Ala during the modeling. The positions are marked.

Click on the model number to visualize its details below.

MODEL 1 DETAILS

Precited structure:


Click on the image to enlarge

Download model 1 structure: PDB, PyMOL session

List of hydrogen bonds:

Donor Acceptor Distance
B, 129, VAL, HA A, 128, ALA, O 3.48Å
B, 132, GLY, HA1 A, 129, VAL, O 3.27Å
A, 129, VAL, HA B, 128, ALA, O 3.48Å
A, 132, GLY, HA1 B, 129, VAL, O 3.27Å