TGF-beta receptor type-1 (Protein name
), TGFR1_HUMAN from NCBI database.
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General Annotation
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Antigen Annotation
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Gene name:
TGFBR1(ALK5;SKR4);
Protein name:
TGF-beta receptor type-1(TGFR-1);
Alternative:
Activin receptor-like kinase 5(ALK-5;ALK5);Activin A receptor type II-like protein kinase of 53kD;TGF-beta type I receptor;Serine/threonine-protein kinase receptor R4(SKR4);Transforming growth factor-beta receptor type I(TGF-beta receptor type I;TbetaR-I);
Organism:
Human (Homo sapiens).
General Annotation
Sub Unit:
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 PAR6A; 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.
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 symetrically 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 PAR6A phosphorylation and activation.
Subcellular Location:
Cell membrane
Single-pass type I membrane protein
Cell junction
tight junction
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s
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Precision
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Intra-assay Precision (Precision within an assay):Three samples of known concentration were tested twenty times on one plate to assess intra-assay precision.
Intra-Assay CV: ≤3.9%
Inter-assay Precision (Precision between assays):Three samples of known concentration were tested in five separate assays to assess inter-assay precision.
Inter-Assay CV: ≤7.7%
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Recovery
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Recovery was determined by spiking various levels of ACE into serum and plasma .
Sample Type
Average(%)
Recovery Range(%)
Serum
99
91-103
Plasma
98
93-106
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Linearity
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The linearity of the kit was assayed by testing samples spiked with appropriate concentration of ACE and their serial dilutions. The results were demonstrated by the percentage of calculated concentration to the expected.
Sample
1:2
1:4
1:8
1:16
serum(n=5)
92-105%
90-101%
95-105%
92-109%
EDTA plasma(n=5)
89-95%
93105%
89-94%
90-106%
heparin plasma(n=5)
93-104%
94-110%
101-111%
91-110%
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)
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Cited for: PROTEIN SEQUENCE OF 34-40;SIGNAL SEQUENCE CLEAVAGE SITE;GLYCOSYLATION;CHARACTERIZATION OF VARIANT TGFBR1*6A ALA-24--26-ALA DEL;VARIANT TGFBR1*10A ALA-26 INS
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2);NUCLEOTIDE SEQUENCE [MRNA] OF 61-155 (ISOFORM 1);ALTERNATIVE SPLICING
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Cited for: FUNCTION;PHOSPHORYLATION AT THR-185; THR-186; SER-187; SER-189 AND SER-191 BY TGFBR2;SUBCELLULAR LOCATION;SUBUNIT;MUTAGENESIS OF 185-THR-THR-186; SER-187; SER-189; SER-191; THR-200 AND THR-204
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Cited for: INTERACTION WITH SMAD2;FUNCTION IN PHOSPHORYLATION OF SMAD2;FUNCTION IN TRANSCRIPTION REGULATION
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Cited for: INTERACTION WITH FKBP1A;ENZYME REGULATION;MUTAGENESIS OF LEU-193 AND PRO-194
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Cited for: INTERACTION WITH SMAD2;FUNCTION IN PHOSPHORYLATION OF SMAD2;FUNCTION IN TRANSCRIPTION REGULATION
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Cited for: INTERACTION WITH SMAD7 AND SMURF2;PROTEASOMAL AND LYSOSOMAL DEGRADATION
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Cited for: INTERACTION WITH SMAD7 AND SMURF1;PROTEASOMAL DEGRADATION
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Cited for: FUNCTION IN EPITHELIAL TO MESENCHYMAL TRANSITION;SUBCELLULAR LOCATION;INTERACTION WITH PARD6A;FUNCTION IN PHOSPHORYLATION OF PARD6A
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Cited for: FUNCTION IN CELLULAR GROWTH INHIBITION;INTERACTION WITH CD109
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Cited for: FUNCTION IN APOPTOSIS;INTERACTION WITH TRAF6 AND MAP3K7
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Cited for: REVIEW ON PROCESSES REGULATED BY THE TGF-BETA CYTOKINES
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 162-503 IN COMPLEX WITH FKBP1A
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Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 162-503;PHOSPHORYLATION;INTERACTION WITH SMAD2 AND FKBP1A
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Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 175-500 IN COMPLEX WITH SYNTHETIC INHIBITOR
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Cited for: VARIANTS MSSE TYR-41; SER-45; ARG-52 AND LEU-83
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Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 201-503 IN COMPLEX WITH SYNTHETIC INHIBITOR
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Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 33-111 IN COMPLEX WITH TGFBR2 AND TGFB3;DISULFIDE BONDS
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Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 31-115 IN COMPLEX WITH TGFBR2 AND TGFB1;RECEPTOR AFFINITY FOR LIGANDS;DISULFIDE BONDS
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Cited for: ANALYSIS OF VARIANT TGFBR1*6A ALA-24--26-ALA DEL IN CANCER RISK
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Cited for: ANALYSIS OF VARIANT TGFBR1*6A ALA-24--26-ALA DEL IN PROSTATE CANCER
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Cited for: VARIANTS LDS1 ILE-200; ARG-318; GLY-400 AND PRO-487
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Cited for: ANALYSIS OF VARIANT TGFBR1*6A ALA-24--26-ALA DEL IN PROSTATE CANCER
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Cited for: VARIANTS LDS1 LEU-241 AND GLN-487;VARIANT HIS-267
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Cited for: VARIANTS LDS1 GLU-232; TRP-487; PRO-487 AND GLN-487
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Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-153 AND CYS-291