DegronMD - P10600(TGFB3)

FUNCTION: Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively. {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202}.; FUNCTION: [Latency-associated peptide]: Required to maintain the Transforming growth factor beta-3 (TGF-beta-3) chain in a latent state during storage in extracellular matrix (By similarity). Associates non-covalently with TGF-beta-3 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-3 (By similarity). Interaction with integrins results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-3 (By similarity). {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202, ECO:0000250|UniProtKB:P17125}.; FUNCTION: Transforming growth factor beta-3: Multifunctional protein that regulates embryogenesis and cell differentiation and is required in various processes such as secondary palate development (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains remain non-covalently linked rendering TGF-beta-3 inactive during storage in extracellular matrix (By similarity). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP that control activation of TGF-beta-3 and maintain it in a latent state during storage in extracellular milieus (By similarity). TGF-beta-3 is released from LAP by integrins: integrin-binding results in distortion of the LAP chain and subsequent release of the active TGF-beta-3 (By similarity). Once activated following release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity). {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202, ECO:0000250|UniProtKB:P17125}. View more >>

GO - Biological processes (BP): aging [GO:0007568]; BMP signaling pathway [GO:0030509]; cell-cell junction organization [GO:0045216]; detection of hypoxia [GO:0070483]; digestive tract development [GO:0048565]; embryonic neurocranium morphogenesis [GO:0048702]; face morphogenesis [GO:0060325]; female pregnancy [GO:0007565]; frontal suture morphogenesis [GO:0060364]; inner ear development [GO:0048839]; in utero embryonic development [GO:0001701]; lung alveolus development [GO:0048286]; mammary gland development [GO:0030879]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of macrophage cytokine production [GO:0010936]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512]; negative regulation of vascular associated smooth muscle cell proliferation [GO:1904706]; odontogenesis [GO:0042476]; ossification involved in bone remodeling [GO:0043932]; positive regulation of apoptotic process [GO:0043065]; positive regulation of bone mineralization [GO:0030501]; positive regulation of cell division [GO:0051781]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of collagen biosynthetic process [GO:0032967]; positive regulation of epithelial to mesenchymal transition [GO:0010718]; positive regulation of filopodium assembly [GO:0051491]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of pathway-restricted SMAD protein phosphorylation [GO:0010862]; positive regulation of protein secretion [GO:0050714]; positive regulation of SMAD protein signal transduction [GO:0060391]; positive regulation of stress fiber assembly [GO:0051496]; positive regulation of tight junction disassembly [GO:1905075]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of cell population proliferation [GO:0042127]; response to estrogen [GO:0043627]; response to hypoxia [GO:0001666]; response to laminar fluid shear stress [GO:0034616]; response to progesterone [GO:0032570]; salivary gland morphogenesis [GO:0007435]; secondary palate development [GO:0062009]; SMAD protein signal transduction [GO:0060395]; transforming growth factor beta receptor signaling pathway [GO:0007179]; uterine wall breakdown [GO:0042704]; wound healing [GO:0042060] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.Q68L	TCGA-A5-A0G1	UCEC	TCGA	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation rewiring degron network	0.1111
p.Q68L	DO42472	UCEC	ICGC	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation rewiring degron network	0.1111
p.P66T	TCGA-D1-A17B	UCEC	TCGA	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation rewiring degron network	0.0556
p.P66T	DO43017	UCEC	ICGC	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation rewiring degron network	0.0556
p.C91Y	TCGA-DF-A2KZ	UCEC	TCGA	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation rewiring degron network	0.1389
p.C91Y	DO52409	UCEC	ICGC	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation rewiring degron network	0.1389
p.R77Q	DO233634	GACA	ICGC	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation altering degron motif	0.7329
p.L70M	SIDM01951	Colorectal Carcinoma	GDSC	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation rewiring degron network	0.1667
p.R77W	SIDM00217	Colorectal Carcinoma	GDSC	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation altering degron motif	0.8634
p.R77W	ACH-000999	Colon/Colorectal Cancer	CCLE	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation altering degron motif	0.8634
p.R77W	SNU-1040	large intestine	COSMIC	TRELLEEMH	DEG_APCC_DBOX_1	76:84	Mutation altering degron motif	0.8634

DegronMD: protein-targeted degradation, mutation and drug response to degrons

TGFB3

UniProt ID: P10600

Entrez ID: 7043

Protein name: Transforming growth factor beta-3 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-3 (TGF-beta-3)]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for TGFB3 in