TGFB2 (transforming growth factor beta 2)

Gene

• Entrez ID: 7042
• Gene name: Transforming growth factor beta 2
• Gene symbol: TGFB2
• Synonyms: G-TSF, LDS4, TGF-beta2
• Chromosome: 1
• Chromosome location: 1q41
• Summary: This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers. A chromosomal translocation that includes this gene is associated with Peters` anomaly, a congenital defect of the anterior chamber of the eye. Mutations in this gene may be associated with Loeys-Dietz syndrome. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs10482810	G>C	Conflicting-interpretations-of-pathogenicity, benign-likely-benign, likely-benign	Non coding transcript variant, missense variant, coding sequence variant
rs11466408	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs387907278	C>A	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs398122884	ACAAT>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs398122885	C>A,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained, non coding transcript variant
rs730880221	C>T	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs863223790	G>T	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs863223792	C>T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs863223793	G>T	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs863223795	->T	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs863223796	A>-,AA	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, intron variant, frameshift variant
rs863223797	C>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs869025531	C>T	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs869025533	->A	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs869312903	C>A,T	Pathogenic-likely-pathogenic, likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, non coding transcript variant
rs1057518029	A>G	Likely-pathogenic	Splice acceptor variant
rs1057518597	A>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1057518684	G>A	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1057521150	G>A	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1064793278	G>A	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1064796256	AA>-	Likely-pathogenic, pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1436552875	C>T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs1553303161	TCAA>G	Likely-pathogenic	Intron variant, splice acceptor variant
rs1553303203	CGGCGGAAGA>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1553303213	G>A	Not-provided, likely-pathogenic, uncertain-significance	Non coding transcript variant, coding sequence variant, missense variant
rs1553303221	G>A	Pathogenic	Splice donor variant
rs1553303352	C>T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1553303357	C>A	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs1571902862	TATAAAGT>A	Pathogenic	Coding sequence variant, intron variant, frameshift variant
rs1571904218	->A	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1571904338	G>A	Likely-pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT002285	hsa-miR-141-3p	Immunoblot, Luciferase reporter assay, qRT-PCR	18483486
MIRT002285	hsa-miR-141-3p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	28115163
MIRT006058	hsa-miR-29b-3p	ELISA, GFP reporter assay, qRT-PCR	21273536
MIRT006058	hsa-miR-29b-3p	Luciferase reporter assay, qRT-PCR	23354167
MIRT017363	hsa-miR-335-5p	Microarray	18185580
MIRT019708	hsa-miR-375	Microarray	20215506
MIRT030844	hsa-miR-21-5p	Microarray	18591254
MIRT030844	hsa-miR-21-5p	Luciferase reporter assay	27388239
MIRT437425	hsa-miR-137	Luciferase reporter assay, qRT-PCR, Western blot	24465609
MIRT652723	hsa-miR-4446-5p	HITS-CLIP	23824327
MIRT652724	hsa-miR-510-3p	HITS-CLIP	23824327
MIRT652725	hsa-miR-3679-3p	HITS-CLIP	23824327
MIRT652726	hsa-miR-8058	HITS-CLIP	23824327
MIRT652727	hsa-miR-5009-5p	HITS-CLIP	23824327
MIRT652728	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT652729	hsa-miR-631	HITS-CLIP	23824327
MIRT652730	hsa-miR-3661	HITS-CLIP	23824327
MIRT652731	hsa-miR-422a	HITS-CLIP	23824327
MIRT652732	hsa-miR-378i	HITS-CLIP	23824327
MIRT652733	hsa-miR-378h	HITS-CLIP	23824327
MIRT652734	hsa-miR-378f	HITS-CLIP	23824327
MIRT652735	hsa-miR-378e	HITS-CLIP	23824327
MIRT652736	hsa-miR-378d	HITS-CLIP	23824327
MIRT652737	hsa-miR-378c	HITS-CLIP	23824327
MIRT652738	hsa-miR-378b	HITS-CLIP	23824327
MIRT652739	hsa-miR-378a-3p	HITS-CLIP	23824327
MIRT652739	hsa-miR-378a-3p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	27855367
MIRT652740	hsa-miR-3690	HITS-CLIP	23824327
MIRT652741	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT652742	hsa-miR-619-3p	HITS-CLIP	23824327
MIRT731238	hsa-miR-193a-3p	Luciferase reporter assay	26822621
MIRT732234	hsa-miR-200a-3p	Luciferase reporter assay, qRT-PCR, Western blot	27267902
MIRT732715	hsa-miR-199a-5p	Luciferase reporter assay, qRT-PCR	27842518
MIRT733135	hsa-miR-148a-3p	Flow, Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blot	26983401
MIRT734688	hsa-miR-142-5p	Western blot	25586666
MIRT735093	hsa-miR-23a-5p	Luciferase reporter assay	27388239
MIRT735094	hsa-miR-23b-5p	Luciferase reporter assay	27388239
MIRT735095	hsa-miR-145-5p	Luciferase reporter assay	27388239
MIRT735113	hsa-miR-153-5p	Luciferase reporter assay, qRT-PCR, Western blot	25793604

Transcription factors

Transcription factor	Regulation	Reference
ATF1	Activation	11776974
ATF2	Repression	1400310
USF1	Activation	11776974
USF2	Activation	11776974
USF2	Unknown	8943301

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000902	Process	Cell morphogenesis	IDA	15896309
GO:0001501	Process	Skeletal system development	ISS
GO:0001540	Function	Amyloid-beta binding	IDA	16227582
GO:0001654	Process	Eye development	IDA	15944186
GO:0001666	Process	Response to hypoxia	IMP	12411310
GO:0001822	Process	Kidney development	ISS
GO:0001837	Process	Epithelial to mesenchymal transition	IDA	10092230, 18223299
GO:0001837	Process	Epithelial to mesenchymal transition	TAS	14679171
GO:0001843	Process	Neural tube closure	ISS
GO:0001942	Process	Hair follicle development	IDA	10433821
GO:0001942	Process	Hair follicle development	ISS
GO:0002576	Process	Platelet degranulation	TAS
GO:0003007	Process	Heart morphogenesis	IDA	10092230
GO:0003148	Process	Outflow tract septum morphogenesis	ISS
GO:0003149	Process	Membranous septum morphogenesis	ISS
GO:0003179	Process	Heart valve morphogenesis	ISS
GO:0003181	Process	Atrioventricular valve morphogenesis	ISS
GO:0003184	Process	Pulmonary valve morphogenesis	ISS
GO:0003203	Process	Endocardial cushion morphogenesis	ISS
GO:0003215	Process	Cardiac right ventricle morphogenesis	ISS
GO:0003222	Process	Ventricular trabecula myocardium morphogenesis	ISS
GO:0003274	Process	Endocardial cushion fusion	ISS
GO:0003289	Process	Atrial septum primum morphogenesis	ISS
GO:0003407	Process	Neural retina development	ISS
GO:0005102	Function	Signaling receptor binding	IMP	16227582
GO:0005114	Function	Type II transforming growth factor beta receptor binding	IBA	21873635
GO:0005114	Function	Type II transforming growth factor beta receptor binding	IDA	11157754
GO:0005114	Function	Type II transforming growth factor beta receptor binding	IMP	8167376
GO:0005114	Function	Type II transforming growth factor beta receptor binding	IPI	1333888, 7852346, 11157754
GO:0005125	Function	Cytokine activity	IBA	21873635
GO:0005160	Function	Transforming growth factor beta receptor binding	IDA	10092230, 16227582
GO:0005515	Function	Protein binding	IPI	2022183, 2119582, 8617200, 10930463, 11157754, 16227582, 17827158, 19651619, 25241761, 32814053
GO:0005576	Component	Extracellular region	IDA	16227582
GO:0005576	Component	Extracellular region	TAS	2119582
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	24263861
GO:0006468	Process	Protein phosphorylation	IDA	18358889
GO:0007050	Process	Cell cycle arrest	IDA	18223299
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IBA	21873635
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IDA	11157754, 18358889
GO:0007435	Process	Salivary gland morphogenesis	IEP	18080134
GO:0007507	Process	Heart development	IDA	15896309
GO:0008083	Function	Growth factor activity	IEA
GO:0008219	Process	Cell death	IDA	16227582
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	15896309
GO:0008285	Process	Negative regulation of cell population proliferation	IDA	15944186
GO:0008347	Process	Glial cell migration	IDA	18431253
GO:0008584	Process	Male gonad development	ISS
GO:0009611	Process	Response to wounding	IEP	16891397, 18040277
GO:0009792	Process	Embryo development ending in birth or egg hatching	TAS	2119582
GO:0010002	Process	Cardioblast differentiation	IDA	15896309
GO:0010629	Process	Negative regulation of gene expression	IDA	25217442
GO:0010634	Process	Positive regulation of epithelial cell migration	IDA	17960115
GO:0010693	Process	Negative regulation of alkaline phosphatase activity	IDA	18358889
GO:0010718	Process	Positive regulation of epithelial to mesenchymal transition	IDA	17999987, 18505915
GO:0010862	Process	Positive regulation of pathway-restricted SMAD protein phosphorylation	IBA	21873635
GO:0010936	Process	Negative regulation of macrophage cytokine production	IDA	20875417
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	IDA	18223299
GO:0016477	Process	Cell migration	IDA	10092230
GO:0016525	Process	Negative regulation of angiogenesis	IDA	25217442, 28977001
GO:0030097	Process	Hemopoiesis	ISS
GO:0030199	Process	Collagen fibril organization	IDA	16891397
GO:0030307	Process	Positive regulation of cell growth	IDA	15896309, 20573232
GO:0030308	Process	Negative regulation of cell growth	IDA	18358889
GO:0030326	Process	Embryonic limb morphogenesis	ISS
GO:0030424	Component	Axon	ISS
GO:0030509	Process	BMP signaling pathway	IBA	21873635
GO:0030593	Process	Neutrophil chemotaxis	ISS
GO:0031069	Process	Hair follicle morphogenesis	ISS
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0032147	Process	Activation of protein kinase activity	IDA	17192487, 17960115
GO:0032570	Process	Response to progesterone	IDA	18039789
GO:0032874	Process	Positive regulation of stress-activated MAPK cascade	IDA	17192487
GO:0032909	Process	Regulation of transforming growth factor beta2 production	IMP	12411310
GO:0033630	Process	Positive regulation of cell adhesion mediated by integrin	IDA	17960115, 18223299
GO:0034714	Function	Type III transforming growth factor beta receptor binding	IBA	21873635
GO:0034714	Function	Type III transforming growth factor beta receptor binding	IMP	8167376
GO:0034714	Function	Type III transforming growth factor beta receptor binding	IPI	7852346, 11157754
GO:0035910	Process	Ascending aorta morphogenesis	ISS
GO:0042060	Process	Wound healing	ISS
GO:0042127	Process	Regulation of cell population proliferation	IBA	21873635
GO:0042416	Process	Dopamine biosynthetic process	ISS
GO:0042476	Process	Odontogenesis	NAS	18078367
GO:0042493	Process	Response to drug	IDA	20573232
GO:0042704	Process	Uterine wall breakdown	TAS	18039789
GO:0042803	Function	Protein homodimerization activity	IDA	2119582
GO:0043025	Component	Neuronal cell body	ISS
GO:0043525	Process	Positive regulation of neuron apoptotic process	IDA	16227582
GO:0045216	Process	Cell-cell junction organization	IDA	18505915
GO:0045726	Process	Positive regulation of integrin biosynthetic process	IDA	17960115
GO:0045747	Process	Positive regulation of Notch signaling pathway	IDA	25217442
GO:0045778	Process	Positive regulation of ossification	IEP	17401695
GO:0045787	Process	Positive regulation of cell cycle	ISS
GO:0045823	Process	Positive regulation of heart contraction	IDA	15896309
GO:0046580	Process	Negative regulation of Ras protein signal transduction	ISS
GO:0048103	Process	Somatic stem cell division	ISS
GO:0048566	Process	Embryonic digestive tract development	IEP	20875417
GO:0048666	Process	Neuron development	ISS
GO:0048699	Process	Generation of neurons	TAS	15944186
GO:0048839	Process	Inner ear development	ISS
GO:0050680	Process	Negative regulation of epithelial cell proliferation	IDA	17217916
GO:0050680	Process	Negative regulation of epithelial cell proliferation	IMP	16943770
GO:0050714	Process	Positive regulation of protein secretion	IDA	18505915
GO:0050778	Process	Positive regulation of immune response	ISS
GO:0051781	Process	Positive regulation of cell division	IEA
GO:0051794	Process	Regulation of timing of catagen	IDA	15955085
GO:0051795	Process	Positive regulation of timing of catagen	IDA	15955085
GO:0051891	Process	Positive regulation of cardioblast differentiation	IDA	15896309
GO:0060038	Process	Cardiac muscle cell proliferation	IDA	15896309
GO:0060065	Process	Uterus development	ISS
GO:0060317	Process	Cardiac epithelial to mesenchymal transition	IDA	10092230
GO:0060389	Process	Pathway-restricted SMAD protein phosphorylation	IDA	11157754, 18358889
GO:0060395	Process	SMAD protein signal transduction	IBA	21873635
GO:0060395	Process	SMAD protein signal transduction	IDA	17192487
GO:0060412	Process	Ventricular septum morphogenesis	ISS
GO:0060413	Process	Atrial septum morphogenesis	ISS
GO:0061626	Process	Pharyngeal arch artery morphogenesis	ISS
GO:0062009	Process	Secondary palate development	ISS
GO:0062023	Component	Collagen-containing extracellular matrix	IDA	18049952
GO:0097191	Process	Extrinsic apoptotic signaling pathway	IDA	17217916
GO:1902256	Process	Regulation of apoptotic process involved in outflow tract morphogenesis	ISS
GO:1902895	Process	Positive regulation of pri-miRNA transcription by RNA polymerase II	IDA	25217442
GO:1903659	Process	Regulation of complement-dependent cytotoxicity	IMP	16034134
GO:1903701	Process	Substantia propria of cornea development	ISS
GO:1904888	Process	Cranial skeletal system development	ISS
GO:1905006	Process	Negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	ISS
GO:1905007	Process	Positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	ISS

Other IDs

• MIM: 190220
• HGNC: 11768
• e!Ensembl: ENSG00000092969

Protein

• UniProt ID: P61812
• Protein name: Transforming growth factor beta-2 proprotein (Cetermin) (Glioblastoma-derived T-cell suppressor factor) (G-TSF) [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-2 (TGF-beta-2)]
• Protein function: Transforming growth factor beta-2 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively. ; [Latency-associated peptide]: Required to maintain the Transforming growth factor beta-2 (TGF-beta-2) chain in a latent state during storage in extracellular matrix (By similarity). Associates non-covalently with TGF-beta-2 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2 (By similarity). ; Transforming growth factor beta-2: Multifunctional protein that regulates various processes such as angiogenesis and heart development (PubMed:22772371, PubMed:22772368). 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-2 (TGF-beta-2) chains remain non-covalently linked rendering TGF-beta-2 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-2 and maintain it in a latent state during storage in extracellular milieus (By similarity). Once activated following release of LAP, TGF-beta-2 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity).
• PDB: 1TFG, 2TGI, 4KXZ, 5TX4, 5TY4, 6I9J
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00688	TGFb_propeptide	20 → 284	TGF-beta propeptide	Family
  PF00019	TGF_beta	316 → 413	Transforming growth factor beta like domain	Domain

• Sequence:

  MHYCVLSAFLILHLVTVALSLSTCSTLDMDQFMRKRIEAIRGQILSKLKLTSPPEDYPEP
  EEVPPEVISIYNSTRDLLQEKASRRAAACERERSDEEYYAKEVYKIDMPPFFPSENAIPP
  TFYRPYFRIVRFDVSAMEKNASNLVKAEFRVFRLQNPKARVPEQRIELYQILKSKDLTSP
  TQRYIDSKVVKTRAEGEWLSFDVTDAVHEWLHHKDRNLGFKISLHCPCCTFVPSNNYIIP
  NKSEELEARFAGIDGTSTYTSGDQKTIKSTRKKNSGKTPHLLLMLLPSYRLESQQTNRRK
  KRALDAAYCFRNVQDNCCLRPLYIDFKRDLGWKWIHEPKGYNANFCAGACPYLWSSDTQH
  SRVLSLYNTINPEASASPCCVSQDLEPLTILYYIGKTPKIEQLSNMIVKSCKCS

• Sequence length: 414