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Protein

Transforming growth factor beta-3 proprotein

Gene

TGFB3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity
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).By similarity
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).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGrowth factor, Mitogen

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-2129379 Molecules associated with elastic fibres
R-HSA-3000178 ECM proteoglycans
SignaLinkiP10600
SIGNORiP10600

Names & Taxonomyi

Protein namesi
Recommended name:
Transforming growth factor beta-3 proprotein
Cleaved into the following 2 chains:
Gene namesi
Name:TGFB3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000119699.7
HGNCiHGNC:11769 TGFB3
MIMi190230 gene
neXtProtiNX_P10600

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Arrhythmogenic right ventricular dysplasia, familial, 1 (ARVD1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias.
See also OMIM:107970
Loeys-Dietz syndrome 5 (LDS5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. LDS5 additional variable features include mitral valve disease, skeletal overgrowth, cervical spine instability, and clubfoot deformity. LDS5 patients do not manifest remarkable aortic or arterial tortuosity, and there is no strong evidence for early aortic dissection.
See also OMIM:615582
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070924409C → Y in LDS5; hypomorphic mutation; results in impaired TGF-beta signaling. 1 PublicationCorresponds to variant dbSNP:rs398122984EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi293Q → R: Abolishes methylation by N6AMT1. 1 Publication1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi7043
GeneReviewsiTGFB3
MalaCardsiTGFB3
MIMi107970 phenotype
615582 phenotype
OpenTargetsiENSG00000119699
Orphaneti293899 Familial isolated arrhythmogenic ventricular dysplasia, biventricular form
293888 Familial isolated arrhythmogenic ventricular dysplasia, left dominant form
293910 Familial isolated arrhythmogenic ventricular dysplasia, right dominant form
91387 Familial thoracic aortic aneurysm and aortic dissection
PharmGKBiPA36483

Chemistry databases

ChEMBLiCHEMBL3712903

Polymorphism and mutation databases

BioMutaiTGFB3
DMDMi135684

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000003379624 – 300Latency-associated peptideBy similarityAdd BLAST277
ChainiPRO_0000033797301 – 412Transforming growth factor beta-3By similarityAdd BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi74N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi135N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi142N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei293N5-methylglutamine1 Publication1
Disulfide bondi307 ↔ 3161 Publication
Disulfide bondi315 ↔ 3781 Publication
Disulfide bondi344 ↔ 4091 Publication
Disulfide bondi348 ↔ 4111 Publication
Disulfide bondi377Interchain1 Publication

Post-translational modificationi

Transforming growth factor beta-3 proprotein: The precursor proprotein is cleaved in the Golgi apparatus to form Transforming growth factor beta-3 (TGF-beta-3) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-3 inactive.By similarity
Methylated at Gln-293 by N6AMT1.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Methylation

Proteomic databases

PaxDbiP10600
PeptideAtlasiP10600
PRIDEiP10600
ProteomicsDBi52617

PTM databases

GlyConnecti1837
iPTMnetiP10600
PhosphoSitePlusiP10600

Miscellaneous databases

PMAP-CutDBiP10600

Expressioni

Gene expression databases

BgeeiENSG00000119699 Expressed in 199 organ(s), highest expression level in left coronary artery
CleanExiHS_TGFB3
ExpressionAtlasiP10600 baseline and differential
GenevisibleiP10600 HS

Organism-specific databases

HPAiHPA063582

Interactioni

Subunit structurei

Interacts with ASPN (PubMed:8819159). Latency-associated peptide: Homodimer; disulfide-linked. Latency-associated peptide: Interacts with Transforming growth factor beta-3 (TGF-beta-3) chain; interaction is non-covalent and maintains (TGF-beta-3) in a latent state (By similarity). Latency-associated peptide: Interacts with LRRC32/GARP; leading to regulate activation of TGF-beta-3 and promote epithelial fusion during palate development (By similarity). Latency-associated peptide: Interacts (via cell attachment site) with integrins, leading to release of the active TGF-beta-3 (By similarity). Transforming growth factor beta-3: Homodimer; disulfide-linked (PubMed:8819159). Transforming growth factor beta-3: Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction (By similarity).By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112901, 7 interactors
ComplexPortaliCPX-2544 TGF-beta-3-TGFR complex
CPX-606 TGF-beta-3 complex
CORUMiP10600
DIPiDIP-5937N
IntActiP10600, 7 interactors
MINTiP10600
STRINGi9606.ENSP00000238682

Structurei

Secondary structure

1412
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP10600
SMRiP10600
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10600

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi261 – 263Cell attachment siteBy similarity3

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00910000143982
HOGENOMiHOG000290198
HOVERGENiHBG074115
InParanoidiP10600
KOiK13377
OMAiPEPSVMT
OrthoDBiEOG091G0BMM
PhylomeDBiP10600
TreeFamiTF351793

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR016319 TGF-beta
IPR015615 TGF-beta-rel
IPR015618 TGFB3
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
PIRSFiPIRSF001787 TGF-beta, 1 hit
PRINTSiPR01423 TGFBETA
PR01426 TGFBETA3
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P10600-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MKMHLQRALV VLALLNFATV SLSLSTCTTL DFGHIKKKRV EAIRGQILSK
60 70 80 90 100
LRLTSPPEPT VMTHVPYQVL ALYNSTRELL EEMHGEREEG CTQENTESEY
110 120 130 140 150
YAKEIHKFDM IQGLAEHNEL AVCPKGITSK VFRFNVSSVE KNRTNLFRAE
160 170 180 190 200
FRVLRVPNPS SKRNEQRIEL FQILRPDEHI AKQRYIGGKN LPTRGTAEWL
210 220 230 240 250
SFDVTDTVRE WLLRRESNLG LEISIHCPCH TFQPNGDILE NIHEVMEIKF
260 270 280 290 300
KGVDNEDDHG RGDLGRLKKQ KDHHNPHLIL MMIPPHRLDN PGQGGQRKKR
310 320 330 340 350
ALDTNYCFRN LEENCCVRPL YIDFRQDLGW KWVHEPKGYY ANFCSGPCPY
360 370 380 390 400
LRSADTTHST VLGLYNTLNP EASASPCCVP QDLEPLTILY YVGRTPKVEQ
410
LSNMVVKSCK CS
Length:412
Mass (Da):47,328
Last modified:July 1, 1989 - v1
Checksum:i3CAD3548D3AEA178
GO
Isoform 2 (identifier: P10600-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     310-412: Missing.

Note: No experimental confirmation available.
Show »
Length:309
Mass (Da):35,708
Checksum:i30F7A936E9467729
GO

Sequence cautioni

The sequence CAA33024 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01631560T → M1 PublicationCorresponds to variant dbSNP:rs4252315EnsemblClinVar.1
Natural variantiVAR_070924409C → Y in LDS5; hypomorphic mutation; results in impaired TGF-beta signaling. 1 PublicationCorresponds to variant dbSNP:rs398122984EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056285310 – 412Missing in isoform 2. 2 PublicationsAdd BLAST103

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03241 mRNA Translation: AAA61161.1
X14149 mRNA Translation: CAA32362.1
X14885
, X14886, X14887, X14888, X14889, X14890, X14891 Genomic DNA Translation: CAA33024.1 Different initiation.
AY140241 Genomic DNA Translation: AAM96819.1
AY208161 Genomic DNA Translation: AAO13495.1
BT007287 mRNA Translation: AAP35951.1
AF107885 Genomic DNA Translation: AAC79727.1
BC018503 mRNA Translation: AAH18503.1
CCDSiCCDS86415.1 [P10600-2]
CCDS9846.1 [P10600-1]
PIRiA36169
RefSeqiNP_001316867.1, NM_001329938.1 [P10600-2]
NP_001316868.1, NM_001329939.1 [P10600-1]
NP_003230.1, NM_003239.4 [P10600-1]
UniGeneiHs.592317
Hs.713281
Hs.736373

Genome annotation databases

EnsembliENST00000238682; ENSP00000238682; ENSG00000119699 [P10600-1]
ENST00000556285; ENSP00000451110; ENSG00000119699 [P10600-2]
GeneIDi7043
KEGGihsa:7043
UCSCiuc001xsc.3 human [P10600-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
SeattleSNPs
Wikipedia

TGF beta-3 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03241 mRNA Translation: AAA61161.1
X14149 mRNA Translation: CAA32362.1
X14885
, X14886, X14887, X14888, X14889, X14890, X14891 Genomic DNA Translation: CAA33024.1 Different initiation.
AY140241 Genomic DNA Translation: AAM96819.1
AY208161 Genomic DNA Translation: AAO13495.1
BT007287 mRNA Translation: AAP35951.1
AF107885 Genomic DNA Translation: AAC79727.1
BC018503 mRNA Translation: AAH18503.1
CCDSiCCDS86415.1 [P10600-2]
CCDS9846.1 [P10600-1]
PIRiA36169
RefSeqiNP_001316867.1, NM_001329938.1 [P10600-2]
NP_001316868.1, NM_001329939.1 [P10600-1]
NP_003230.1, NM_003239.4 [P10600-1]
UniGeneiHs.592317
Hs.713281
Hs.736373

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KTZX-ray2.15A301-412[»]
1TGJX-ray2.00A301-412[»]
1TGKX-ray3.30A301-412[»]
2PJYX-ray3.00A301-412[»]
3EO1X-ray3.10C/F/I/L301-412[»]
4UM9X-ray2.50E/F259-269[»]
ProteinModelPortaliP10600
SMRiP10600
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112901, 7 interactors
ComplexPortaliCPX-2544 TGF-beta-3-TGFR complex
CPX-606 TGF-beta-3 complex
CORUMiP10600
DIPiDIP-5937N
IntActiP10600, 7 interactors
MINTiP10600
STRINGi9606.ENSP00000238682

Chemistry databases

ChEMBLiCHEMBL3712903

PTM databases

GlyConnecti1837
iPTMnetiP10600
PhosphoSitePlusiP10600

Polymorphism and mutation databases

BioMutaiTGFB3
DMDMi135684

Proteomic databases

PaxDbiP10600
PeptideAtlasiP10600
PRIDEiP10600
ProteomicsDBi52617

Protocols and materials databases

DNASUi7043
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000238682; ENSP00000238682; ENSG00000119699 [P10600-1]
ENST00000556285; ENSP00000451110; ENSG00000119699 [P10600-2]
GeneIDi7043
KEGGihsa:7043
UCSCiuc001xsc.3 human [P10600-1]

Organism-specific databases

CTDi7043
DisGeNETi7043
EuPathDBiHostDB:ENSG00000119699.7
GeneCardsiTGFB3
GeneReviewsiTGFB3
HGNCiHGNC:11769 TGFB3
HPAiHPA063582
MalaCardsiTGFB3
MIMi107970 phenotype
190230 gene
615582 phenotype
neXtProtiNX_P10600
OpenTargetsiENSG00000119699
Orphaneti293899 Familial isolated arrhythmogenic ventricular dysplasia, biventricular form
293888 Familial isolated arrhythmogenic ventricular dysplasia, left dominant form
293910 Familial isolated arrhythmogenic ventricular dysplasia, right dominant form
91387 Familial thoracic aortic aneurysm and aortic dissection
PharmGKBiPA36483
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00910000143982
HOGENOMiHOG000290198
HOVERGENiHBG074115
InParanoidiP10600
KOiK13377
OMAiPEPSVMT
OrthoDBiEOG091G0BMM
PhylomeDBiP10600
TreeFamiTF351793

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-2129379 Molecules associated with elastic fibres
R-HSA-3000178 ECM proteoglycans
SignaLinkiP10600
SIGNORiP10600

Miscellaneous databases

ChiTaRSiTGFB3 human
EvolutionaryTraceiP10600
GeneWikiiTransforming_growth_factor,_beta_3
GenomeRNAii7043
PMAP-CutDBiP10600
PROiPR:P10600
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119699 Expressed in 199 organ(s), highest expression level in left coronary artery
CleanExiHS_TGFB3
ExpressionAtlasiP10600 baseline and differential
GenevisibleiP10600 HS

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR016319 TGF-beta
IPR015615 TGF-beta-rel
IPR015618 TGFB3
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
PIRSFiPIRSF001787 TGF-beta, 1 hit
PRINTSiPR01423 TGFBETA
PR01426 TGFBETA3
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTGFB3_HUMAN
AccessioniPrimary (citable) accession number: P10600
Secondary accession number(s): Q8WV88
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 7, 2018
This is version 207 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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