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P10600 (TGFB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transforming growth factor beta-3

Short name=TGF-beta-3

Cleaved into the following chain:

  1. Latency-associated peptide
    Short name=LAP
Gene names
Name:TGFB3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length412 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in embryogenesis and cell differentiation.

Subunit structure

Homodimer; disulfide-linked. Interacts with ASPN. Ref.8

Subcellular location

Secreted.

Post-translational modification

The precursor is cleaved into mature TGF-beta-3 and LAP, which remains non-covalently linked to mature TGF-beta-3 rendering it inactive By similarity.

Involvement in disease

Arrhythmogenic right ventricular dysplasia, familial, 1 (ARVD1) [MIM:107970]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the TGF-beta family.

Sequence caution

The sequence CAA33024.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseCardiomyopathy
   DomainSignal
   Molecular functionGrowth factor
Mitogen
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

activation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

aging

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

cell growth

Inferred from electronic annotation. Source: InterPro

cell-cell junction organization

Inferred from direct assay PubMed 18505915. Source: BHF-UCL

detection of hypoxia

Inferred from direct assay PubMed 18156205. Source: BHF-UCL

digestive tract development

Inferred from electronic annotation. Source: Ensembl

embryonic neurocranium morphogenesis

Inferred from electronic annotation. Source: Ensembl

extracellular matrix organization

Traceable author statement. Source: Reactome

face morphogenesis

Inferred from mutant phenotype PubMed 12651933. Source: BHF-UCL

female pregnancy

Inferred from electronic annotation. Source: Ensembl

frontal suture morphogenesis

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from sequence or structural similarity. Source: BHF-UCL

inner ear development

Inferred from electronic annotation. Source: Ensembl

lung alveolus development

Inferred from sequence or structural similarity. Source: BHF-UCL

mammary gland development

Inferred from sequence or structural similarity. Source: BHF-UCL

menstrual cycle phase

Inferred from expression pattern PubMed 18039789. Source: BHF-UCL

negative regulation of DNA replication

Inferred from mutant phenotype PubMed 11158066. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of macrophage cytokine production

Inferred from direct assay PubMed 20875417. Source: DFLAT

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

odontogenesis

Non-traceable author statement PubMed 18078367. Source: BHF-UCL

ossification involved in bone remodeling

Inferred from expression pattern PubMed 17401695. Source: BHF-UCL

palate development

Inferred from sequence or structural similarity. Source: BHF-UCL

platelet activation

Traceable author statement. Source: Reactome

platelet degranulation

Traceable author statement. Source: Reactome

positive regulation of DNA replication

Inferred from mutant phenotype PubMed 11158066. Source: BHF-UCL

positive regulation of SMAD protein import into nucleus

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of bone mineralization

Inferred from expression pattern PubMed 17401695. Source: BHF-UCL

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of collagen biosynthetic process

Inferred from mutant phenotype PubMed 11158066. Source: BHF-UCL

positive regulation of epithelial to mesenchymal transition

Inferred from direct assay PubMed 18505915. Source: BHF-UCL

positive regulation of filopodium assembly

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of protein secretion

Inferred from direct assay PubMed 18505915. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18156205. Source: BHF-UCL

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from direct assay PubMed 18156205. Source: BHF-UCL

response to laminar fluid shear stress

Inferred from electronic annotation. Source: Ensembl

response to progesterone

Inferred from direct assay PubMed 18039789. Source: BHF-UCL

salivary gland morphogenesis

Inferred from expression pattern PubMed 18080134. Source: BHF-UCL

transforming growth factor beta receptor signaling pathway

Inferred from direct assay PubMed 11157754. Source: BHF-UCL

   Cellular_componentT-tubule

Inferred from electronic annotation. Source: Ensembl

cell surface

Inferred from electronic annotation. Source: Ensembl

extracellular matrix

Inferred from direct assay PubMed 18049952. Source: BHF-UCL

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred by curator PubMed 11157754. Source: BHF-UCL

platelet alpha granule lumen

Traceable author statement. Source: Reactome

   Molecular_functionidentical protein binding

Inferred from direct assay PubMed 18243111. Source: BHF-UCL

transforming growth factor beta binding

Inferred from direct assay PubMed 18243111. Source: BHF-UCL

type I transforming growth factor beta receptor binding

Inferred from direct assay PubMed 18243111. Source: BHF-UCL

type II transforming growth factor beta receptor binding

Inferred from direct assay PubMed 11157754PubMed 18243111. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TGFBR2P371738EBI-1033020,EBI-296151

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 300277Latency-associated peptide
PRO_0000033796
Chain301 – 412112Transforming growth factor beta-3
PRO_0000033797

Regions

Motif261 – 2633Cell attachment site Potential

Amino acid modifications

Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation1351N-linked (GlcNAc...) Potential
Glycosylation1421N-linked (GlcNAc...) Potential
Disulfide bond307 ↔ 316
Disulfide bond315 ↔ 378
Disulfide bond344 ↔ 409
Disulfide bond348 ↔ 411
Disulfide bond377Interchain By similarity

Natural variations

Natural variant601T → M. Ref.5
Corresponds to variant rs4252315 [ dbSNP | Ensembl ].
VAR_016315

Secondary structure

........................... 412
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10600 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 3CAD3548D3AEA178

FASTA41247,328
        10         20         30         40         50         60 
MKMHLQRALV VLALLNFATV SLSLSTCTTL DFGHIKKKRV EAIRGQILSK LRLTSPPEPT 

        70         80         90        100        110        120 
VMTHVPYQVL ALYNSTRELL EEMHGEREEG CTQENTESEY YAKEIHKFDM IQGLAEHNEL 

       130        140        150        160        170        180 
AVCPKGITSK VFRFNVSSVE KNRTNLFRAE FRVLRVPNPS SKRNEQRIEL FQILRPDEHI 

       190        200        210        220        230        240 
AKQRYIGGKN LPTRGTAEWL SFDVTDTVRE WLLRRESNLG LEISIHCPCH TFQPNGDILE 

       250        260        270        280        290        300 
NIHEVMEIKF KGVDNEDDHG RGDLGRLKKQ KDHHNPHLIL MMIPPHRLDN PGQGGQRKKR 

       310        320        330        340        350        360 
ALDTNYCFRN LEENCCVRPL YIDFRQDLGW KWVHEPKGYY ANFCSGPCPY LRSADTTHST 

       370        380        390        400        410 
VLGLYNTLNP EASASPCCVP QDLEPLTILY YVGRTPKVEQ LSNMVVKSCK CS 

« Hide

References

« Hide 'large scale' references
[1]"Identification of another member of the transforming growth factor type beta gene family."
ten Dijke P., Hansen P., Iwata K., Pieler C., Foulkes J.G.
Proc. Natl. Acad. Sci. U.S.A. 85:4715-4719(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"A new type of transforming growth factor-beta, TGF-beta 3."
Derynck R., Lindquist P.B., Lee A., Wen D., Tamm J., Graycar J.L., Rhee L., Mason A.J., Miller D.A., Coffey R.J., Moses H.L., Chen E.Y.
EMBO J. 7:3737-3743(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[3]"Complete genomic sequence of human transforming growth factor-beta 3."
Madan A., Rowen L., Qin S., Dickhoff R., Shaffer T., James R., Abbasi N., Loretz C., Madan A., Dors M., Dahl T., Hall J., Lasky S., Hood L.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]NIEHS SNPs program
Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]SeattleSNPs variation discovery resource
Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-60.
[6]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"Inhibition of translation of transforming growth factor-beta 3 mRNA by its 5' untranslated region."
Arrick B.A., Lee A.L., Grendell R.L., Derynck R.
Mol. Cell. Biol. 11:4306-4313(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-48.
[8]"Mechanisms for asporin function and regulation in articular cartilage."
Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S.
J. Biol. Chem. 282:32185-32192(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ASPN.
[9]"The crystal structure of TGF-beta 3 and comparison to TGF-beta 2: implications for receptor binding."
Mittl P.R.E., Priestle J.P., Cox D.A., McMaster G., Cerletti N., Gruetter M.G.
Protein Sci. 5:1261-1271(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 301-412.
[10]"Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1."
Beffagna G., Occhi G., Nava A., Vitiello L., Ditadi A., Basso C., Bauce B., Carraro G., Thiene G., Towbin J.A., Danieli G.A., Rampazzo A.
Cardiovasc. Res. 65:366-373(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ARVD1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03241 mRNA. Translation: AAA61161.1.
X14149 mRNA. Translation: CAA32362.1.
X14885 expand/collapse EMBL AC list , 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.
AF107885 Genomic DNA. Translation: AAC79727.1.
PIRA36169.
RefSeqNP_003230.1. NM_003239.2.
XP_005268085.1. XM_005268028.1.
UniGeneHs.592317.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP10600.
SMRP10600. Positions 24-412.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112901. 7 interactions.
DIPDIP-5937N.
IntActP10600. 6 interactions.
MINTMINT-8177755.
STRING9606.ENSP00000238682.

PTM databases

PhosphoSiteP10600.

Polymorphism databases

DMDM135684.

Proteomic databases

PaxDbP10600.
PRIDEP10600.

Protocols and materials databases

DNASU7043.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000238682; ENSP00000238682; ENSG00000119699.
GeneID7043.
KEGGhsa:7043.
UCSCuc001xsc.2. human.

Organism-specific databases

CTD7043.
GeneCardsGC14M076424.
HGNCHGNC:11769. TGFB3.
HPACAB018337.
HPA027923.
MIM107970. phenotype.
190230. gene.
neXtProtNX_P10600.
Orphanet293899. 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.
PharmGKBPA36483.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG269146.
HOGENOMHOG000290198.
HOVERGENHBG074115.
InParanoidP10600.
KOK13377.
OMAPEPSVMT.
OrthoDBEOG70GMFT.
PhylomeDBP10600.
TreeFamTF351793.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.
REACT_604. Hemostasis.
SignaLinkP10600.

Gene expression databases

ArrayExpressP10600.
BgeeP10600.
CleanExHS_TGFB3.
GenevestigatorP10600.

Family and domain databases

InterProIPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR016319. TGF-beta.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
IPR015618. Transform_grow_fac_b3.
[Graphical view]
PANTHERPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF34. PTHR11848:SF34. 1 hit.
PfamPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
PIRSFPIRSF001787. TGF-beta. 1 hit.
PRINTSPR01423. TGFBETA.
PR01426. TGFBETA3.
SMARTSM00204. TGFB. 1 hit.
[Graphical view]
PROSITEPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTGFB3. human.
EvolutionaryTraceP10600.
GeneWikiTransforming_growth_factor,_beta_3.
GenomeRNAi7043.
NextBio27521.
PMAP-CutDBP10600.
PROP10600.
SOURCESearch...

Entry information

Entry nameTGFB3_HUMAN
AccessionPrimary (citable) accession number: P10600
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 164 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM