P10600 (TGFB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Familial arrhythmogenic right ventricular dysplasia 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 component	Secreted
Coding sequence diversity	Polymorphism
Disease	Cardiomyopathy
Domain	Signal
Molecular function	Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	SMAD protein import into nucleus Inferred from electronic annotation. Source: Compara activation of MAPK activity Inferred from electronic annotation. Source: Compara aging Inferred from electronic annotation. Source: Compara 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: Compara embryonic neurocranium morphogenesis Inferred from electronic annotation. Source: Compara face morphogenesis Inferred from mutant phenotype PubMed 12651933. Source: BHF-UCL female pregnancy Inferred from electronic annotation. Source: Compara frontal suture morphogenesis Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from sequence or structural similarity. Source: BHF-UCL induction of apoptosis Inferred from sequence or structural similarity. Source: BHF-UCL inner ear development Inferred from electronic annotation. Source: Compara 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: Compara 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 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 response to estrogen stimulus Inferred from electronic annotation. Source: Compara response to laminar fluid shear stress Inferred from electronic annotation. Source: Compara response to progesterone stimulus 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_component	T-tubule Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara 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: Compara neuronal cell body Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara plasma membrane Inferred by curator PubMed 11157754. Source: BHF-UCL platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular_function	identical 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...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Chain

24 – 300

277

Latency-associated peptide

PRO_0000033796

Chain

301 – 412

112

Transforming growth factor beta-3

PRO_0000033797

Regions

Motif

261 – 263

3

Cell attachment site Potential

Amino acid modifications

Glycosylation

74

1

N-linked (GlcNAc...) Potential

Glycosylation

135

1

N-linked (GlcNAc...) Potential

Glycosylation

142

1

N-linked (GlcNAc...) Potential

Disulfide bond

307 ↔ 316

Disulfide bond

315 ↔ 378

Disulfide bond

344 ↔ 409

Disulfide bond

348 ↔ 411

Disulfide bond

377

Interchain By similarity

Natural variations

Natural variant

60

1

T → M. Ref.5
Corresponds to variant rs4252315 [ dbSNP | Ensembl ].

VAR_016315

Secondary structure

1

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412

Helix Strand Turn

Details...

Helix

304 – 309

6

Beta strand

314 – 318

5

Beta strand

321 – 323

3

Helix

324 – 328

5

Beta strand

333 – 335

3

Beta strand

337 – 340

4

Beta strand

343 – 346

4

Turn

350 – 353

4

Helix

357 – 368

12

Helix

370 – 372

3

Beta strand

377 – 380

4

Beta strand

382 – 392

11

Beta strand

395 – 406

12

Beta strand

408 – 412

5

Sequences

	Sequence		Length	Mass (Da)
	P10600 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 3CAD3548D3AEA178	FASTA	412	47,328
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

Web resources

GeneReviews

NIEHS-SNPs

SeattleSNPs

Wikipedia

TGF beta-3 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
AF107885 Genomic DNA. Translation: AAC79727.1.

IPI

IPI00021780.

PIR

A36169.

RefSeq

NP_003230.1. NM_003239.2.

UniGene

Hs.592317.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KTZ	X-ray	2.15	A	301-412	[»]
1TGJ	X-ray	2.00	A	301-412	[»]
1TGK	X-ray	3.30	A	301-412	[»]
2PJY	X-ray	3.00	A	301-412	[»]
3EO1	X-ray	3.10	C/F/I/L	301-412	[»]

ProteinModelPortal

P10600.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5937N.

IntAct

P10600. 4 interactions.

STRING

9606.ENSP00000238682.

PTM databases

PhosphoSite

P10600.

Polymorphism databases

DMDM

135684.

Proteomic databases

PaxDb

P10600.

PRIDE

P10600.

Protocols and materials databases

DNASU

7043.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000238682; ENSP00000238682; ENSG00000119699.

GeneID

7043.

KEGG

hsa:7043.

UCSC

uc001xsc.2. human.

Organism-specific databases

CTD

7043.

GeneCards

GC14M076424.

HGNC

HGNC:11769. TGFB3.

HPA

CAB018337.
HPA027923.

MIM

107970. phenotype.
190230. gene.

neXtProt

NX_P10600.

Orphanet

293899. 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.

PharmGKB

PA36483.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG269146.

HOGENOM

HOG000290198.

HOVERGEN

HBG074115.

InParanoid

P10600.

KO

K13377.

OMA

PEPSVMT.

OrthoDB

EOG434W67.

PhylomeDB

P10600.

Enzyme and pathway databases

Pathway_Interaction_DB

glypican_1pathway. Glypican 1 network.
tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_118779. Extracellular matrix organization.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P10600.

Bgee

P10600.

CleanEx

HS_TGFB3.

Genevestigator

P10600.

GermOnline

ENSG00000119699. Homo sapiens.

Family and domain databases

InterPro

IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR016319. TGF-beta.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
IPR015618. Transform_grow_fac_b3.
[Graphical view]

PANTHER

PTHR11848. PTHR11848. 1 hit.
PTHR11848:SF34. PTHR11848:SF34. 1 hit.

Pfam

PF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]

PIRSF

PIRSF001787. TGF-beta. 1 hit.

PRINTS

PR01423. TGFBETA.
PR01426. TGFBETA3.

SMART

SM00204. TGFB. 1 hit.
[Graphical view]

PROSITE

PS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TGFB3. human.

EvolutionaryTrace

P10600.

GenomeRNAi

7043.

NextBio

27521.

PMAP-CutDB

P10600.

SOURCE

Search...

Entry information

Entry name

TGFB3_HUMAN

Accession

Primary (citable) accession number: P10600

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 154 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.