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Protein

Transforming growth factor beta-2 proprotein

Gene

TGFB2

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

Functioni

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.By similarity
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).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).By similarity2 Publications

Caution

In contrast to other members of the family, does not contain a R-G-D cell attachment site motif that mediates binding to integrins and promotes release of Latency-associated peptide (LAP) chain from TGF-beta-2.Curated

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
SignaLinkiP61812
SIGNORiP61812

Names & Taxonomyi

Protein namesi
Recommended name:
Transforming growth factor beta-2 proprotein
Alternative name(s):
Cetermin
Glioblastoma-derived T-cell suppressor factor1 Publication
Short name:
G-TSF1 Publication
Cleaved into the following 2 chains:
Gene namesi
Name:TGFB2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000092969.11
HGNCiHGNC:11768 TGFB2
MIMi190220 gene
neXtProtiNX_P61812

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

A chromosomal aberration involving TGFB2 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9.1 Publication
Loeys-Dietz syndrome 4 (LDS4)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae.
See also OMIM:614816
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068931100 – 104Missing in LDS4. 1 Publication5
Natural variantiVAR_080342102 – 414Missing in LDS4. 1 PublicationAdd BLAST313
Natural variantiVAR_080343229 – 414Missing in LDS4. 1 PublicationAdd BLAST186
Natural variantiVAR_068932299R → W in LDS4. 1 PublicationCorresponds to variant dbSNP:rs863223792EnsemblClinVar.1
Natural variantiVAR_068933302R → C in LDS4. 1 PublicationCorresponds to variant dbSNP:rs869312903Ensembl.1
Natural variantiVAR_068934338P → H in LDS4. 1 PublicationCorresponds to variant dbSNP:rs387907278Ensembl.1
Defects in TGFB2 may be a cause of non-syndromic aortic disease (NSAD). NSAD is a frequently asymptomatic but potentially lethal disease characterized by thoracic aortic aneurysms and dissections without additional syndromic features.1 Publication

Keywords - Diseasei

Aortic aneurysm, Disease mutation

Organism-specific databases

DisGeNETi7042
GeneReviewsiTGFB2
MalaCardsiTGFB2
MIMi614816 phenotype
OpenTargetsiENSG00000092969
Orphaneti91387 Familial thoracic aortic aneurysm and aortic dissection
708 Peters anomaly
PharmGKBiPA36482

Chemistry databases

ChEMBLiCHEMBL3217393

Polymorphism and mutation databases

BioMutaiTGFB2
DMDMi48429157

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000003378421 – 302Latency-associated peptide1 PublicationAdd BLAST282
ChainiPRO_0000033785303 – 414Transforming growth factor beta-21 PublicationAdd BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi72N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi140N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi241N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi309 ↔ 3182 Publications
Disulfide bondi317 ↔ 3802 Publications
Disulfide bondi346 ↔ 4112 Publications
Disulfide bondi350 ↔ 4132 Publications
Disulfide bondi379Interchain2 Publications

Post-translational modificationi

Transforming growth factor beta-2 proprotein: The precursor proprotein is cleaved in the Golgi apparatus to form Transforming growth factor beta-2 (TGF-beta-2) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-2 inactive.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

EPDiP61812
MaxQBiP61812
PeptideAtlasiP61812
PRIDEiP61812
ProteomicsDBi57335
57336 [P61812-2]

PTM databases

GlyConnecti1836
iPTMnetiP61812
PhosphoSitePlusiP61812

Miscellaneous databases

PMAP-CutDBiP61812

Expressioni

Gene expression databases

BgeeiENSG00000092969 Expressed in 158 organ(s), highest expression level in lung
CleanExiHS_TGFB2
GenevisibleiP61812 HS

Interactioni

Subunit structurei

Interacts with the serine proteases, HTRA1 and HTRA3 (By similarity). Interacts with ASPN (PubMed:17827158). Interacts with MFAP5 (By similarity). Latency-associated peptide: Interacts with Transforming growth factor beta-2 (TGF-beta-2) chain; interaction is non-covalent and maintains (TGF-beta-2) in a latent state (By similarity). Latency-associated peptide: Interacts with LRRC32/GARP; leading to regulate activation of TGF-beta-2 (PubMed:19651619). Latency-associated peptide: Interacts with NREP; the interaction results in a decrease in TGFB2 autoinduction (By similarity). Transforming growth factor beta-2: Homodimer; disulfide-linked (PubMed:1631557, PubMed:1641027). Transforming growth factor beta-2: Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050677EBI-779581,EBI-77613

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112900, 8 interactors
ComplexPortaliCPX-605 TGF-beta-2 complex
CPX-834 TGF-beta-2-TGFR complex
DIPiDIP-5936N
IntActiP61812, 2 interactors

Structurei

Secondary structure

1414
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP61812
SMRiP61812
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61812

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

GeneTreeiENSGT00910000143982
HOGENOMiHOG000290198
HOVERGENiHBG074115
InParanoidiP61812
KOiK13376
OMAiNERAATC
OrthoDBiEOG091G0BMM
PhylomeDBiP61812
TreeFamiTF318514

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
IPR003940 TGFb2
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PTHR11848:SF141 PTHR11848:SF141, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
PIRSFiPIRSF001787 TGF-beta, 1 hit
PRINTSiPR01423 TGFBETA
PR01425 TGFBETA2
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 A (identifier: P61812-1) [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
MHYCVLSAFL ILHLVTVALS LSTCSTLDMD QFMRKRIEAI RGQILSKLKL
60 70 80 90 100
TSPPEDYPEP EEVPPEVISI YNSTRDLLQE KASRRAAACE RERSDEEYYA
110 120 130 140 150
KEVYKIDMPP FFPSENAIPP TFYRPYFRIV RFDVSAMEKN ASNLVKAEFR
160 170 180 190 200
VFRLQNPKAR VPEQRIELYQ ILKSKDLTSP TQRYIDSKVV KTRAEGEWLS
210 220 230 240 250
FDVTDAVHEW LHHKDRNLGF KISLHCPCCT FVPSNNYIIP NKSEELEARF
260 270 280 290 300
AGIDGTSTYT SGDQKTIKST RKKNSGKTPH LLLMLLPSYR LESQQTNRRK
310 320 330 340 350
KRALDAAYCF RNVQDNCCLR PLYIDFKRDL GWKWIHEPKG YNANFCAGAC
360 370 380 390 400
PYLWSSDTQH SRVLSLYNTI NPEASASPCC VSQDLEPLTI LYYIGKTPKI
410
EQLSNMIVKS CKCS
Length:414
Mass (Da):47,748
Last modified:August 1, 1988 - v1
Checksum:i7D9D569E0F4A07D0
GO
Isoform B (identifier: P61812-2) [UniParc] [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     116-116: N → TVCPVVTTPSGSVGSLCSRQSQVLCGYLD

Show »
Length:442
Mass (Da):50,573
Checksum:i5D7A3C2ED51753D5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti32F → L in AAA61162 (PubMed:1764261).Curated1
Sequence conflicti116Missing in AAA50405 (PubMed:2850146).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01270891R → H2 PublicationsCorresponds to variant dbSNP:rs10482721EnsemblClinVar.1
Natural variantiVAR_068931100 – 104Missing in LDS4. 1 Publication5
Natural variantiVAR_080342102 – 414Missing in LDS4. 1 PublicationAdd BLAST313
Natural variantiVAR_018923207V → L1 PublicationCorresponds to variant dbSNP:rs10482810Ensembl.1
Natural variantiVAR_080343229 – 414Missing in LDS4. 1 PublicationAdd BLAST186
Natural variantiVAR_068932299R → W in LDS4. 1 PublicationCorresponds to variant dbSNP:rs863223792EnsemblClinVar.1
Natural variantiVAR_068933302R → C in LDS4. 1 PublicationCorresponds to variant dbSNP:rs869312903Ensembl.1
Natural variantiVAR_072740320R → C Probable disease-associated mutation found in a family with non-syndromic aortic disease. 1 Publication1
Natural variantiVAR_068934338P → H in LDS4. 1 PublicationCorresponds to variant dbSNP:rs387907278Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006417116N → TVCPVVTTPSGSVGSLCSRQ SQVLCGYLD in isoform B. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00083 mRNA Translation: CAA68279.1
M19154 mRNA Translation: AAA50404.1
M19154 mRNA Translation: AAA50405.1
AY438979 Genomic DNA Translation: AAR05442.1
AK296504 mRNA Translation: BAG59137.1
CH471100 Genomic DNA Translation: EAW93326.1
BC096235 mRNA Translation: AAH96235.1
BC099635 mRNA Translation: AAH99635.1
M87843 Genomic DNA Translation: AAA61162.1
CCDSiCCDS1521.1
CCDS44318.1 [P61812-2]
PIRiA29478 B31249
S06216 A31249
RefSeqiNP_001129071.1, NM_001135599.3 [P61812-2]
NP_003229.1, NM_003238.4 [P61812-1]
UniGeneiHs.133379

Genome annotation databases

EnsembliENST00000366929; ENSP00000355896; ENSG00000092969 [P61812-2]
ENST00000366930; ENSP00000355897; ENSG00000092969 [P61812-1]
GeneIDi7042
KEGGihsa:7042
UCSCiuc001hlm.4 human

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

TGF beta-2 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00083 mRNA Translation: CAA68279.1
M19154 mRNA Translation: AAA50404.1
M19154 mRNA Translation: AAA50405.1
AY438979 Genomic DNA Translation: AAR05442.1
AK296504 mRNA Translation: BAG59137.1
CH471100 Genomic DNA Translation: EAW93326.1
BC096235 mRNA Translation: AAH96235.1
BC099635 mRNA Translation: AAH99635.1
M87843 Genomic DNA Translation: AAA61162.1
CCDSiCCDS1521.1
CCDS44318.1 [P61812-2]
PIRiA29478 B31249
S06216 A31249
RefSeqiNP_001129071.1, NM_001135599.3 [P61812-2]
NP_003229.1, NM_003238.4 [P61812-1]
UniGeneiHs.133379

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TFGX-ray1.95A303-414[»]
2TGIX-ray1.80A303-414[»]
4KXZX-ray2.83A/B/D/E303-414[»]
5TX4X-ray1.88B303-414[»]
5TY4electron microscopy2.90B317-413[»]
ProteinModelPortaliP61812
SMRiP61812
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112900, 8 interactors
ComplexPortaliCPX-605 TGF-beta-2 complex
CPX-834 TGF-beta-2-TGFR complex
DIPiDIP-5936N
IntActiP61812, 2 interactors

Chemistry databases

ChEMBLiCHEMBL3217393

PTM databases

GlyConnecti1836
iPTMnetiP61812
PhosphoSitePlusiP61812

Polymorphism and mutation databases

BioMutaiTGFB2
DMDMi48429157

Proteomic databases

EPDiP61812
MaxQBiP61812
PeptideAtlasiP61812
PRIDEiP61812
ProteomicsDBi57335
57336 [P61812-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366929; ENSP00000355896; ENSG00000092969 [P61812-2]
ENST00000366930; ENSP00000355897; ENSG00000092969 [P61812-1]
GeneIDi7042
KEGGihsa:7042
UCSCiuc001hlm.4 human

Organism-specific databases

CTDi7042
DisGeNETi7042
EuPathDBiHostDB:ENSG00000092969.11
GeneCardsiTGFB2
GeneReviewsiTGFB2
HGNCiHGNC:11768 TGFB2
MalaCardsiTGFB2
MIMi190220 gene
614816 phenotype
neXtProtiNX_P61812
OpenTargetsiENSG00000092969
Orphaneti91387 Familial thoracic aortic aneurysm and aortic dissection
708 Peters anomaly
PharmGKBiPA36482
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00910000143982
HOGENOMiHOG000290198
HOVERGENiHBG074115
InParanoidiP61812
KOiK13376
OMAiNERAATC
OrthoDBiEOG091G0BMM
PhylomeDBiP61812
TreeFamiTF318514

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-2129379 Molecules associated with elastic fibres
R-HSA-3000178 ECM proteoglycans
SignaLinkiP61812
SIGNORiP61812

Miscellaneous databases

ChiTaRSiTGFB2 human
EvolutionaryTraceiP61812
GeneWikiiTGF_beta_2
GenomeRNAii7042
PMAP-CutDBiP61812
PROiPR:P61812
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000092969 Expressed in 158 organ(s), highest expression level in lung
CleanExiHS_TGFB2
GenevisibleiP61812 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
IPR003940 TGFb2
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PTHR11848:SF141 PTHR11848:SF141, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
PIRSFiPIRSF001787 TGF-beta, 1 hit
PRINTSiPR01423 TGFBETA
PR01425 TGFBETA2
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 nameiTGFB2_HUMAN
AccessioniPrimary (citable) accession number: P61812
Secondary accession number(s): B4DKC5
, P08112, Q15579, Q15581, Q4VAV9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: October 10, 2018
This is version 167 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, Direct protein sequencing, Reference proteome

Documents

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