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)]

 TGFB2_HUMAN             Reviewed;         414 AA.
 P61812; B4DKC5; P08112; Q15579; Q15581; Q4VAV9;
 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
 01-AUG-1988, sequence version 1.
 02-JUN-2021, entry version 188.
 RecName: Full=Transforming growth factor beta-2 proprotein;
 AltName: Full=Cetermin;
 AltName: Full=Glioblastoma-derived T-cell suppressor factor {ECO:0000303|PubMed:3322813};
          Short=G-TSF {ECO:0000303|PubMed:3322813};
 Contains:
   RecName: Full=Latency-associated peptide;
            Short=LAP;
 Contains:
   RecName: Full=Transforming growth factor beta-2;
            Short=TGF-beta-2;
 Flags: Precursor;
 Name=TGFB2;
 Homo sapiens (Human).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
 Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
 Homo.
 NCBI_TaxID=9606;
 [1]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
 PubMed=3322813;
 de Martin R., Haendler B., Hofer-Warbinek R., Gaugitsch H., Wrann M.,
 Schluesener H., Seifert J.M., Bodmer S., Fontana A., Hofer E.;
 "Complementary DNA for human glioblastoma-derived T cell suppressor factor,
 a novel member of the transforming growth factor-beta gene family.";
 EMBO J. 6:3673-3677(1987).
 [2]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
 PubMed=3162414; DOI=10.1089/dna.1988.7.1;
 Madisen L., Webb N.R., Rose T.M., Marquardt H., Ikeda T., Twardzik D.R.,
 Seyedin S., Purchio A.F.;
 "Transforming growth factor-beta 2: cDNA cloning and sequence analysis.";
 DNA 7:1-8(1988).
 [3]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
 PubMed=2850146; DOI=10.1089/dna.1.1988.7.493;
 Webb N.R., Madisen L., Rose T.M., Purchio A.F.;
 "Structural and sequence analysis of TGF-beta 2 cDNA clones predicts two
 different precursor proteins produced by alternative mRNA splicing.";
 DNA 7:493-497(1988).
 [4]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-91 AND LEU-207.
 NIEHS SNPs program;
 Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
 [5]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
 TISSUE=Thalamus;
 PubMed=14702039; DOI=10.1038/ng1285;
 Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
 Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
 Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
 Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
 Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
 Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
 Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
 Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
 Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
 Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
 Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
 Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
 Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
 Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
 Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
 Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
 Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
 Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
 Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
 Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
 Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
 Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
 Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
 Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
 Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
 Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
 Isogai T., Sugano S.;
 "Complete sequencing and characterization of 21,243 full-length human
 cDNAs.";
 Nat. Genet. 36:40-45(2004).
 [6]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
 Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
 Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
 Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
 Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
 Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
 Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
 Hunkapiller M.W., Myers E.W., Venter J.C.;
 Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
 [7]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
 PubMed=15489334; DOI=10.1101/gr.2596504;
 The MGC Project Team;
 "The status, quality, and expansion of the NIH full-length cDNA project:
 the Mammalian Gene Collection (MGC).";
 Genome Res. 14:2121-2127(2004).
 [8]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-115.
 TISSUE=Lung;
 PubMed=1764261; DOI=10.3109/08977199109043910;
 Noma T., Glick A.B., Geiser A.G., O'Reilly M.A., Miller J., Roberts A.B.,
 Sporn M.B.;
 "Molecular cloning and structure of the human transforming growth factor-
 beta 2 gene promoter.";
 Growth Factors 4:247-255(1991).
 [9]
 PROTEIN SEQUENCE OF 303-414.
 PubMed=3476488;
 Marquardt H., Lioubin M.N., Ikeda T.;
 "Complete amino acid sequence of human transforming growth factor type beta
 2.";
 J. Biol. Chem. 262:12127-12131(1987).
 [10]
 CHROMOSOMAL TRANSLOCATION WITH HDAC9.
 PubMed=12706107; DOI=10.1016/s0888-7543(03)00046-6;
 David D., Cardoso J., Marques B., Marques R., Silva E.D., Santos H.,
 Boavida M.G.;
 "Molecular characterization of a familial translocation implicates
 disruption of HDAC9 and possible position effect on TGFbeta2 in the
 pathogenesis of Peters' anomaly.";
 Genomics 81:489-503(2003).
 [11]
 INTERACTION WITH ASPN.
 PubMed=17827158; DOI=10.1074/jbc.m700522200;
 Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S.;
 "Mechanisms for asporin function and regulation in articular cartilage.";
 J. Biol. Chem. 282:32185-32192(2007).
 [12]
 INTERACTION WITH LRRC32.
 PubMed=19651619; DOI=10.1073/pnas.0901944106;
 Tran D.Q., Andersson J., Wang R., Ramsey H., Unutmaz D., Shevach E.M.;
 "GARP (LRRC32) is essential for the surface expression of latent TGF-beta
 on platelets and activated FOXP3+ regulatory T cells.";
 Proc. Natl. Acad. Sci. U.S.A. 106:13445-13450(2009).
 [13]
 X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 303-414, DISULFIDE BOND, AND
 SUBUNIT.
 PubMed=1631557; DOI=10.1126/science.1631557;
 Daopin S., Piez K.A., Ogawa Y., Davies D.R.;
 "Crystal structure of transforming growth factor-beta 2: an unusual fold
 for the superfamily.";
 Science 257:369-373(1992).
 [14]
 X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)OF 303-414, DISULFIDE BOND, AND
 SUBUNIT.
 PubMed=1641027; DOI=10.1038/358430a0;
 Schlunegger M.P., Gruetter M.G.;
 "An unusual feature revealed by the crystal structure at 2.2-A resolution
 of human transforming growth factor-beta 2.";
 Nature 358:430-434(1992).
 [15]
 VARIANT HIS-91.
 PubMed=11528528; DOI=10.1038/sj.gene.6363780;
 Alansari A., Hajeer A.H., Bayat A., Eyre S., Carthy D., Ollier W.E.;
 "Two novel polymorphisms in the human transforming growth factor beta 2
 gene.";
 Genes Immun. 2:295-296(2001).
 [16]
 INVOLVEMENT IN LDS4, VARIANTS LDS4 102-GLU--SER-414 DEL AND
 229-CYS--SER-414 DEL, AND FUNCTION.
 PubMed=22772371; DOI=10.1038/ng.2348;
 National Heart, Lung, and Blood Institute (NHLBI) Go Exome Sequencing Project;
 Boileau C., Guo D.C., Hanna N., Regalado E.S., Detaint D., Gong L.,
 Varret M., Prakash S.K., Li A.H., d'Indy H., Braverman A.C., Grandchamp B.,
 Kwartler C.S., Gouya L., Santos-Cortez R.L., Abifadel M., Leal S.M.,
 Muti C., Shendure J., Gross M.S., Rieder M.J., Vahanian A., Nickerson D.A.,
 Michel J.B., Jondeau G., Milewicz D.M.;
 "TGFB2 mutations cause familial thoracic aortic aneurysms and dissections
 associated with mild systemic features of Marfan syndrome.";
 Nat. Genet. 44:916-921(2012).
 [17]
 VARIANTS LDS4 100-ALA--TYR-104 DEL; TRP-299; CYS-302 AND HIS-338, AND
 FUNCTION.
 PubMed=22772368; DOI=10.1038/ng.2349;
 Lindsay M.E., Schepers D., Bolar N.A., Doyle J.J., Gallo E., Fert-Bober J.,
 Kempers M.J., Fishman E.K., Chen Y., Myers L., Bjeda D., Oswald G.,
 Elias A.F., Levy H.P., Anderlid B.M., Yang M.H., Bongers E.M.,
 Timmermans J., Braverman A.C., Canham N., Mortier G.R., Brunner H.G.,
 Byers P.H., Van Eyk J., Van Laer L., Dietz H.C., Loeys B.L.;
 "Loss-of-function mutations in TGFB2 cause a syndromic presentation of
 thoracic aortic aneurysm.";
 Nat. Genet. 44:922-927(2012).
 [18]
 INVOLVEMENT IN NON-SYNDROMIC AORTIC DISEASE, AND VARIANT CYS-320.
 PubMed=25046559; DOI=10.1016/j.cca.2014.07.016;
 Gago-Diaz M., Blanco-Verea A., Teixido-Tura G., Valenzuela I.,
 Del Campo M., Borregan M., Sobrino B., Amigo J., Garcia-Dorado D.,
 Evangelista A., Carracedo A., Brion M.;
 "Whole exome sequencing for the identification of a new mutation in TGFB2
 involved in a familial case of non-syndromic aortic disease.";
 Clin. Chim. Acta 437:88-92(2014).
 -!- 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. {ECO:0000250|UniProtKB:P01137,
     ECO:0000250|UniProtKB:P04202}.
 -!- FUNCTION: [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).
     {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202}.
 -!- FUNCTION: 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).
     {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202,
     ECO:0000269|PubMed:22772368, ECO:0000269|PubMed:22772371}.
 -!- SUBUNIT: 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). {ECO:0000250|UniProtKB:P01137,
     ECO:0000250|UniProtKB:P27090, ECO:0000269|PubMed:1631557,
     ECO:0000269|PubMed:1641027, ECO:0000269|PubMed:17827158,
     ECO:0000269|PubMed:19651619}.
 -!- INTERACTION:
     P61812; P05067: APP; NbExp=7; IntAct=EBI-779581, EBI-77613;
     P61812; P13051-2: UNG; NbExp=3; IntAct=EBI-779581, EBI-25834258;
 -!- SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted,
     extracellular space, extracellular matrix
     {ECO:0000250|UniProtKB:P01137}.
 -!- SUBCELLULAR LOCATION: [Transforming growth factor beta-2]: Secreted
     {ECO:0000250|UniProtKB:P01137}.
 -!- ALTERNATIVE PRODUCTS:
     Event=Alternative splicing; Named isoforms=2;
     Name=A;
       IsoId=P61812-1, P08112-1;
       Sequence=Displayed;
     Name=B;
       IsoId=P61812-2, P08112-2;
       Sequence=VSP_006417;
 -!- PTM: 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. {ECO:0000250|UniProtKB:P01137}.
 -!- DISEASE: Note=A chromosomal aberration involving TGFB2 is found in a
     family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9.
     {ECO:0000269|PubMed:12706107}.
 -!- DISEASE: Loeys-Dietz syndrome 4 (LDS4) [MIM:614816]: An 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. {ECO:0000269|PubMed:22772368, ECO:0000269|PubMed:22772371}.
     Note=The disease is caused by variants affecting the gene represented
     in this entry.
 -!- DISEASE: Note=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.
     {ECO:0000269|PubMed:25046559}.
 -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
 -!- 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. {ECO:0000305}.
 -!- WEB RESOURCE: Name=NIEHS-SNPs;
     URL="http://egp.gs.washington.edu/data/tgfb2/";
 -!- WEB RESOURCE: Name=Wikipedia; Note=TGF beta-2 entry;
     URL="https://en.wikipedia.org/wiki/TGF_beta_2";
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 EMBL; Y00083; CAA68279.1; -; mRNA.
 EMBL; M19154; AAA50404.1; -; mRNA.
 EMBL; M19154; AAA50405.1; -; mRNA.
 EMBL; AY438979; AAR05442.1; -; Genomic_DNA.
 EMBL; AK296504; BAG59137.1; -; mRNA.
 EMBL; CH471100; EAW93326.1; -; Genomic_DNA.
 EMBL; BC096235; AAH96235.1; -; mRNA.
 EMBL; BC099635; AAH99635.1; -; mRNA.
 EMBL; M87843; AAA61162.1; -; Genomic_DNA.
 CCDS; CCDS1521.1; -.
 CCDS; CCDS44318.1; -. [P61812-2]
 PIR; A29478; B31249.
 PIR; S06216; A31249.
 RefSeq; NP_001129071.1; NM_001135599.3. [P61812-2]
 RefSeq; NP_003229.1; NM_003238.4. [P61812-1]
 PDB; 1TFG; X-ray; 1.95 A; A=303-414.
 PDB; 2TGI; X-ray; 1.80 A; A=303-414.
 PDB; 4KXZ; X-ray; 2.83 A; A/B/D/E=303-414.
 PDB; 5TX4; X-ray; 1.88 A; B=303-414.
 PDB; 5TY4; EM; 2.90 A; B=317-413.
 PDB; 6I9J; X-ray; 2.00 A; A=303-414.
 PDBsum; 1TFG; -.
 PDBsum; 2TGI; -.
 PDBsum; 4KXZ; -.
 PDBsum; 5TX4; -.
 PDBsum; 5TY4; -.
 PDBsum; 6I9J; -.
 SMR; P61812; -.
 BioGRID; 112900; 13.
 ComplexPortal; CPX-605; TGF-beta-2 complex.
 ComplexPortal; CPX-834; TGF-beta-2-TGFR complex.
 DIP; DIP-5936N; -.
 IntAct; P61812; 4.
 STRING; 9606.ENSP00000355896; -.
 ChEMBL; CHEMBL3217393; -.
 GlyConnect; 1836; 1 N-Linked glycan (1 site).
 GlyGen; P61812; 3 sites.
 iPTMnet; P61812; -.
 PhosphoSitePlus; P61812; -.
 BioMuta; TGFB2; -.
 DMDM; 48429157; -.
 EPD; P61812; -.
 jPOST; P61812; -.
 MassIVE; P61812; -.
 MaxQB; P61812; -.
 PeptideAtlas; P61812; -.
 PRIDE; P61812; -.
 ProteomicsDB; 57335; -.
 ProteomicsDB; 57336; -. [P61812-2]
 ABCD; P61812; 7 sequenced antibodies.
 Antibodypedia; 20732; 597 antibodies.
 DNASU; 7042; -.
 Ensembl; ENST00000366929; ENSP00000355896; ENSG00000092969. [P61812-2]
 Ensembl; ENST00000366930; ENSP00000355897; ENSG00000092969. [P61812-1]
 GeneID; 7042; -.
 KEGG; hsa:7042; -.
 UCSC; uc001hlm.4; human.
 CTD; 7042; -.
 DisGeNET; 7042; -.
 GeneCards; TGFB2; -.
 GeneReviews; TGFB2; -.
 HGNC; HGNC:11768; TGFB2.
 HPA; ENSG00000092969; Low tissue specificity.
 MalaCards; TGFB2; -.
 MIM; 190220; gene.
 MIM; 614816; phenotype.
 neXtProt; NX_P61812; -.
 OpenTargets; ENSG00000092969; -.
 Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
 PharmGKB; PA36482; -.
 VEuPathDB; HostDB:ENSG00000092969.11; -.
 eggNOG; KOG3900; Eukaryota.
 GeneTree; ENSGT00940000157390; -.
 HOGENOM; CLU_039840_0_0_1; -.
 InParanoid; P61812; -.
 OMA; QPFYPEN; -.
 PhylomeDB; P61812; -.
 TreeFam; TF318514; -.
 PathwayCommons; P61812; -.
 Reactome; R-HSA-114608; Platelet degranulation.
 Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
 Reactome; R-HSA-3000178; ECM proteoglycans.
 SignaLink; P61812; -.
 SIGNOR; P61812; -.
 BioGRID-ORCS; 7042; 7 hits in 996 CRISPR screens.
 ChiTaRS; TGFB2; human.
 EvolutionaryTrace; P61812; -.
 GeneWiki; TGF_beta_2; -.
 GenomeRNAi; 7042; -.
 Pharos; P61812; Tbio.
 PRO; PR:P61812; -.
 Proteomes; UP000005640; Chromosome 1.
 RNAct; P61812; protein.
 Bgee; ENSG00000092969; Expressed in calcaneal tendon and 175 other tissues.
 Genevisible; P61812; HS.
 GO; GO:0030424; C:axon; ISS:UniProtKB.
 GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL.
 GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
 GO; GO:0005615; C:extracellular space; IDA:AgBase.
 GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
 GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
 GO; GO:0001540; F:amyloid-beta binding; IDA:UniProtKB.
 GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
 GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
 GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO; GO:0005102; F:signaling receptor binding; IMP:UniProtKB.
 GO; GO:0005160; F:transforming growth factor beta receptor binding; IDA:UniProtKB.
 GO; GO:0005114; F:type II transforming growth factor beta receptor binding; IDA:BHF-UCL.
 GO; GO:0034714; F:type III transforming growth factor beta receptor binding; IMP:AgBase.
 GO; GO:0032147; P:activation of protein kinase activity; IDA:BHF-UCL.
 GO; GO:0035910; P:ascending aorta morphogenesis; ISS:BHF-UCL.
 GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL.
 GO; GO:0003289; P:atrial septum primum morphogenesis; ISS:BHF-UCL.
 GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:BHF-UCL.
 GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
 GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IDA:BHF-UCL.
 GO; GO:0060038; P:cardiac muscle cell proliferation; IDA:UniProtKB.
 GO; GO:0003215; P:cardiac right ventricle morphogenesis; ISS:BHF-UCL.
 GO; GO:0010002; P:cardioblast differentiation; IDA:UniProtKB.
 GO; GO:0007050; P:cell cycle arrest; IDA:BHF-UCL.
 GO; GO:0008219; P:cell death; IDA:UniProtKB.
 GO; GO:0016477; P:cell migration; IDA:BHF-UCL.
 GO; GO:0000902; P:cell morphogenesis; IDA:UniProtKB.
 GO; GO:0045216; P:cell-cell junction organization; IDA:BHF-UCL.
 GO; GO:0030199; P:collagen fibril organization; IDA:BHF-UCL.
 GO; GO:1904888; P:cranial skeletal system development; ISS:BHF-UCL.
 GO; GO:0042416; P:dopamine biosynthetic process; ISS:UniProtKB.
 GO; GO:0009792; P:embryo development ending in birth or egg hatching; TAS:UniProtKB.
 GO; GO:0048566; P:embryonic digestive tract development; IEP:DFLAT.
 GO; GO:0030326; P:embryonic limb morphogenesis; ISS:BHF-UCL.
 GO; GO:0003274; P:endocardial cushion fusion; ISS:BHF-UCL.
 GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
 GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:BHF-UCL.
 GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL.
 GO; GO:0001654; P:eye development; IDA:UniProtKB.
 GO; GO:0048699; P:generation of neurons; TAS:UniProtKB.
 GO; GO:0008347; P:glial cell migration; IDA:BHF-UCL.
 GO; GO:0001942; P:hair follicle development; IDA:UniProtKB.
 GO; GO:0031069; P:hair follicle morphogenesis; ISS:UniProtKB.
 GO; GO:0007507; P:heart development; IDA:UniProtKB.
 GO; GO:0003007; P:heart morphogenesis; IDA:BHF-UCL.
 GO; GO:0003179; P:heart valve morphogenesis; ISS:BHF-UCL.
 GO; GO:0030097; P:hemopoiesis; ISS:UniProtKB.
 GO; GO:0048839; P:inner ear development; ISS:BHF-UCL.
 GO; GO:0001822; P:kidney development; ISS:BHF-UCL.
 GO; GO:0008584; P:male gonad development; ISS:BHF-UCL.
 GO; GO:0003149; P:membranous septum morphogenesis; ISS:BHF-UCL.
 GO; GO:0010693; P:negative regulation of alkaline phosphatase activity; IDA:BHF-UCL.
 GO; GO:0016525; P:negative regulation of angiogenesis; IDA:BHF-UCL.
 GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
 GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
 GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:BHF-UCL.
 GO; GO:1905006; P:negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
 GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
 GO; GO:0010936; P:negative regulation of macrophage cytokine production; IDA:DFLAT.
 GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISS:BHF-UCL.
 GO; GO:0003407; P:neural retina development; ISS:BHF-UCL.
 GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL.
 GO; GO:0048666; P:neuron development; ISS:UniProtKB.
 GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
 GO; GO:0042476; P:odontogenesis; NAS:BHF-UCL.
 GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:BHF-UCL.
 GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
 GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISS:BHF-UCL.
 GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
 GO; GO:0051891; P:positive regulation of cardioblast differentiation; IDA:UniProtKB.
 GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IDA:BHF-UCL.
 GO; GO:0045787; P:positive regulation of cell cycle; ISS:UniProtKB.
 GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
 GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
 GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
 GO; GO:0010634; P:positive regulation of epithelial cell migration; IDA:BHF-UCL.
 GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:BHF-UCL.
 GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
 GO; GO:0045823; P:positive regulation of heart contraction; IDA:UniProtKB.
 GO; GO:0050778; P:positive regulation of immune response; ISS:UniProtKB.
 GO; GO:0045726; P:positive regulation of integrin biosynthetic process; IDA:BHF-UCL.
 GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:UniProtKB.
 GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:BHF-UCL.
 GO; GO:0045778; P:positive regulation of ossification; IEP:BHF-UCL.
 GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
 GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
 GO; GO:1902895; P:positive regulation of pri-miRNA transcription by RNA polymerase II; IDA:BHF-UCL.
 GO; GO:0050714; P:positive regulation of protein secretion; IDA:BHF-UCL.
 GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IDA:BHF-UCL.
 GO; GO:0051795; P:positive regulation of timing of catagen; IDA:UniProtKB.
 GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL.
 GO; GO:0003184; P:pulmonary valve morphogenesis; ISS:BHF-UCL.
 GO; GO:1902256; P:regulation of apoptotic process involved in outflow tract morphogenesis; ISS:BHF-UCL.
 GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
 GO; GO:0051794; P:regulation of timing of catagen; IDA:UniProtKB.
 GO; GO:0032909; P:regulation of transforming growth factor beta2 production; IMP:BHF-UCL.
 GO; GO:0042493; P:response to drug; IDA:UniProtKB.
 GO; GO:0001666; P:response to hypoxia; IMP:BHF-UCL.
 GO; GO:0032570; P:response to progesterone; IDA:BHF-UCL.
 GO; GO:0009611; P:response to wounding; IEP:BHF-UCL.
 GO; GO:0007435; P:salivary gland morphogenesis; IEP:BHF-UCL.
 GO; GO:0062009; P:secondary palate development; ISS:BHF-UCL.
 GO; GO:0001501; P:skeletal system development; ISS:BHF-UCL.
 GO; GO:0060395; P:SMAD protein signal transduction; IDA:BHF-UCL.
 GO; GO:0048103; P:somatic stem cell division; ISS:UniProtKB.
 GO; GO:1903701; P:substantia propria of cornea development; ISS:BHF-UCL.
 GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
 GO; GO:0042704; P:uterine wall breakdown; TAS:BHF-UCL.
 GO; GO:0060065; P:uterus development; ISS:BHF-UCL.
 GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
 GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; ISS:BHF-UCL.
 GO; GO:0042060; P:wound healing; ISS:UniProtKB.
 Gene3D; 2.10.90.10; -; 1.
 InterPro; IPR029034; Cystine-knot_cytokine.
 InterPro; IPR001839; TGF-b_C.
 InterPro; IPR001111; TGF-b_propeptide.
 InterPro; IPR016319; TGF-beta.
 InterPro; IPR015615; TGF-beta-rel.
 InterPro; IPR003940; TGFb2.
 InterPro; IPR017948; TGFb_CS.
 PANTHER; PTHR11848; PTHR11848; 1.
 Pfam; PF00019; TGF_beta; 1.
 Pfam; PF00688; TGFb_propeptide; 1.
 PIRSF; PIRSF001787; TGF-beta; 1.
 PRINTS; PR01423; TGFBETA.
 PRINTS; PR01425; TGFBETA2.
 SMART; SM00204; TGFB; 1.
 SUPFAM; SSF57501; SSF57501; 1.
 PROSITE; PS00250; TGF_BETA_1; 1.
 PROSITE; PS51362; TGF_BETA_2; 1.
 1: Evidence at protein level;
 3D-structure; Alternative splicing; Aortic aneurysm;
 Chromosomal rearrangement; Cleavage on pair of basic residues;
 Direct protein sequencing; Disease variant; Disulfide bond;
 Extracellular matrix; Glycoprotein; Growth factor; Mitogen;
 Reference proteome; Secreted; Signal.
 SIGNAL          1..20
                 /evidence="ECO:0000255"
 CHAIN           21..302
                 /note="Latency-associated peptide"
                 /evidence="ECO:0000305|PubMed:3476488"
                 /id="PRO_0000033784"
 CHAIN           303..414
                 /note="Transforming growth factor beta-2"
                 /evidence="ECO:0000305|PubMed:3476488"
                 /id="PRO_0000033785"
 CARBOHYD        72
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        140
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 CARBOHYD        241
                 /note="N-linked (GlcNAc...) asparagine"
                 /evidence="ECO:0000255"
 DISULFID        309..318
                 /evidence="ECO:0000269|PubMed:1631557,
                 ECO:0000269|PubMed:1641027"
 DISULFID        317..380
                 /evidence="ECO:0000269|PubMed:1631557,
                 ECO:0000269|PubMed:1641027"
 DISULFID        346..411
                 /evidence="ECO:0000269|PubMed:1631557,
                 ECO:0000269|PubMed:1641027"
 DISULFID        350..413
                 /evidence="ECO:0000269|PubMed:1631557,
                 ECO:0000269|PubMed:1641027"
 DISULFID        379
                 /note="Interchain"
                 /evidence="ECO:0000269|PubMed:1631557,
                 ECO:0000269|PubMed:1641027"
 VAR_SEQ         116
                 /note="N -> TVCPVVTTPSGSVGSLCSRQSQVLCGYLD (in isoform B)"
                 /evidence="ECO:0000303|PubMed:14702039,
                 ECO:0000303|PubMed:2850146, ECO:0000303|PubMed:3162414"
                 /id="VSP_006417"
 VARIANT         91
                 /note="R -> H (in dbSNP:rs10482721)"
                 /evidence="ECO:0000269|PubMed:11528528, ECO:0000269|Ref.4"
                 /id="VAR_012708"
 VARIANT         100..104
                 /note="Missing (in LDS4)"
                 /evidence="ECO:0000269|PubMed:22772368"
                 /id="VAR_068931"
 VARIANT         102..414
                 /note="Missing (in LDS4)"
                 /evidence="ECO:0000269|PubMed:22772371"
                 /id="VAR_080342"
 VARIANT         207
                 /note="V -> L (in dbSNP:rs10482810)"
                 /evidence="ECO:0000269|Ref.4"
                 /id="VAR_018923"
 VARIANT         229..414
                 /note="Missing (in LDS4)"
                 /evidence="ECO:0000269|PubMed:22772371"
                 /id="VAR_080343"
 VARIANT         299
                 /note="R -> W (in LDS4; dbSNP:rs863223792)"
                 /evidence="ECO:0000269|PubMed:22772368"
                 /id="VAR_068932"
 VARIANT         302
                 /note="R -> C (in LDS4; dbSNP:rs869312903)"
                 /evidence="ECO:0000269|PubMed:22772368"
                 /id="VAR_068933"
 VARIANT         320
                 /note="R -> C (probable disease-associated variant found in
                 a family with non-syndromic aortic disease;
                 dbSNP:rs1553303352)"
                 /evidence="ECO:0000269|PubMed:25046559"
                 /id="VAR_072740"
 VARIANT         338
                 /note="P -> H (in LDS4; dbSNP:rs387907278)"
                 /evidence="ECO:0000269|PubMed:22772368"
                 /id="VAR_068934"
 CONFLICT        32
                 /note="F -> L (in Ref. 8; AAA61162)"
                 /evidence="ECO:0000305"
 CONFLICT        116
                 /note="Missing (in Ref. 3; AAA50405)"
                 /evidence="ECO:0000305"
 HELIX           306..309
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          315..320
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          323..325
                 /evidence="ECO:0007829|PDB:2TGI"
 HELIX           326..330
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          335..337
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          339..342
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          345..347
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          354..356
                 /evidence="ECO:0007829|PDB:2TGI"
 HELIX           359..370
                 /evidence="ECO:0007829|PDB:2TGI"
 HELIX           372..374
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          379..382
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          384..394
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          397..408
                 /evidence="ECO:0007829|PDB:2TGI"
 STRAND          411..414
                 /evidence="ECO:0007829|PDB:2TGI"
 SEQUENCE   414 AA;  47748 MW;  7D9D569E0F4A07D0 CRC64;
 MHYCVLSAFL ILHLVTVALS LSTCSTLDMD QFMRKRIEAI RGQILSKLKL TSPPEDYPEP
 EEVPPEVISI YNSTRDLLQE KASRRAAACE RERSDEEYYA KEVYKIDMPP FFPSENAIPP
 TFYRPYFRIV RFDVSAMEKN ASNLVKAEFR VFRLQNPKAR VPEQRIELYQ ILKSKDLTSP
 TQRYIDSKVV KTRAEGEWLS FDVTDAVHEW LHHKDRNLGF KISLHCPCCT FVPSNNYIIP
 NKSEELEARF AGIDGTSTYT SGDQKTIKST RKKNSGKTPH LLLMLLPSYR LESQQTNRRK
 KRALDAAYCF RNVQDNCCLR PLYIDFKRDL GWKWIHEPKG YNANFCAGAC PYLWSSDTQH
 SRVLSLYNTI NPEASASPCC VSQDLEPLTI LYYIGKTPKI EQLSNMIVKS CKCS

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