TGFB2_HUMAN
ID TGFB2_HUMAN Reviewed; 414 AA.
AC P61812; B4DKC5; P08112; Q15579; Q15581; Q4VAV9;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Transforming growth factor beta-2 proprotein;
DE AltName: Full=Cetermin;
DE AltName: Full=Glioblastoma-derived T-cell suppressor factor {ECO:0000303|PubMed:3322813};
DE Short=G-TSF {ECO:0000303|PubMed:3322813};
DE Contains:
DE RecName: Full=Latency-associated peptide;
DE Short=LAP;
DE Contains:
DE RecName: Full=Transforming growth factor beta-2;
DE Short=TGF-beta-2;
DE Flags: Precursor;
GN Name=TGFB2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX PubMed=3322813;
RA de Martin R., Haendler B., Hofer-Warbinek R., Gaugitsch H., Wrann M.,
RA Schluesener H., Seifert J.M., Bodmer S., Fontana A., Hofer E.;
RT "Complementary DNA for human glioblastoma-derived T cell suppressor factor,
RT a novel member of the transforming growth factor-beta gene family.";
RL EMBO J. 6:3673-3677(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RX PubMed=3162414; DOI=10.1089/dna.1988.7.1;
RA Madisen L., Webb N.R., Rose T.M., Marquardt H., Ikeda T., Twardzik D.R.,
RA Seyedin S., Purchio A.F.;
RT "Transforming growth factor-beta 2: cDNA cloning and sequence analysis.";
RL DNA 7:1-8(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
RX PubMed=2850146; DOI=10.1089/dna.1.1988.7.493;
RA Webb N.R., Madisen L., Rose T.M., Purchio A.F.;
RT "Structural and sequence analysis of TGF-beta 2 cDNA clones predicts two
RT different precursor proteins produced by alternative mRNA splicing.";
RL DNA 7:493-497(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-91 AND LEU-207.
RG NIEHS SNPs program;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-115.
RC TISSUE=Lung;
RX PubMed=1764261; DOI=10.3109/08977199109043910;
RA Noma T., Glick A.B., Geiser A.G., O'Reilly M.A., Miller J., Roberts A.B.,
RA Sporn M.B.;
RT "Molecular cloning and structure of the human transforming growth factor-
RT beta 2 gene promoter.";
RL Growth Factors 4:247-255(1991).
RN [9]
RP PROTEIN SEQUENCE OF 303-414.
RX PubMed=3476488; DOI=10.1016/s0021-9258(18)45325-2;
RA Marquardt H., Lioubin M.N., Ikeda T.;
RT "Complete amino acid sequence of human transforming growth factor type beta
RT 2.";
RL J. Biol. Chem. 262:12127-12131(1987).
RN [10]
RP CHROMOSOMAL TRANSLOCATION WITH HDAC9.
RX PubMed=12706107; DOI=10.1016/s0888-7543(03)00046-6;
RA David D., Cardoso J., Marques B., Marques R., Silva E.D., Santos H.,
RA Boavida M.G.;
RT "Molecular characterization of a familial translocation implicates
RT disruption of HDAC9 and possible position effect on TGFbeta2 in the
RT pathogenesis of Peters' anomaly.";
RL Genomics 81:489-503(2003).
RN [11]
RP INTERACTION WITH ASPN.
RX PubMed=17827158; DOI=10.1074/jbc.m700522200;
RA Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S.;
RT "Mechanisms for asporin function and regulation in articular cartilage.";
RL J. Biol. Chem. 282:32185-32192(2007).
RN [12]
RP INTERACTION WITH LRRC32.
RX PubMed=19651619; DOI=10.1073/pnas.0901944106;
RA Tran D.Q., Andersson J., Wang R., Ramsey H., Unutmaz D., Shevach E.M.;
RT "GARP (LRRC32) is essential for the surface expression of latent TGF-beta
RT on platelets and activated FOXP3+ regulatory T cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:13445-13450(2009).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 303-414, DISULFIDE BOND, AND
RP SUBUNIT.
RX PubMed=1631557; DOI=10.1126/science.1631557;
RA Daopin S., Piez K.A., Ogawa Y., Davies D.R.;
RT "Crystal structure of transforming growth factor-beta 2: an unusual fold
RT for the superfamily.";
RL Science 257:369-373(1992).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)OF 303-414, DISULFIDE BOND, AND
RP SUBUNIT.
RX PubMed=1641027; DOI=10.1038/358430a0;
RA Schlunegger M.P., Gruetter M.G.;
RT "An unusual feature revealed by the crystal structure at 2.2-A resolution
RT of human transforming growth factor-beta 2.";
RL Nature 358:430-434(1992).
RN [15]
RP VARIANT HIS-91.
RX PubMed=11528528; DOI=10.1038/sj.gene.6363780;
RA Alansari A., Hajeer A.H., Bayat A., Eyre S., Carthy D., Ollier W.E.;
RT "Two novel polymorphisms in the human transforming growth factor beta 2
RT gene.";
RL Genes Immun. 2:295-296(2001).
RN [16]
RP INVOLVEMENT IN LDS4, VARIANTS LDS4 102-GLU--SER-414 DEL AND
RP 229-CYS--SER-414 DEL, AND FUNCTION.
RX PubMed=22772371; DOI=10.1038/ng.2348;
RG National Heart, Lung, and Blood Institute (NHLBI) Go Exome Sequencing Project;
RA Boileau C., Guo D.C., Hanna N., Regalado E.S., Detaint D., Gong L.,
RA Varret M., Prakash S.K., Li A.H., d'Indy H., Braverman A.C., Grandchamp B.,
RA Kwartler C.S., Gouya L., Santos-Cortez R.L., Abifadel M., Leal S.M.,
RA Muti C., Shendure J., Gross M.S., Rieder M.J., Vahanian A., Nickerson D.A.,
RA Michel J.B., Jondeau G., Milewicz D.M.;
RT "TGFB2 mutations cause familial thoracic aortic aneurysms and dissections
RT associated with mild systemic features of Marfan syndrome.";
RL Nat. Genet. 44:916-921(2012).
RN [17]
RP VARIANTS LDS4 100-ALA--TYR-104 DEL; TRP-299; CYS-302 AND HIS-338, AND
RP FUNCTION.
RX PubMed=22772368; DOI=10.1038/ng.2349;
RA Lindsay M.E., Schepers D., Bolar N.A., Doyle J.J., Gallo E., Fert-Bober J.,
RA Kempers M.J., Fishman E.K., Chen Y., Myers L., Bjeda D., Oswald G.,
RA Elias A.F., Levy H.P., Anderlid B.M., Yang M.H., Bongers E.M.,
RA Timmermans J., Braverman A.C., Canham N., Mortier G.R., Brunner H.G.,
RA Byers P.H., Van Eyk J., Van Laer L., Dietz H.C., Loeys B.L.;
RT "Loss-of-function mutations in TGFB2 cause a syndromic presentation of
RT thoracic aortic aneurysm.";
RL Nat. Genet. 44:922-927(2012).
RN [18]
RP INVOLVEMENT IN NON-SYNDROMIC AORTIC DISEASE, AND VARIANT CYS-320.
RX PubMed=25046559; DOI=10.1016/j.cca.2014.07.016;
RA Gago-Diaz M., Blanco-Verea A., Teixido-Tura G., Valenzuela I.,
RA Del Campo M., Borregan M., Sobrino B., Amigo J., Garcia-Dorado D.,
RA Evangelista A., Carracedo A., Brion M.;
RT "Whole exome sequencing for the identification of a new mutation in TGFB2
RT involved in a familial case of non-syndromic aortic disease.";
RL Clin. Chim. Acta 437:88-92(2014).
CC -!- FUNCTION: [Transforming growth factor beta-2 proprotein]: Precursor of
CC the Latency-associated peptide (LAP) and Transforming growth factor
CC beta-2 (TGF-beta-2) chains, which constitute the regulatory and active
CC subunit of TGF-beta-2, respectively. {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P04202}.
CC -!- FUNCTION: [Latency-associated peptide]: Required to maintain the
CC Transforming growth factor beta-2 (TGF-beta-2) chain in a latent state
CC during storage in extracellular matrix (By similarity). Associates non-
CC covalently with TGF-beta-2 and regulates its activation via interaction
CC with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control
CC activation of TGF-beta-2 (By similarity).
CC {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202}.
CC -!- FUNCTION: [Transforming growth factor beta-2]: Multifunctional protein
CC that regulates various processes such as angiogenesis and heart
CC development (PubMed:22772371, PubMed:22772368). Activation into mature
CC form follows different steps: following cleavage of the proprotein in
CC the Golgi apparatus, Latency-associated peptide (LAP) and Transforming
CC growth factor beta-2 (TGF-beta-2) chains remain non-covalently linked
CC rendering TGF-beta-2 inactive during storage in extracellular matrix
CC (By similarity). At the same time, LAP chain interacts with 'milieu
CC molecules', such as LTBP1 and LRRC32/GARP, that control activation of
CC TGF-beta-2 and maintain it in a latent state during storage in
CC extracellular milieus (By similarity). Once activated following release
CC of LAP, TGF-beta-2 acts by binding to TGF-beta receptors (TGFBR1 and
CC TGFBR2), which transduce signal (By similarity).
CC {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P04202,
CC ECO:0000269|PubMed:22772368, ECO:0000269|PubMed:22772371}.
CC -!- SUBUNIT: Interacts with the serine proteases, HTRA1 and HTRA3 (By
CC similarity). Interacts with ASPN (PubMed:17827158). Interacts with
CC MFAP5 (By similarity). {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P27090, ECO:0000269|PubMed:17827158}.
CC -!- SUBUNIT: [Latency-associated peptide]: Interacts with Transforming
CC growth factor beta-2 (TGF-beta-2) chain; interaction is non-covalent
CC and maintains (TGF-beta-2) in a latent state (By similarity). Interacts
CC with LRRC32/GARP; leading to regulate activation of TGF-beta-2
CC (PubMed:19651619). Interacts with NREP; the interaction results in a
CC decrease in TGFB2 autoinduction (By similarity).
CC {ECO:0000250|UniProtKB:P01137, ECO:0000250|UniProtKB:P27090,
CC ECO:0000269|PubMed:19651619}.
CC -!- SUBUNIT: [Transforming growth factor beta-2]: Homodimer; disulfide-
CC linked (PubMed:1631557, PubMed:1641027). Interacts with TGF-beta
CC receptors (TGFBR1 and TGFBR2), leading to signal transduction (By
CC similarity). {ECO:0000250|UniProtKB:P01137,
CC ECO:0000250|UniProtKB:P27090, ECO:0000269|PubMed:1631557,
CC ECO:0000269|PubMed:1641027}.
CC -!- INTERACTION:
CC P61812; P05067: APP; NbExp=7; IntAct=EBI-779581, EBI-77613;
CC P61812; P13051-2: UNG; NbExp=3; IntAct=EBI-779581, EBI-25834258;
CC -!- SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted,
CC extracellular space, extracellular matrix
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- SUBCELLULAR LOCATION: [Transforming growth factor beta-2]: Secreted
CC {ECO:0000250|UniProtKB:P01137}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=P61812-1, P08112-1;
CC Sequence=Displayed;
CC Name=B;
CC IsoId=P61812-2, P08112-2;
CC Sequence=VSP_006417;
CC -!- PTM: [Transforming growth factor beta-2 proprotein]: The precursor
CC proprotein is cleaved in the Golgi apparatus to form Transforming
CC growth factor beta-2 (TGF-beta-2) and Latency-associated peptide (LAP)
CC chains, which remain non-covalently linked, rendering TGF-beta-2
CC inactive. {ECO:0000250|UniProtKB:P01137}.
CC -!- DISEASE: Note=A chromosomal aberration involving TGFB2 is found in a
CC family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9.
CC {ECO:0000269|PubMed:12706107}.
CC -!- DISEASE: Loeys-Dietz syndrome 4 (LDS4) [MIM:614816]: An aortic aneurysm
CC syndrome with widespread systemic involvement. LDS4 is characterized by
CC arterial tortuosity, aortic dissection, intracranial aneurysm and
CC subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity,
CC bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities,
CC dural ectasia, joint hyperflexibility, and thin skin with easy bruising
CC and striae. {ECO:0000269|PubMed:22772368, ECO:0000269|PubMed:22772371}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Note=Defects in TGFB2 may be a cause of non-syndromic aortic
CC disease (NSAD). NSAD is a frequently asymptomatic but potentially
CC lethal disease characterized by thoracic aortic aneurysms and
CC dissections without additional syndromic features.
CC {ECO:0000269|PubMed:25046559}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC -!- CAUTION: In contrast to other members of the family, does not contain a
CC R-G-D cell attachment site motif that mediates binding to integrins and
CC promotes release of Latency-associated peptide (LAP) chain from TGF-
CC beta-2. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tgfb2/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=TGF beta-2 entry;
CC URL="https://en.wikipedia.org/wiki/TGF_beta_2";
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DR EMBL; Y00083; CAA68279.1; -; mRNA.
DR EMBL; M19154; AAA50404.1; -; mRNA.
DR EMBL; M19154; AAA50405.1; -; mRNA.
DR EMBL; AY438979; AAR05442.1; -; Genomic_DNA.
DR EMBL; AK296504; BAG59137.1; -; mRNA.
DR EMBL; CH471100; EAW93326.1; -; Genomic_DNA.
DR EMBL; BC096235; AAH96235.1; -; mRNA.
DR EMBL; BC099635; AAH99635.1; -; mRNA.
DR EMBL; M87843; AAA61162.1; -; Genomic_DNA.
DR CCDS; CCDS1521.1; -.
DR CCDS; CCDS44318.1; -. [P61812-2]
DR PIR; A29478; B31249.
DR PIR; S06216; A31249.
DR RefSeq; NP_001129071.1; NM_001135599.3. [P61812-2]
DR RefSeq; NP_003229.1; NM_003238.4. [P61812-1]
DR PDB; 1TFG; X-ray; 1.95 A; A=303-414.
DR PDB; 2TGI; X-ray; 1.80 A; A=303-414.
DR PDB; 4KXZ; X-ray; 2.83 A; A/B/D/E=303-414.
DR PDB; 5TX4; X-ray; 1.88 A; B=303-414.
DR PDB; 5TY4; EM; 2.90 A; B=317-413.
DR PDB; 6I9J; X-ray; 2.00 A; A=303-414.
DR PDB; 6XM2; X-ray; 1.91 A; I/J/K/L=303-414.
DR PDB; 7RCO; X-ray; 2.90 A; A/B=303-414.
DR PDBsum; 1TFG; -.
DR PDBsum; 2TGI; -.
DR PDBsum; 4KXZ; -.
DR PDBsum; 5TX4; -.
DR PDBsum; 5TY4; -.
DR PDBsum; 6I9J; -.
DR PDBsum; 6XM2; -.
DR PDBsum; 7RCO; -.
DR AlphaFoldDB; P61812; -.
DR SMR; P61812; -.
DR BioGRID; 112900; 47.
DR ComplexPortal; CPX-605; TGF-beta-2 complex.
DR ComplexPortal; CPX-834; TGF-beta-2-TGFR complex.
DR DIP; DIP-5936N; -.
DR IntAct; P61812; 5.
DR STRING; 9606.ENSP00000355896; -.
DR ChEMBL; CHEMBL3217393; -.
DR DrugBank; DB05697; Trabedersen.
DR GlyConnect; 1836; 1 N-Linked glycan (1 site).
DR GlyGen; P61812; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P61812; -.
DR PhosphoSitePlus; P61812; -.
DR BioMuta; TGFB2; -.
DR DMDM; 48429157; -.
DR EPD; P61812; -.
DR jPOST; P61812; -.
DR MassIVE; P61812; -.
DR MaxQB; P61812; -.
DR PeptideAtlas; P61812; -.
DR PRIDE; P61812; -.
DR ProteomicsDB; 57335; -.
DR ProteomicsDB; 57336; -. [P61812-2]
DR ABCD; P61812; 7 sequenced antibodies.
DR Antibodypedia; 20732; 599 antibodies from 37 providers.
DR DNASU; 7042; -.
DR Ensembl; ENST00000366929.4; ENSP00000355896.4; ENSG00000092969.12. [P61812-2]
DR Ensembl; ENST00000366930.9; ENSP00000355897.4; ENSG00000092969.12. [P61812-1]
DR GeneID; 7042; -.
DR KEGG; hsa:7042; -.
DR MANE-Select; ENST00000366930.9; ENSP00000355897.4; NM_003238.6; NP_003229.1.
DR UCSC; uc001hlm.4; human.
DR CTD; 7042; -.
DR DisGeNET; 7042; -.
DR GeneCards; TGFB2; -.
DR GeneReviews; TGFB2; -.
DR HGNC; HGNC:11768; TGFB2.
DR HPA; ENSG00000092969; Tissue enhanced (brain).
DR MalaCards; TGFB2; -.
DR MIM; 190220; gene.
DR MIM; 614816; phenotype.
DR neXtProt; NX_P61812; -.
DR OpenTargets; ENSG00000092969; -.
DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
DR PharmGKB; PA36482; -.
DR VEuPathDB; HostDB:ENSG00000092969; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000157390; -.
DR HOGENOM; CLU_039840_0_0_1; -.
DR InParanoid; P61812; -.
DR OMA; IDSKVIR; -.
DR PhylomeDB; P61812; -.
DR TreeFam; TF318514; -.
DR PathwayCommons; P61812; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR SignaLink; P61812; -.
DR SIGNOR; P61812; -.
DR BioGRID-ORCS; 7042; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; TGFB2; human.
DR EvolutionaryTrace; P61812; -.
DR GeneWiki; TGF_beta_2; -.
DR GenomeRNAi; 7042; -.
DR Pharos; P61812; Tbio.
DR PRO; PR:P61812; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P61812; protein.
DR Bgee; ENSG00000092969; Expressed in calcaneal tendon and 133 other tissues.
DR Genevisible; P61812; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:AgBase.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0099126; C:transforming growth factor beta complex; IPI:ComplexPortal.
DR GO; GO:0001540; F:amyloid-beta binding; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IMP:UniProtKB.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IDA:UniProtKB.
DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; IDA:BHF-UCL.
DR GO; GO:0034714; F:type III transforming growth factor beta receptor binding; IMP:AgBase.
DR GO; GO:0032147; P:activation of protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0035910; P:ascending aorta morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003289; P:atrial septum primum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IDA:BHF-UCL.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IDA:UniProtKB.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; ISS:BHF-UCL.
DR GO; GO:0010002; P:cardioblast differentiation; IDA:UniProtKB.
DR GO; GO:0008219; P:cell death; IDA:UniProtKB.
DR GO; GO:0016477; P:cell migration; IDA:BHF-UCL.
DR GO; GO:0000902; P:cell morphogenesis; IDA:UniProtKB.
DR GO; GO:0045216; P:cell-cell junction organization; IDA:BHF-UCL.
DR GO; GO:0030199; P:collagen fibril organization; IDA:BHF-UCL.
DR GO; GO:1904888; P:cranial skeletal system development; ISS:BHF-UCL.
DR GO; GO:0042416; P:dopamine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; TAS:UniProtKB.
DR GO; GO:0048566; P:embryonic digestive tract development; IEP:DFLAT.
DR GO; GO:0030326; P:embryonic limb morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003274; P:endocardial cushion fusion; ISS:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:BHF-UCL.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL.
DR GO; GO:0001654; P:eye development; IDA:UniProtKB.
DR GO; GO:0048699; P:generation of neurons; TAS:UniProtKB.
DR GO; GO:0008347; P:glial cell migration; IDA:BHF-UCL.
DR GO; GO:0001942; P:hair follicle development; IDA:UniProtKB.
DR GO; GO:0031069; P:hair follicle morphogenesis; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IDA:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; IDA:BHF-UCL.
DR GO; GO:0003179; P:heart valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030097; P:hemopoiesis; ISS:UniProtKB.
DR GO; GO:0048839; P:inner ear development; ISS:BHF-UCL.
DR GO; GO:0001822; P:kidney development; ISS:BHF-UCL.
DR GO; GO:0008584; P:male gonad development; ISS:BHF-UCL.
DR GO; GO:0003149; P:membranous septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0010693; P:negative regulation of alkaline phosphatase activity; IDA:BHF-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:BHF-UCL.
DR GO; GO:1905006; P:negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; IDA:DFLAT.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISS:BHF-UCL.
DR GO; GO:0003407; P:neural retina development; ISS:BHF-UCL.
DR GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL.
DR GO; GO:0048666; P:neuron development; ISS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:0042476; P:odontogenesis; NAS:BHF-UCL.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISS:BHF-UCL.
DR GO; GO:0051891; P:positive regulation of cardioblast differentiation; IDA:UniProtKB.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IDA:BHF-UCL.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IDA:BHF-UCL.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:BHF-UCL.
DR GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0045823; P:positive regulation of heart contraction; IDA:UniProtKB.
DR GO; GO:0050778; P:positive regulation of immune response; ISS:UniProtKB.
DR GO; GO:0045726; P:positive regulation of integrin biosynthetic process; IDA:BHF-UCL.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:BHF-UCL.
DR GO; GO:0045778; P:positive regulation of ossification; IEP:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:ComplexPortal.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:BHF-UCL.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IDA:BHF-UCL.
DR GO; GO:0051795; P:positive regulation of timing of catagen; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:1902256; P:regulation of apoptotic process involved in outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0051794; P:regulation of timing of catagen; IDA:UniProtKB.
DR GO; GO:0032909; P:regulation of transforming growth factor beta2 production; IMP:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; IMP:BHF-UCL.
DR GO; GO:0032570; P:response to progesterone; IDA:BHF-UCL.
DR GO; GO:0009611; P:response to wounding; IEP:BHF-UCL.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0007435; P:salivary gland morphogenesis; IEP:BHF-UCL.
DR GO; GO:0062009; P:secondary palate development; ISS:BHF-UCL.
DR GO; GO:0001501; P:skeletal system development; ISS:BHF-UCL.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:BHF-UCL.
DR GO; GO:0048103; P:somatic stem cell division; ISS:UniProtKB.
DR GO; GO:1903701; P:substantia propria of cornea development; ISS:BHF-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0042704; P:uterine wall breakdown; TAS:BHF-UCL.
DR GO; GO:0060065; P:uterus development; ISS:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0042060; P:wound healing; ISS:UniProtKB.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR016319; TGF-beta.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR003940; TGFb2.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR PIRSF; PIRSF001787; TGF-beta; 1.
DR PRINTS; PR01423; TGFBETA.
DR PRINTS; PR01425; TGFBETA2.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Aortic aneurysm;
KW Chromosomal rearrangement; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Growth factor; Mitogen;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..414
FT /note="Transforming growth factor beta-2 proprotein"
FT /id="PRO_0000456180"
FT CHAIN 21..302
FT /note="Latency-associated peptide"
FT /evidence="ECO:0000305|PubMed:3476488"
FT /id="PRO_0000033784"
FT CHAIN 303..414
FT /note="Transforming growth factor beta-2"
FT /evidence="ECO:0000305|PubMed:3476488"
FT /id="PRO_0000033785"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 309..318
FT /evidence="ECO:0000269|PubMed:1631557,
FT ECO:0000269|PubMed:1641027"
FT DISULFID 317..380
FT /evidence="ECO:0000269|PubMed:1631557,
FT ECO:0000269|PubMed:1641027"
FT DISULFID 346..411
FT /evidence="ECO:0000269|PubMed:1631557,
FT ECO:0000269|PubMed:1641027"
FT DISULFID 350..413
FT /evidence="ECO:0000269|PubMed:1631557,
FT ECO:0000269|PubMed:1641027"
FT DISULFID 379
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:1631557,
FT ECO:0000269|PubMed:1641027"
FT VAR_SEQ 116
FT /note="N -> TVCPVVTTPSGSVGSLCSRQSQVLCGYLD (in isoform B)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:2850146, ECO:0000303|PubMed:3162414"
FT /id="VSP_006417"
FT VARIANT 91
FT /note="R -> H (in dbSNP:rs10482721)"
FT /evidence="ECO:0000269|PubMed:11528528, ECO:0000269|Ref.4"
FT /id="VAR_012708"
FT VARIANT 100..104
FT /note="Missing (in LDS4)"
FT /evidence="ECO:0000269|PubMed:22772368"
FT /id="VAR_068931"
FT VARIANT 102..414
FT /note="Missing (in LDS4)"
FT /evidence="ECO:0000269|PubMed:22772371"
FT /id="VAR_080342"
FT VARIANT 207
FT /note="V -> L (in dbSNP:rs10482810)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_018923"
FT VARIANT 229..414
FT /note="Missing (in LDS4)"
FT /evidence="ECO:0000269|PubMed:22772371"
FT /id="VAR_080343"
FT VARIANT 299
FT /note="R -> W (in LDS4; dbSNP:rs863223792)"
FT /evidence="ECO:0000269|PubMed:22772368"
FT /id="VAR_068932"
FT VARIANT 302
FT /note="R -> C (in LDS4; dbSNP:rs869312903)"
FT /evidence="ECO:0000269|PubMed:22772368"
FT /id="VAR_068933"
FT VARIANT 320
FT /note="R -> C (probable disease-associated variant found in
FT a family with non-syndromic aortic disease;
FT dbSNP:rs1553303352)"
FT /evidence="ECO:0000269|PubMed:25046559"
FT /id="VAR_072740"
FT VARIANT 338
FT /note="P -> H (in LDS4; dbSNP:rs387907278)"
FT /evidence="ECO:0000269|PubMed:22772368"
FT /id="VAR_068934"
FT CONFLICT 32
FT /note="F -> L (in Ref. 8; AAA61162)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="Missing (in Ref. 3; AAA50405)"
FT /evidence="ECO:0000305"
FT HELIX 306..309
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 315..320
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:2TGI"
FT HELIX 326..330
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 339..342
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 345..347
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:2TGI"
FT HELIX 359..370
FT /evidence="ECO:0007829|PDB:2TGI"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 384..394
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 397..408
FT /evidence="ECO:0007829|PDB:2TGI"
FT STRAND 411..414
FT /evidence="ECO:0007829|PDB:2TGI"
SQ 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
