P01137 (TGFB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transforming growth factor beta-1
Short name=TGF-beta-1

Cleaved into the following chain:

1. Latency-associated peptide
   Short name=LAP

Gene names

Name:	TGFB1
Synonyms:	TGFB

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	390 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	Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts.
Subunit structure	Homodimer; disulfide-linked, or heterodimer with TGFB2 By similarity. Secreted and stored as a biologically inactive form in the extracellular matrix in a 290 kDa complex (large latent TGF-beta1 complex) containing the TGFB1 homodimer, the latency-associated peptide (LAP), and the latent TGFB1 binding protein-1 (LTBP1). The complex without LTBP1 is known as the'small latent TGF-beta1 complex'. Dissociation of the TGFB1 from LAP is required for growth factor activation and biological activity. Release of the large latent TGF-beta1 complex from the extracellular matrix is carried out by the matrix metalloproteinase MMP3 By similarity. May interact with THSD4; this interaction may lead to sequestration by FBN1 microfibril assembly and attenuation of TGFB signaling. Interacts with the serine proteases, HTRA1 and HTRA3: the interaction with either inhibits TGFB1-mediated signaling. The HTRA protease activity is required for this inhibition By similarity. Latency-associated peptide interacts with NREP; the interaction results in a decrease in TGFB1 autoinduction By similarity. Interacts with CD109, DPT and ASPN. Ref.12 Ref.15 Ref.17
Subcellular location	Secreted › extracellular space › extracellular matrix Ref.17.
Tissue specificity	Highly expressed in bone. Abundantly expressed in articular cartilage and chondrocytes and is increased in osteoarthritis (OA). Co-localizes with ASPN in chondrocytes within OA lesions of articular cartilage. Ref.13 Ref.17
Induction	Activated in vitro at pH below 3.5 and over 12.5.
Domain	The 'straitjacket' and 'arm' domains encircle the growth factor monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104. Activation of TGF-beta1 requires the binding of integrin alpha-V to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-beta binding proteins. The sheer physical force unfastens the straitjacket and releases the active growth factor dimer By similarity.
Post-translational modification	Glycosylated. The precursor is cleaved into mature TGF-beta-1 and LAP, which remains non-covalently linked to mature TGF-beta-1 rendering it inactive.
Polymorphism	In post-menopausal Japanese women, the frequency of Leu-10 is higher in subjects with osteoporosis than in controls.
Involvement in disease	Camurati-Engelmann disease (CE) [MIM:131300]: Autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. The disease typically presents in early childhood with pain, muscular weakness and waddling gait, and in some cases other features such as exophthalmos, facial paralysis, hearing difficulties and loss of vision. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.24 Ref.26 Ref.27 Ref.28
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ATP biosynthetic process Inferred from direct assay PubMed 10513816. Source: BHF-UCL MAPK cascade Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB SMAD protein complex assembly Inferred from direct assay PubMed 17438144. Source: BHF-UCL SMAD protein import into nucleus Inferred from direct assay PubMed 15334054. Source: BHF-UCL T cell homeostasis Inferred from electronic annotation. Source: Compara active induction of host immune response by virus Traceable author statement. Source: Reactome adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains Inferred from electronic annotation. Source: Compara aging Inferred from electronic annotation. Source: Compara branch elongation involved in mammary gland duct branching Inferred from electronic annotation. Source: Compara cell cycle arrest Inferred from direct assay PubMed 14555988. Source: BHF-UCL cell death 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 cellular calcium ion homeostasis Inferred from electronic annotation. Source: Compara cellular response to dexamethasone stimulus Inferred from electronic annotation. Source: Compara cellular response to organic cyclic compound Inferred from direct assay PubMed 21147091. Source: UniProtKB chondrocyte differentiation Inferred from direct assay PubMed 15040835. Source: UniProtKB common-partner SMAD protein phosphorylation Inferred from direct assay PubMed 20573232. Source: UniProtKB connective tissue replacement involved in inflammatory response wound healing Traceable author statement PubMed 9639571. Source: BHF-UCL defense response to fungus, incompatible interaction Inferred from electronic annotation. Source: Compara digestive tract development Inferred from electronic annotation. Source: Compara embryo development Inferred from electronic annotation. Source: Compara endoderm development Inferred from electronic annotation. Source: Compara epidermal growth factor receptor signaling pathway Inferred from direct assay PubMed 18625725. Source: BHF-UCL epithelial to mesenchymal transition Inferred from electronic annotation. Source: Compara evasion or tolerance of host defenses by virus Inferred from direct assay PubMed 15334054. Source: BHF-UCL extracellular matrix assembly Inferred from direct assay PubMed 19734317. Source: BHF-UCL face morphogenesis Inferred from electronic annotation. Source: Compara female pregnancy Inferred from electronic annotation. Source: Compara frontal suture morphogenesis Inferred from electronic annotation. Source: Compara germ cell migration Inferred from electronic annotation. Source: Compara hematopoietic progenitor cell differentiation Inferred from direct assay PubMed 15451575. Source: UniProtKB hyaluronan catabolic process Inferred from direct assay PubMed 17324121. Source: UniProtKB induction of apoptosis Inferred from direct assay PubMed 15334054. Source: BHF-UCL inner ear development Inferred from electronic annotation. Source: Compara lens fiber cell differentiation Inferred from electronic annotation. Source: Compara lipopolysaccharide-mediated signaling pathway Inferred from direct assay PubMed 21147091. Source: UniProtKB lymph node development Inferred from sequence or structural similarity. Source: UniProtKB macrophage derived foam cell differentiation Inferred by curator PubMed 15219857. Source: BHF-UCL mammary gland branching involved in thelarche Inferred from electronic annotation. Source: Compara mitotic cell cycle checkpoint Inferred from direct assay PubMed 15334054. Source: BHF-UCL mononuclear cell proliferation Inferred from electronic annotation. Source: Compara myelination Inferred from electronic annotation. Source: Compara myeloid dendritic cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of DNA replication Inferred from mutant phenotype PubMed 11158066. Source: BHF-UCL negative regulation of T cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of blood vessel endothelial cell migration Inferred from direct assay PubMed 18555217. Source: BHF-UCL negative regulation of cell growth Inferred from direct assay PubMed 15334054. Source: BHF-UCL negative regulation of cell-cell adhesion Inferred from direct assay PubMed 18593713. Source: BHF-UCL negative regulation of epithelial cell proliferation Inferred from direct assay PubMed 9950587. Source: BHF-UCL negative regulation of fat cell differentiation Inferred from direct assay PubMed 15040835. Source: UniProtKB negative regulation of hyaluronan biosynthetic process Inferred from direct assay PubMed 17324121. Source: UniProtKB negative regulation of immune response Inferred from electronic annotation. Source: Compara negative regulation of macrophage cytokine production Inferred from direct assay PubMed 20875417. Source: DFLAT negative regulation of mitotic cell cycle Inferred from direct assay PubMed 14555988. Source: BHF-UCL negative regulation of myoblast differentiation Inferred from direct assay PubMed 9770491. Source: UniProtKB negative regulation of neuroblast proliferation Inferred from electronic annotation. Source: Compara negative regulation of ossification Inferred from electronic annotation. Source: Compara negative regulation of phagocytosis Inferred from electronic annotation. Source: Compara negative regulation of protein phosphorylation Inferred from direct assay PubMed 8053900. Source: BHF-UCL negative regulation of release of sequestered calcium ion into cytosol Inferred from electronic annotation. Source: Compara negative regulation of skeletal muscle tissue development Inferred from direct assay PubMed 9770491. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 18832382. Source: UniProtKB negative regulation of transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome organ regeneration Inferred from electronic annotation. Source: Compara ossification involved in bone remodeling Inferred from expression pattern PubMed 17401695. Source: BHF-UCL pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 11157754PubMed 17999987PubMed 18453574. Source: BHF-UCL platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome positive regulation of MAP kinase activity Inferred from direct assay PubMed 18625725. Source: BHF-UCL positive regulation of NAD+ ADP-ribosyltransferase activity Inferred from direct assay PubMed 22073128. Source: BHF-UCL positive regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of SMAD protein import into nucleus Inferred from direct assay PubMed 19366691PubMed 9389648. Source: BHF-UCL positive regulation of blood vessel endothelial cell migration Inferred from direct assay PubMed 18555217. Source: BHF-UCL positive regulation of bone mineralization Inferred from expression pattern PubMed 17401695. Source: BHF-UCL positive regulation of branching involved in ureteric bud morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of cell cycle arrest Inferred from electronic annotation. Source: Compara positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Inferred from direct assay PubMed 10513816. Source: BHF-UCL positive regulation of chemotaxis Inferred from direct assay PubMed 18555217. Source: BHF-UCL positive regulation of collagen biosynthetic process Inferred from direct assay PubMed 19734317. Source: BHF-UCL positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of epithelial to mesenchymal transition Inferred from direct assay PubMed 17999987PubMed 18505915. Source: BHF-UCL positive regulation of exit from mitosis Inferred from electronic annotation. Source: Compara positive regulation of fibroblast migration Inferred from direct assay PubMed 18555217. Source: BHF-UCL positive regulation of histone acetylation Inferred from electronic annotation. Source: Compara positive regulation of histone deacetylation Inferred from electronic annotation. Source: Compara positive regulation of interleukin-17 production Inferred from direct assay PubMed 18453574. Source: BHF-UCL positive regulation of isotype switching to IgA isotypes Inferred from direct assay PubMed 14988498. Source: MGI positive regulation of odontogenesis Inferred from electronic annotation. Source: Compara positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 19736306PubMed 9389648. Source: BHF-UCL positive regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 18625725PubMed 19736306. Source: BHF-UCL positive regulation of peptidyl-threonine phosphorylation Inferred from direct assay PubMed 18625725PubMed 19736306. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase activity Inferred from direct assay PubMed 18625725. Source: BHF-UCL positive regulation of protein complex assembly Inferred from direct assay PubMed 19366691. Source: BHF-UCL positive regulation of protein dephosphorylation Inferred from direct assay PubMed 14555988. Source: BHF-UCL positive regulation of protein kinase B signaling cascade Inferred from direct assay PubMed 18625725. Source: BHF-UCL positive regulation of protein secretion Inferred from direct assay PubMed 18505915. Source: BHF-UCL positive regulation of smooth muscle cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of superoxide anion generation Inferred from direct assay PubMed 22073128. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 18832382. Source: UniProtKB positive regulation of transcription regulatory region DNA binding Inferred from direct assay PubMed 22073128. Source: BHF-UCL positive regulation vascular endothelial growth factor production Traceable author statement PubMed 19506300. Source: BHF-UCL protein export from nucleus Inferred from direct assay PubMed 18588859PubMed 9770491. Source: UniProtKB protein import into nucleus, translocation Inferred from direct assay PubMed 21390327. Source: UniProtKB protein kinase B signaling cascade Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB receptor catabolic process Inferred from direct assay PubMed 17878231. Source: BHF-UCL regulation of branching involved in mammary gland duct morphogenesis Inferred from electronic annotation. Source: Compara regulation of cartilage development Inferred from electronic annotation. Source: Compara regulation of sodium ion transport Inferred from electronic annotation. Source: Compara regulatory T cell differentiation Inferred from electronic annotation. Source: Compara response to cholesterol Inferred from direct assay PubMed 17878231. Source: BHF-UCL response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from direct assay PubMed 18039789. Source: BHF-UCL response to glucose stimulus Inferred from electronic annotation. Source: Compara response to hypoxia 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 response to radiation Inferred from electronic annotation. Source: Compara response to vitamin D Inferred from electronic annotation. Source: Compara salivary gland morphogenesis Inferred from expression pattern PubMed 18080134. Source: BHF-UCL tolerance induction to self antigen Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 11157754PubMed 9389648. Source: BHF-UCL ureteric bud development Inferred from electronic annotation. Source: Compara viral infectious cycle Traceable author statement. Source: Reactome
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome axon Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 19734317. Source: BHF-UCL neuronal cell body Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay PubMed 18040277. Source: BHF-UCL platelet alpha granule lumen Traceable author statement. Source: Reactome proteinaceous extracellular matrix Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	eukaryotic cell surface binding Inferred from mutant phenotype PubMed 19366691. Source: BHF-UCL type II transforming growth factor beta receptor binding Inferred from direct assay PubMed 11157754. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	2	EBI-779636,EBI-77613
ENG	P17813	2	EBI-779636,EBI-2834630
TGFBR1	P36897	2	EBI-779636,EBI-1027557
TGFBR2	P37173	4	EBI-779636,EBI-296151
TGFBR3	Q03167	2	EBI-779636,EBI-2852679
THBS1	P07996	2	EBI-779636,EBI-2530274

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Ref.10

Chain

30 – 278

249

Latency-associated peptide

PRO_0000033762

Chain

279 – 390

112

Transforming growth factor beta-1

PRO_0000033763

Regions

Region

30 – 74

45

Straightjacket domain By similarity

Region

75 – 271

197

Arm domain By similarity

Motif

244 – 246

3

Cell attachment site Potential

Amino acid modifications

Glycosylation

82

1

N-linked (GlcNAc...) Ref.14 Ref.16

Glycosylation

136

1

N-linked (GlcNAc...) By similarity

Glycosylation

176

1

N-linked (GlcNAc...) By similarity

Disulfide bond

33

Interchain (with C-1359 or C-1384 in LTBP1); in inactive form By similarity

Disulfide bond

223

Interchain (with C-225) By similarity

Disulfide bond

225

Interchain (with C-223) By similarity

Disulfide bond

285 ↔ 294

Disulfide bond

293 ↔ 356

Disulfide bond

322 ↔ 387

Disulfide bond

326 ↔ 389

Disulfide bond

355

Interchain

Natural variations

Natural variant

10

1

L → P Associated with higher bone mineral density and lower frequency of vertebral fractures in Japanese post-menopausal women. Ref.2 Ref.22 Ref.25
Corresponds to variant rs1800470 [ dbSNP | Ensembl ].

VAR_016171

Natural variant

25

1

R → P. Ref.2
Corresponds to variant rs1800471 [ dbSNP | Ensembl ].

VAR_016172

Natural variant

81

1

Y → H in CE; leads to TGF-beta-1 intracellular accumulation. Ref.24 Ref.26

VAR_017607

Natural variant

218

1

R → C in CE; higher levels of active TGF-beta-1 in the culture medium; enhances osteoclast formation in vitro. Ref.23 Ref.24 Ref.26 Ref.27

VAR_017608

Natural variant

218

1

R → H in CE. Ref.23

VAR_017609

Natural variant

222

1

H → D in CE; sporadic case; higher levels of active TGF-beta-1 in the culture medium. Ref.26

VAR_017610

Natural variant

223

1

C → G in CE. Ref.28

VAR_067303

Natural variant

223

1

C → R in CE. Ref.28

VAR_067304

Natural variant

225

1

C → R in CE; higher levels of active TGF-beta-1 in the culture medium. Ref.23 Ref.24 Ref.26

VAR_017611

Natural variant

263

1

T → I.
Corresponds to variant rs1800472 [ dbSNP | Ensembl ].

VAR_016173

Experimental info

Sequence conflict

159

1

R → RR in CAA26580. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

390

Helix Strand Turn

Details...

Helix

282 – 285

4

Beta strand

291 – 296

6

Beta strand

299 – 301

3

Helix

302 – 306

5

Beta strand

311 – 313

3

Beta strand

315 – 318

4

Beta strand

321 – 324

4

Beta strand

330 – 332

3

Helix

335 – 346

12

Beta strand

347 – 349

3

Beta strand

356 – 370

15

Beta strand

373 – 389

17

Sequences

	Sequence		Length	Mass (Da)
	P01137 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: 75391614250288FE	FASTA	390	44,341
	10 20 30 40 50 60 MPPSGLRLLL LLLPLLWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR GQILSKLRLA 70 80 90 100 110 120 SPPSQGEVPP GPLPEAVLAL YNSTRDRVAG ESAEPEPEPE ADYYAKEVTR VLMVETHNEI 130 140 150 160 170 180 YDKFKQSTHS IYMFFNTSEL REAVPEPVLL SRAELRLLRL KLKVEQHVEL YQKYSNNSWR 190 200 210 220 230 240 YLSNRLLAPS DSPEWLSFDV TGVVRQWLSR GGEIEGFRLS AHCSCDSRDN TLQVDINGFT 250 260 270 280 290 300 TGRRGDLATI HGMNRPFLLL MATPLERAQH LQSSRHRRAL DTNYCFSSTE KNCCVRQLYI 310 320 330 340 350 360 DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA SAAPCCVPQA 370 380 390 LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Intron-exon structure of the human transforming growth factor-beta precursor gene." Derynck R., Rhee L., Chen E.Y., van Tilburg A. Nucleic Acids Res. 15:3188-3189(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells." Derynck R., Jarrett J.A., Chen E.Y., Eaton D.H., Bell J.R., Assoian R.K., Roberts A.B., Sporn M.B., Goeddel D.V. Nature 316:701-705(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PRO-10 AND PRO-25.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Duodenum and Eye.
[7]	"Cloning and expression of the gene for human transforming growth factor-beta in Escherichia coli." Urushizaki Y., Niitsu Y., Terui T., Koshida Y., Mahara K., Kohgo Y., Urushizaki I., Takahashi Y., Ito H. Tumor Res. 22:41-55(1987) Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 279-390. Tissue: Carcinoma.
[8]	"Recombinant human transforming growth factor-beta 1: expression by Chinese hamster ovary cells, isolation, and characterization." Bourdrel L., Lin C.-H., Lauren S.L., Elmore R.H., Sugarman B.J., Hu S., Westcott K.R. Protein Expr. Purif. 4:130-140(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 279-329. Tissue: Urinary bladder carcinoma.
[9]	"Cellular receptors for type beta transforming growth factor. Ligand binding and affinity labeling in human and rodent cell lines." Massague J., Like B. J. Biol. Chem. 260:2636-2645(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 279-301.
[10]	"Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization." Miyazono K., Hellman U., Wernstedt C., Heldin C.H. J. Biol. Chem. 263:6407-6415(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 30-42 AND 279-290, CHARACTERIZATION.
[11]	"Latent transforming growth factor-beta: structural features and mechanisms of activation." Munger J.S., Harpel J.G., Gleizes P.E., Mazzieri R., Nunes I., Rifkin D.B. Kidney Int. 51:1376-1382(1997) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"Dermatopontin interacts with transforming growth factor beta and enhances its biological activity." Okamoto O., Fujiwara S., Abe M., Sato Y. Biochem. J. 337:537-541(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DPT.
[13]	"Differential gene expression of cultured human osteoblasts." Shur I., Lokiec F., Bleiberg I., Benayahu D. J. Cell. Biochem. 83:547-553(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[14]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-82, MASS SPECTROMETRY. Tissue: Plasma.
[15]	"Identification of CD109 as part of the TGF-beta receptor system in human keratinocytes." Finnson K.W., Tam B.Y.Y., Liu K., Marcoux A., Lepage P., Roy S., Bizet A.A., Philip A. FASEB J. 20:1525-1527(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD109.
[16]	"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach." Lewandrowski U., Moebius J., Walter U., Sickmann A. Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-82, MASS SPECTROMETRY. Tissue: Platelet.
[17]	"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH ASPN.
[18]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"Transforming growth factor beta 1: NMR signal assignments of the recombinant protein expressed and isotopically enriched using Chinese hamster ovary cells." Archer S.J., Bax A., Roberts A.B., Sporn M.B., Ogawa Y., Piez K.A., Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., Torchia D.A. Biochemistry 32:1152-1163(1993) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 279-390.
[20]	"Transforming growth factor beta 1: secondary structure as determined by heteronuclear magnetic resonance spectroscopy." Archer S.J., Bax A., Roberts A.B., Sporn M.B., Ogawa Y., Piez K.A., Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., Torchia D.A. Biochemistry 32:1164-1171(1993) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 279-390.
[21]	"Transforming growth factor beta 1: three-dimensional structure in solution and comparison with the X-ray structure of transforming growth factor beta 2." Hinck A.P., Archer S.J., Qian S.W., Roberts A.B., Sporn M.B., Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., Torchia D.A. Biochemistry 35:8517-8534(1996) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 279-390.
[22]	"Association of a polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women." Yamada Y., Miyauchi A., Goto J., Takagi Y., Okuizumi H., Kanematsu M., Hase M., Takai H., Harada A., Ikeda K. J. Bone Miner. Res. 13:1569-1576(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PRO-10.
[23]	"Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease." Kinoshita A., Saito T., Tomita H., Makita Y., Yoshida K., Ghadami M., Yamada K., Kondo S., Ikegawa S., Nishimura G., Fukushima Y., Nakagomi T., Saito H., Sugimoto T., Kamegaya M., Hisa K., Murray J.C., Taniguchi N., Niikawa N., Yoshiura K. Nat. Genet. 26:19-20(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CE CYS-218; HIS-218 AND ARG-225.
[24]	"Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease." Janssens K., Gershoni-Baruch R., Guanabens N., Migone N., Ralston S., Bonduelle M., Lissens W., Van Maldergem L., Vanhoenacker F., Verbruggen L., Van Hul W. Nat. Genet. 26:273-275(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CE HIS-81; CYS-218 AND ARG-225.
[25]	"A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types of variations in genes for transforming growth factor-beta1 (TGF-beta1) and its signaling pathway." Watanabe Y., Kinoshita A., Yamada T., Ohta T., Kishino T., Matsumoto N., Ishikawa M., Niikawa N., Yoshiura K. J. Hum. Genet. 47:478-483(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PRO-10.
[26]	"Transforming growth factor-beta-1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein." Janssens K., ten Dijke P., Ralston S.H., Bergmann C., Van Hul W. J. Biol. Chem. 278:7718-7724(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CE HIS-81; CYS-218; ASP-222 AND ARG-225.
[27]	"A mutation affecting the latency-associated peptide of TGFbeta1 in Camurati-Engelmann disease enhances osteoclast formation in vitro." McGowan N.W., MacPherson H., Janssens K., Van Hul W., Frith J.C., Fraser W.D., Ralston S.H., Helfrich M.H. J. Clin. Endocrinol. Metab. 88:3321-3326(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT CE CYS-218.
[28]	"TGFB1 mutations in four new families with Camurati-Engelmann disease: confirmation of independently arising LAP-domain-specific mutations." Kinoshita A., Fukumaki Y., Shirahama S., Miyahara A., Nishimura G., Haga N., Namba A., Ueda H., Hayashi H., Ikegawa S., Seidel J., Niikawa N., Yoshiura K. Am. J. Med. Genet. 127A:104-107(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CE GLY-223 AND ARG-223.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

TGF beta-1 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X05839 , X05840, X05843, X05844, X05849, X05850 Genomic DNA. Translation: CAA29283.1.
X02812 mRNA. Translation: CAA26580.1.
BT007245 mRNA. Translation: AAP35909.1.
AK291907 mRNA. Translation: BAF84596.1.
CH471126 Genomic DNA. Translation: EAW57032.1.
BC001180 mRNA. Translation: AAH01180.1.
BC000125 mRNA. Translation: AAH00125.1.
BC022242 mRNA. Translation: AAH22242.1.
M38449 mRNA. Translation: AAA36735.1.

IPI

IPI00000075.

PIR

WFHU2. A27513.

RefSeq

NP_000651.3. NM_000660.4.

UniGene

Hs.645227.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KLA	NMR	-	A/B	279-390	[»]
1KLC	NMR	-	A/B	279-390	[»]
1KLD	NMR	-	A/B	279-390	[»]
3KFD	X-ray	3.00	A/B/C/D	279-390	[»]

ProteinModelPortal

P01137.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5934N.

IntAct

P01137. 10 interactions.

MINT

MINT-6806111.

STRING

9606.ENSP00000221930.

PTM databases

PhosphoSite

P01137.

Polymorphism databases

DMDM

135674.

2D gel databases

OGP

P01137.

Proteomic databases

PaxDb

P01137.

PRIDE

P01137.

Protocols and materials databases

DNASU

7040.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000221930; ENSP00000221930; ENSG00000105329.

GeneID

7040.

KEGG

hsa:7040.

UCSC

uc002oqh.2. human.

Organism-specific databases

CTD

7040.

GeneCards

GC19M041837.

H-InvDB

HIX0015152.

HGNC

HGNC:11766. TGFB1.

HPA

CAB000361.

MIM

131300. phenotype.
190180. gene.

neXtProt

NX_P01137.

Orphanet

1328. Camurati-Engelmann disease.
586. Cystic fibrosis.

PharmGKB

PA350.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG279949.

HOGENOM

HOG000290198.

HOVERGEN

HBG074115.

InParanoid

P01137.

KO

K13375.

OrthoDB

EOG4NKBVP.

Enzyme and pathway databases

Pathway_Interaction_DB

glypican_1pathway. Glypican 1 network.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il27pathway. IL27-mediated signaling events.
rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_604. Hemostasis.

SignaLink

P01137.

Gene expression databases

ArrayExpress

P01137.

Bgee

P01137.

CleanEx

HS_TGFB1.

Genevestigator

P01137.

GermOnline

ENSG00000105329. Homo sapiens.

Family and domain databases

InterPro

IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR016319. TGF-beta.
IPR015615. TGF-beta-rel.
IPR003939. TGFb1.
IPR017948. TGFb_CS.
[Graphical view]

PANTHER

PTHR11848. PTHR11848. 1 hit.

Pfam

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

PIRSF

PIRSF001787. TGF-beta. 1 hit.

PRINTS

PR01423. TGFBETA.
PR01424. TGFBETA1.

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

BindingDB

P01137.

ChEMBL

CHEMBL1795178.

ChiTaRS

TGFB1. human.

DrugBank

DB00070. Hyaluronidase.

EvolutionaryTrace

P01137.

GenomeRNAi

7040.

NextBio

27507.

SOURCE

Search...

Entry information

Entry name

TGFB1_HUMAN

Accession

Primary (citable) accession number: P01137
Secondary accession number(s): A8K792, Q9UCG4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 1, 1991
Last modified:	May 29, 2013
This is version 183 of the entry and version 2 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.