The domain within your query sequence starts at position 265 and ends at position 356; the E-value for the TGFB domain shown below is 5.78e-7.

CCRQEMYLDLQGMKWAENWILEPPGFLTYECVGSCLQLPESLTSRWPFLGPRQCVASEMT
SLPMIVSVKEGGRTRPQVVSLPNMRVQTCSCA

TGFB

Transforming growth factor-beta (TGF-beta) family

• SMART accession number: SM00204
• Description: Family members are active as disulphide-linked homo- or heterodimers. TGFB is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types.
• Interpro abstract (IPR001839):

  Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that controls proliferation, differentiation and other functions in many cell types. TGF-beta-1 is a peptide of 112 amino acid residues derived by proteolytic cleavage from the C-terminal of a precursor protein [ (PUBMED:8679613) ].

  A number of proteins are known to be related to TGF-beta-1 [ (PUBMED:1575734) (PUBMED:8199356) ]. Proteins from the TGF-beta family are only active as homo- or heterodimer; the two chains being linked by a single disulphide bond. From X-ray studies of TGF-beta-2 [ (PUBMED:1631557) ], it is known that all the other cysteines are involved in intrachain disulphide bonds. There are four disulphide bonds in the TGF-beta's and in inhibin beta chains, while the other members of this family lack the first bond.

  The regulatory cytokine TGFbeta exerts tumour-suppressive effects, but also modulates cell invasion and immune regulation [ (PUBMED:18662538) ]. Misregulation of the TGF-beta signalling pathway can result in tumour development.

• GO function: growth factor activity (GO:0008083)

There are 13842 TGFB domains in 13809 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Hoodless PA, Wrana JL
• Mechanism and function of signaling by the TGF beta superfamily.
• Curr Top Microbiol Immunol. 1998; 228: 235-72

• Padgett RW, Savage C, Das P
• Genetic and biochemical analysis of TGF beta signal transduction.
• Cytokine Growth Factor Rev. 1997; 8: 1-9

TGF beta-like ligands are involved in many different developmental processes that pattern a variety of tissues in invertebrates and vertebrates. In the last few years, rapid progress has been made toward elucidating the developmental roles of the TGF beta-like pathways and identifying the novel components involved in transducing their signals, particularly the newly discovered Smads. This rapid progress has been the result of a synergy between classical genetic approaches and biochemical approaches, and this combined approach is likely to propel future understanding of the signaling pathway used by TGF beta.

• Moses HL, Serra R
• Regulation of differentiation by TGF-beta.
• Curr Opin Genet Dev. 1996; 6: 581-6

Recent experiments in neural, skeletal, endothelial, and hematopoietic tissues have provided new insights into the way members of the transforming growth factor-beta (TGF-beta) superfamily regulate cellular differentiation. TGF-betas regulate the fate of multipotential stem cells instructively (in the neural crest) by regulating the expression or function of tissue-specific transcription factors, as well as selectively (in the mesenchyme) by regulating the expression of required growth factors and their receptors. During skeletal development, TGF-betas have unique functions and act sequentially to modulate chondrocyte and osteoblast differentiation. Responsiveness to TGF-betas changes as cells differentiate and evidence now suggests that changes in TGF-beta receptor profile may account for some of these differences. Drosophila and transgenic mouse models are now providing useful insights into mechanisms of TGF-beta action in vivo.

• Derynck R et al.
• Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells.
• Nature. 1985; 316: 701-5

The partial amino-acid sequence of purified human transforming growth factor-beta (TGF-beta) was used to identify a series of cDNA clones encoding the protein. The cDNA sequence indicates that the 112-amino acid monomeric form of the natural TGF-beta homodimer is derived proteolytically from a much longer precursor polypeptide which may be secreted. TGF-beta messenger RNA is synthesized in various normal and transformed cells.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the TGFB domain.

Protein	Disease
Muellerian-inhibiting factor (P03971) (SMART)	OMIM:600957: Persistent Mullerian duct syndrome, type I OMIM:261550:
Left-right determination factor 2 (O00292) (SMART)	OMIM:601877: Left-right axis malformation
Glial cell line-derived neurotrophic factor (P39905) (SMART)	OMIM:600837: Hirschsprung disease OMIM:142623:

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
30.64	map04350	TGF-beta signaling pathway
25.89	map04060	Cytokine-cytokine receptor interaction
9.98	map04340	Hedgehog signaling pathway
4.99	map05217	Basal cell carcinoma
4.75	map05210	Colorectal cancer
4.75	map05211	Renal cell carcinoma
4.75	map04110	Cell cycle
4.75	map04010	MAPK signaling pathway
4.75	map05212	Pancreatic cancer
4.75	map05220	Chronic myeloid leukemia

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with TGFB domain which could be assigned to a KEGG orthologous group, and not all proteins containing TGFB domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of TGFB domains in PDB

PDB code	Title
1agq	GLIAL CELL-DERIVED NEUROTROPHIC FACTOR FROM RAT
1bmp	BONE MORPHOGENETIC PROTEIN-7
1es7	COMPLEX BETWEEN BMP-2 AND TWO BMP RECEPTOR IA ECTODOMAINS
1kla	SOLUTION STRUCTURE OF TGF-B1, NMR, MODELS 1-17 OF 33 STRUCTURES
1klc	SOLUTION STRUCTURE OF TGF-B1, NMR, MINIMIZED AVERAGE STRUCTURE
1kld	SOLUTION STRUCTURE OF TGF-B1, NMR, MODELS 18-33 OF 33 STRUCTURES
1ktz	Crystal Structure of the Human TGF-beta Type II Receptor Extracellular Domain in Complex with TGF-beta3
1lx5	Crystal Structure of the BMP7/ActRII Extracellular Domain Complex
1lxi	Refinement of BMP7 crystal structure
1m4u	Crystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist Noggin
1nys	Crystal Structure of Activin A Bound to the ECD of ActRIIB P41
1nyu	Crystal Structure of Activin A Bound to the ECD of ActRIIB
1reu	Structure of the bone morphogenetic protein 2 mutant L51P
1rew	Structural refinement of the complex of bone morphogenetic protein 2 and its type IA receptor
1s4y	Crystal structure of the activin/actrIIb extracellular domain
1tfg	AN UNUSUAL FEATURE REVEALED BY THE CRYSTAL STRUCTURE AT 2.2 ANGSTROMS RESOLUTION OF HUMAN TRANSFORMING GROWTH FACTOR-BETA2
1tgj	HUMAN TRANSFORMING GROWTH FACTOR-BETA 3, CRYSTALLIZED FROM DIOXANE
1tgk	HUMAN TRANSFORMING GROWTH FACTOR BETA 3, CRYSTALLIZED FROM PEG 4000
1waq	Crystal structure of human Growth and Differentiation Factor 5 (GDF-5)
1zkz	Crystal Structure of BMP9
2arp	Activin A in complex with Fs12 fragment of follistatin
2arv	Structure of human Activin A
2ask	Structure of human Artemin
2b0u	The Structure of the Follistatin:Activin Complex
2bhk	Crystal structure of human growth and differentiation factor 5 (GDF5)
2gh0	Growth factor/receptor complex
2goo	Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD
2gyr	Crystal structure of human artemin
2gyz	Crystal structure of human artemin
2h62	Crystal structure of a ternary ligand-receptor complex of BMP-2
2h64	Crystal structure of a ternary ligand-receptor complex of BMP-2
2p6a	The structure of the Activin:Follistatin 315 complex
2pjy	Structural basis for cooperative assembly of the TGF-beta signaling complex
2qcq	Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)
2qcw	Crystal Structure of Bone Morphogenetic Protein-6 (BMP-6)
2qj9	Crystal structure analysis of BMP-2 in complex with BMPR-IA variant B1
2qja	Crystal structure analysis of BMP-2 in complex with BMPR-IA variant B12
2qjb	Crystal structure analysis of BMP-2 in complex with BMPR-IA variant IA/IB
2r52	Crystal structure analysis of Bone Morphogenetic Protein-6 (BMP-6)
2r53	Crystal structure analysis of Bone Morphogenetic Protein-6 variant B2 (B2-BMP-6)
2tgi	CRYSTAL STRUCTURE OF TRANSFORMING GROWTH FACTOR-BETA2: AN UNUSUAL FOLD FOR THE SUPERFAMILY
2v5e	The structure of the GDNF:Coreceptor complex: Insights into RET signalling and heparin binding.
3b4v	X-Ray structure of Activin in complex with FSTL3
3bk3	Crystal structure of the complex of BMP-2 and the first Von Willebrand domain type C of Crossveinless-2
3bmp	HUMAN BONE MORPHOGENETIC PROTEIN-2 (BMP-2)
3eo1	Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3
3evs	Crystal structure of the GDF-5:BMP receptor IB complex.
3fub	Crystal structure of GDNF-GFRalpha1 complex
3hh2	Crystal structure of the myostatin:follistatin 288 complex
3kfd	Ternary complex of TGF-b1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily
3qb4	Crystal structure of a TGF-beta ligand-receptor complex
3rjr	Crystal Structure of pro-TGF beta 1
3sek	Crystal Structure of the Myostatin:Follistatin-like 3 Complex
4fao	Specificity and Structure of a high affinity Activin-like 1 (ALK1) signaling complex
4kv5	4KV5
4kxz	4KXZ
4mid	Crystal Structure of Activin A/BMP2 chimera
4mpl	4MPL
4n1d	Nodal/BMP2 chimera NB250
4nt5	Crystal structure of human von Willebrand factor CTCK domain
4uhy	4UHY
4uhz	4UHZ
4ui0	4UI0
4ui1	4UI1
4ui2	4UI2
4ux8	4UX8
4ycg	4YCG
4yci	4YCI
5e4g	5E4G
5f3b	5F3B
5f3h	5F3H
5hk5	5HK5
5hly	5HLY
5hlz	5HLZ

Links (links to other resources describing this domain)

• INTERPRO: IPR001839
• PFAM: TGF-beta
• PROSITE: TGFB_DOMAIN