P04202 (TGFB1_MOUSE) 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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. Interacts with CD109 and DPT. Interacts with ASPN 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. Latency-associated peptide interacts with NREP; the interaction results in a decrease in TGFB1 autoinduction. Ref.5 Ref.6 Ref.7 Ref.8
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
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 By similarity. The precursor is cleaved into mature TGF-beta-1 and LAP, which remains non-covalently linked to mature TGF-beta-1 rendering it inactive By similarity.
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Domain	Signal
Molecular function	Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB MAPK cascade Inferred from sequence or structural similarity. Source: UniProtKB SMAD protein complex assembly Inferred from sequence or structural similarity. Source: UniProtKB SMAD protein import into nucleus Inferred from sequence or structural similarity. Source: UniProtKB T cell homeostasis Inferred from mutant phenotype PubMed 17481928. Source: MGI adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains Inferred from direct assay PubMed 19501566. Source: BHF-UCL aging Inferred from electronic annotation. Source: Compara branch elongation involved in mammary gland duct branching Inferred from mutant phenotype PubMed 18614704. Source: MGI cell cycle arrest Inferred from sequence or structural similarity. Source: UniProtKB cell death Inferred from mutant phenotype PubMed 1436033PubMed 8421714. Source: MGI cell growth Inferred from electronic annotation. Source: InterPro cell-cell junction organization Inferred from sequence or structural similarity. Source: UniProtKB cellular calcium ion homeostasis Inferred from mutant phenotype PubMed 12646629. Source: MGI cellular response to dexamethasone stimulus Inferred from electronic annotation. Source: Compara cellular response to organic cyclic compound Inferred from sequence or structural similarity. Source: UniProtKB chondrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB common-partner SMAD protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB 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 direct assay PubMed 9921650. Source: MGI epidermal growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB epithelial to mesenchymal transition Inferred from electronic annotation. Source: Compara evasion or tolerance of host defenses by virus Inferred from sequence or structural similarity. Source: UniProtKB extracellular matrix assembly Inferred from direct assay PubMed 19734317. Source: BHF-UCL face morphogenesis Inferred from expression pattern PubMed 18498113. Source: UniProtKB female pregnancy Inferred from electronic annotation. Source: Compara frontal suture morphogenesis Inferred from electronic annotation. Source: Compara germ cell migration Inferred from direct assay PubMed 15993878. Source: MGI hematopoietic progenitor cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB hyaluronan catabolic process Inferred from sequence or structural similarity. Source: UniProtKB induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB inflammatory response Inferred from mutant phenotype PubMed 1436033PubMed 8421714. Source: MGI inner ear development Inferred from electronic annotation. Source: Compara lens fiber cell differentiation Inferred from mutant phenotype PubMed 17215516. Source: MGI lipopolysaccharide-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB lymph node development Inferred from mutant phenotype PubMed 1436033. Source: MGI mammary gland branching involved in thelarche Inferred from mutant phenotype PubMed 18614704. Source: MGI mitotic cell cycle checkpoint Inferred from sequence or structural similarity. Source: UniProtKB mononuclear cell proliferation Inferred from mutant phenotype PubMed 17481928. Source: MGI myelination Inferred from electronic annotation. Source: Compara myeloid dendritic cell differentiation Inferred from mutant phenotype PubMed 17938236. Source: MGI negative regulation of DNA replication Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of T cell proliferation Inferred from mutant phenotype PubMed 17481928. Source: MGI negative regulation of blood vessel endothelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from direct assay PubMed 12773577. Source: BHF-UCL negative regulation of cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of fat cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of hyaluronan biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of immune response Inferred from electronic annotation. Source: Compara negative regulation of macrophage cytokine production Inferred from electronic annotation. Source: Compara negative regulation of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of myoblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of neuroblast proliferation Inferred from electronic annotation. Source: Compara negative regulation of ossification Inferred from direct assay PubMed 15820682. Source: MGI negative regulation of phagocytosis Inferred from electronic annotation. Source: Compara negative regulation of protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB 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 sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 15657445. Source: MGI organ morphogenesis Traceable author statement PubMed 8421714. Source: MGI organ regeneration Inferred from electronic annotation. Source: Compara ossification involved in bone remodeling Inferred from electronic annotation. Source: Compara pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 12773577. Source: BHF-UCL positive regulation of MAP kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of NAD+ ADP-ribosyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of SMAD protein import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of blood vessel endothelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of bone mineralization Inferred from electronic annotation. Source: Compara positive regulation of branching involved in ureteric bud morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of cell cycle arrest Inferred from direct assay PubMed 19056892. Source: MGI positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Inferred from direct assay PubMed 15604101. Source: MGI positive regulation of chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB 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 18794329. Source: MGI positive regulation of exit from mitosis Inferred from electronic annotation. Source: Compara positive regulation of fibroblast migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of histone acetylation Inferred from direct assay PubMed 15990875. Source: MGI positive regulation of histone deacetylation Inferred from direct assay PubMed 15657445PubMed 15990875. Source: MGI positive regulation of interleukin-17 production Inferred from direct assay PubMed 19501566. Source: BHF-UCL positive regulation of isotype switching to IgA isotypes Inferred from sequence orthology PubMed 14988498. Source: MGI positive regulation of odontogenesis Inferred from direct assay PubMed 7848824. Source: MGI positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of peptidyl-threonine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein complex assembly Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of smooth muscle cell differentiation Inferred from sequence orthology PubMed 8616889. Source: MGI positive regulation of superoxide anion generation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 15990875PubMed 17951031PubMed 18997793. Source: MGI positive regulation of transcription regulatory region DNA binding Inferred from sequence or structural similarity. Source: UniProtKB protein export from nucleus Inferred from sequence or structural similarity. Source: UniProtKB protein import into nucleus, translocation Inferred from sequence or structural similarity. Source: UniProtKB protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB receptor catabolic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of branching involved in mammary gland duct morphogenesis Inferred from genetic interaction PubMed 17898001. Source: MGI regulation of cartilage development Inferred from direct assay PubMed 20501701. Source: MGI regulation of protein import into nucleus Inferred from direct assay PubMed 11799106. Source: MGI regulation of sodium ion transport Inferred from direct assay PubMed 16941024. Source: MGI regulation of transforming growth factor beta receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulatory T cell differentiation Inferred from direct assay PubMed 15100250. Source: MGI response to cholesterol Inferred from sequence or structural similarity. Source: UniProtKB response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from sequence or structural similarity. Source: UniProtKB 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 sequence or structural similarity. Source: UniProtKB response to radiation Inferred from electronic annotation. Source: Compara response to vitamin D Inferred from electronic annotation. Source: Compara salivary gland morphogenesis Inferred from electronic annotation. Source: Compara skeletal muscle tissue development Traceable author statement PubMed 1436033. Source: MGI tolerance induction to self antigen Inferred from mutant phenotype PubMed 17481928. Source: MGI transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 12208849PubMed 8429908. Source: MGI ureteric bud development Inferred from expression pattern PubMed 14656760. Source: UniProtKB wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB extracellular space Inferred from direct assay PubMed 19734317. Source: BHF-UCL microvillus Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara nucleus Inferred from sequence or structural similarity. Source: UniProtKB proteinaceous extracellular matrix Inferred from direct assay PubMed 12208849PubMed 9008713. Source: MGI secretory granule Inferred from electronic annotation. Source: Compara
Molecular_function	eukaryotic cell surface binding Inferred from sequence or structural similarity. Source: UniProtKB type II transforming growth factor beta receptor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	By similarity
	Chain	30 – 278	249	Latency-associated peptide		PRO_0000033766
	Chain	279 – 390	112	Transforming growth factor beta-1		PRO_0000033767
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...) By similarity
	Glycosylation	136	1	N-linked (GlcNAc...) By similarity
	Glycosylation	176	1	N-linked (GlcNAc...) By similarity
	Disulfide bond	33		Interchain (with C-1350 or C-1375 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		By similarity
	Disulfide bond	293 ↔ 356		By similarity
	Disulfide bond	322 ↔ 387		By similarity
	Disulfide bond	326 ↔ 389		By similarity
	Disulfide bond	355		Interchain By similarity

Sequences

	Sequence		Length	Mass (Da)
	P04202 [UniParc]. Last modified March 20, 1987. Version 1. Checksum: 4381A51B711D689E	FASTA	390	44,310
	10 20 30 40 50 60 MPPSGLRLLP LLLPLPWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR GQILSKLRLA 70 80 90 100 110 120 SPPSQGEVPP GPLPEAVLAL YNSTRDRVAG ESADPEPEPE ADYYAKEVTR VLMVDRNNAI 130 140 150 160 170 180 YEKTKDISHS IYMFFNTSDI REAVPEPPLL SRAELRLQRL KSSVEQHVEL YQKYSNNSWR 190 200 210 220 230 240 YLGNRLLTPT DTPEWLSFDV TGVVRQWLNQ GDGIQGFRFS AHCSCDSKDN KLHVEINGIS 250 260 270 280 290 300 PKRRGDLGTI HDMNRPFLLL MATPLERAQH LHSSRHRRAL DTNYCFSSTE KNCCVRQLYI 310 320 330 340 350 360 DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA SASPCCVPQA 370 380 390 LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The murine transforming growth factor-beta precursor." Derynck R., Jarrett J.A., Chen E.Y., Goeddel D.V. J. Biol. Chem. 261:4377-4379(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular organization of the gene encoding murine transforming growth factor beta 1." Guron C., Sudarshan C., Raghow R. Gene 165:325-326(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: BALB/c.
[3]	"Transforming growth factor-beta 1 sequence and expression: no difference between NOD/Lt and C57Bl/6 mouse strains." Poirot L., Benoist C., Mathis D. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6 and NOD/LT. Tissue: Spleen.
[4]	"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]. Strain: FVB/N. Tissue: Mammary tumor.
[5]	"P311 binds to the latency associated protein and downregulates the expression of TGF-beta1 and TGF-beta2." Paliwal S., Shi J., Dhru U., Zhou Y., Schuger L. Biochem. Biophys. Res. Commun. 315:1104-1109(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NREP.
[6]	"Developmentally regulated expression of mouse HtrA3 and its role as an inhibitor of TGF-beta signaling." Tocharus J., Tsuchiya A., Kajikawa M., Ueta Y., Oka C., Kawaichi M. Dev. Growth Differ. 46:257-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HTRA3.
[7]	"HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins." Oka C., Tsujimoto R., Kajikawa M., Koshiba-Takeuchi K., Ina J., Yano M., Tsuchiya A., Ueta Y., Soma A., Kanda H., Matsumoto M., Kawaichi M. Development 131:1041-1053(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HTRA1.
[8]	"ADAMTSL6beta protein rescues fibrillin-1 microfibril disorder in a Marfan syndrome mouse model through the promotion of fibrillin-1 assembly." Saito M., Kurokawa M., Oda M., Oshima M., Tsutsui K., Kosaka K., Nakao K., Ogawa M., Manabe R., Suda N., Ganjargal G., Hada Y., Noguchi T., Teranaka T., Sekiguchi K., Yoneda T., Tsuji T. J. Biol. Chem. 286:38602-38613(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH THSD4.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M13177 mRNA. Translation: AAA40423.1. L42462 , L42456, L42457, L42458, L42459, L42460, L42461 Genomic DNA. Translation: AAB00138.1. AJ009862 mRNA. Translation: CAA08900.1. BC013738 mRNA. Translation: AAH13738.1.
IPI	IPI00114457.
PIR	WFMS2. A01396.
RefSeq	NP_035707.1. NM_011577.1.
UniGene	Mm.248380.
3D structure databases
ProteinModelPortal	P04202.
SMR	P04202. Positions 30-390.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48640N.
STRING	10090.ENSMUSP00000002678.
PTM databases
PhosphoSite	P04202.
Proteomic databases
PaxDb	P04202.
PRIDE	P04202.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000002678; ENSMUSP00000002678; ENSMUSG00000002603.
GeneID	21803.
KEGG	mmu:21803.
Organism-specific databases
CTD	7040.
MGI	MGI:98725. Tgfb1.
Phylogenomic databases
eggNOG	NOG279949.
HOGENOM	HOG000290198.
HOVERGEN	HBG074115.
InParanoid	P04202.
KO	K13375.
OMA	SHSIYMF.
OrthoDB	EOG4NKBVP.
Gene expression databases
ArrayExpress	P04202.
Bgee	P04202.
CleanEx	MM_TGFB1.
Genevestigator	P04202.
GermOnline	ENSMUSG00000002603. Mus musculus.
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
NextBio	301176.
PMAP-CutDB	P04202.
SOURCE	Search...

Entry information

Entry name

TGFB1_MOUSE

Accession

Primary (citable) accession number: P04202

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	March 20, 1987
Last modified:	May 1, 2013
This is version 149 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program