P17246 (TGFB1_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

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. Ref.5
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. Interacts with CD109 and DPT. Interacts with ASPN. 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. Ref.4
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Abundant in the bone matrix. Ref.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 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 direct assay PubMed 12702545. Source: RGD T cell homeostasis Inferred from electronic annotation. Source: Compara adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains Inferred from electronic annotation. Source: Compara aging Inferred from expression pattern PubMed 12051734. Source: RGD branch elongation involved in mammary gland duct branching Inferred from electronic annotation. Source: Compara cell cycle arrest Inferred from sequence or structural similarity. Source: UniProtKB cell death Inferred from electronic annotation. Source: Compara 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 electronic annotation. Source: Compara cellular response to dexamethasone stimulus Inferred from direct assay PubMed 17537984. 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 direct assay PubMed 16272332. Source: RGD digestive tract development Inferred from expression pattern PubMed 12815632. Source: RGD embryo development Inferred from expression pattern PubMed 17428384. Source: RGD endoderm development Inferred from electronic annotation. Source: Compara epidermal growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB epithelial to mesenchymal transition Inferred from direct assay PubMed 10504497. Source: RGD evasion or tolerance of host defenses by virus Inferred from sequence or structural similarity. Source: UniProtKB extracellular matrix assembly Inferred from sequence or structural similarity. Source: UniProtKB face morphogenesis Inferred from electronic annotation. Source: Compara female pregnancy Inferred from expression pattern PubMed 15927076. Source: RGD frontal suture morphogenesis Inferred from expression pattern PubMed 12416537. Source: RGD germ cell migration Inferred from electronic annotation. Source: Compara 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 electronic annotation. Source: Compara inner ear development Inferred from expression pattern PubMed 16479080. Source: RGD lens fiber cell differentiation Inferred from electronic annotation. Source: Compara lipopolysaccharide-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB lung development Traceable author statement PubMed 7852342. Source: RGD lymph node development Inferred from electronic annotation. Source: Compara mammary gland branching involved in thelarche Inferred from electronic annotation. Source: Compara mitotic cell cycle checkpoint Inferred from sequence or structural similarity. Source: UniProtKB mononuclear cell proliferation Inferred from electronic annotation. Source: Compara morphogenesis of a branching structure Inferred from direct assay PubMed 15192047. Source: RGD myelination Inferred from mutant phenotype PubMed 14648590. Source: RGD myeloid dendritic cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of DNA replication Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of T cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of blood vessel endothelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from direct assay PubMed 15192047. Source: RGD 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 direct assay PubMed 12130550. Source: RGD 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 direct assay PubMed 16177030. Source: RGD negative regulation of ossification Inferred from electronic annotation. Source: Compara negative regulation of phagocytosis Inferred from direct assay PubMed 16272332. Source: RGD 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 direct assay PubMed 12876066. Source: RGD 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 electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB organ regeneration Inferred from mutant phenotype PubMed 9699514. Source: RGD ossification involved in bone remodeling Inferred from electronic annotation. Source: Compara pathway-restricted SMAD protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB 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 direct assay PubMed 15781474. Source: RGD 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 mutant phenotype PubMed 17537984. Source: UniProtKB 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 chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of collagen biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of epithelial cell proliferation Inferred from direct assay PubMed 15192047. Source: RGD positive regulation of epithelial to mesenchymal transition Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of exit from mitosis Inferred from direct assay PubMed 16177030. Source: RGD positive regulation of fibroblast migration Inferred from sequence or structural similarity. Source: UniProtKB 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 sequence or structural similarity. Source: UniProtKB positive regulation of isotype switching to IgA isotypes Inferred from electronic annotation. Source: Compara positive regulation of odontogenesis Inferred from electronic annotation. Source: Compara 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 direct assay 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 electronic annotation. Source: Compara positive regulation of transcription regulatory region DNA binding Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent 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 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 regulation of transforming growth factor beta receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulatory T cell differentiation Inferred from electronic annotation. Source: Compara response to cholesterol Inferred from sequence or structural similarity. Source: UniProtKB response to drug Inferred from expression pattern PubMed 11597910PubMed 18291259PubMed 19406119. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 15746252. Source: RGD response to glucose stimulus Inferred from expression pattern PubMed 18587447. Source: RGD response to hypoxia Inferred from expression pattern PubMed 17213961. Source: RGD response to laminar fluid shear stress Inferred from expression pattern PubMed 16217485. Source: RGD response to progesterone stimulus Inferred from sequence or structural similarity. Source: UniProtKB response to radiation Inferred from expression pattern PubMed 11774400. Source: RGD response to vitamin D Inferred from expression pattern PubMed 11956143. Source: RGD salivary gland morphogenesis Inferred from electronic annotation. Source: Compara tolerance induction to self antigen Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB ureteric bud development Inferred from electronic annotation. Source: Compara wound healing Inferred from mutant phenotype PubMed 17117936. Source: RGD
Cellular_component	axon Inferred from direct assay PubMed 15214860. Source: RGD cell surface Inferred from direct assay PubMed 10487979. Source: BHF-UCL extracellular space Inferred from direct assay PubMed 16837651. Source: RGD microvillus Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from direct assay PubMed 15214860. Source: RGD nucleus Inferred from sequence or structural similarity. Source: UniProtKB proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell secretory granule Inferred from direct assay PubMed 15214860. Source: RGD
Molecular_function	eukaryotic cell surface binding Inferred from sequence or structural similarity. Source: UniProtKB protein N-terminus binding Inferred from mutant phenotype PubMed 8106553. Source: RGD protein heterodimerization activity Inferred from direct assay PubMed 18406405. Source: RGD protein homodimerization activity Inferred from direct assay PubMed 18406405. Source: RGD 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_0000033770
	Chain	279 – 390	112	Transforming growth factor beta-1		PRO_0000033771
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)
	P17246 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 5E21108ED50D853C	FASTA	390	44,329
	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 YDKTKDITHS IYMFFNTSDI REAVPEPPLL SRAELRLQRF KSTVEQHVEL YQKYSNNSWR 190 200 210 220 230 240 YLGNRLLTPT DTPEWLSFDV TGVVRQWLNQ GDGIQGFRFS AHCSCDSKDN VLHVEINGIS 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]	"cDNA cloning by PCR of rat transforming growth factor beta-1." Qian S.W., Kondaiah P., Roberts A.B., Sporn M.B. Nucleic Acids Res. 18:3059-3059(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Heart.
[2]	"Open reading frame sequence of rat TGF beta 1." Dai W.-J., Jiang H.-C., Fu S.-B. Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"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: Kidney.
[4]	"The first stage of transforming growth factor beta1 activation is release of the large latent complex from the extracellular matrix of growth plate chondrocytes by matrix vesicle stromelysin-1 (MMP-3)." Maeda S., Dean D.D., Gomez R., Schwartz Z., Boyan B.D. Calcif. Tissue Int. 70:54-65(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[5]	"The effects of TGF-beta on bone." Mundy G.R. Ciba Found. Symp. 157:137-143(1991) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN BONE REMODELING, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X52498 mRNA. Translation: CAA36741.1. AY550025 mRNA. Translation: AAS55640.1. BC076380 mRNA. Translation: AAH76380.1.
IPI	IPI00214538.
PIR	S10219.
RefSeq	NP_067589.1. NM_021578.2.
UniGene	Rn.40136.
3D structure databases
ProteinModelPortal	P17246.
SMR	P17246. Positions 279-390.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-6247N.
Proteomic databases
PaxDb	P17246.
PRIDE	P17246.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000028051; ENSRNOP00000028051; ENSRNOG00000020652.
GeneID	59086.
KEGG	rno:59086.
UCSC	RGD:69051. rat.
Organism-specific databases
CTD	7040.
RGD	69051. Tgfb1.
Phylogenomic databases
eggNOG	NOG279949.
GeneTree	ENSGT00620000087687.
HOGENOM	HOG000290198.
HOVERGEN	HBG074115.
InParanoid	P17246.
KO	K13375.
OMA	SHSIYMF.
OrthoDB	EOG4NKBVP.
Gene expression databases
ArrayExpress	P17246.
Genevestigator	P17246.
GermOnline	ENSRNOG00000020652. Rattus norvegicus.
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	611708.

Entry information

Entry name

TGFB1_RAT

Accession

Primary (citable) accession number: P17246
Secondary accession number(s): Q53YM8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program