O19011 (TGFB1_HORSE) 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

Equus caballus (Horse) [Reference proteome]

Taxonomic identifier

9796 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Perissodactyla › Equidae › Equus › Equus

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 transcript 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 By similarity.
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. 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.
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 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 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 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 endoderm development Inferred from electronic annotation. Source: Compara epidermal growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB 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 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 lens fiber cell differentiation Inferred from electronic annotation. Source: Compara lipopolysaccharide-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB 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 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 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 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 ossification Inferred from electronic annotation. Source: Compara negative regulation of protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB 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 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 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 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 sequence or structural similarity. Source: UniProtKB 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 to mesenchymal transition Inferred from sequence or structural similarity. Source: UniProtKB 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 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 estradiol stimulus Inferred from sequence or structural similarity. Source: UniProtKB response to progesterone stimulus Inferred from sequence or structural similarity. Source: UniProtKB 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
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB extracellular space Inferred from sequence or structural similarity. Source: UniProtKB microvillus Inferred from electronic annotation. Source: Compara nucleus Inferred from sequence or structural similarity. Source: UniProtKB proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
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 By similarity		PRO_0000033764
	Chain	279 – 390	112	Transforming growth factor beta-1		PRO_0000033765
Regions
	Region	30 – 74	45	Straightjacket domain By similarity
	Region	75 – 271	197	Arm domain By similarity
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-? in LTBP1 TB3 domain); 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
Experimental info
	Sequence conflict	137	1	T → A in AAD49431. Ref.2
	Sequence conflict	217	1	F → L in AAD49431. Ref.2
	Sequence conflict	224	1	S → P in AAD49431. Ref.2
	Sequence conflict	286	1	F → S in AAD49431. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O19011 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: A86D715F44549691	FASTA	390	43,975
	10 20 30 40 50 60 MPPSGLRLLP LLLPLLWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR GQILSKLRLA 70 80 90 100 110 120 SPPSQGEVPP GPLPEAVLAL YNSTRAQVAG ESAETEPEPE ADYYAKEVTR VLMVEKENEI 130 140 150 160 170 180 YKTVETGSHS IYMFFNTSEL RAAVPDPMLL SRAELRLLRL KLSVEQHVEL YQKYSNNSWR 190 200 210 220 230 240 YLSNRLLTPS DSPEWLSFDV TGVVRQWLSQ GGAMEGFRLS AHCSCDSKDN TLRVGINGFS 250 260 270 280 290 300 SSRRGDLATI DGMNRPFLLL MATPLERAQQ LHSSRHRRAL DTNYCFSSTE KNCCVRQLYI 310 320 330 340 350 360 DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA SAAPCCVPQV 370 380 390 LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS

References

[1]	"Cloning and sequencing of equine transforming growth factor-beta 1 (TGF beta-1) cDNA." Penha-Goncalves M.N., Onions D.E., Nicolson L. DNA Seq. 7:375-378(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lymph node.
[2]	"Molecular cloning of equine transforming growth factor beta 1 reveals a divergent nucleotide structure that encodes a novel bioactive peptide among mammalian species." Nixon A.J., Brower-Toland B.T., Sandell L.J. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	X99438 mRNA. Translation: CAA67801.1. AF175709 mRNA. Translation: AAD49431.1.
RefSeq	NP_001075318.1. NM_001081849.1.
UniGene	Eca.6371.
3D structure databases
ProteinModelPortal	O19011.
SMR	O19011. Positions 279-390.
ModBase	Search...
Protein-protein interaction databases
STRING	9796.ENSECAP00000009480.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSECAT00000012048; ENSECAP00000009480; ENSECAG00000011671.
GeneID	100033900.
KEGG	ecb:100033900.
Organism-specific databases
CTD	7040.
Phylogenomic databases
eggNOG	NOG279949.
GeneTree	ENSGT00620000087687.
HOGENOM	HOG000290198.
HOVERGEN	HBG074115.
InParanoid	O19011.
KO	K13375.
OMA	SHSIYMF.
OrthoDB	EOG4NKBVP.
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...

Entry information

Entry name

TGFB1_HORSE

Accession

Primary (citable) accession number: O19011
Secondary accession number(s): Q9TUM8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program