P38438 (TGFR2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TGF-beta receptor type-2
Short name=TGFR-2
EC=2.7.11.30

Alternative name(s):
TGF-beta type II receptor
Transforming growth factor-beta receptor type II
Short name=TGF-beta receptor type II
Short name=TbetaR-II

Gene names

Name:

Tgfbr2

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	567 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	Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways By similarity.
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Subunit structure	Homodimer. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGFRB1 and TGFRB2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Interacts with DAXX. Interacts with TCTEX1D4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor By similarity. Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2 By similarity. Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Post-translational modification	Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Differentiation Growth regulation
Cellular component	Cell membrane Membrane
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of protein kinase activity Inferred from electronic annotation. Source: Compara aging Inferred from expression pattern PubMed 12051734. Source: RGD apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW brain development Inferred from electronic annotation. Source: Compara bronchus morphogenesis Inferred from electronic annotation. Source: Compara cartilage development Inferred from electronic annotation. Source: Compara common-partner SMAD protein phosphorylation Inferred from direct assay PubMed 14729511. Source: RGD digestive tract development Inferred from expression pattern PubMed 12815632. Source: RGD embryo development Inferred from expression pattern PubMed 17428384. Source: RGD embryo implantation Inferred from expression pattern PubMed 16426643. Source: RGD embryonic cranial skeleton morphogenesis Inferred from electronic annotation. Source: Compara embryonic hemopoiesis Inferred from electronic annotation. Source: Compara gastrulation Inferred from electronic annotation. Source: Compara heart development Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara lens development in camera-type eye Inferred from electronic annotation. Source: Compara lung development Inferred from expression pattern PubMed 7573476. Source: RGD lung lobe morphogenesis Inferred from electronic annotation. Source: Compara mammary gland morphogenesis Inferred from electronic annotation. Source: Compara myeloid dendritic cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of cardiac muscle cell proliferation Inferred from mutant phenotype PubMed 15537505. Source: RGD organ regeneration Inferred from expression pattern PubMed 9699514. Source: RGD palate development Inferred from electronic annotation. Source: Compara pathway-restricted SMAD protein phosphorylation Inferred from electronic annotation. Source: Compara patterning of blood vessels Inferred from electronic annotation. Source: Compara peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara peptidyl-threonine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of B cell tolerance induction Inferred from electronic annotation. Source: Compara positive regulation of NK T cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of T cell tolerance induction Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell migration Inferred from electronic annotation. Source: Compara positive regulation of mesenchymal cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of reactive oxygen species metabolic process Inferred from electronic annotation. Source: Compara positive regulation of skeletal muscle tissue regeneration Inferred from expression pattern PubMed 10672325. Source: RGD positive regulation of smooth muscle cell proliferation Inferred from mutant phenotype PubMed 11178962. Source: RGD positive regulation of tolerance induction to self antigen Inferred from electronic annotation. Source: Compara receptor-mediated endocytosis Inferred from direct assay PubMed 14729511. Source: RGD response to cholesterol Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from expression pattern PubMed 8759618. Source: RGD response to glucose stimulus Inferred from expression pattern PubMed 11178962. Source: RGD response to hypoxia Inferred from expression pattern PubMed 18760335. Source: RGD response to mechanical stimulus Inferred from expression pattern PubMed 10432381. Source: RGD response to nutrient Inferred from expression pattern PubMed 11675406. Source: RGD signal transduction by phosphorylation Inferred from electronic annotation. Source: GOC smoothened signaling pathway Inferred from electronic annotation. Source: Compara trachea formation Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype PubMed 18684975. Source: RGD vasculogenesis Inferred from expression pattern PubMed 9507219. Source: RGD wound healing Inferred from expression pattern PubMed 11381048. Source: RGD
Cellular_component	caveola Inferred from direct assay PubMed 17878231. Source: MGI cell surface Inferred from direct assay PubMed 14729511. Source: RGD cytosol Inferred from direct assay PubMed 14729511. Source: RGD external side of plasma membrane Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor homodimeric complex Inferred by curator PubMed 18684975. Source: RGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW glycosaminoglycan binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein heterodimerization activity Traceable author statement PubMed 14729511. Source: RGD protein homodimerization activity Traceable author statement PubMed 14729511. Source: RGD receptor signaling protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro transforming growth factor beta receptor activity, type II Inferred from mutant phenotype PubMed 18684975. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 567	544	TGF-beta receptor type-2		PRO_0000024429
Regions
	Topological domain	24 – 166	143	Extracellular Potential
	Transmembrane	167 – 187	21	Helical; Potential
	Topological domain	188 – 567	380	Cytoplasmic Potential
	Domain	244 – 546	303	Protein kinase
	Nucleotide binding	250 – 258	9	ATP By similarity
Sites
	Active site	379	1	Proton acceptor By similarity
	Binding site	277	1	ATP By similarity
Amino acid modifications
	Modified residue	548	1	Phosphoserine By similarity
	Glycosylation	70	1	N-linked (GlcNAc...) Potential
	Glycosylation	94	1	N-linked (GlcNAc...) Potential
	Disulfide bond	51 ↔ 84		By similarity
	Disulfide bond	54 ↔ 71		By similarity
	Disulfide bond	61 ↔ 67		By similarity
	Disulfide bond	77 ↔ 101		By similarity
	Disulfide bond	121 ↔ 136		By similarity
	Disulfide bond	138 ↔ 143		By similarity
Experimental info
	Sequence conflict	388 – 389	2	KN → RS in AAB29352. Ref.2
	Sequence conflict	403	1	R → G in AAB29352. Ref.2
	Sequence conflict	405	1	D → S in AAB29352. Ref.2
	Sequence conflict	477	1	K → R in AAB29352. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P38438 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: EC1D7642A51A3B75	FASTA	567	64,241
	10 20 30 40 50 60 MGRGLLRGLW PLHIVLWTRI ASTIPPHVPK SVNSDLMAGD NSGAVKLPQL CKFCDVTLST 70 80 90 100 110 120 CDNQKSCMSN CSVTSICEKP QEVCVAVWRK NDKNITLETV CHDPKFTYHG FTLEDATSPT 130 140 150 160 170 180 CVMKEKKRAG ETFFMCSCNT EECNDYIIFN EEYTTSSPDL LLVIIQVTGV SLLPPLGIAI 190 200 210 220 230 240 AVIAIFYCYR VHRQQKLSPS WESSKPRKLM DFSDNCAIIL EDDRSDISST CANNINHNTE 250 260 270 280 290 300 LLPIELDTLV GKGRFAEVYK AKLKQNTSEQ FETVAVKIFP YEEYSSWKTE KDIFSDINLK 310 320 330 340 350 360 HENILQFLTA EERKTEMGKQ YWLITAFHAK GNLQEYLTRH VISWEDLRKL GSSLARGIAH 370 380 390 400 410 420 LHSDHTPCGR PKMPIVHRDL KSSNILVKND LTCCLCDFGL SLRLDPTLSV DDLANSGQVG 430 440 450 460 470 480 TARYMAPEVL ESRMNLENME SFKQTDVYSM ALVLWEMTSR CNAVGEVKDY EPPFGSKVRE 490 500 510 520 530 540 HPCVESMKDN VLRDRGRPEI PSFWLNHQGI QIVCETLTEC WDHDPEARLT AQCVAERFSE 550 560 LEHPDRLSGR SCSQEKIPED GSLNTTK

References

[1]	"Molecular characterization of rat transforming growth factor-beta type II receptor." Tsuchida K., Lewis K.A., Mathews L.S., Vale W.W. Biochem. Biophys. Res. Commun. 191:790-795(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Pituitary.
[2]	"Rat mesangial cell hypertrophy in response to transforming growth factor-beta 1." Choi M.E., Kim E.G., Huang Q., Ballermann B.J. Kidney Int. 44:948-958(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L09653 mRNA. Translation: AAA42237.1. S67770 mRNA. Translation: AAB29352.2.
IPI	IPI00327360.
PIR	JN0459.
RefSeq	NP_112394.3. NM_031132.3.
UniGene	Rn.9954.
3D structure databases
ProteinModelPortal	P38438.
SMR	P38438. Positions 40-159.
ModBase	Search...
Protein-protein interaction databases
IntAct	P38438. 1 interaction.
STRING	10116.ENSRNOP00000017950.
Proteomic databases
PaxDb	P38438.
PRIDE	P38438.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000037883; ENSRNOP00000035501; ENSRNOG00000013265.
GeneID	81810.
KEGG	rno:81810.
UCSC	RGD:69651. rat.
Organism-specific databases
CTD	7048.
RGD	69651. Tgfbr2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00560000076906.
HOGENOM	HOG000231495.
HOVERGEN	HBG104975.
KO	K04388.
Enzyme and pathway databases
BRENDA	2.7.10.2. 5301.
Gene expression databases
ArrayExpress	P38438.
Genevestigator	P38438.
GermOnline	ENSRNOG00000013265. Rattus norvegicus.
Family and domain databases
InterPro	IPR000333. Activin_II/TGFBeta-II_recpt. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. IPR017194. Transform_growth_fac-b_typ-2. IPR015013. Transforming_GF_b_rcpt_2_ecto. [Graphical view]
PANTHER	PTHR23255:SF11. PTHR23255:SF11. 1 hit.
Pfam	PF08917. ecTbetaR2. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF037393. TGFRII. 1 hit.
PRINTS	PR00653. ACTIVIN2R.
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	615691.

Entry information

Entry name

TGFR2_RAT

Accession

Primary (citable) accession number: P38438

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	April 3, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program