Q62312 (TGFR2_MOUSE) 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

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	592 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.
Tissue specificity	Widely expressed in adult. Expressed primarily in mesenchyme and epidermis of the midgestational fetus.
Post-translational modification	Phosphorylated on a Ser/Thr residue in the cytoplasmic domain By similarity.
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
Coding sequence diversity	Alternative splicing
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 direct assay PubMed 16806156. Source: MGI aging Inferred from electronic annotation. Source: Compara apoptotic process Inferred from mutant phenotype PubMed 11641223. Source: MGI brain development Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL bronchus morphogenesis Inferred from mutant phenotype PubMed 18990706. Source: MGI cartilage development Inferred from mutant phenotype PubMed 18498113. Source: UniProtKB common-partner SMAD protein phosphorylation Inferred from electronic annotation. Source: Compara digestive tract development Inferred from electronic annotation. Source: Compara embryo implantation Inferred from electronic annotation. Source: Compara embryonic cranial skeleton morphogenesis Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL embryonic hemopoiesis Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL gastrulation Inferred from mutant phenotype PubMed 10030593. Source: MGI heart development Inferred from mutant phenotype PubMed 16332365PubMed 17078885. Source: MGI in utero embryonic development Inferred from mutant phenotype PubMed 10030593PubMed 18990706. Source: MGI lens development in camera-type eye Inferred from mutant phenotype PubMed 11641223. Source: MGI lung lobe morphogenesis Inferred from mutant phenotype PubMed 18990706. Source: MGI mammary gland morphogenesis Inferred from mutant phenotype PubMed 15781643. Source: MGI myeloid dendritic cell differentiation Inferred from mutant phenotype PubMed 17938236. Source: MGI negative regulation of cardiac muscle cell proliferation Inferred from electronic annotation. Source: Compara organ regeneration Inferred from electronic annotation. Source: Compara palate development Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL pathway-restricted SMAD protein phosphorylation Inferred from electronic annotation. Source: Compara patterning of blood vessels Inferred from mutant phenotype PubMed 17078885. Source: MGI 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 mutant phenotype PubMed 16973387. Source: MGI positive regulation of NK T cell differentiation Inferred from mutant phenotype PubMed 16973387. Source: MGI positive regulation of T cell tolerance induction Inferred from mutant phenotype PubMed 16973387. Source: MGI positive regulation of epithelial cell migration Inferred from mutant phenotype PubMed 11641223. Source: MGI positive regulation of mesenchymal cell proliferation Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL positive regulation of reactive oxygen species metabolic process Inferred from electronic annotation. Source: Compara positive regulation of skeletal muscle tissue regeneration Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of tolerance induction to self antigen Inferred from mutant phenotype PubMed 16973387. Source: MGI receptor-mediated endocytosis Inferred from electronic annotation. Source: Compara response to cholesterol Inferred from direct assay PubMed 17878231. Source: BHF-UCL response to drug Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara signal transduction by phosphorylation Inferred from electronic annotation. Source: GOC smoothened signaling pathway Inferred from mutant phenotype PubMed 18990706. Source: MGI trachea formation Inferred from mutant phenotype PubMed 18990706. Source: MGI transforming growth factor beta receptor signaling pathway Inferred from electronic annotation. Source: InterPro vasculogenesis Inferred from mutant phenotype PubMed 12975342. Source: BHF-UCL wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	caveola Inferred from sequence orthology PubMed 17878231. Source: MGI cytosol Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from direct assay PubMed 16973387. Source: MGI integral to plasma membrane Inferred from electronic annotation. Source: Compara receptor complex Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW SMAD binding Inferred from direct assay PubMed 12773577. Source: BHF-UCL glycosaminoglycan binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro transforming growth factor beta receptor activity, type II Inferred from electronic annotation. Source: InterPro transforming growth factor beta-activated receptor activity Inferred from genetic interaction PubMed 17878231. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform RII-2 (identifier: Q62312-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform RII-1 (identifier: Q62312-2)

The sequence of this isoform differs from the canonical sequence as follows:
     32-56: Missing.
     57-57: F → V

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 592	569	TGF-beta receptor type-2		PRO_0000024427
Regions
	Topological domain	24 – 184	161	Extracellular Potential
	Transmembrane	185 – 214	30	Helical; Potential
	Topological domain	215 – 592	378	Cytoplasmic Potential
	Domain	269 – 569	301	Protein kinase
	Nucleotide binding	275 – 283	9	ATP By similarity
Sites
	Active site	404	1	Proton acceptor By similarity
	Binding site	302	1	ATP By similarity
Amino acid modifications
	Modified residue	573	1	Phosphoserine By similarity
	Glycosylation	48	1	N-linked (GlcNAc...) Potential
	Glycosylation	95	1	N-linked (GlcNAc...) Potential
	Glycosylation	119	1	N-linked (GlcNAc...) Potential
	Disulfide bond	76 ↔ 109		By similarity
	Disulfide bond	79 ↔ 96		By similarity
	Disulfide bond	86 ↔ 92		By similarity
	Disulfide bond	102 ↔ 126		By similarity
	Disulfide bond	146 ↔ 161		By similarity
	Disulfide bond	163 ↔ 168		By similarity
Natural variations
	Alternative sequence	32 – 56	25	Missing in isoform RII-1.		VSP_004955
	Alternative sequence	57	1	F → V in isoform RII-1.		VSP_004956
Experimental info
	Sequence conflict	8	1	G → A in AAB30100. Ref.2
	Sequence conflict	117	1	D → N in AAB30100. Ref.2
	Sequence conflict	354	1	A → R in AAB30100. Ref.2
	Sequence conflict	440 – 443	4	NSGQ → KQRE in AAB30100. Ref.2
	Sequence conflict	486	1	C → W in AAB30100. Ref.2
	Sequence conflict	506	1	H → P in AAB30100. Ref.2
	Sequence conflict	569 – 570	2	PE → MD in AAB30100. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform RII-2 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 1A12D58550921F5E	FASTA	592	67,122
	10 20 30 40 50 60 MGRGLLRGLW PLHIVLWTRI ASTIPPHVPK SDVEMEAQKD ASIHLSCNRT IHPLKHFNSD 70 80 90 100 110 120 VMASDNGGAV KLPQLCKFCD VRLSTCDNQK SCMSNCSITA ICEKPHEVCV AVWRKNDKNI 130 140 150 160 170 180 TLETVCHDPK LTYHGFTLED AASPKCVMKE KKRAGETFFM CACNMEECND YIIFSEEYTT 190 200 210 220 230 240 SSPDLLLVII QVTGVSLLPP LGIAIAVIII FYCYRVHRQQ KLSPSWESSK PRKLMDFSDN 250 260 270 280 290 300 CAIILEDDRS DISSTCANNI NHNTELLPIE LDTLVGKGRF AEVYKAKLKQ NTSEQFETVA 310 320 330 340 350 360 VKIFPYEEYS SWKTEKDIFS DINLKHENIL QFLTAEERKT ELGKQYWLIT AFHAKGNLQE 370 380 390 400 410 420 YLTRHVISWE DLRKLGSSLA RGIAHLHSDH TPCGRPKMPI VHRDLKSSNI LVKNDLTCCL 430 440 450 460 470 480 CDFGLSLRLD PTLSVDDLAN SGQVGTARYM APEVLESRMN LENVESFKQT DVYSMALVLW 490 500 510 520 530 540 EMTSRCNAVG EVKDYEPPFG SKVREHPCVE SMKDSVLRDR GRPEIPSFWL NHQGIQIVCE 550 560 570 580 590 TLTECWDHDP EARLTAQCVA ERFSELEHPE RLSGRSCSQE KIPEDGSLNT TK
	Isoform RII-1 [UniParc]. Checksum: 4C66067ADA84F986	FASTA	567	64,219
	10 20 30 40 50 60 MGRGLLRGLW PLHIVLWTRI ASTIPPHVPK SVNSDVMASD NGGAVKLPQL CKFCDVRLST 70 80 90 100 110 120 CDNQKSCMSN CSITAICEKP HEVCVAVWRK NDKNITLETV CHDPKLTYHG FTLEDAASPK 130 140 150 160 170 180 CVMKEKKRAG ETFFMCACNM EECNDYIIFS EEYTTSSPDL LLVIIQVTGV SLLPPLGIAI 190 200 210 220 230 240 AVIIIFYCYR VHRQQKLSPS WESSKPRKLM DFSDNCAIIL EDDRSDISST CANNINHNTE 250 260 270 280 290 300 LLPIELDTLV GKGRFAEVYK AKLKQNTSEQ FETVAVKIFP YEEYSSWKTE KDIFSDINLK 310 320 330 340 350 360 HENILQFLTA EERKTELGKQ YWLITAFHAK GNLQEYLTRH VISWEDLRKL GSSLARGIAH 370 380 390 400 410 420 LHSDHTPCGR PKMPIVHRDL KSSNILVKND LTCCLCDFGL SLRLDPTLSV DDLANSGQVG 430 440 450 460 470 480 TARYMAPEVL ESRMNLENVE SFKQTDVYSM ALVLWEMTSR CNAVGEVKDY EPPFGSKVRE 490 500 510 520 530 540 HPCVESMKDS VLRDRGRPEI PSFWLNHQGI QIVCETLTEC WDHDPEARLT AQCVAERFSE 550 560 LEHPERLSGR SCSQEKIPED GSLNTTK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of an isoform of mouse TGF-beta type II receptor gene." Suzuki A., Shioda N., Maeda T., Tada M., Ueno N. FEBS Lett. 355:19-22(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Brain.
[2]	"The murine type II TGF-beta receptor has a coincident embryonic expression and binding preference for TGF-beta 1." Lawler S., Candia A.F., Ebner R., Shum L., Lopez A.R., Moses H.L., Wright C.V., Derynck R. Development 120:165-175(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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] (ISOFORM RII-2). Tissue: Olfactory epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D32072 mRNA. Translation: BAA06840.1. S69114 mRNA. Translation: AAB30100.2. BC052629 mRNA. No translation available.
IPI	IPI00124569. IPI00227844.
PIR	S51371.
RefSeq	NP_033397.3. NM_009371.3.
UniGene	Mm.172346.
3D structure databases
ProteinModelPortal	Q62312.
SMR	Q62312. Positions 73-178, 269-564.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-44605N.
IntAct	Q62312. 3 interactions.
MINT	MINT-5181700.
PTM databases
PhosphoSite	Q62312.
Proteomic databases
PaxDb	Q62312.
PRIDE	Q62312.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000035014; ENSMUSP00000035014; ENSMUSG00000032440. ENSMUST00000061101; ENSMUSP00000062333; ENSMUSG00000032440.
GeneID	21813.
KEGG	mmu:21813.
UCSC	uc009ryt.2. mouse.
Organism-specific databases
CTD	7048.
MGI	MGI:98729. Tgfbr2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00560000076906.
HOGENOM	HOG000231495.
HOVERGEN	HBG104975.
InParanoid	Q62312.
KO	K04388.
OMA	MMVTDNN.
OrthoDB	EOG4FTW0J.
Enzyme and pathway databases
BRENDA	2.7.10.2. 3474.
Gene expression databases
ArrayExpress	Q62312.
Bgee	Q62312.
CleanEx	MM_TGFBR2.
Genevestigator	Q62312.
GermOnline	ENSMUSG00000032440. Mus musculus.
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
ChiTaRS	TGFBR2. mouse.
NextBio	301206.
SOURCE	Search...

Entry information

Entry name

TGFR2_MOUSE

Accession

Primary (citable) accession number: Q62312
Secondary accession number(s): Q63947

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program