Reviewed, UniProtKB/Swiss-Prot P37173 (TGFR2_HUMAN)

Names and origin

Protein names

Recommended name:
    TGF-beta receptor type-2
    EC=2.7.11.30
Alternative name(s):
    Transforming growth factor-beta receptor type II
      Short name=TGF-beta receptor type II
    TGF-beta type II receptor
    TbetaR-II
    TGFR-2

Gene names

Name:

TGFBR2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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 protein level.

General annotation (Comments)

Function	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for TGF-beta.
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Subunit structure	Binds to DAXX. Interacts with TCTEX1D4. Ref.9 Ref.11
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Phosphorylated on a Ser/Thr residue in the cytoplasmic domain. Ref.10 Ref.12
Involvement in disease	Defects in TGFBR2 are the cause of hereditary non-polyposis colorectal cancer type 6 (HNPCC6) [MIM:190182]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. HNPCC6 is a type of colorectal cancer complying with the clinical criteria of HNPCC, except that the onset of cancer was beyond 50 years of age in all cases. Ref.16 Defects in TGFBR2 are a cause of esophageal cancer [MIM:133239]. Ref.17 Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 1B (LDS1B) [MIM:610168]. LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree. Ref.22 Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 2B (LDS2B) [MIM:610380]; formerly Marfan syndrome type 2. LDS2 is an aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients. Defects in TGFBR2 are the cause of aortic aneurysm familial thoracic type 3 (AAT3) [MIM:610380]. Aneurysms and dissections of the aorta usually result from degenerative changes in the aortic wall. Thoracic aortic aneurysms and dissections are primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. AAT3 is an autosomal dominant disorder with reduced penetrance and variable expression. Ref.21
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Aortic aneurysm Disease mutation Hereditary nonpolyposis colorectal cancer
Domain	Signal Transmembrane
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	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	activation of protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB brain development Inferred from sequence or structural similarity. Source: UniProtKB embryonic cranial skeleton morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB embryonic hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB heart development Inferred from sequence or structural similarity. Source: UniProtKB myeloid dendritic cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB palate development Inferred from sequence or structural similarity. Source: UniProtKB pathway-restricted SMAD protein phosphorylation Inferred from direct assay. Source: UniProtKB patterning of blood vessels Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-serine phosphorylation Inferred from direct assay. Source: UniProtKB peptidyl-threonine phosphorylation Inferred from direct assay. Source: UniProtKB positive regulation of B cell tolerance induction Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of NK T cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of T cell tolerance induction Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mesenchymal cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of tolerance induction to self antigen Inferred from sequence or structural similarity. Source: UniProtKB response to cholesterol Inferred from direct assay. Source: UniProtKB response to drug Inferred from direct assay. Source: UniProtKB transforming growth factor beta receptor signaling pathway Inferred from direct assay. Source: UniProtKB vasculogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	caveola Inferred from direct assay. Source: UniProtKB external side of plasma membrane Inferred from direct assay. Source: UniProtKB transforming growth factor beta receptor complex Inferred by curator. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW SMAD binding Inferred from direct assay. Source: UniProtKB glycosaminoglycan binding Inferred from direct assay. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.9 Ref.13 Inferred from physical interaction. Source: UniProtKB protein heterodimerization activity Inferred from direct assay. Source: UniProtKB transforming growth factor beta binding Inferred from direct assay. Source: UniProtKB transforming growth factor beta receptor activity, type II Inferred from electronic annotation. Source: InterPro type I transforming growth factor beta receptor binding Inferred from direct assay. Source: UniProtKB type III transforming growth factor beta receptor binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	1	EBI-296151,EBI-77321
Daxx	O35613	1	EBI-296151,EBI-77304	From a different organism.
TGFB1	P07200	1	EBI-296151,EBI-907660	From a different organism.
TGFB3	P10600	1	EBI-296151,EBI-1033020

Alternative products

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

Isoform 1 (identifier: P37173-1)

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 2 (identifier: P37173-2)

The sequence of this isoform differs from the canonical sequence as follows:
     31-32: SV → SDVEMEAQKDEIICPSCNRTAHPLRHI

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.8

Chain

23 – 567

545

TGF-beta receptor type-2

PRO_0000024426

Regions

Topological domain

23 – 166

144

Extracellular Potential

Transmembrane

167 – 187

21

Potential

Topological domain

188 – 567

380

Cytoplasmic Potential

Domain

244 – 544

301

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 Ref.10 Ref.12

Glycosylation

70

1

N-linked (GlcNAc...) Potential

Glycosylation

94

1

N-linked (GlcNAc...) Potential

Glycosylation

154

1

N-linked (GlcNAc...) Potential

Disulfide bond

51 ↔ 84

Disulfide bond

54 ↔ 71

Disulfide bond

61 ↔ 67

Disulfide bond

77 ↔ 101

Disulfide bond

121 ↔ 136

Disulfide bond

138 ↔ 143

Natural variations

Alternative sequence

31 – 32

2

SV → SDVEMEAQKDEIICPSCNRT AHPLRHI in isoform 2.

VSP_012157

Natural variant

36

1

M → V: dbSNP rs17025864. Ref.7

VAR_020510

Natural variant

61

1

C → R in a gastric adenocarcinoma sample; somatic mutation. Ref.24

VAR_041414

Natural variant

73

1

I → V in a colorectal cancer sample; somatic mutation. Ref.23

VAR_036070

Natural variant

191

1

V → I: dbSNP rs56105708. Ref.24 Ref.19

VAR_017606

Natural variant

308

1

L → P in LDS2B; has a negative effect on TGF-beta signaling. dbSNP rs28934568. Ref.20

VAR_022351

Natural variant

315

1

T → M in HNPCC6. dbSNP rs34833812. Ref.16 Ref.24

VAR_008156

Natural variant

328

1

H → Y in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.24

VAR_041415

Natural variant

336

1

Y → N in LDS1B. Ref.22

VAR_022352

Natural variant

355

1

A → P in LDS1B. Ref.22

VAR_022353

Natural variant

357

1

G → W in LDS1B. Ref.22

VAR_022354

Natural variant

373

1

M → I: dbSNP rs35719192. Ref.24

VAR_041416

Natural variant

387

1

V → M in a breast tumor. dbSNP rs35766612. Ref.24 Ref.18

VAR_022355

Natural variant

435

1

N → S in a breast tumor; signaling of TGF-beta significantly inhibited. Ref.18

VAR_022356

Natural variant

439

1

V → A: dbSNP rs1050833. Ref.1 Ref.4 Ref.5 Ref.6

VAR_028063

Natural variant

447

1

V → A in a breast tumor; signaling of TGF-beta significantly inhibited. Ref.18

VAR_022357

Natural variant

449

1

S → F in LDS2B; has a negative effect on TGF-beta signaling. Ref.20

VAR_022358

Natural variant

452

1

L → M in a breast tumor; signaling of TGF-beta significantly inhibited. Ref.18

VAR_022359

Natural variant

460

1

R → C in AAT3. Ref.21

VAR_029760

Natural variant

460

1

R → H in AAT3. Ref.21

VAR_029761

Natural variant

490

1

N → S in a gastric adenocarcinoma sample; somatic mutation. Ref.24

VAR_041417

Natural variant

526

1

E → Q in esophageal cancer. Ref.17

VAR_015816

Natural variant

528

1

R → C in LDS1B. Ref.22

VAR_022360

Natural variant

528

1

R → H in LDS1B. Ref.22 Ref.23

VAR_022361

Natural variant

537

1

R → C in LDS2B; has a negative effect on TGF-beta signaling. Ref.20

VAR_022362

Experimental info

Mutagenesis

277

1

K → R: Abolishes kinase activity, TGF-beta signaling and interaction with DAXX. Ref.9

Sequence conflict

381

1

K → N in BAA09332. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

567

Helix Strand Turn

Details...

Beta strand

50 – 52

3

Beta strand

55 – 58

4

Beta strand

65 – 68

4

Beta strand

74 – 76

3

Beta strand

83 – 90

8

Beta strand

95 – 102

8

Turn

114 – 117

4

Beta strand

119 – 122

4

Beta strand

124 – 126

3

Beta strand

131 – 138

8

Helix

143 – 145

3

Beta strand

146 – 148

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: C541DA751FFBDBEB	FASTA	567	64,568
	10 20 30 40 50 60 MGRGLLRGLW PLHIVLWTRI ASTIPPHVQK SVNNDMIVTD NNGAVKFPQL CKFCDVRFST 70 80 90 100 110 120 CDNQKSCMSN CSITSICEKP QEVCVAVWRK NDENITLETV CHDPKLPYHD FILEDAASPK 130 140 150 160 170 180 CIMKEKKKPG ETFFMCSCSS DECNDNIIFS EEYNTSNPDL LLVIFQVTGI SLLPPLGVAI 190 200 210 220 230 240 SVIIIFYCYR VNRQQKLSST WETGKTRKLM EFSEHCAIIL EDDRSDISST CANNINHNTE 250 260 270 280 290 300 LLPIELDTLV GKGRFAEVYK AKLKQNTSEQ FETVAVKIFP YEEYASWKTE 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 HPCVESMKDN VLRDRGRPEI PSFWLNHQGI QMVCETLTEC WDHDPEARLT AQCVAERFSE 550 560 LEHLDRLSGR SCSEEKIPED GSLNTTK
	Isoform 2. Checksum: 8ADCBA70F95E1CBB	FASTA	592	67,457
	10 20 30 40 50 60 MGRGLLRGLW PLHIVLWTRI ASTIPPHVQK SDVEMEAQKD EIICPSCNRT AHPLRHINND 70 80 90 100 110 120 MIVTDNNGAV KFPQLCKFCD VRFSTCDNQK SCMSNCSITS ICEKPQEVCV AVWRKNDENI 130 140 150 160 170 180 TLETVCHDPK LPYHDFILED AASPKCIMKE KKKPGETFFM CSCSSDECND NIIFSEEYNT 190 200 210 220 230 240 SNPDLLLVIF QVTGISLLPP LGVAISVIII FYCYRVNRQQ KLSSTWETGK TRKLMEFSEH 250 260 270 280 290 300 CAIILEDDRS DISSTCANNI NHNTELLPIE LDTLVGKGRF AEVYKAKLKQ NTSEQFETVA 310 320 330 340 350 360 VKIFPYEEYA 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 SMKDNVLRDR GRPEIPSFWL NHQGIQMVCE 550 560 570 580 590 TLTECWDHDP EARLTAQCVA ERFSELEHLD RLSGRSCSEE KIPEDGSLNT TK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase." Lin H.Y., Wang X.-F., Ng-Eaton E., Weinberg R.A., Lodish H.F. Cell 68:775-785(1992) [PubMed: 1310899] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-439. Tissue: Liver.
[2]	Erratum Lin H.Y., Wang X.-F., Ng-Eaton E., Weinberg R.A., Lodish H.F. Cell 70:1069-1069(1992) [PubMed: 1525823] [Abstract]
[3]	"A cDNA encoding the human transforming growth factor beta receptor suppresses the growth defect of a yeast mutant." Nikawa J. Gene 149:367-372(1994) [PubMed: 7959019] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Glial cell.
[4]	"The genomic structure of the gene encoding the human transforming growth factor beta type II receptor (TGF-beta RII)." Takenoshita S., Hagiwara K., Nagashima M., Gemma A., Bennett W.P., Harris C.C. Genomics 36:341-344(1996) [PubMed: 8812462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANT ALA-439.
[5]	"Genomic structure of the transforming growth factor beta type II receptor gene and its mutations in hereditary nonpolyposis colorectal cancers." Lu S.-L., Zhang W.C., Akiyama Y., Nomizu T., Yuasa Y. Cancer Res. 56:4595-4598(1996) [PubMed: 8840968] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANT ALA-439.
[6]	"Cloning of a cDNA encoding the human transforming growth factor-beta type II receptor: heterogeneity of the mRNA." Ogasa H., Noma T., Murata H., Kawai S., Nakazawa A. Gene 181:185-190(1996) [PubMed: 8973329] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-439. Tissue: Liver.
[7]	NIEHS SNPs program Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-36.
[8]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-37.
[9]	"TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation." Perlman R., Schiemann W.P., Brooks M.W., Lodish H.F., Weinberg R.A. Nat. Cell Biol. 3:708-714(2001) [PubMed: 11483955] [Abstract] Cited for: INTERACTION WITH DAXX, MUTAGENESIS OF LYS-277.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Identification of Tctex2beta, a novel dynein light chain family member that interacts with different transforming growth factor-beta receptors." Meng Q.-J., Lux A., Holloschi A., Li J., Hughes J.M.X., Foerg T., McCarthy J.E.G., Heagerty A.M., Kioschis P., Hafner M., Garland J.M. J. Biol. Chem. 281:37069-37080(2006) [PubMed: 16982625] [Abstract] Cited for: INTERACTION WITH TCTEX1D4.
[12]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548, MASS SPECTROMETRY.
[13]	"Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex." Hart P.J., Deep S., Taylor A.B., Shu Z., Hinck C.S., Hinck A.P. Nat. Struct. Biol. 9:203-208(2002) [PubMed: 11850637] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 38-159 IN COMPLEX WITH TGF-BETA3.
[14]	"The 1.1 A crystal structure of human TGF-beta type II receptor ligand binding domain." Boesen C.C., Radaev S., Motyka S.A., Patamawenu A., Sun P.D. Structure 10:913-919(2002) [PubMed: 12121646] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 49-159.
[15]	"Solution structure and backbone dynamics of the TGFbeta type II receptor extracellular domain." Deep S., Walker K.P. III, Shu Z., Hinck A.P. Biochemistry 42:10126-10139(2003) [PubMed: 12939140] [Abstract] Cited for: STRUCTURE BY NMR OF 38-159.
[16]	"HNPCC associated with germline mutation in the TGF-beta type II receptor gene." Lu S.-L., Kawabata M., Imamura T., Akiyama Y., Nomizu T., Miyazono K., Yuasa Y. Nat. Genet. 19:17-18(1998) [PubMed: 9590282] [Abstract] Cited for: VARIANT HNPCC6 MET-315.
[17]	"A dominant negative mutation of transforming growth factor-beta receptor type II gene in microsatellite stable oesophageal carcinoma." Tanaka S., Mori M., Mafune K., Ohno S., Sugimachi K. Br. J. Cancer 82:1557-1560(2000) [PubMed: 10789724] [Abstract] Cited for: VARIANT ESOPHAGEAL CANCER GLN-526.
[18]	"Inhibiting mutations in the transforming growth factor beta type 2 receptor in recurrent human breast cancer." Luecke C.D., Philpott A., Metcalfe J.C., Thompson A.M., Hughes-Davies L., Kemp P.R., Hesketh R. Cancer Res. 61:482-485(2001) [PubMed: 11212236] [Abstract] Cited for: VARIANTS BREAST TUMOR MET-387; SER-435; ALA-447 AND MET-452, CHARACTERIZATION OF VARIANTS BREAST TUMOR SER-435; ALA-447 AND MET-452.
[19]	"A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types of variations in genes for transforming growth factor-beta1 (TGF-beta1) and its signaling pathway." Watanabe Y., Kinoshita A., Yamada T., Ohta T., Kishino T., Matsumoto N., Ishikawa M., Niikawa N., Yoshiura K. J. Hum. Genet. 47:478-483(2002) [PubMed: 12202987] [Abstract] Cited for: VARIANT ILE-191.
[20]	"Heterozygous TGFBR2 mutations in Marfan syndrome." Mizuguchi T., Collod-Beroud G., Akiyama T., Abifadel M., Harada N., Morisaki T., Allard D., Varret M., Claustres M., Morisaki H., Ihara M., Kinoshita A., Yoshiura K., Junien C., Kajii T., Jondeau G., Ohta T., Kishino T. , Furukawa Y., Nakamura Y., Niikawa N., Boileau C., Matsumoto N. Nat. Genet. 36:855-860(2004) [PubMed: 15235604] [Abstract] Cited for: VARIANTS LDS2B PRO-308; PHE-449 AND CYS-537, CHARACTERIZATION OF VARIANTS LDS2B PRO-308; PHE-449 AND CYS-537.
[21]	"Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections." Pannu H., Fadulu V.T., Chang J., Lafont A., Hasham S.N., Sparks E., Giampietro P.F., Zaleski C., Estrera A.L., Safi H.J., Shete S., Willing M.C., Raman C.S., Milewicz D.M. Circulation 112:513-520(2005) [PubMed: 16027248] [Abstract] Cited for: VARIANTS AAT3 CYS-460 AND HIS-460.
[22]	"A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2." Loeys B.L., Chen J., Neptune E.R., Judge D.P., Podowski M., Holm T., Meyers J., Leitch C.C., Katsanis N., Sharifi N., Xu F.L., Myers L.A., Spevak P.J., Cameron D.E., De Backer J.F., Hellemans J., Chen Y., Davis E.C. , Webb C.L., Kress W., Coucke P.J., Rifkin D.B., De Paepe A.M., Dietz H.C. Nat. Genet. 37:275-281(2005) [PubMed: 15731757] [Abstract] Cited for: VARIANTS LDS1B ASN-336; PRO-355; TRP-357; HIS-528 AND CYS-528.
[23]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-73 AND HIS-528.
[24]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-61; ILE-191; MET-315; TYR-328; ILE-373; MET-387 AND SER-490.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

M85079 mRNA. Translation: AAA61164.1.
D28131 mRNA. Translation: BAA05673.1.
U52246 , U52240, U52241, U52242, U52244, U52245 Genomic DNA. Translation: AAB17553.1.
U69152 , U69146, U69147, U69148, U69149, U69150, U69151 Genomic DNA. Translation: AAB40916.1.
D50683 mRNA. Translation: BAA09332.1.
AY675319 Genomic DNA. Translation: AAT70724.1.

IPI

IPI00020431.
IPI00164934.

PIR

A42100.

RefSeq

NP_001020018.1.
NP_003233.4.

UniGene

Hs.604277
Hs.82028

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KTZ	X-ray	2.15	B	38-159	[»]
1M9Z	X-ray	1.05	A	50-159	[»]
1PLO	NMR	-	A	38-159	[»]
2PJY	X-ray	3.00	B	43-149	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5939N.

IntAct

P37173. 5 interactions.

STRING

P37173.

PTM databases

PhosphoSite

P37173.

Proteomic databases

PRIDE

P37173.

Genome annotation databases

Ensembl

ENST00000295754; ENSP00000295754; ENSG00000163513; Homo sapiens. [Genome view]
ENST00000359013; ENSP00000351905; ENSG00000163513; Homo sapiens. [Genome view]
ENST00000383765; ENSP00000373275; ENSG00000163513; Homo sapiens. [Genome view]
ENST00000427981; ENSP00000400898; ENSG00000163513; Homo sapiens. [Genome view]
ENST00000439925; ENSP00000392572; ENSG00000163513; Homo sapiens. [Genome view]

GeneID

7048.

KEGG

hsa:7048.

NMPDR

fig|9606.3.peg.22244.

UCSC

uc003cen.1. human.
uc003ceo.1. human.

Organism-specific databases

CTD

7048.

GeneCards

GC03P030623.

H-InvDB

HIX0024332.

HGNC

HGNC:11773. TGFBR2.

MIM

133239. phenotype.
190182. gene+phenotype.
610168. phenotype.
610380. phenotype.

Orphanet

60030. Aortic aneurysm syndrome, Loeys-Dietz type.
144. Colon cancer, familial nonpolyposis.
558. Marfan syndrome.
91387. Thoracic aortic aneurysm, familial form.

PharmGKB

PA36486.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P37173.

OMA

MVTDNNG.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.
2.7.11.30. 247.

Pathway_Interaction_DB

glypican_1pathway. Glypican 1 network.
avb3_integrin_pathway. Integrins in angiogenesis.
tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_6844. Signaling by TGF beta.

Gene expression databases

ArrayExpress

P37173.

Bgee

P37173.

CleanEx

HS_TGFBR2.

Genevestigator

P37173.

GermOnline

ENSG00000163513. Homo sapiens.

Family and domain databases

InterPro

IPR000333. Activin_II_recpt.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR015769. TGF-beta-2_rcpt_C.
IPR017194. Transform_growth_fac-b_typ-2.
IPR015013. Transforming_GF_b_rcpt_2_ecto.
[Graphical view]

PANTHER

PTHR23255:SF11. TGF-beta_II_C. 1 hit.

Pfam

PF08917. ecTbetaR2. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

PIRSF

PIRSF037393. TGFRII. 1 hit.

PRINTS

PR00653. ACTIVIN2R.

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

27541.

SOURCE

Search...

Entry information

Entry name

TGFR2_HUMAN

Accession

Primary (citable) accession number: P37173
Secondary accession number(s): Q15580, Q6DKT6, Q99474

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 17, 2006
Last modified:	November 3, 2009
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.