Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

TGF-beta receptor type-2

Gene

TGFBR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei277 – 2771ATPPROSITE-ProRule annotation
Active sitei379 – 3791Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi250 – 2589ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • glycosaminoglycan binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • receptor signaling protein serine/threonine kinase activity Source: InterPro
  • SMAD binding Source: BHF-UCL
  • transforming growth factor beta-activated receptor activity Source: BHF-UCL
  • transforming growth factor beta binding Source: BHF-UCL
  • transforming growth factor beta receptor activity, type II Source: InterPro
  • transmembrane receptor protein serine/threonine kinase activity Source: BHF-UCL
  • type III transforming growth factor beta receptor binding Source: BHF-UCL
  • type I transforming growth factor beta receptor binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Differentiation, Growth regulation

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-2173788. Downregulation of TGF-beta receptor signaling.
R-HSA-2173789. TGF-beta receptor signaling activates SMADs.
R-HSA-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
R-HSA-3304356. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
R-HSA-3315487. SMAD2/3 MH2 Domain Mutants in Cancer.
R-HSA-3642279. TGFBR2 MSI Frameshift Mutants in Cancer.
R-HSA-3645790. TGFBR2 Kinase Domain Mutants in Cancer.
R-HSA-3656532. TGFBR1 KD Mutants in Cancer.
R-HSA-3656535. TGFBR1 LBD Mutants in Cancer.
SignaLinkiP37173.
SIGNORiP37173.

Names & Taxonomyi

Protein namesi
Recommended name:
TGF-beta receptor type-2 (EC:2.7.11.30)
Short name:
TGFR-2
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 namesi
Name:TGFBR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:11773. TGFBR2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 166144ExtracellularSequence analysisAdd
BLAST
Transmembranei167 – 18721HelicalSequence analysisAdd
BLAST
Topological domaini188 – 567380CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • caveola Source: BHF-UCL
  • cytosol Source: Reactome
  • external side of plasma membrane Source: BHF-UCL
  • integral component of membrane Source: BHF-UCL
  • membrane raft Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • receptor complex Source: BHF-UCL
  • transforming growth factor beta receptor homodimeric complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 6 (HNPCC6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors 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. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by 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.
See also OMIM:614331
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti315 – 3151T → M in HNPCC6. 2 Publications
Corresponds to variant rs34833812 [ dbSNP | Ensembl ].
VAR_008156
Esophageal cancer (ESCR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage.
See also OMIM:133239
Loeys-Dietz syndrome 2 (LDS2)10 Publications
The disease is caused by mutations affecting the gene represented in this entry. TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries (PubMed:16027248), they have been considered as LDS2 by the OMIM resource.1 Publication
Disease descriptionAn aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. 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, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit.
See also OMIM:610168
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti190 – 1901R → H in LDS2. 1 Publication
VAR_076167
Natural varianti247 – 2471D → V in LDS2. 1 Publication
VAR_076168
Natural varianti306 – 3061Q → HE in LDS2. 1 Publication
VAR_066723
Natural varianti308 – 3081L → P in LDS2; has a negative effect on TGF-beta signaling. 2 Publications
Corresponds to variant rs28934568 [ dbSNP | Ensembl ].
VAR_022351
Natural varianti325 – 3251T → P in LDS2. 1 Publication
VAR_076169
Natural varianti336 – 3361Y → N in LDS2. 1 Publication
Corresponds to variant rs104893812 [ dbSNP | Ensembl ].
VAR_022352
Natural varianti355 – 3551A → P in LDS2. 1 Publication
Corresponds to variant rs104893813 [ dbSNP | Ensembl ].
VAR_022353
Natural varianti357 – 3571G → R in LDS2. 1 Publication
VAR_076170
Natural varianti357 – 3571G → W in LDS2. 1 Publication
Corresponds to variant rs104893814 [ dbSNP | Ensembl ].
VAR_022354
Natural varianti377 – 3771H → R in LDS2. 1 Publication
VAR_066724
Natural varianti446 – 4461D → N in LDS2. 1 Publication
VAR_066725
Natural varianti449 – 4491S → F in LDS2; has a negative effect on TGF-beta signaling. 2 Publications
Corresponds to variant rs104893807 [ dbSNP | Ensembl ].
VAR_022358
Natural varianti457 – 4571M → K in LDS2. 1 Publication
VAR_066726
Natural varianti460 – 4601R → C in LDS2. 1 Publication
Corresponds to variant rs104893811 [ dbSNP | Ensembl ].
VAR_029760
Natural varianti460 – 4601R → H in LDS2. 1 Publication
Corresponds to variant rs104893816 [ dbSNP | Ensembl ].
VAR_029761
Natural varianti509 – 5091G → V in LDS2. 1 Publication
VAR_066727
Natural varianti510 – 5101I → F in LDS2. 1 Publication
VAR_066728
Natural varianti510 – 5101I → S in LDS2. 1 Publication
VAR_066729
Natural varianti514 – 5141C → R in LDS2. 1 Publication
Corresponds to variant rs193922664 [ dbSNP | Ensembl ].
VAR_066730
Natural varianti521 – 5211W → R in LDS2. 1 Publication
VAR_066731
Natural varianti528 – 5281R → C in LDS2. 1 Publication
Corresponds to variant rs104893810 [ dbSNP | Ensembl ].
VAR_022360
Natural varianti528 – 5281R → H in LDS2. 2 Publications
Corresponds to variant rs104893815 [ dbSNP | Ensembl ].
VAR_022361
Natural varianti530 – 5301T → I in LDS2. 1 Publication
VAR_076171
Natural varianti537 – 5371R → C in LDS2; has a negative effect on TGF-beta signaling. 1 Publication
Corresponds to variant rs28934869 [ dbSNP | Ensembl ].
VAR_022362

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi277 – 2771K → R: Abolishes kinase activity, TGF-beta signaling and interaction with DAXX. 1 Publication

Keywords - Diseasei

Aortic aneurysm, Disease mutation, Hereditary nonpolyposis colorectal cancer

Organism-specific databases

MalaCardsiTGFBR2.
MIMi133239. phenotype.
610168. phenotype.
614331. phenotype.
Orphaneti91387. Familial thoracic aortic aneurysm and aortic dissection.
144. Hereditary nonpolyposis colon cancer.
60030. Loeys-Dietz syndrome.
284973. Marfan syndrome type 2.
PharmGKBiPA36486.

Chemistry

ChEMBLiCHEMBL4267.
GuidetoPHARMACOLOGYi1795.

Polymorphism and mutation databases

BioMutaiTGFBR2.
DMDMi116242818.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 22221 PublicationAdd
BLAST
Chaini23 – 567545TGF-beta receptor type-2PRO_0000024426Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi51 ↔ 845 Publications
Disulfide bondi54 ↔ 715 Publications
Disulfide bondi61 ↔ 675 Publications
Glycosylationi70 – 701N-linked (GlcNAc...)Sequence analysis
Disulfide bondi77 ↔ 1015 Publications
Glycosylationi94 – 941N-linked (GlcNAc...)Sequence analysis
Disulfide bondi121 ↔ 1365 Publications
Disulfide bondi138 ↔ 1435 Publications
Glycosylationi154 – 1541N-linked (GlcNAc...)Sequence analysis
Modified residuei409 – 4091PhosphoserineBy similarity
Modified residuei548 – 5481PhosphoserineCombined sources
Modified residuei553 – 5531PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP37173.
PaxDbiP37173.
PeptideAtlasiP37173.
PRIDEiP37173.

PTM databases

iPTMnetiP37173.
PhosphoSiteiP37173.

Expressioni

Gene expression databases

BgeeiENSG00000163513.
CleanExiHS_TGFBR2.
ExpressionAtlasiP37173. baseline and differential.
GenevisibleiP37173. HS.

Organism-specific databases

HPAiCAB073537.

Interactioni

Subunit structurei

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. Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2. Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DAXXQ9UER72EBI-296151,EBI-77321
MED12Q930743EBI-296151,EBI-394357
Med12A2AGH63EBI-296151,EBI-5744969From a different organism.
SCUBE3Q8IX306EBI-296151,EBI-4479975
TGFB1P011376EBI-296151,EBI-779636
TGFB1P072002EBI-296151,EBI-907660From a different organism.
TGFB3P106008EBI-296151,EBI-1033020

GO - Molecular functioni

  • SMAD binding Source: BHF-UCL
  • transforming growth factor beta binding Source: BHF-UCL
  • type III transforming growth factor beta receptor binding Source: BHF-UCL
  • type I transforming growth factor beta receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112906. 85 interactions.
DIPiDIP-5939N.
IntActiP37173. 26 interactions.
MINTiMINT-206666.
STRINGi9606.ENSP00000351905.

Chemistry

BindingDBiP37173.

Structurei

Secondary structure

1
567
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi40 – 456Combined sources
Beta strandi50 – 523Combined sources
Beta strandi55 – 584Combined sources
Beta strandi65 – 684Combined sources
Beta strandi74 – 763Combined sources
Beta strandi78 – 814Combined sources
Beta strandi83 – 908Combined sources
Beta strandi95 – 1028Combined sources
Beta strandi106 – 1105Combined sources
Turni114 – 1174Combined sources
Beta strandi119 – 1224Combined sources
Beta strandi124 – 1263Combined sources
Beta strandi131 – 1388Combined sources
Beta strandi140 – 1423Combined sources
Helixi143 – 1453Combined sources
Beta strandi146 – 1483Combined sources
Beta strandi149 – 1546Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KTZX-ray2.15B38-159[»]
1M9ZX-ray1.05A49-159[»]
1PLONMR-A38-159[»]
2PJYX-ray3.00B42-149[»]
3KFDX-ray3.00E/F/G/H38-153[»]
4P7UX-ray1.50A49-159[»]
4XJJX-ray1.40A50-159[»]
5E8VX-ray1.69A237-549[»]
5E8YX-ray2.05A237-549[»]
5E91X-ray2.42A237-549[»]
5E92X-ray2.08A237-549[»]
ProteinModelPortaliP37173.
SMRiP37173. Positions 48-153, 244-539.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP37173.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini244 – 544301Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG104975.
InParanoidiP37173.
KOiK04388.
OMAiTRHIISW.
PhylomeDBiP37173.
TreeFamiTF314724.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
IPR017194. Transform_growth_fac-b_typ-2.
IPR015013. Transforming_GF_b_rcpt_2_ecto.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF08917. ecTbetaR2. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF037393. TGFRII. 1 hit.
PRINTSiPR00653. ACTIVIN2R.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P37173-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGRGLLRGLW PLHIVLWTRI ASTIPPHVQK SVNNDMIVTD NNGAVKFPQL
60 70 80 90 100
CKFCDVRFST CDNQKSCMSN CSITSICEKP QEVCVAVWRK NDENITLETV
110 120 130 140 150
CHDPKLPYHD FILEDAASPK CIMKEKKKPG ETFFMCSCSS DECNDNIIFS
160 170 180 190 200
EEYNTSNPDL LLVIFQVTGI SLLPPLGVAI SVIIIFYCYR VNRQQKLSST
210 220 230 240 250
WETGKTRKLM EFSEHCAIIL EDDRSDISST CANNINHNTE LLPIELDTLV
260 270 280 290 300
GKGRFAEVYK AKLKQNTSEQ FETVAVKIFP YEEYASWKTE KDIFSDINLK
310 320 330 340 350
HENILQFLTA EERKTELGKQ YWLITAFHAK GNLQEYLTRH VISWEDLRKL
360 370 380 390 400
GSSLARGIAH LHSDHTPCGR PKMPIVHRDL KSSNILVKND LTCCLCDFGL
410 420 430 440 450
SLRLDPTLSV DDLANSGQVG TARYMAPEVL ESRMNLENVE SFKQTDVYSM
460 470 480 490 500
ALVLWEMTSR CNAVGEVKDY EPPFGSKVRE HPCVESMKDN VLRDRGRPEI
510 520 530 540 550
PSFWLNHQGI QMVCETLTEC WDHDPEARLT AQCVAERFSE LEHLDRLSGR
560
SCSEEKIPED GSLNTTK
Length:567
Mass (Da):64,568
Last modified:October 17, 2006 - v2
Checksum:iC541DA751FFBDBEB
GO
Isoform 2 (identifier: P37173-2) [UniParc]FASTAAdd to basket

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

Show »
Length:592
Mass (Da):67,457
Checksum:i8ADCBA70F95E1CBB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti381 – 3811K → N in BAA09332 (PubMed:8973329).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti36 – 361M → V.1 Publication
Corresponds to variant rs17025864 [ dbSNP | Ensembl ].
VAR_020510
Natural varianti61 – 611C → R in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
VAR_041414
Natural varianti73 – 731I → V in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036070
Natural varianti190 – 1901R → H in LDS2. 1 Publication
VAR_076167
Natural varianti191 – 1911V → I.2 Publications
Corresponds to variant rs56105708 [ dbSNP | Ensembl ].
VAR_017606
Natural varianti247 – 2471D → V in LDS2. 1 Publication
VAR_076168
Natural varianti306 – 3061Q → HE in LDS2. 1 Publication
VAR_066723
Natural varianti308 – 3081L → P in LDS2; has a negative effect on TGF-beta signaling. 2 Publications
Corresponds to variant rs28934568 [ dbSNP | Ensembl ].
VAR_022351
Natural varianti315 – 3151T → M in HNPCC6. 2 Publications
Corresponds to variant rs34833812 [ dbSNP | Ensembl ].
VAR_008156
Natural varianti325 – 3251T → P in LDS2. 1 Publication
VAR_076169
Natural varianti328 – 3281H → Y in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication
VAR_041415
Natural varianti336 – 3361Y → N in LDS2. 1 Publication
Corresponds to variant rs104893812 [ dbSNP | Ensembl ].
VAR_022352
Natural varianti355 – 3551A → P in LDS2. 1 Publication
Corresponds to variant rs104893813 [ dbSNP | Ensembl ].
VAR_022353
Natural varianti357 – 3571G → R in LDS2. 1 Publication
VAR_076170
Natural varianti357 – 3571G → W in LDS2. 1 Publication
Corresponds to variant rs104893814 [ dbSNP | Ensembl ].
VAR_022354
Natural varianti373 – 3731M → I.1 Publication
Corresponds to variant rs35719192 [ dbSNP | Ensembl ].
VAR_041416
Natural varianti377 – 3771H → R in LDS2. 1 Publication
VAR_066724
Natural varianti387 – 3871V → M in a breast tumor. 2 Publications
Corresponds to variant rs35766612 [ dbSNP | Ensembl ].
VAR_022355
Natural varianti435 – 4351N → S in a breast tumor; signaling of TGF-beta significantly inhibited. 1 Publication
VAR_022356
Natural varianti439 – 4391V → A.4 Publications
Corresponds to variant rs1050833 [ dbSNP | Ensembl ].
VAR_028063
Natural varianti446 – 4461D → N in LDS2. 1 Publication
VAR_066725
Natural varianti447 – 4471V → A in a breast tumor; signaling of TGF-beta significantly inhibited. 1 Publication
VAR_022357
Natural varianti449 – 4491S → F in LDS2; has a negative effect on TGF-beta signaling. 2 Publications
Corresponds to variant rs104893807 [ dbSNP | Ensembl ].
VAR_022358
Natural varianti452 – 4521L → M in a breast tumor; signaling of TGF-beta significantly inhibited. 1 Publication
VAR_022359
Natural varianti457 – 4571M → K in LDS2. 1 Publication
VAR_066726
Natural varianti460 – 4601R → C in LDS2. 1 Publication
Corresponds to variant rs104893811 [ dbSNP | Ensembl ].
VAR_029760
Natural varianti460 – 4601R → H in LDS2. 1 Publication
Corresponds to variant rs104893816 [ dbSNP | Ensembl ].
VAR_029761
Natural varianti490 – 4901N → S in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
VAR_041417
Natural varianti509 – 5091G → V in LDS2. 1 Publication
VAR_066727
Natural varianti510 – 5101I → F in LDS2. 1 Publication
VAR_066728
Natural varianti510 – 5101I → S in LDS2. 1 Publication
VAR_066729
Natural varianti514 – 5141C → R in LDS2. 1 Publication
Corresponds to variant rs193922664 [ dbSNP | Ensembl ].
VAR_066730
Natural varianti521 – 5211W → R in LDS2. 1 Publication
VAR_066731
Natural varianti526 – 5261E → Q in esophageal cancer. 1 Publication
Corresponds to variant rs121918714 [ dbSNP | Ensembl ].
VAR_015816
Natural varianti528 – 5281R → C in LDS2. 1 Publication
Corresponds to variant rs104893810 [ dbSNP | Ensembl ].
VAR_022360
Natural varianti528 – 5281R → H in LDS2. 2 Publications
Corresponds to variant rs104893815 [ dbSNP | Ensembl ].
VAR_022361
Natural varianti530 – 5301T → I in LDS2. 1 Publication
VAR_076171
Natural varianti537 – 5371R → C in LDS2; has a negative effect on TGF-beta signaling. 1 Publication
Corresponds to variant rs28934869 [ dbSNP | Ensembl ].
VAR_022362

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei31 – 322SV → SDVEMEAQKDEIICPSCNRT AHPLRHI in isoform 2. 2 PublicationsVSP_012157

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK300383 mRNA. Translation: BAG62117.1.
CH471055 Genomic DNA. Translation: EAW64412.1.
CCDSiCCDS2648.1. [P37173-1]
CCDS33727.1. [P37173-2]
PIRiA42100.
RefSeqiNP_001020018.1. NM_001024847.2. [P37173-2]
NP_003233.4. NM_003242.5. [P37173-1]
UniGeneiHs.604277.
Hs.82028.

Genome annotation databases

EnsembliENST00000295754; ENSP00000295754; ENSG00000163513. [P37173-1]
ENST00000359013; ENSP00000351905; ENSG00000163513. [P37173-2]
GeneIDi7048.
KEGGihsa:7048.
UCSCiuc003cen.4. human. [P37173-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK300383 mRNA. Translation: BAG62117.1.
CH471055 Genomic DNA. Translation: EAW64412.1.
CCDSiCCDS2648.1. [P37173-1]
CCDS33727.1. [P37173-2]
PIRiA42100.
RefSeqiNP_001020018.1. NM_001024847.2. [P37173-2]
NP_003233.4. NM_003242.5. [P37173-1]
UniGeneiHs.604277.
Hs.82028.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KTZX-ray2.15B38-159[»]
1M9ZX-ray1.05A49-159[»]
1PLONMR-A38-159[»]
2PJYX-ray3.00B42-149[»]
3KFDX-ray3.00E/F/G/H38-153[»]
4P7UX-ray1.50A49-159[»]
4XJJX-ray1.40A50-159[»]
5E8VX-ray1.69A237-549[»]
5E8YX-ray2.05A237-549[»]
5E91X-ray2.42A237-549[»]
5E92X-ray2.08A237-549[»]
ProteinModelPortaliP37173.
SMRiP37173. Positions 48-153, 244-539.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112906. 85 interactions.
DIPiDIP-5939N.
IntActiP37173. 26 interactions.
MINTiMINT-206666.
STRINGi9606.ENSP00000351905.

Chemistry

BindingDBiP37173.
ChEMBLiCHEMBL4267.
GuidetoPHARMACOLOGYi1795.

PTM databases

iPTMnetiP37173.
PhosphoSiteiP37173.

Polymorphism and mutation databases

BioMutaiTGFBR2.
DMDMi116242818.

Proteomic databases

MaxQBiP37173.
PaxDbiP37173.
PeptideAtlasiP37173.
PRIDEiP37173.

Protocols and materials databases

DNASUi7048.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295754; ENSP00000295754; ENSG00000163513. [P37173-1]
ENST00000359013; ENSP00000351905; ENSG00000163513. [P37173-2]
GeneIDi7048.
KEGGihsa:7048.
UCSCiuc003cen.4. human. [P37173-1]

Organism-specific databases

CTDi7048.
GeneCardsiTGFBR2.
GeneReviewsiTGFBR2.
H-InvDBHIX0024332.
HGNCiHGNC:11773. TGFBR2.
HPAiCAB073537.
MalaCardsiTGFBR2.
MIMi133239. phenotype.
190182. gene.
610168. phenotype.
614331. phenotype.
neXtProtiNX_P37173.
Orphaneti91387. Familial thoracic aortic aneurysm and aortic dissection.
144. Hereditary nonpolyposis colon cancer.
60030. Loeys-Dietz syndrome.
284973. Marfan syndrome type 2.
PharmGKBiPA36486.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3653. Eukaryota.
ENOG410XS2Z. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000231495.
HOVERGENiHBG104975.
InParanoidiP37173.
KOiK04388.
OMAiTRHIISW.
PhylomeDBiP37173.
TreeFamiTF314724.

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-2173788. Downregulation of TGF-beta receptor signaling.
R-HSA-2173789. TGF-beta receptor signaling activates SMADs.
R-HSA-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
R-HSA-3304356. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
R-HSA-3315487. SMAD2/3 MH2 Domain Mutants in Cancer.
R-HSA-3642279. TGFBR2 MSI Frameshift Mutants in Cancer.
R-HSA-3645790. TGFBR2 Kinase Domain Mutants in Cancer.
R-HSA-3656532. TGFBR1 KD Mutants in Cancer.
R-HSA-3656535. TGFBR1 LBD Mutants in Cancer.
SignaLinkiP37173.
SIGNORiP37173.

Miscellaneous databases

ChiTaRSiTGFBR2. human.
EvolutionaryTraceiP37173.
GeneWikiiTGF_beta_receptor_2.
GenomeRNAii7048.
PROiP37173.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163513.
CleanExiHS_TGFBR2.
ExpressionAtlasiP37173. baseline and differential.
GenevisibleiP37173. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
IPR017194. Transform_growth_fac-b_typ-2.
IPR015013. Transforming_GF_b_rcpt_2_ecto.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF08917. ecTbetaR2. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF037393. TGFRII. 1 hit.
PRINTSiPR00653. ACTIVIN2R.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTGFR2_HUMAN
AccessioniPrimary (citable) accession number: P37173
Secondary accession number(s): B4DTV5
, Q15580, Q6DKT6, Q99474
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 17, 2006
Last modified: September 7, 2016
This is version 198 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.