P37173 · TGFR2_HUMAN
- ProteinTGF-beta receptor type-2
- GeneTGFBR2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids567 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Isoform 1
Isoform 2
Isoform 3
Catalytic activity
- ATP + L-threonyl-[receptor-protein] = ADP + H+ + O-phospho-L-threonyl-[receptor-protein]
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTGF-beta receptor type-2
- EC number
- Short namesTGFR-2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP37173
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Isoform 3
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 23-166 | Extracellular | ||||
Sequence: TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDLLLVIFQ | ||||||
Transmembrane | 167-187 | Helical | ||||
Sequence: VTGISLLPPLGVAISVIIIFY | ||||||
Topological domain | 188-567 | Cytoplasmic | ||||
Sequence: CYRVNRQQKLSSTWETGKTRKLMEFSEHCAIILEDDRSDISSTCANNINHNTELLPIELDTLVGKGRFAEVYKAKLKQNTSEQFETVAVKIFPYEEYASWKTEKDIFSDINLKHENILQFLTAEERKTELGKQYWLITAFHAKGNLQEYLTRHVISWEDLRKLGSSLARGIAHLHSDHTPCGRPKMPIVHRDLKSSNILVKNDLTCCLCDFGLSLRLDPTLSVDDLANSGQVGTARYMAPEVLESRMNLENVESFKQTDVYSMALVLWEMTSRCNAVGEVKDYEPPFGSKVREHPCVESMKDNVLRDRGRPEIPSFWLNHQGIQMVCETLTECWDHDPEARLTAQCVAERFSELEHLDRLSGRSCSEEKIPEDGSLNTTK |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Hereditary non-polyposis colorectal cancer 6 (HNPCC6)
- Note
- 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 alsoMIM:614331
Natural variants in HNPCC6
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_008156 | 315 | T>M | in HNPCC6; dbSNP:rs34833812 |
Esophageal cancer (ESCR)
- Note
- 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 alsoMIM:133239
Loeys-Dietz syndrome 2 (LDS2)
- Note
- 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 alsoMIM:610168
Natural variants in LDS2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_076167 | 190 | R>H | in LDS2; dbSNP:rs780542125 | |
VAR_076168 | 247 | D>V | in LDS2; dbSNP:rs761231369 | |
VAR_066723 | 306 | Q>HE | in LDS2 | |
VAR_022351 | 308 | L>P | in LDS2; has a negative effect on TGF-beta signaling; dbSNP:rs28934568 | |
VAR_076169 | 325 | T>P | in LDS2; dbSNP:rs2125435431 | |
VAR_022352 | 336 | Y>N | in LDS2; dbSNP:rs104893812 | |
VAR_022353 | 355 | A>P | in LDS2; dbSNP:rs104893813 | |
VAR_076170 | 357 | G>R | in LDS2 | |
VAR_022354 | 357 | G>W | in LDS2; dbSNP:rs104893814 | |
VAR_066724 | 377 | H>R | in LDS2; dbSNP:rs1553630274 | |
VAR_066725 | 446 | D>N | in LDS2; dbSNP:rs886039551 | |
VAR_022358 | 449 | S>F | in LDS2; has a negative effect on TGF-beta signaling; dbSNP:rs104893807 | |
VAR_066726 | 457 | M>K | in LDS2 | |
VAR_029760 | 460 | R>C | in LDS2; dbSNP:rs104893811 | |
VAR_029761 | 460 | R>H | in LDS2; dbSNP:rs104893816 | |
VAR_066727 | 509 | G>V | in LDS2; dbSNP:rs863223853 | |
VAR_066728 | 510 | I>F | in LDS2; dbSNP:rs2125455070 | |
VAR_066729 | 510 | I>S | in LDS2 | |
VAR_066730 | 514 | C>R | in LDS2; dbSNP:rs193922664 | |
VAR_066731 | 521 | W>R | in LDS2; dbSNP:rs1575166666 | |
VAR_022360 | 528 | R>C | in LDS2; dbSNP:rs104893810 | |
VAR_022361 | 528 | R>H | in LDS2; dbSNP:rs104893815 | |
VAR_076171 | 530 | T>I | in LDS2; dbSNP:rs1699708963 | |
VAR_022362 | 537 | R>C | in LDS2; has a negative effect on TGF-beta signaling; dbSNP:rs104893809 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_020510 | 36 | in dbSNP:rs17025864 | |||
Sequence: M → V | ||||||
Natural variant | VAR_041414 | 61 | in a gastric adenocarcinoma sample; somatic mutation | |||
Sequence: C → R | ||||||
Natural variant | VAR_036070 | 73 | in a colorectal cancer sample; somatic mutation | |||
Sequence: I → V | ||||||
Natural variant | VAR_076167 | 190 | in LDS2; dbSNP:rs780542125 | |||
Sequence: R → H | ||||||
Natural variant | VAR_017606 | 191 | in dbSNP:rs56105708 | |||
Sequence: V → I | ||||||
Natural variant | VAR_076168 | 247 | in LDS2; dbSNP:rs761231369 | |||
Sequence: D → V | ||||||
Mutagenesis | 277 | Abolishes kinase activity, TGF-beta signaling and interaction with DAXX. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_066723 | 306 | in LDS2 | |||
Sequence: Q → HE | ||||||
Natural variant | VAR_022351 | 308 | in LDS2; has a negative effect on TGF-beta signaling; dbSNP:rs28934568 | |||
Sequence: L → P | ||||||
Natural variant | VAR_008156 | 315 | in HNPCC6; dbSNP:rs34833812 | |||
Sequence: T → M | ||||||
Natural variant | VAR_076169 | 325 | in LDS2; dbSNP:rs2125435431 | |||
Sequence: T → P | ||||||
Natural variant | VAR_041415 | 328 | in a lung neuroendocrine carcinoma sample; somatic mutation; dbSNP:rs2125435491 | |||
Sequence: H → Y | ||||||
Natural variant | VAR_022352 | 336 | in LDS2; dbSNP:rs104893812 | |||
Sequence: Y → N | ||||||
Natural variant | VAR_022353 | 355 | in LDS2; dbSNP:rs104893813 | |||
Sequence: A → P | ||||||
Natural variant | VAR_076170 | 357 | in LDS2 | |||
Sequence: G → R | ||||||
Natural variant | VAR_022354 | 357 | in LDS2; dbSNP:rs104893814 | |||
Sequence: G → W | ||||||
Natural variant | VAR_041416 | 373 | in dbSNP:rs35719192 | |||
Sequence: M → I | ||||||
Natural variant | VAR_066724 | 377 | in LDS2; dbSNP:rs1553630274 | |||
Sequence: H → R | ||||||
Natural variant | VAR_022355 | 387 | in a breast tumor; dbSNP:rs35766612 | |||
Sequence: V → M | ||||||
Natural variant | VAR_022356 | 435 | in a breast tumor; signaling of TGF-beta significantly inhibited | |||
Sequence: N → S | ||||||
Natural variant | VAR_028063 | 439 | in dbSNP:rs1050833 | |||
Sequence: V → A | ||||||
Natural variant | VAR_066725 | 446 | in LDS2; dbSNP:rs886039551 | |||
Sequence: D → N | ||||||
Natural variant | VAR_022357 | 447 | in a breast tumor; signaling of TGF-beta significantly inhibited | |||
Sequence: V → A | ||||||
Natural variant | VAR_022358 | 449 | in LDS2; has a negative effect on TGF-beta signaling; dbSNP:rs104893807 | |||
Sequence: S → F | ||||||
Natural variant | VAR_022359 | 452 | in a breast tumor; signaling of TGF-beta significantly inhibited | |||
Sequence: L → M | ||||||
Natural variant | VAR_066726 | 457 | in LDS2 | |||
Sequence: M → K | ||||||
Natural variant | VAR_029760 | 460 | in LDS2; dbSNP:rs104893811 | |||
Sequence: R → C | ||||||
Natural variant | VAR_029761 | 460 | in LDS2; dbSNP:rs104893816 | |||
Sequence: R → H | ||||||
Natural variant | VAR_041417 | 490 | in a gastric adenocarcinoma sample; somatic mutation; dbSNP:rs1699660823 | |||
Sequence: N → S | ||||||
Natural variant | VAR_066727 | 509 | in LDS2; dbSNP:rs863223853 | |||
Sequence: G → V | ||||||
Natural variant | VAR_066728 | 510 | in LDS2; dbSNP:rs2125455070 | |||
Sequence: I → F | ||||||
Natural variant | VAR_066729 | 510 | in LDS2 | |||
Sequence: I → S | ||||||
Natural variant | VAR_066730 | 514 | in LDS2; dbSNP:rs193922664 | |||
Sequence: C → R | ||||||
Natural variant | VAR_066731 | 521 | in LDS2; dbSNP:rs1575166666 | |||
Sequence: W → R | ||||||
Natural variant | VAR_015816 | 526 | in esophageal cancer; dbSNP:rs121918714 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_022360 | 528 | in LDS2; dbSNP:rs104893810 | |||
Sequence: R → C | ||||||
Natural variant | VAR_022361 | 528 | in LDS2; dbSNP:rs104893815 | |||
Sequence: R → H | ||||||
Natural variant | VAR_076171 | 530 | in LDS2; dbSNP:rs1699708963 | |||
Sequence: T → I | ||||||
Natural variant | VAR_022362 | 537 | in LDS2; has a negative effect on TGF-beta signaling; dbSNP:rs104893809 | |||
Sequence: R → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2,046 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-22 | UniProt | |||||
Sequence: MGRGLLRGLWPLHIVLWTRIAS | |||||||
Chain | PRO_0000024426 | 23-567 | UniProt | TGF-beta receptor type-2 | |||
Sequence: TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDLLLVIFQVTGISLLPPLGVAISVIIIFYCYRVNRQQKLSSTWETGKTRKLMEFSEHCAIILEDDRSDISSTCANNINHNTELLPIELDTLVGKGRFAEVYKAKLKQNTSEQFETVAVKIFPYEEYASWKTEKDIFSDINLKHENILQFLTAEERKTELGKQYWLITAFHAKGNLQEYLTRHVISWEDLRKLGSSLARGIAHLHSDHTPCGRPKMPIVHRDLKSSNILVKNDLTCCLCDFGLSLRLDPTLSVDDLANSGQVGTARYMAPEVLESRMNLENVESFKQTDVYSMALVLWEMTSRCNAVGEVKDYEPPFGSKVREHPCVESMKDNVLRDRGRPEIPSFWLNHQGIQMVCETLTECWDHDPEARLTAQCVAERFSELEHLDRLSGRSCSEEKIPEDGSLNTTK | |||||||
Disulfide bond | 51↔84 | UniProt | |||||
Sequence: CKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVC | |||||||
Disulfide bond | 54↔71 | UniProt | |||||
Sequence: CDVRFSTCDNQKSCMSNC | |||||||
Disulfide bond | 61↔67 | UniProt | |||||
Sequence: CDNQKSC | |||||||
Glycosylation | 70 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 77↔101 | UniProt | |||||
Sequence: CEKPQEVCVAVWRKNDENITLETVC | |||||||
Glycosylation | 94 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 121↔136 | UniProt | |||||
Sequence: CIMKEKKKPGETFFMC | |||||||
Disulfide bond | 138↔143 | UniProt | |||||
Sequence: CSSDEC | |||||||
Glycosylation | 154 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 409 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 409 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 486 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 548 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 548 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 551 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 553 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 553 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts with DAXX. Interacts with DYNLT4. 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. Interacts with CLU (PubMed:8555189).
Isoform 3
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 244-544 | Protein kinase | ||||
Sequence: IELDTLVGKGRFAEVYKAKLKQNTSEQFETVAVKIFPYEEYASWKTEKDIFSDINLKHENILQFLTAEERKTELGKQYWLITAFHAKGNLQEYLTRHVISWEDLRKLGSSLARGIAHLHSDHTPCGRPKMPIVHRDLKSSNILVKNDLTCCLCDFGLSLRLDPTLSVDDLANSGQVGTARYMAPEVLESRMNLENVESFKQTDVYSMALVLWEMTSRCNAVGEVKDYEPPFGSKVREHPCVESMKDNVLRDRGRPEIPSFWLNHQGIQMVCETLTECWDHDPEARLTAQCVAERFSELEHL | ||||||
Region | 439-567 | Sufficient for interaction with CLU | ||||
Sequence: VESFKQTDVYSMALVLWEMTSRCNAVGEVKDYEPPFGSKVREHPCVESMKDNVLRDRGRPEIPSFWLNHQGIQMVCETLTECWDHDPEARLTAQCVAERFSELEHLDRLSGRSCSEEKIPEDGSLNTTK |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
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.
- Name1
- SynonymsbetaR-II
- Length567
- Mass (Da)64,568
- Last updated2006-10-17 v2
- ChecksumC541DA751FFBDBEB
P37173-2
- Name2
- SynonymsbetaR-IIB
- Differences from canonical
- 31-32: SV → SDVEMEAQKDEIICPSCNRTAHPLRHI
P37173-3
- Name3
- SynonymsTbetaRII-SE
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0AAQ5BI02 | A0AAQ5BI02_HUMAN | TGFBR2 | 87 | ||
A0AAQ5BI03 | A0AAQ5BI03_HUMAN | TGFBR2 | 558 | ||
A0AAQ5BI06 | A0AAQ5BI06_HUMAN | TGFBR2 | 532 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_012157 | 31-32 | in isoform 2 | |||
Sequence: SV → SDVEMEAQKDEIICPSCNRTAHPLRHI | ||||||
Alternative sequence | VSP_061513 | 68-80 | in isoform 3 | |||
Sequence: MSNCSITSICEKP → FSKVHYEGKKKAW | ||||||
Alternative sequence | VSP_061514 | 81-567 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 381 | in Ref. 6; BAA09332 | ||||
Sequence: K → N |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M85079 EMBL· GenBank· DDBJ | AAA61164.1 EMBL· GenBank· DDBJ | mRNA | ||
D28131 EMBL· GenBank· DDBJ | BAA05673.1 EMBL· GenBank· DDBJ | mRNA | ||
U52246 EMBL· GenBank· DDBJ | AAB17553.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U52240 EMBL· GenBank· DDBJ | AAB17553.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U52241 EMBL· GenBank· DDBJ | AAB17553.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U52242 EMBL· GenBank· DDBJ | AAB17553.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U52244 EMBL· GenBank· DDBJ | AAB17553.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U52245 EMBL· GenBank· DDBJ | AAB17553.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U69152 EMBL· GenBank· DDBJ | AAB40916.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U69146 EMBL· GenBank· DDBJ | AAB40916.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U69147 EMBL· GenBank· DDBJ | AAB40916.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U69148 EMBL· GenBank· DDBJ | AAB40916.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U69149 EMBL· GenBank· DDBJ | AAB40916.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U69150 EMBL· GenBank· DDBJ | AAB40916.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U69151 EMBL· GenBank· DDBJ | AAB40916.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
D50683 EMBL· GenBank· DDBJ | BAA09332.1 EMBL· GenBank· DDBJ | mRNA | ||
MW881156 EMBL· GenBank· DDBJ | UDE22710.1 EMBL· GenBank· DDBJ | mRNA | ||
AY675319 EMBL· GenBank· DDBJ | AAT70724.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK300383 EMBL· GenBank· DDBJ | BAG62117.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471055 EMBL· GenBank· DDBJ | EAW64412.1 EMBL· GenBank· DDBJ | Genomic DNA |