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Protein

TGF-beta receptor type-1

Gene

TGFBR1

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 II serine/threonine kinase receptor, TGFBR2, 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 TGFBR1 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. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.7 Publications

Catalytic activityi

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

Cofactori

Mg2+By similarity, Mn2+By similarity

Enzyme regulationi

Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei232ATPPROSITE-ProRule annotation1
Active sitei333Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi211 – 219ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: HGNC
  • I-SMAD binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activity Source: BHF-UCL
  • protein serine/threonine kinase activity Source: HGNC
  • receptor signaling protein serine/threonine kinase activity Source: Ensembl
  • signal transducer activity, downstream of receptor Source: AgBase
  • SMAD binding Source: HGNC
  • 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 I Source: BHF-UCL
  • type II 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

BioCyciZFISH:HS02952-MONOMER.
BRENDAi2.7.10.2. 2681.
2.7.11.30. 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-3645790. TGFBR2 Kinase Domain Mutants in Cancer.
R-HSA-3656532. TGFBR1 KD Mutants in Cancer.
R-HSA-3656535. TGFBR1 LBD Mutants in Cancer.
R-HSA-5689603. UCH proteinases.
R-HSA-5689880. Ub-specific processing proteases.
SignaLinkiP36897.
SIGNORiP36897.

Names & Taxonomyi

Protein namesi
Recommended name:
TGF-beta receptor type-1 (EC:2.7.11.30)
Short name:
TGFR-1
Alternative name(s):
Activin A receptor type II-like protein kinase of 53kD
Activin receptor-like kinase 5
Short name:
ALK-5
Short name:
ALK5
Serine/threonine-protein kinase receptor R4
Short name:
SKR4
TGF-beta type I receptor
Transforming growth factor-beta receptor type I
Short name:
TGF-beta receptor type I
Short name:
TbetaR-I
Gene namesi
Name:TGFBR1
Synonyms:ALK5, SKR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:11772. TGFBR1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini34 – 126ExtracellularSequence analysisAdd BLAST93
Transmembranei127 – 147HelicalSequence analysisAdd BLAST21
Topological domaini148 – 503CytoplasmicSequence analysisAdd BLAST356

GO - Cellular componenti

  • bicellular tight junction Source: UniProtKB
  • cell Source: AgBase
  • cell surface Source: UniProtKB
  • endosome Source: Ensembl
  • intracellular Source: GOC
  • membrane Source: AgBase
  • 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 junction, Cell membrane, Membrane, Tight junction

Pathology & Biotechi

Involvement in diseasei

Loeys-Dietz syndrome 1 (LDS1)6 Publications
The disease is caused by mutations affecting the gene represented in this entry. TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS1 by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS1 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:609192
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022344200T → I in LDS1. 1 PublicationCorresponds to variant rs121918712dbSNPEnsembl.1
Natural variantiVAR_029481232K → E in LDS1. 1 Publication1
Natural variantiVAR_029482241S → L in LDS1. 2 PublicationsCorresponds to variant rs111854391dbSNPEnsembl.1
Natural variantiVAR_066720266D → Y in LDS1. 1 Publication1
Natural variantiVAR_022345318M → R in LDS1. 1 PublicationCorresponds to variant rs121918710dbSNPEnsembl.1
Natural variantiVAR_066721351D → G in LDS1. 1 Publication1
Natural variantiVAR_066722375T → R in LDS1. 1 Publication1
Natural variantiVAR_022346400D → G in LDS1. 1 PublicationCorresponds to variant rs121918711dbSNPEnsembl.1
Natural variantiVAR_022347487R → P in LDS1. 2 PublicationsCorresponds to variant rs113605875dbSNPEnsembl.1
Natural variantiVAR_029484487R → Q in LDS1. 3 PublicationsCorresponds to variant rs113605875dbSNPEnsembl.1
Natural variantiVAR_029485487R → W in LDS1. 1 PublicationCorresponds to variant rs111426349dbSNPEnsembl.1
Multiple self-healing squamous epithelioma (MSSE)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.
See also OMIM:132800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06582641C → Y in MSSE; hypomorphic mutation. 1 Publication1
Natural variantiVAR_06582745N → S in MSSE; hypomorphic mutation. 1 PublicationCorresponds to variant rs387906696dbSNPEnsembl.1
Natural variantiVAR_06582852G → R in MSSE; hypomorphic mutation. 1 PublicationCorresponds to variant rs587776865dbSNPEnsembl.1
Natural variantiVAR_06582983P → L in MSSE; hypomorphic mutation. 1 PublicationCorresponds to variant rs757374917dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi185 – 186TT → VV: Loss of phosphorylation on threonine residues. Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with A-187; A-189 and A-191. 1 Publication2
Mutagenesisi187S → A: Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-189 and A-191. 1 Publication1
Mutagenesisi189S → A: Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-187 and A-191. 1 Publication1
Mutagenesisi191S → A: Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-187 and A-189. 1 Publication1
Mutagenesisi193L → G: Loss of interaction with FKBP1A. 1 Publication1
Mutagenesisi194P → K: Loss of interaction with FKBP1A. 1 Publication1
Mutagenesisi200T → D: Loss of response to TGF-beta. 1 Publication1
Mutagenesisi200T → V: Loss of phosphorylation. Loss of response to TGF-beta. 1 Publication1
Mutagenesisi204T → D: Constitutive activation. 1 Publication1
Mutagenesisi204T → V: Reduced phosphorylation. Reduced response to TGF-beta. 1 Publication1

Keywords - Diseasei

Aortic aneurysm, Craniosynostosis, Disease mutation

Organism-specific databases

DisGeNETi7046.
MalaCardsiTGFBR1.
MIMi132800. phenotype.
609192. phenotype.
OpenTargetsiENSG00000106799.
Orphaneti91387. Familial thoracic aortic aneurysm and aortic dissection.
60030. Loeys-Dietz syndrome.
65748. Multiple keratoacanthoma, Ferguson-Smith type.
PharmGKBiPA36485.

Chemistry databases

ChEMBLiCHEMBL4439.
GuidetoPHARMACOLOGYi1788.

Polymorphism and mutation databases

BioMutaiTGFBR1.
DMDMi547777.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 331 PublicationAdd BLAST33
ChainiPRO_000002442334 – 503TGF-beta receptor type-1Add BLAST470

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 542 Publications
Disulfide bondi38 ↔ 412 Publications
Glycosylationi45N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi48 ↔ 712 Publications
Disulfide bondi86 ↔ 1002 Publications
Disulfide bondi101 ↔ 1062 Publications
Modified residuei165PhosphoserineCombined sources1
Modified residuei185Phosphothreonine; by TGFBR21 Publication1
Modified residuei186Phosphothreonine; by TGFBR21 Publication1
Modified residuei187Phosphoserine; by TGFBR21 Publication1
Modified residuei189Phosphoserine; by TGFBR21 Publication1
Modified residuei191Phosphoserine; by TGFBR21 Publication1
Cross-linki391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Phosphorylated at basal levels in the absence of ligand. Activated upon phosphorylation by TGFBR2, mainly in the GS domain. Phosphorylation in the GS domain abrogates FKBP1A-binding.2 Publications
N-Glycosylated.1 Publication
Ubiquitinated; undergoes ubiquitination catalyzed by several E3 ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the proteasomal and/or lysosomal degradation of the receptor thereby negatively regulating its activity. Deubiquitinated by USP15, leading to stabilization of the protein and enhanced TGF-beta signal. Its ubiquitination and proteasome-mediated degradation is negatively regulated by SDCBP (PubMed:25893292).3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP36897.
PaxDbiP36897.
PeptideAtlasiP36897.
PRIDEiP36897.

PTM databases

iPTMnetiP36897.
PhosphoSitePlusiP36897.

Expressioni

Tissue specificityi

Found in all tissues examined, most abundant in placenta and least abundant in brain and heart. Expressed in a variety of cancer cell lines (PubMed:25893292).1 Publication

Gene expression databases

BgeeiENSG00000106799.
CleanExiHS_TGFBR1.
ExpressionAtlasiP36897. baseline and differential.
GenevisibleiP36897. HS.

Organism-specific databases

HPAiCAB002441.
CAB031481.

Interactioni

Subunit structurei

Homodimer; in the endoplasmic reticulum but also at the cell membrane. 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 TGBRB1 and TGFBR2 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 CD109; inhibits TGF-beta receptor activation in keratinocytes. Interacts with RBPMS. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with SMAD7, NEDD4L, SMURF1 and SMURF2; SMAD7 recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor. Interacts with USP15 and VPS39. Interacts with SDCBP (via C-terminus) (PubMed:25893292) Interacts with CAV1 and this interaction is impaired in the presence of SDCBP (PubMed:25893292).21 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q99IB85EBI-1027557,EBI-6858501From a different organism.
FKBP1AP629422EBI-1027557,EBI-1027571
TGFB1P011372EBI-1027557,EBI-779636
YWHAZP631044EBI-1027557,EBI-347088

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi112904. 181 interactors.
DIPiDIP-5935N.
IntActiP36897. 14 interactors.
MINTiMINT-152959.
STRINGi9606.ENSP00000364133.

Chemistry databases

BindingDBiP36897.

Structurei

Secondary structure

1503
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 37Combined sources3
Turni42 – 46Combined sources5
Beta strandi51 – 57Combined sources7
Beta strandi61 – 63Combined sources3
Beta strandi69 – 72Combined sources4
Turni74 – 76Combined sources3
Beta strandi77 – 82Combined sources6
Turni84 – 86Combined sources3
Helixi89 – 92Combined sources4
Beta strandi94 – 101Combined sources8
Beta strandi102 – 105Combined sources4
Helixi107 – 109Combined sources3
Helixi177 – 183Combined sources7
Beta strandi187 – 190Combined sources4
Beta strandi191 – 193Combined sources3
Helixi202 – 204Combined sources3
Beta strandi205 – 213Combined sources9
Beta strandi215 – 224Combined sources10
Beta strandi227 – 234Combined sources8
Helixi236 – 238Combined sources3
Helixi239 – 249Combined sources11
Beta strandi251 – 253Combined sources3
Beta strandi262 – 269Combined sources8
Beta strandi271 – 281Combined sources11
Helixi288 – 294Combined sources7
Helixi299 – 317Combined sources19
Beta strandi322 – 324Combined sources3
Beta strandi328 – 330Combined sources3
Helixi336 – 338Combined sources3
Beta strandi339 – 341Combined sources3
Beta strandi347 – 349Combined sources3
Helixi352 – 354Combined sources3
Beta strandi356 – 359Combined sources4
Turni360 – 363Combined sources4
Beta strandi364 – 367Combined sources4
Beta strandi368 – 371Combined sources4
Helixi376 – 378Combined sources3
Helixi381 – 384Combined sources4
Helixi393 – 413Combined sources21
Beta strandi417 – 419Combined sources3
Turni427 – 431Combined sources5
Helixi438 – 445Combined sources8
Helixi456 – 460Combined sources5
Helixi462 – 474Combined sources13
Helixi479 – 481Combined sources3
Helixi485 – 497Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B6CX-ray2.60B/D/F/H162-503[»]
1IASX-ray2.90A/B/C/D/E162-503[»]
1PY5X-ray2.30A175-500[»]
1RW8X-ray2.40A200-500[»]
1TBImodel-A34-114[»]
1VJYX-ray2.00A201-503[»]
2L5SNMR-A31-115[»]
2PJYX-ray3.00C33-111[»]
2WOTX-ray1.85A200-503[»]
2WOUX-ray2.30A200-503[»]
2X7OX-ray3.70A/B/C/D/E162-503[»]
3FAAX-ray3.35A/B/C/D/E162-503[»]
3GXLX-ray1.80A201-503[»]
3HMMX-ray1.70A201-503[»]
3KCFX-ray2.80A/B/C/D/E162-503[»]
3KFDX-ray3.00I/J/K/L31-115[»]
3TZMX-ray1.70A200-503[»]
4X0MX-ray1.68A200-503[»]
4X2FX-ray1.49A200-503[»]
4X2GX-ray1.51A200-503[»]
4X2JX-ray1.69A200-503[»]
4X2KX-ray1.69A200-503[»]
4X2NX-ray1.80A200-503[»]
5E8SX-ray1.45A200-503[»]
5E8TX-ray1.70A200-503[»]
5E8UX-ray2.03A200-503[»]
5E8WX-ray1.86A200-503[»]
5E8XX-ray1.45A200-503[»]
5E8ZX-ray1.51A200-503[»]
5E90X-ray2.05A200-503[»]
5FRIX-ray2.00A200-498[»]
ProteinModelPortaliP36897.
SMRiP36897.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP36897.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini175 – 204GSPROSITE-ProRule annotationAdd BLAST30
Domaini205 – 495Protein kinasePROSITE-ProRule annotationAdd BLAST291

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi193 – 194FKBP1A-binding2

Sequence similaritiesi

Contains 1 GS domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2052. Eukaryota.
ENOG410XQT0. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiP36897.
KOiK04674.
OMAiGATALQC.
OrthoDBiEOG091G0BIU.
PhylomeDBiP36897.
TreeFamiTF314724.

Family and domain databases

InterProiIPR000472. Activin_recp.
IPR003605. GS_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTiSM00467. GS. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P36897-1) [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
MEAAVAAPRP RLLLLVLAAA AAAAAALLPG ATALQCFCHL CTKDNFTCVT
60 70 80 90 100
DGLCFVSVTE TTDKVIHNSM CIAEIDLIPR DRPFVCAPSS KTGSVTTTYC
110 120 130 140 150
CNQDHCNKIE LPTTVKSSPG LGPVELAAVI AGPVCFVCIS LMLMVYICHN
160 170 180 190 200
RTVIHHRVPN EEDPSLDRPF ISEGTTLKDL IYDMTTSGSG SGLPLLVQRT
210 220 230 240 250
IARTIVLQES IGKGRFGEVW RGKWRGEEVA VKIFSSREER SWFREAEIYQ
260 270 280 290 300
TVMLRHENIL GFIAADNKDN GTWTQLWLVS DYHEHGSLFD YLNRYTVTVE
310 320 330 340 350
GMIKLALSTA SGLAHLHMEI VGTQGKPAIA HRDLKSKNIL VKKNGTCCIA
360 370 380 390 400
DLGLAVRHDS ATDTIDIAPN HRVGTKRYMA PEVLDDSINM KHFESFKRAD
410 420 430 440 450
IYAMGLVFWE IARRCSIGGI HEDYQLPYYD LVPSDPSVEE MRKVVCEQKL
460 470 480 490 500
RPNIPNRWQS CEALRVMAKI MRECWYANGA ARLTALRIKK TLSQLSQQEG

IKM
Length:503
Mass (Da):55,960
Last modified:June 1, 1994 - v1
Checksum:i179F11404725DDCB
GO
Isoform 2 (identifier: P36897-2) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     114-114: T → TGPFS

Show »
Length:507
Mass (Da):56,348
Checksum:i9EFAF4435F30E4C2
GO
Isoform 3 (identifier: P36897-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     115-191: Missing.

Show »
Length:426
Mass (Da):47,690
Checksum:i97EA2F587AFA08F6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02234224 – 26Missing in allele TGFBR1*6A; could be a tumor susceptibility allele. 3
Natural variantiVAR_02234326A → AA in allele TGFBR1*10A; rare polymorphism. 1 Publication1
Natural variantiVAR_06582641C → Y in MSSE; hypomorphic mutation. 1 Publication1
Natural variantiVAR_06582745N → S in MSSE; hypomorphic mutation. 1 PublicationCorresponds to variant rs387906696dbSNPEnsembl.1
Natural variantiVAR_06582852G → R in MSSE; hypomorphic mutation. 1 PublicationCorresponds to variant rs587776865dbSNPEnsembl.1
Natural variantiVAR_06582983P → L in MSSE; hypomorphic mutation. 1 PublicationCorresponds to variant rs757374917dbSNPEnsembl.1
Natural variantiVAR_054160139I → V.1 PublicationCorresponds to variant rs148176750dbSNPEnsembl.1
Natural variantiVAR_041412153V → I.1 PublicationCorresponds to variant rs56014374dbSNPEnsembl.1
Natural variantiVAR_022344200T → I in LDS1. 1 PublicationCorresponds to variant rs121918712dbSNPEnsembl.1
Natural variantiVAR_029481232K → E in LDS1. 1 Publication1
Natural variantiVAR_029482241S → L in LDS1. 2 PublicationsCorresponds to variant rs111854391dbSNPEnsembl.1
Natural variantiVAR_066720266D → Y in LDS1. 1 Publication1
Natural variantiVAR_029483267N → H in a patient with Marfan syndrome. 1 Publication1
Natural variantiVAR_041413291Y → C.1 PublicationCorresponds to variant rs35974499dbSNPEnsembl.1
Natural variantiVAR_022345318M → R in LDS1. 1 PublicationCorresponds to variant rs121918710dbSNPEnsembl.1
Natural variantiVAR_066721351D → G in LDS1. 1 Publication1
Natural variantiVAR_066722375T → R in LDS1. 1 Publication1
Natural variantiVAR_022346400D → G in LDS1. 1 PublicationCorresponds to variant rs121918711dbSNPEnsembl.1
Natural variantiVAR_022347487R → P in LDS1. 2 PublicationsCorresponds to variant rs113605875dbSNPEnsembl.1
Natural variantiVAR_029484487R → Q in LDS1. 3 PublicationsCorresponds to variant rs113605875dbSNPEnsembl.1
Natural variantiVAR_029485487R → W in LDS1. 1 PublicationCorresponds to variant rs111426349dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041326114T → TGPFS in isoform 2. 1 Publication1
Alternative sequenceiVSP_041327115 – 191Missing in isoform 3. 1 PublicationAdd BLAST77

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11695 mRNA. Translation: AAA16073.1.
AF054598
, AF054590, AF054591, AF054592, AF054593, AF054594, AF054595, AF054596, AF054597 Genomic DNA. Translation: AAC08998.1.
AF035670
, AF035662, AF035663, AF035664, AF035665, AF035666, AF035667, AF035668, AF035669 Genomic DNA. Translation: AAD02042.1.
AY497473 Genomic DNA. Translation: AAR32097.1.
AL162427 Genomic DNA. No translation available.
BC071181 mRNA. Translation: AAH71181.1.
AJ619019 mRNA. Translation: CAF02096.2.
AJ619020 mRNA. Translation: CAF02097.1.
CCDSiCCDS47998.1. [P36897-3]
CCDS6738.1. [P36897-1]
CCDS78413.1. [P36897-2]
PIRiA49432.
RefSeqiNP_001124388.1. NM_001130916.2. [P36897-3]
NP_001293139.1. NM_001306210.1. [P36897-2]
NP_004603.1. NM_004612.3. [P36897-1]
UniGeneiHs.494622.

Genome annotation databases

EnsembliENST00000374990; ENSP00000364129; ENSG00000106799. [P36897-3]
ENST00000374994; ENSP00000364133; ENSG00000106799. [P36897-1]
ENST00000552516; ENSP00000447297; ENSG00000106799. [P36897-2]
GeneIDi7046.
KEGGihsa:7046.
UCSCiuc004azd.4. human. [P36897-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11695 mRNA. Translation: AAA16073.1.
AF054598
, AF054590, AF054591, AF054592, AF054593, AF054594, AF054595, AF054596, AF054597 Genomic DNA. Translation: AAC08998.1.
AF035670
, AF035662, AF035663, AF035664, AF035665, AF035666, AF035667, AF035668, AF035669 Genomic DNA. Translation: AAD02042.1.
AY497473 Genomic DNA. Translation: AAR32097.1.
AL162427 Genomic DNA. No translation available.
BC071181 mRNA. Translation: AAH71181.1.
AJ619019 mRNA. Translation: CAF02096.2.
AJ619020 mRNA. Translation: CAF02097.1.
CCDSiCCDS47998.1. [P36897-3]
CCDS6738.1. [P36897-1]
CCDS78413.1. [P36897-2]
PIRiA49432.
RefSeqiNP_001124388.1. NM_001130916.2. [P36897-3]
NP_001293139.1. NM_001306210.1. [P36897-2]
NP_004603.1. NM_004612.3. [P36897-1]
UniGeneiHs.494622.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B6CX-ray2.60B/D/F/H162-503[»]
1IASX-ray2.90A/B/C/D/E162-503[»]
1PY5X-ray2.30A175-500[»]
1RW8X-ray2.40A200-500[»]
1TBImodel-A34-114[»]
1VJYX-ray2.00A201-503[»]
2L5SNMR-A31-115[»]
2PJYX-ray3.00C33-111[»]
2WOTX-ray1.85A200-503[»]
2WOUX-ray2.30A200-503[»]
2X7OX-ray3.70A/B/C/D/E162-503[»]
3FAAX-ray3.35A/B/C/D/E162-503[»]
3GXLX-ray1.80A201-503[»]
3HMMX-ray1.70A201-503[»]
3KCFX-ray2.80A/B/C/D/E162-503[»]
3KFDX-ray3.00I/J/K/L31-115[»]
3TZMX-ray1.70A200-503[»]
4X0MX-ray1.68A200-503[»]
4X2FX-ray1.49A200-503[»]
4X2GX-ray1.51A200-503[»]
4X2JX-ray1.69A200-503[»]
4X2KX-ray1.69A200-503[»]
4X2NX-ray1.80A200-503[»]
5E8SX-ray1.45A200-503[»]
5E8TX-ray1.70A200-503[»]
5E8UX-ray2.03A200-503[»]
5E8WX-ray1.86A200-503[»]
5E8XX-ray1.45A200-503[»]
5E8ZX-ray1.51A200-503[»]
5E90X-ray2.05A200-503[»]
5FRIX-ray2.00A200-498[»]
ProteinModelPortaliP36897.
SMRiP36897.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112904. 181 interactors.
DIPiDIP-5935N.
IntActiP36897. 14 interactors.
MINTiMINT-152959.
STRINGi9606.ENSP00000364133.

Chemistry databases

BindingDBiP36897.
ChEMBLiCHEMBL4439.
GuidetoPHARMACOLOGYi1788.

PTM databases

iPTMnetiP36897.
PhosphoSitePlusiP36897.

Polymorphism and mutation databases

BioMutaiTGFBR1.
DMDMi547777.

Proteomic databases

EPDiP36897.
PaxDbiP36897.
PeptideAtlasiP36897.
PRIDEiP36897.

Protocols and materials databases

DNASUi7046.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374990; ENSP00000364129; ENSG00000106799. [P36897-3]
ENST00000374994; ENSP00000364133; ENSG00000106799. [P36897-1]
ENST00000552516; ENSP00000447297; ENSG00000106799. [P36897-2]
GeneIDi7046.
KEGGihsa:7046.
UCSCiuc004azd.4. human. [P36897-1]

Organism-specific databases

CTDi7046.
DisGeNETi7046.
GeneCardsiTGFBR1.
GeneReviewsiTGFBR1.
HGNCiHGNC:11772. TGFBR1.
HPAiCAB002441.
CAB031481.
MalaCardsiTGFBR1.
MIMi132800. phenotype.
190181. gene.
609192. phenotype.
neXtProtiNX_P36897.
OpenTargetsiENSG00000106799.
Orphaneti91387. Familial thoracic aortic aneurysm and aortic dissection.
60030. Loeys-Dietz syndrome.
65748. Multiple keratoacanthoma, Ferguson-Smith type.
PharmGKBiPA36485.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2052. Eukaryota.
ENOG410XQT0. LUCA.
GeneTreeiENSGT00760000118876.
HOGENOMiHOG000230587.
HOVERGENiHBG054502.
InParanoidiP36897.
KOiK04674.
OMAiGATALQC.
OrthoDBiEOG091G0BIU.
PhylomeDBiP36897.
TreeFamiTF314724.

Enzyme and pathway databases

BioCyciZFISH:HS02952-MONOMER.
BRENDAi2.7.10.2. 2681.
2.7.11.30. 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-3645790. TGFBR2 Kinase Domain Mutants in Cancer.
R-HSA-3656532. TGFBR1 KD Mutants in Cancer.
R-HSA-3656535. TGFBR1 LBD Mutants in Cancer.
R-HSA-5689603. UCH proteinases.
R-HSA-5689880. Ub-specific processing proteases.
SignaLinkiP36897.
SIGNORiP36897.

Miscellaneous databases

ChiTaRSiTGFBR1. human.
EvolutionaryTraceiP36897.
GeneWikiiTGF_beta_receptor_1.
GenomeRNAii7046.
PROiP36897.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106799.
CleanExiHS_TGFBR1.
ExpressionAtlasiP36897. baseline and differential.
GenevisibleiP36897. HS.

Family and domain databases

InterProiIPR000472. Activin_recp.
IPR003605. GS_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR000333. TGFB_receptor.
[Graphical view]
PANTHERiPTHR23255. PTHR23255. 1 hit.
PfamiPF01064. Activin_recp. 1 hit.
PF00069. Pkinase. 1 hit.
PF08515. TGF_beta_GS. 1 hit.
[Graphical view]
SMARTiSM00467. GS. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51256. GS. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTGFR1_HUMAN
AccessioniPrimary (citable) accession number: P36897
Secondary accession number(s): Q6IR47, Q706C0, Q706C1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 30, 2016
This is version 197 of the entry and version 1 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

Caution

One report originally reported variant Ile-375 (PubMed:22113417). This variant has been subsequently corrected to Arg-375 by the same authors (Ref. 48).2 Publications