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Protein

Tumor necrosis factor receptor superfamily member 16

Gene

NGFR

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

Functioni

Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Low affinity receptor which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells. Necessary for the circadian oscillation of the clock genes ARNTL/BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver.By similarity2 Publications

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB
  • coreceptor activity Source: UniProtKB
  • death receptor activity Source: ARUK-UCL
  • nerve growth factor binding Source: UniProtKB
  • neurotrophin binding Source: UniProtKB
  • Rab GTPase binding Source: UniProtKB
  • signaling receptor activity Source: ProtInc
  • transmembrane signaling receptor activity Source: ProtInc
  • tumor necrosis factor-activated receptor activity Source: GO_Central
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processApoptosis, Biological rhythms, Differentiation, Neurogenesis

Enzyme and pathway databases

ReactomeiR-HSA-193634 Axonal growth inhibition (RHOA activation)
R-HSA-193648 NRAGE signals death through JNK
R-HSA-193670 p75NTR negatively regulates cell cycle via SC1
R-HSA-193681 Ceramide signalling
R-HSA-193692 Regulated proteolysis of p75NTR
R-HSA-205017 NFG and proNGF binds to p75NTR
R-HSA-205025 NADE modulates death signalling
R-HSA-205043 NRIF signals cell death from the nucleus
R-HSA-209543 p75NTR recruits signalling complexes
R-HSA-209560 NF-kB is activated and signals survival
R-HSA-209563 Axonal growth stimulation
SignaLinkiP08138
SIGNORiP08138

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 16
Alternative name(s):
Gp80-LNGFR
Low affinity neurotrophin receptor p75NTR
Low-affinity nerve growth factor receptor
Short name:
NGF receptor
p75 ICD
CD_antigen: CD271
Gene namesi
Name:NGFR
Synonyms:TNFRSF16
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000064300.8
HGNCiHGNC:7809 NGFR
MIMi162010 gene
neXtProtiNX_P08138

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 250ExtracellularSequence analysisAdd BLAST222
Transmembranei251 – 272HelicalSequence analysisAdd BLAST22
Topological domaini273 – 427CytoplasmicSequence analysisAdd BLAST155

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi4804
OpenTargetsiENSG00000064300
PharmGKBiPA31615

Chemistry databases

ChEMBLiCHEMBL4762
GuidetoPHARMACOLOGYi1888

Polymorphism and mutation databases

BioMutaiNGFR
DMDMi128156

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Add BLAST28
ChainiPRO_000003459129 – 427Tumor necrosis factor receptor superfamily member 16Add BLAST399

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 43PROSITE-ProRule annotation
Disulfide bondi44 ↔ 57PROSITE-ProRule annotation
Disulfide bondi47 ↔ 64PROSITE-ProRule annotation
GlycosylationiCAR_00023160N-linked (GlcNAc...) asparagineCurated1
Disulfide bondi67 ↔ 83PROSITE-ProRule annotation
Disulfide bondi86 ↔ 99PROSITE-ProRule annotation
Disulfide bondi89 ↔ 107PROSITE-ProRule annotation
Disulfide bondi109 ↔ 122PROSITE-ProRule annotation
Disulfide bondi125 ↔ 138PROSITE-ProRule annotation
Disulfide bondi128 ↔ 146PROSITE-ProRule annotation
Disulfide bondi149 ↔ 164PROSITE-ProRule annotation
Disulfide bondi167 ↔ 180PROSITE-ProRule annotation
Disulfide bondi170 ↔ 188PROSITE-ProRule annotation
Modified residuei311PhosphoserineCombined sources1

Post-translational modificationi

N- and O-glycosylated.
O-linked glycans consist of Gal1-3GalNAc core elongated by 1 or 2 NeuNAc.
Phosphorylated on serine residues.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP08138
MaxQBiP08138
PaxDbiP08138
PeptideAtlasiP08138
PRIDEiP08138
ProteomicsDBi52073

PTM databases

GlyConnecti611
iPTMnetiP08138
PhosphoSitePlusiP08138
UniCarbKBiP08138

Miscellaneous databases

PMAP-CutDBiP08138

Expressioni

Gene expression databases

BgeeiENSG00000064300 Expressed in 146 organ(s), highest expression level in tibial nerve
CleanExiHS_NGFR
GenevisibleiP08138 HS

Organism-specific databases

HPAiCAB000143
CAB001995
HPA004765

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with p75NTR-associated cell death executor. Interacts with RTN4R. Interacts with TRAF2, TRAF4, TRAF6, PTPN13 and RANBP9. Interacts through TRAF6 with SQSTM1 which bridges NGFR to NTRK1. Interacts with BEX1 and BEX3. Interacts with KIDINS220 and NTRK1. Can form a ternary complex with NTRK1 and KIDINS220 and this complex is affected by the expression levels of KIDINS220. An increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1. Interacts with NTRK2; may regulate the ligand specificity of the NTRK2 receptor. Interacts (via death domain) with RAB31. Interacts with LINGO1 and NRADD. Interacts with MAGED1; the interaction antagonizes the association NGFR:NTRK1.By similarity7 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110870, 37 interactors
CORUMiP08138
DIPiDIP-406N
IntActiP08138, 20 interactors
MINTiP08138
STRINGi9606.ENSP00000172229

Chemistry databases

BindingDBiP08138

Structurei

Secondary structure

1427
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP08138
SMRiP08138
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08138

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati31 – 64TNFR-Cys 1Add BLAST34
Repeati66 – 107TNFR-Cys 2Add BLAST42
Repeati108 – 146TNFR-Cys 3Add BLAST39
Repeati148 – 188TNFR-Cys 4Add BLAST41
Domaini344 – 421DeathPROSITE-ProRule annotationAdd BLAST78

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni326 – 341Mediates interaction with KIDINS220By similarityAdd BLAST16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi197 – 248Ser/Thr-richAdd BLAST52

Domaini

Death domain is responsible for interaction with RANBP9.
The extracellular domain is responsible for interaction with NTRK1.By similarity

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IQFC Eukaryota
ENOG4111F3C LUCA
GeneTreeiENSGT00730000110974
HOGENOMiHOG000059587
HOVERGENiHBG060431
InParanoidiP08138
KOiK02583
OMAiAQPCGAN
OrthoDBiEOG091G0M0X
PhylomeDBiP08138
TreeFamiTF106466

Family and domain databases

CDDicd13416 TNFRSF16, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR022325 TNFR_16
IPR034046 TNFRSF16_N
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF00020 TNFR_c6, 2 hits
PRINTSiPR01966 TNFACTORR16
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00208 TNFR, 4 hits
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS00652 TNFR_NGFR_1, 3 hits
PS50050 TNFR_NGFR_2, 4 hits

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: P08138-1) [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
MGAGATGRAM DGPRLLLLLL LGVSLGGAKE ACPTGLYTHS GECCKACNLG
60 70 80 90 100
EGVAQPCGAN QTVCEPCLDS VTFSDVVSAT EPCKPCTECV GLQSMSAPCV
110 120 130 140 150
EADDAVCRCA YGYYQDETTG RCEACRVCEA GSGLVFSCQD KQNTVCEECP
160 170 180 190 200
DGTYSDEANH VDPCLPCTVC EDTERQLREC TRWADAECEE IPGRWITRST
210 220 230 240 250
PPEGSDSTAP STQEPEAPPE QDLIASTVAG VVTTVMGSSQ PVVTRGTTDN
260 270 280 290 300
LIPVYCSILA AVVVGLVAYI AFKRWNSCKQ NKQGANSRPV NQTPPPEGEK
310 320 330 340 350
LHSDSGISVD SQSLHDQQPH TQTASGQALK GDGGLYSSLP PAKREEVEKL
360 370 380 390 400
LNGSAGDTWR HLAGELGYQP EHIDSFTHEA CPVRALLASW ATQDSATLDA
410 420
LLAALRRIQR ADLVESLCSE STATSPV
Length:427
Mass (Da):45,183
Last modified:August 1, 1988 - v1
Checksum:iB09FA143FB3D625B
GO
Isoform 2 (identifier: P08138-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.

Note: No experimental confirmation available.
Show »
Length:333
Mass (Da):35,767
Checksum:iFC38A7379D84CB28
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020010205S → L. Corresponds to variant dbSNP:rs2072446Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0568501 – 94Missing in isoform 2. 1 PublicationAdd BLAST94

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14764 mRNA Translation: AAB59544.1
AK303278 mRNA Translation: BAG64358.1
AK313654 mRNA Translation: BAG36408.1
AC006487 Genomic DNA No translation available.
AC015656 Genomic DNA No translation available.
CH471109 Genomic DNA Translation: EAW94677.1
BC050309 mRNA Translation: AAH50309.1
M21621 Genomic DNA Translation: AAA36363.1
CCDSiCCDS11549.1 [P08138-1]
PIRiA25218 GQHUN
RefSeqiNP_002498.1, NM_002507.3 [P08138-1]
UniGeneiHs.415768
Hs.681726

Genome annotation databases

EnsembliENST00000172229; ENSP00000172229; ENSG00000064300 [P08138-1]
ENST00000504201; ENSP00000421731; ENSG00000064300 [P08138-2]
GeneIDi4804
KEGGihsa:4804
UCSCiuc002ioz.5 human [P08138-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14764 mRNA Translation: AAB59544.1
AK303278 mRNA Translation: BAG64358.1
AK313654 mRNA Translation: BAG36408.1
AC006487 Genomic DNA No translation available.
AC015656 Genomic DNA No translation available.
CH471109 Genomic DNA Translation: EAW94677.1
BC050309 mRNA Translation: AAH50309.1
M21621 Genomic DNA Translation: AAA36363.1
CCDSiCCDS11549.1 [P08138-1]
PIRiA25218 GQHUN
RefSeqiNP_002498.1, NM_002507.3 [P08138-1]
UniGeneiHs.415768
Hs.681726

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N80NMR-A334-427[»]
2N83NMR-A330-427[»]
2N97NMR-A/B330-427[»]
3EWVX-ray2.60E396-412[»]
ProteinModelPortaliP08138
SMRiP08138
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110870, 37 interactors
CORUMiP08138
DIPiDIP-406N
IntActiP08138, 20 interactors
MINTiP08138
STRINGi9606.ENSP00000172229

Chemistry databases

BindingDBiP08138
ChEMBLiCHEMBL4762
GuidetoPHARMACOLOGYi1888

PTM databases

GlyConnecti611
iPTMnetiP08138
PhosphoSitePlusiP08138
UniCarbKBiP08138

Polymorphism and mutation databases

BioMutaiNGFR
DMDMi128156

Proteomic databases

EPDiP08138
MaxQBiP08138
PaxDbiP08138
PeptideAtlasiP08138
PRIDEiP08138
ProteomicsDBi52073

Protocols and materials databases

DNASUi4804
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000172229; ENSP00000172229; ENSG00000064300 [P08138-1]
ENST00000504201; ENSP00000421731; ENSG00000064300 [P08138-2]
GeneIDi4804
KEGGihsa:4804
UCSCiuc002ioz.5 human [P08138-1]

Organism-specific databases

CTDi4804
DisGeNETi4804
EuPathDBiHostDB:ENSG00000064300.8
GeneCardsiNGFR
HGNCiHGNC:7809 NGFR
HPAiCAB000143
CAB001995
HPA004765
MIMi162010 gene
neXtProtiNX_P08138
OpenTargetsiENSG00000064300
PharmGKBiPA31615
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQFC Eukaryota
ENOG4111F3C LUCA
GeneTreeiENSGT00730000110974
HOGENOMiHOG000059587
HOVERGENiHBG060431
InParanoidiP08138
KOiK02583
OMAiAQPCGAN
OrthoDBiEOG091G0M0X
PhylomeDBiP08138
TreeFamiTF106466

Enzyme and pathway databases

ReactomeiR-HSA-193634 Axonal growth inhibition (RHOA activation)
R-HSA-193648 NRAGE signals death through JNK
R-HSA-193670 p75NTR negatively regulates cell cycle via SC1
R-HSA-193681 Ceramide signalling
R-HSA-193692 Regulated proteolysis of p75NTR
R-HSA-205017 NFG and proNGF binds to p75NTR
R-HSA-205025 NADE modulates death signalling
R-HSA-205043 NRIF signals cell death from the nucleus
R-HSA-209543 p75NTR recruits signalling complexes
R-HSA-209560 NF-kB is activated and signals survival
R-HSA-209563 Axonal growth stimulation
SignaLinkiP08138
SIGNORiP08138

Miscellaneous databases

ChiTaRSiNGFR human
EvolutionaryTraceiP08138
GeneWikiiLow-affinity_nerve_growth_factor_receptor
GenomeRNAii4804
PMAP-CutDBiP08138
PROiPR:P08138
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000064300 Expressed in 146 organ(s), highest expression level in tibial nerve
CleanExiHS_NGFR
GenevisibleiP08138 HS

Family and domain databases

CDDicd13416 TNFRSF16, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR022325 TNFR_16
IPR034046 TNFRSF16_N
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF00020 TNFR_c6, 2 hits
PRINTSiPR01966 TNFACTORR16
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00208 TNFR, 4 hits
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS00652 TNFR_NGFR_1, 3 hits
PS50050 TNFR_NGFR_2, 4 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTNR16_HUMAN
AccessioniPrimary (citable) accession number: P08138
Secondary accession number(s): B2R961, B4E096
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: September 12, 2018
This is version 200 of the entry and version 1 of the sequence. See 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, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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