Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P08138 (TNR16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:NGFR
Synonyms:TNFRSF16
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11

Subunit structure

Homodimer; disulfide-linked. Interacts with p75NTR-associated cell death executor. Interacts with TRAF2, TRAF4, TRAF6, PTPN13 and RANBP9. Interacts through TRAF6 with SQSTM1 which bridges NGFR to NTRK1. Interacts with BEX1 and NGFRAP1/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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Subcellular location

Membrane; Single-pass type I membrane protein.

Domain

Death domain is responsible for interaction with RANBP9.

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

Post-translational modification

N- and O-glycosylated. Ref.12

O-linked glycans consist of Gal1-3GalNAc core elongated by 1 or 2 NeuNAc.

Phosphorylated on serine residues.

Sequence similarities

Contains 1 death domain.

Contains 4 TNFR-Cys repeats.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Neurogenesis
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
Receptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic signaling pathway

Traceable author statement. Source: Reactome

axon guidance

Inferred from electronic annotation. Source: Ensembl

central nervous system development

Inferred from electronic annotation. Source: Ensembl

detection of temperature stimulus

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

hair follicle morphogenesis

Inferred from electronic annotation. Source: Ensembl

intracellular protein transport

Inferred from sequence or structural similarity. Source: UniProtKB

membrane protein intracellular domain proteolysis

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Traceable author statement. Source: Reactome

negative regulation of axonogenesis

Traceable author statement. Source: Reactome

negative regulation of cell cycle

Traceable author statement. Source: Reactome

negative regulation of fibroblast growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of hair follicle development

Inferred from electronic annotation. Source: Ensembl

nerve development

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

positive regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of axonogenesis

Traceable author statement. Source: Reactome

positive regulation of fibroblast proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

regulation of axonogenesis

Traceable author statement. Source: Reactome

regulation of cysteine-type endopeptidase activity involved in apoptotic process

Traceable author statement. Source: Reactome

regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

regulation of glucose import in response to insulin stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell surface

Inferred from sequence or structural similarity. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

endosome

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

nucleoplasm

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionRab GTPase binding

Inferred from sequence or structural similarity. Source: UniProtKB

death receptor activity

Inferred from electronic annotation. Source: Ensembl

receptor activity

Traceable author statement Ref.1. Source: ProtInc

signal transducer activity

Traceable author statement Ref.1. Source: ProtInc

transmembrane signaling receptor activity

Traceable author statement PubMed 1846035. Source: ProtInc

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 11279055. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

APPP050672EBI-1387782,EBI-77613
CD80P336813EBI-1387782,EBI-1031024
NdnP252333EBI-1387782,EBI-1801080From a different organism.
Ndnl2Q9CPR83EBI-1387782,EBI-5529102From a different organism.
SALL2Q9Y4673EBI-1387782,EBI-8541433

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828
Chain29 – 427399Tumor necrosis factor receptor superfamily member 16
PRO_0000034591

Regions

Topological domain29 – 250222Extracellular Potential
Transmembrane251 – 27222Helical; Potential
Topological domain273 – 427155Cytoplasmic Potential
Repeat31 – 6434TNFR-Cys 1
Repeat66 – 10742TNFR-Cys 2
Repeat108 – 14639TNFR-Cys 3
Repeat148 – 18841TNFR-Cys 4
Domain344 – 42178Death
Region326 – 34116Mediates interaction with KIDINS220 By similarity
Compositional bias197 – 24852Ser/Thr-rich

Amino acid modifications

Glycosylation601N-linked (GlcNAc...) Probable
CAR_000231
Disulfide bond32 ↔ 43 By similarity
Disulfide bond44 ↔ 57 By similarity
Disulfide bond47 ↔ 64 By similarity
Disulfide bond67 ↔ 83 By similarity
Disulfide bond86 ↔ 99 By similarity
Disulfide bond89 ↔ 107 By similarity
Disulfide bond109 ↔ 122 By similarity
Disulfide bond125 ↔ 138 By similarity
Disulfide bond128 ↔ 146 By similarity
Disulfide bond149 ↔ 164 By similarity
Disulfide bond167 ↔ 180 By similarity
Disulfide bond170 ↔ 188 By similarity

Natural variations

Natural variant2051S → L.
Corresponds to variant rs2072446 [ dbSNP | Ensembl ].
VAR_020010

Secondary structure

... 427
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08138 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: B09FA143FB3D625B

FASTA42745,183
        10         20         30         40         50         60 
MGAGATGRAM DGPRLLLLLL LGVSLGGAKE ACPTGLYTHS GECCKACNLG EGVAQPCGAN 

        70         80         90        100        110        120 
QTVCEPCLDS VTFSDVVSAT EPCKPCTECV GLQSMSAPCV EADDAVCRCA YGYYQDETTG 

       130        140        150        160        170        180 
RCEACRVCEA GSGLVFSCQD KQNTVCEECP DGTYSDEANH VDPCLPCTVC EDTERQLREC 

       190        200        210        220        230        240 
TRWADAECEE IPGRWITRST PPEGSDSTAP STQEPEAPPE QDLIASTVAG VVTTVMGSSQ 

       250        260        270        280        290        300 
PVVTRGTTDN LIPVYCSILA AVVVGLVAYI AFKRWNSCKQ NKQGANSRPV NQTPPPEGEK 

       310        320        330        340        350        360 
LHSDSGISVD SQSLHDQQPH TQTASGQALK GDGGLYSSLP PAKREEVEKL LNGSAGDTWR 

       370        380        390        400        410        420 
HLAGELGYQP EHIDSFTHEA CPVRALLASW ATQDSATLDA LLAALRRIQR ADLVESLCSE 


STATSPV 

« Hide

References

« Hide 'large scale' references
[1]"Expression and structure of the human NGF receptor."
Johnson D., Lanahan A., Buck C.R., Sehgal A., Morgan C., Mercer E., Bothwell M., Chao M.
Cell 47:545-554(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cerebellum.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"A constitutive promoter directs expression of the nerve growth factor receptor gene."
Sehgal A., Patil N., Chao M.
Mol. Cell. Biol. 8:3160-3167(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[6]"TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction."
Ye X., Mehlen P., Rabizadeh S., VanArsdale T., Zhang H., Shin H., Wang J.J.L., Leo E., Zapata J.M., Hauser C.A., Reed J.C., Bredesen D.E.
J. Biol. Chem. 274:30202-30208(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAF2; TRAF4 AND TRAF6.
[7]"Association of the p75 neurotrophin receptor with TRAF6."
Khursigara G., Orlinick J.R., Chao M.V.
J. Biol. Chem. 274:2597-2600(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAF6.
[8]"Functional interaction of Fas-associated phosphatase-1 (FAP-1) with p75(NTR) and their effect on NF-kappaB activation."
Irie S., Hachiya T., Rabizadeh S., Maruyama W., Mukai J., Li Y., Reed J.C., Bredesen D.E., Sato T.A.
FEBS Lett. 460:191-198(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN13.
[9]"The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor."
Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A., Moscat J.
J. Biol. Chem. 276:7709-7712(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAF6 AND SQSTM1.
[10]"RanBPM is a novel binding protein for p75NTR."
Bai D., Chen H., Huang B.-R.
Biochem. Biophys. Res. Commun. 309:552-557(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RANBP9.
Tissue: Brain.
[11]"LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex."
Mi S., Lee X., Shao Z., Thill G., Ji B., Relton J., Levesque M., Allaire N., Perrin S., Sands B., Crowell T., Cate R.L., McCoy J.M., Pepinsky R.B.
Nat. Neurosci. 7:221-228(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH LINGO1.
[12]"O-linked oligosaccharide on the 75-kDa neurotrophin receptor."
Chapman B.S., Eckart M.R., Kaufman S.E., Lapointe G.R.
J. Neurochem. 66:1707-1716(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF O-LINKED CARBOHYDRATE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M14764 mRNA. Translation: AAB59544.1.
AK313654 mRNA. Translation: BAG36408.1.
CH471109 Genomic DNA. Translation: EAW94677.1.
BC050309 mRNA. Translation: AAH50309.1.
M21621 Genomic DNA. Translation: AAA36363.1.
PIRGQHUN. A25218.
RefSeqNP_002498.1. NM_002507.3.
UniGeneHs.415768.
Hs.681726.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EWVX-ray2.60E396-412[»]
ProteinModelPortalP08138.
SMRP08138. Positions 32-189, 335-419.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110870. 38 interactions.
DIPDIP-406N.
IntActP08138. 17 interactions.
MINTMINT-107412.
STRING9606.ENSP00000172229.

Chemistry

BindingDBP08138.
ChEMBLCHEMBL4762.
GuidetoPHARMACOLOGY1888.

PTM databases

PhosphoSiteP08138.
UniCarbKBP08138.

Polymorphism databases

DMDM128156.

Proteomic databases

PaxDbP08138.
PeptideAtlasP08138.
PRIDEP08138.

Protocols and materials databases

DNASU4804.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000172229; ENSP00000172229; ENSG00000064300.
GeneID4804.
KEGGhsa:4804.
UCSCuc002ioz.4. human.

Organism-specific databases

CTD4804.
GeneCardsGC17P047572.
HGNCHGNC:7809. NGFR.
HPACAB000143.
CAB001995.
HPA004765.
MIM162010. gene.
neXtProtNX_P08138.
PharmGKBPA31615.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39106.
HOGENOMHOG000059587.
HOVERGENHBG060431.
InParanoidP08138.
KOK02583.
OMARQLRECT.
OrthoDBEOG77T14T.
PhylomeDBP08138.
TreeFamTF106466.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP08138.

Gene expression databases

ArrayExpressP08138.
BgeeP08138.
CleanExHS_NGFR.
GenevestigatorP08138.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022325. TNFR_16.
[Graphical view]
PfamPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PRINTSPR01966. TNFACTORR16.
SMARTSM00005. DEATH. 1 hit.
SM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
PROSITEPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 3 hits.
PS50050. TNFR_NGFR_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNGFR. human.
EvolutionaryTraceP08138.
GeneWikiLow-affinity_nerve_growth_factor_receptor.
GenomeRNAi4804.
NextBio18518.
PMAP-CutDBP08138.
PROP08138.
SOURCESearch...

Entry information

Entry nameTNR16_HUMAN
AccessionPrimary (citable) accession number: P08138
Secondary accession number(s): B2R961
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: April 16, 2014
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries