P08138 (TNR16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	NGFR
Synonyms:	TNFRSF16

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity. Interacts with LINGO1. 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 process	Apoptosis Differentiation Neurogenesis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome induction of apoptosis by extracellular signals Traceable author statement. Source: Reactome membrane protein intracellular domain proteolysis Traceable author statement. Source: Reactome negative regulation of axonogenesis Traceable author statement. Source: Reactome negative regulation of cell cycle Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of axonogenesis Traceable author statement. Source: Reactome
Cellular component	cell 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 to plasma membrane Traceable author statement. Source: ProtInc nucleoplasm Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	4	EBI-1387782,EBI-77613
CD80	P33681	3	EBI-1387782,EBI-1031024

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Chain

29 – 427

399

Tumor necrosis factor receptor superfamily member 16

PRO_0000034591

Regions

Topological domain

29 – 250

222

Extracellular Potential

Transmembrane

251 – 272

22

Helical; Potential

Topological domain

273 – 427

155

Cytoplasmic Potential

Repeat

31 – 64

34

TNFR-Cys 1

Repeat

66 – 107

42

TNFR-Cys 2

Repeat

108 – 146

39

TNFR-Cys 3

Repeat

148 – 188

41

TNFR-Cys 4

Domain

344 – 421

78

Death

Region

326 – 341

16

Mediates interaction with KIDINS220 By similarity

Compositional bias

197 – 248

52

Ser/Thr-rich

Amino acid modifications

Modified residue

293

1

Phosphothreonine By similarity

Glycosylation

60

1

N-linked (GlcNAc...) Probable

CAR_000231

Disulfide bond

32 ↔ 43

By similarity

Disulfide bond

44 ↔ 57

By similarity

Disulfide bond

47 ↔ 64

By similarity

Disulfide bond

67 ↔ 83

By similarity

Disulfide bond

86 ↔ 99

By similarity

Disulfide bond

89 ↔ 107

By similarity

Disulfide bond

109 ↔ 122

By similarity

Disulfide bond

125 ↔ 138

By similarity

Disulfide bond

128 ↔ 146

By similarity

Disulfide bond

149 ↔ 164

By similarity

Disulfide bond

167 ↔ 180

By similarity

Disulfide bond

170 ↔ 188

By similarity

Natural variations

Natural variant

205

1

S → L.
Corresponds to variant rs2072446 [ dbSNP | Ensembl ].

VAR_020010

Secondary structure

1

.

.

.

427

Helix Strand Turn

Details...

Helix

398 – 409

12

Sequences

	Sequence		Length	Mass (Da)
	P08138 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: B09FA143FB3D625B	FASTA	427	45,183
	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

References

	« Hide 'large scale' referencesShow '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: 3022937] [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. , 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: 14702039] [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. , 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: 15489334] [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: 2850481] [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: 10514511] [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: 9915784] [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: 10544233] [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: 11244088] [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: 12963025] [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: 14966521] [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: 8627329] [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.

IPI

IPI00027436.

PIR

GQHUN. A25218.

RefSeq

NP_002498.1. NM_002507.3.

UniGene

Hs.415768.
Hs.681726.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EWV	X-ray	2.60	E	396-412	[»]

ProteinModelPortal

P08138.

SMR

P08138. Positions 32-189, 333-420.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-406N.

IntAct

P08138. 7 interactions.

MINT

MINT-107412.

STRING

P08138.

PTM databases

GlycoSuiteDB

P08138.

PhosphoSite

P08138.

Polymorphism databases

DMDM

128156.

Proteomic databases

PeptideAtlas

P08138.

PRIDE

P08138.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000172229; ENSP00000172229; ENSG00000064300.

GeneID

4804.

KEGG

hsa:4804.

UCSC

uc002ioz.2. human.

Organism-specific databases

CTD

4804.

GeneCards

GC17P047572.

H-InvDB

HIX0027193.

HGNC

HGNC:7809. NGFR.

HPA

CAB000143.
CAB001995.
HPA004765.

MIM

162010. gene.

neXtProt

NX_P08138.

PharmGKB

PA31615.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13585.

GeneTree

ENSGT00550000074207.

HOGENOM

HBG715212.

HOVERGEN

HBG060431.

InParanoid

P08138.

OMA

FSCQDKQ.

OrthoDB

EOG4ZKJM8.

PhylomeDB

P08138.

Enzyme and pathway databases

Pathway_Interaction_DB

trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
p75ntrpathway. p75(NTR)-mediated signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P08138.

Bgee

P08138.

CleanEx

HS_NGFR.

Genevestigator

P08138.

GermOnline

ENSG00000064300. Homo sapiens.

Family and domain databases

InterPro

IPR000488. Death.
IPR011029. DEATH-like.
IPR022325. TNFR_16.
IPR001368. TNFR_Cys_rich_reg.
[Graphical view]

Gene3D

G3DSA:1.10.533.10. DEATH_like. 1 hit.

KO

K02583.

Pfam

PF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]

PRINTS

PR01966. TNFACTORR16.

SMART

SM00005. DEATH. 1 hit.
SM00208. TNFR. 4 hits.
[Graphical view]

SUPFAM

SSF47986. DEATH_like. 1 hit.

PROSITE

PS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 3 hits.
PS50050. TNFR_NGFR_2. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

18518.

PMAP-CutDB

P08138.

SOURCE

Search...

Entry information

Entry name

TNR16_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 136 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.