Reviewed, UniProtKB/Swiss-Prot P08138 (TNR16_HUMAN)

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor superfamily member 16

Alternative name(s):
Low-affinity nerve growth factor receptor
Short name=NGF receptor
Gp80-LNGFR
p75 ICD
Low affinity neurotrophin receptor p75NTR
CD_antigen=CD271

Gene names

Name:	NGFR
Synonyms:	TNFRSF16

Organism

Homo sapiens (Human) [Complete proteome]

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 By similarity. Interacts with LINGO1. Ref.11 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
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
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from Experiment. Source: Reactome apoptosis Inferred from Experiment. Source: Reactome induction of apoptosis by extracellular signals Inferred from Experiment. Source: Reactome membrane protein intracellular domain proteolysis Inferred from Experiment. Source: Reactome negative regulation of axonogenesis Inferred from Experiment. Source: Reactome negative regulation of cell cycle Inferred from Experiment. Source: Reactome positive regulation of axonogenesis Inferred from Experiment. Source: Reactome
Cellular component	cytosol Inferred from Experiment. Source: Reactome endosome Inferred from Experiment. Source: Reactome integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc nucleoplasm Inferred from Experiment. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	2	EBI-1387782,EBI-77613

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	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: dbSNP rs2072446.		VAR_020010

Sequences

	Sequence		Length	Mass (Da)
	P08138-1 [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.

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	[»]

SMR

P08138. Positions 30-189, 333-420.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-406N.

IntAct

P08138. 4 interactions.

STRING

P08138.

PTM databases

GlycoSuiteDB

P08138.

PhosphoSite

P08138.

Proteomic databases

PeptideAtlas

P08138.

PRIDE

P08138.

Genome annotation databases

Ensembl

ENST00000172229; ENSP00000172229; ENSG00000064300; Homo sapiens. [Genome view]

GeneID

4804.

KEGG

hsa:4804.

UCSC

uc002ioz.2. human.

Organism-specific databases

CTD

4804.

GeneCards

GC17P044927.

H-InvDB

HIX0027193.

HGNC

HGNC:7809. NGFR.

HPA

CAB000143.
CAB001995.
HPA004765.

MIM

162010. gene.

PharmGKB

PA31615.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13585.

HOGENOM

HBG715212.

HOVERGEN

HBG060431.

InParanoid

P08138.

OMA

QALKGDG.

OrthoDB

EOG9C5G3N.

PhylomeDB

P08138.

Enzyme and pathway databases

Pathway_Interaction_DB

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

Reactome

REACT_11061. Signalling by NGF.

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.
IPR001368. TNFR_Cys_rich_reg.
[Graphical view]

Gene3D

G3DSA:1.10.533.10. DEATH_like. 1 hit.

Pfam

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

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 Resources

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:	March 2, 2010
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.