O35714 (TNR18_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor superfamily member 18

Alternative name(s):
Glucocorticoid-induced TNFR-related protein
CD_antigen=CD357

Gene names

Name:	Tnfrsf18
Synonyms:	Gitr

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	228 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	Receptor for TNFSF18. Seems to be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B activation via the TRAF2/NIK pathway By similarity.
Subunit structure	Binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6 By similarity. Binds through its C-terminus to SIVA1/SIVA. Ref.5
Subcellular location	Isoform A: Cell membrane; Single-pass type I membrane protein. Isoform B: Cell membrane; Single-pass type I membrane protein. Isoform C: Cell membrane; Single-pass type I membrane protein. Isoform D: Secreted.
Tissue specificity	Preferentially expressed in activated T lymphocytes.
Induction	Up-regulated in peripherical mononuclear cells after antigen stimulation/lymphocyte activation.
Sequence similarities	Contains 3 TNFR-Cys repeats.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 16227984PubMed 16769892. Source: MGI extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Tnfsf18	Q7TS55	3	EBI-523358,EBI-523345

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: O35714-1)

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.

Isoform B (identifier: O35714-2)

The sequence of this isoform differs from the canonical sequence as follows:
     189-228: ETQPFAEVQL...EKCHLGGRWP → VLLQRPSHSR...RLGPMAAFLI

Isoform C (identifier: O35714-3)

The sequence of this isoform differs from the canonical sequence as follows:
     189-228: ETQPFAEVQLSAEDACSFQFPEEERGEQTEEKCHLGGRWP → GQLCPREGENVSQAPHLPQFYYRDPAIRGGAVVS

Isoform D (identifier: O35714-4)

The sequence of this isoform differs from the canonical sequence as follows:
     121-228: NCSQFGFLTM...EKCHLGGRWP → KDPAIRGGAVVS

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 228	209	Tumor necrosis factor receptor superfamily member 18		PRO_0000034596
Regions
	Topological domain	20 – 153	134	Extracellular Potential
	Transmembrane	154 – 174	21	Helical; Potential
	Topological domain	175 – 228	54	Cytoplasmic Potential
	Repeat	28 – 61	34	TNFR-Cys 1
	Repeat	62 – 101	40	TNFR-Cys 2
	Repeat	102 – 142	41	TNFR-Cys 3
Amino acid modifications
	Glycosylation	36	1	N-linked (GlcNAc...) Potential
	Glycosylation	40	1	N-linked (GlcNAc...) Potential
	Glycosylation	121	1	N-linked (GlcNAc...) Potential
	Glycosylation	134	1	N-linked (GlcNAc...) Potential
	Disulfide bond	29 ↔ 44		By similarity
	Disulfide bond	62 ↔ 74		By similarity
	Disulfide bond	69 ↔ 82		By similarity
	Disulfide bond	103 ↔ 122		By similarity
	Disulfide bond	116 ↔ 141		By similarity
Natural variations
	Alternative sequence	121 – 228	108	NCSQF…GGRWP → KDPAIRGGAVVS in isoform D.		VSP_006509
	Alternative sequence	189 – 228	40	ETQPF…GGRWP → VLLQRPSHSRRCSCQLRMLA ASSSLRRNAGSRQKKSVIWG VGGHEAWSSSVPQARRYKTC PAIPLVRAGAMLCTLPWAWP CSPQQWRKWVYESGELRLGP MAAFLI in isoform B.		VSP_006510
	Alternative sequence	189 – 228	40	ETQPF…GGRWP → GQLCPREGENVSQAPHLPQF YYRDPAIRGGAVVS in isoform C.		VSP_006511
Experimental info
	Mutagenesis	199	1	S → A: Does not bind to SIVA1. Ref.5
	Mutagenesis	201	1	E → R: No effect on binding to SIVA1; when associated with G-204. Ref.5
	Mutagenesis	204	1	C → G: No effect on binding to SIVA1; when associated with R-201. Ref.5
	Mutagenesis	209	1	P → A: Does not bind to SIVA1. Ref.5
	Mutagenesis	210 – 212	3	EEE → RVV: Does not bind to SIVA1. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 50D8C275D9C56259	FASTA	228	25,334
	10 20 30 40 50 60 MGAWAMLYGV SMLCVLDLGQ PSVVEEPGCG PGKVQNGSGN NTRCCSLYAP GKEDCPKERC 70 80 90 100 110 120 ICVTPEYHCG DPQCKICKHY PCQPGQRVES QGDIVFGFRC VACAMGTFSA GRDGHCRLWT 130 140 150 160 170 180 NCSQFGFLTM FPGNKTHNAV CIPEPLPTEQ YGHLTVIFLV MAACIFFLTT VQLGLHIWQL 190 200 210 220 RRQHMCPRET QPFAEVQLSA EDACSFQFPE EERGEQTEEK CHLGGRWP
	Isoform B [UniParc]. Checksum: FE0D4AE6A007BA9A	FASTA	294	32,658
	10 20 30 40 50 60 MGAWAMLYGV SMLCVLDLGQ PSVVEEPGCG PGKVQNGSGN NTRCCSLYAP GKEDCPKERC 70 80 90 100 110 120 ICVTPEYHCG DPQCKICKHY PCQPGQRVES QGDIVFGFRC VACAMGTFSA GRDGHCRLWT 130 140 150 160 170 180 NCSQFGFLTM FPGNKTHNAV CIPEPLPTEQ YGHLTVIFLV MAACIFFLTT VQLGLHIWQL 190 200 210 220 230 240 RRQHMCPRVL LQRPSHSRRC SCQLRMLAAS SSLRRNAGSR QKKSVIWGVG GHEAWSSSVP 250 260 270 280 290 QARRYKTCPA IPLVRAGAML CTLPWAWPCS PQQWRKWVYE SGELRLGPMA AFLI
	Isoform C [UniParc]. Checksum: 594932BA425A79CA	FASTA	222	24,450
	10 20 30 40 50 60 MGAWAMLYGV SMLCVLDLGQ PSVVEEPGCG PGKVQNGSGN NTRCCSLYAP GKEDCPKERC 70 80 90 100 110 120 ICVTPEYHCG DPQCKICKHY PCQPGQRVES QGDIVFGFRC VACAMGTFSA GRDGHCRLWT 130 140 150 160 170 180 NCSQFGFLTM FPGNKTHNAV CIPEPLPTEQ YGHLTVIFLV MAACIFFLTT VQLGLHIWQL 190 200 210 220 RRQHMCPRGQ LCPREGENVS QAPHLPQFYY RDPAIRGGAV VS
	Isoform D [UniParc]. Checksum: F586A5404B1DFEDE	FASTA	132	14,106
	10 20 30 40 50 60 MGAWAMLYGV SMLCVLDLGQ PSVVEEPGCG PGKVQNGSGN NTRCCSLYAP GKEDCPKERC 70 80 90 100 110 120 ICVTPEYHCG DPQCKICKHY PCQPGQRVES QGDIVFGFRC VACAMGTFSA GRDGHCRLWT 130 KDPAIRGGAV VS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis." Nocentini G., Giunchi L., Ronchetti S., Krausz L.T., Bartoli A., Moraca R., Migliorati G., Riccardi C. Proc. Natl. Acad. Sci. U.S.A. 94:6216-6221(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). Strain: C3H.
[2]	"Gene structure and chromosomal assignment of mouse GITR, a member of the tumor necrosis factor/nerve growth factor receptor family." Nocentini G., Bartoli A., Ronchetti S., Giunchi L., Cupelli A., Delfino D., Migliorati G., Riccardi C. DNA Cell Biol. 19:205-217(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM A). Strain: BALB/c.
[3]	"Identification of three novel mRNA splice variants of GITR." Nocentini G., Ronchetti S., Bartoli A., Spinicelli S., Delfino D., Brunetti L., Migliorati G., Riccardi C. Cell Death Differ. 7:408-410(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B; C AND D). Tissue: Thymus.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: C57BL/6J. Tissue: Thymus.
[5]	"GITR interacts with the pro-apoptotic protein Siva and induces apoptosis." Spinicelli S., Nocentini G., Ronchetti S., Krausz L.T., Bianchini R., Riccardi C. Cell Death Differ. 9:1382-1384(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIVA1, MUTAGENESIS OF SER-199; GLU-201; CYS-204; PRO-209 AND 210-GLU--GLU-212.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U82534 mRNA. Translation: AAB81243.1. AF109216 Genomic DNA. Translation: AAF14231.1. AF229432 mRNA. Translation: AAF61566.1. AF229433 mRNA. Translation: AAF61567.1. AF229434 mRNA. Translation: AAF61568.1. AK020762 mRNA. Translation: BAC25639.1.
IPI	IPI00229461. IPI00229462. IPI00229463. IPI00989641.
RefSeq	NP_033426.1. NM_009400.2. NP_068820.1. NM_021985.2.
UniGene	Mm.3180.
3D structure databases
ProteinModelPortal	O35714.
SMR	O35714. Positions 29-146.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29666N.
IntAct	O35714. 1 interaction.
Proteomic databases
PRIDE	O35714.
Protocols and materials databases
DNASU	21936.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000040274; ENSMUSP00000040035; ENSMUSG00000041954. ENSMUST00000103173; ENSMUSP00000099462; ENSMUSG00000041954.
GeneID	21936.
KEGG	mmu:21936.
Organism-specific databases
CTD	8784.
MGI	MGI:894675. Tnfrsf18.
Phylogenomic databases
eggNOG	NOG46178.
GeneTree	ENSGT00700000104530.
HOGENOM	HOG000049155.
HOVERGEN	HBG054195.
KO	K05154.
OrthoDB	EOG437RG7.
Gene expression databases
ArrayExpress	O35714.
Bgee	O35714.
Genevestigator	O35714.
GermOnline	ENSMUSG00000041954. Mus musculus.
Family and domain databases
InterPro	IPR000742. EG-like_dom. IPR001368. TNFR/NGFR_Cys_rich_reg. IPR022318. TNFR_18. [Graphical view]
PRINTS	PR01968. TNFACTORR18.
SMART	SM00181. EGF. 1 hit. SM00208. TNFR. 2 hits. [Graphical view]
PROSITE	PS00652. TNFR_NGFR_1. False negative. PS50050. TNFR_NGFR_2. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TNFRSF18. mouse.
NextBio	301540.
SOURCE	Search...

Entry information

Entry name

TNR18_MOUSE

Accession

Primary (citable) accession number: O35714
Secondary accession number(s): Q9JKR1, Q9JKR2, Q9JKR3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	January 1, 1998
Last modified:	April 3, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program