TNR18_MOUSE
ID TNR18_MOUSE Reviewed; 228 AA.
AC O35714; Q9JKR1; Q9JKR2; Q9JKR3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 18;
DE AltName: Full=Glucocorticoid-induced TNFR-related protein;
DE AltName: CD_antigen=CD357;
DE Flags: Precursor;
GN Name=Tnfrsf18; Synonyms=Gitr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC STRAIN=C3H/HeJ;
RX PubMed=9177197; DOI=10.1073/pnas.94.12.6216;
RA Nocentini G., Giunchi L., Ronchetti S., Krausz L.T., Bartoli A., Moraca R.,
RA Migliorati G., Riccardi C.;
RT "A new member of the tumor necrosis factor/nerve growth factor receptor
RT family inhibits T cell receptor-induced apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:6216-6221(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM A).
RC STRAIN=BALB/cJ;
RX PubMed=10798444; DOI=10.1089/104454900314474;
RA Nocentini G., Bartoli A., Ronchetti S., Giunchi L., Cupelli A., Delfino D.,
RA Migliorati G., Riccardi C.;
RT "Gene structure and chromosomal assignment of mouse GITR, a member of the
RT tumor necrosis factor/nerve growth factor receptor family.";
RL DNA Cell Biol. 19:205-217(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B; C AND D).
RC TISSUE=Thymus;
RX PubMed=10836847; DOI=10.1038/sj.cdd.4400670;
RA Nocentini G., Ronchetti S., Bartoli A., Spinicelli S., Delfino D.,
RA Brunetti L., Migliorati G., Riccardi C.;
RT "Identification of three novel mRNA splice variants of GITR.";
RL Cell Death Differ. 7:408-410(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP INTERACTION WITH SIVA1, AND MUTAGENESIS OF SER-199; GLU-201; CYS-204;
RP PRO-209 AND 210-GLU--GLU-212.
RX PubMed=12478477; DOI=10.1038/sj.cdd.4401140;
RA Spinicelli S., Nocentini G., Ronchetti S., Krausz L.T., Bianchini R.,
RA Riccardi C.;
RT "GITR interacts with the pro-apoptotic protein Siva and induces
RT apoptosis.";
RL Cell Death Differ. 9:1382-1384(2002).
CC -!- FUNCTION: Receptor for TNFSF18. Seems to be involved in interactions
CC between activated T-lymphocytes and endothelial cells and in the
CC regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B
CC activation via the TRAF2/NIK pathway (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6 (By
CC similarity). Binds through its C-terminus to SIVA1/SIVA. {ECO:0000250}.
CC -!- INTERACTION:
CC O35714; Q7TS55: Tnfsf18; NbExp=4; IntAct=EBI-523358, EBI-523345;
CC -!- SUBCELLULAR LOCATION: [Isoform A]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform B]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform C]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform D]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=A;
CC IsoId=O35714-1; Sequence=Displayed;
CC Name=B;
CC IsoId=O35714-2; Sequence=VSP_006510;
CC Name=C;
CC IsoId=O35714-3; Sequence=VSP_006511;
CC Name=D;
CC IsoId=O35714-4; Sequence=VSP_006509;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in activated T
CC lymphocytes.
CC -!- INDUCTION: Up-regulated in peripherical mononuclear cells after antigen
CC stimulation/lymphocyte activation.
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DR EMBL; U82534; AAB81243.1; -; mRNA.
DR EMBL; AF109216; AAF14231.1; -; Genomic_DNA.
DR EMBL; AF229432; AAF61566.1; -; mRNA.
DR EMBL; AF229433; AAF61567.1; -; mRNA.
DR EMBL; AF229434; AAF61568.1; -; mRNA.
DR EMBL; AK020762; BAC25639.1; -; mRNA.
DR CCDS; CCDS19056.1; -. [O35714-1]
DR CCDS; CCDS19057.1; -. [O35714-4]
DR RefSeq; NP_033426.1; NM_009400.2. [O35714-1]
DR RefSeq; NP_068820.1; NM_021985.2. [O35714-4]
DR PDB; 7E57; X-ray; 3.30 A; C/D=1-228.
DR PDB; 7KHX; X-ray; 3.21 A; C/D=20-153.
DR PDB; 7RFP; EM; 4.40 A; A/B=1-228.
DR PDBsum; 7E57; -.
DR PDBsum; 7KHX; -.
DR PDBsum; 7RFP; -.
DR AlphaFoldDB; O35714; -.
DR SMR; O35714; -.
DR BioGRID; 204248; 1.
DR DIP; DIP-29666N; -.
DR IntAct; O35714; 1.
DR STRING; 10090.ENSMUSP00000099462; -.
DR GlyGen; O35714; 4 sites.
DR PhosphoSitePlus; O35714; -.
DR EPD; O35714; -.
DR PaxDb; O35714; -.
DR PRIDE; O35714; -.
DR ProteomicsDB; 260634; -. [O35714-1]
DR ProteomicsDB; 260635; -. [O35714-2]
DR ProteomicsDB; 260636; -. [O35714-3]
DR ProteomicsDB; 260637; -. [O35714-4]
DR Antibodypedia; 2154; 992 antibodies from 41 providers.
DR DNASU; 21936; -.
DR Ensembl; ENSMUST00000040274; ENSMUSP00000040035; ENSMUSG00000041954. [O35714-4]
DR Ensembl; ENSMUST00000103173; ENSMUSP00000099462; ENSMUSG00000041954. [O35714-1]
DR GeneID; 21936; -.
DR KEGG; mmu:21936; -.
DR UCSC; uc008wfw.1; mouse. [O35714-4]
DR UCSC; uc008wfx.1; mouse. [O35714-1]
DR CTD; 8784; -.
DR MGI; MGI:894675; Tnfrsf18.
DR VEuPathDB; HostDB:ENSMUSG00000041954; -.
DR eggNOG; ENOG502SAN0; Eukaryota.
DR GeneTree; ENSGT00730000111424; -.
DR HOGENOM; CLU_076906_1_0_1; -.
DR InParanoid; O35714; -.
DR OMA; HFCIWSL; -.
DR OrthoDB; 1081476at2759; -.
DR TreeFam; TF336151; -.
DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors.
DR BioGRID-ORCS; 21936; 2 hits in 73 CRISPR screens.
DR PRO; PR:O35714; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; O35714; protein.
DR Bgee; ENSMUSG00000041954; Expressed in retinal neural layer and 80 other tissues.
DR ExpressionAtlas; O35714; baseline and differential.
DR Genevisible; O35714; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005031; F:tumor necrosis factor receptor activity; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR CDD; cd13417; TNFRSF18; 1.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR022318; TNFR_18.
DR InterPro; IPR034018; TNFRSF18_N.
DR PRINTS; PR01968; TNFACTORR18.
DR SMART; SM00208; TNFR; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell membrane;
KW Disulfide bond; Glycoprotein; Membrane; Receptor; Reference proteome;
KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..228
FT /note="Tumor necrosis factor receptor superfamily member
FT 18"
FT /id="PRO_0000034596"
FT TOPO_DOM 20..153
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 28..61
FT /note="TNFR-Cys 1"
FT REPEAT 62..101
FT /note="TNFR-Cys 2"
FT REPEAT 102..142
FT /note="TNFR-Cys 3"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..44
FT /evidence="ECO:0000250"
FT DISULFID 62..74
FT /evidence="ECO:0000250"
FT DISULFID 69..82
FT /evidence="ECO:0000250"
FT DISULFID 103..122
FT /evidence="ECO:0000250"
FT DISULFID 116..141
FT /evidence="ECO:0000250"
FT VAR_SEQ 121..228
FT /note="NCSQFGFLTMFPGNKTHNAVCIPEPLPTEQYGHLTVIFLVMAACIFFLTTVQ
FT LGLHIWQLRRQHMCPRETQPFAEVQLSAEDACSFQFPEEERGEQTEEKCHLGGRWP ->
FT KDPAIRGGAVVS (in isoform D)"
FT /evidence="ECO:0000303|PubMed:10836847"
FT /id="VSP_006509"
FT VAR_SEQ 189..228
FT /note="ETQPFAEVQLSAEDACSFQFPEEERGEQTEEKCHLGGRWP -> VLLQRPSH
FT SRRCSCQLRMLAASSSLRRNAGSRQKKSVIWGVGGHEAWSSSVPQARRYKTCPAIPLVR
FT AGAMLCTLPWAWPCSPQQWRKWVYESGELRLGPMAAFLI (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10836847"
FT /id="VSP_006510"
FT VAR_SEQ 189..228
FT /note="ETQPFAEVQLSAEDACSFQFPEEERGEQTEEKCHLGGRWP -> GQLCPREG
FT ENVSQAPHLPQFYYRDPAIRGGAVVS (in isoform C)"
FT /evidence="ECO:0000303|PubMed:10836847"
FT /id="VSP_006511"
FT MUTAGEN 199
FT /note="S->A: Does not bind to SIVA1."
FT /evidence="ECO:0000269|PubMed:12478477"
FT MUTAGEN 201
FT /note="E->R: No effect on binding to SIVA1; when associated
FT with G-204."
FT /evidence="ECO:0000269|PubMed:12478477"
FT MUTAGEN 204
FT /note="C->G: No effect on binding to SIVA1; when associated
FT with R-201."
FT /evidence="ECO:0000269|PubMed:12478477"
FT MUTAGEN 209
FT /note="P->A: Does not bind to SIVA1."
FT /evidence="ECO:0000269|PubMed:12478477"
FT MUTAGEN 210..212
FT /note="EEE->RVV: Does not bind to SIVA1."
FT /evidence="ECO:0000269|PubMed:12478477"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:7E57"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:7E57"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:7E57"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:7KHX"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:7E57"
SQ SEQUENCE 228 AA; 25334 MW; 50D8C275D9C56259 CRC64;
MGAWAMLYGV SMLCVLDLGQ PSVVEEPGCG PGKVQNGSGN NTRCCSLYAP GKEDCPKERC
ICVTPEYHCG DPQCKICKHY PCQPGQRVES QGDIVFGFRC VACAMGTFSA GRDGHCRLWT
NCSQFGFLTM FPGNKTHNAV CIPEPLPTEQ YGHLTVIFLV MAACIFFLTT VQLGLHIWQL
RRQHMCPRET QPFAEVQLSA EDACSFQFPE EERGEQTEEK CHLGGRWP
