TR19L_HUMAN
ID TR19L_HUMAN Reviewed; 430 AA.
AC Q969Z4; Q86V34; Q96JU1; Q9BUX7;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 19L;
DE AltName: Full=Receptor expressed in lymphoid tissues;
DE Flags: Precursor;
GN Name=RELT; Synonyms=TNFRSF19L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, AND INTERACTION
RP WITH TRAF1.
RC TISSUE=Lymphoma;
RX PubMed=11313261; DOI=10.1182/blood.v97.9.2702;
RA Sica G.L., Zhu G., Tamada K., Liu D., Ni J., Chen L.;
RT "RELT, a new member of the tumor necrosis factor receptor superfamily, is
RT selectively expressed in hematopoietic tissues and activates transcription
RT factor NF-kappaB.";
RL Blood 97:2702-2707(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retinoblastoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-332.
RC TISSUE=Blood, Colon, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 121-430.
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 26-40.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [6]
RP FUNCTION, INTERACTION WITH STK39, PHOSPHORYLATION, MUTAGENESIS OF PHE-350,
RP AND DOMAIN RFRV MOTIF.
RX PubMed=16530727; DOI=10.1016/j.bbrc.2006.02.125;
RA Polek T.C., Talpaz M., Spivak-Kroizman T.;
RT "The TNF receptor, RELT, binds SPAK and uses it to mediate p38 and JNK
RT activation.";
RL Biochem. Biophys. Res. Commun. 343:125-134(2006).
RN [7]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH RELL1; RELL2 AND
RP OXSR1, AND PHOSPHORYLATION.
RX PubMed=16389068; DOI=10.1016/j.bbrc.2005.12.033;
RA Cusick J.K., Xu L.-G., Bin L.-H., Han K.-J., Shu H.-B.;
RT "Identification of RELT homologues that associate with RELT and are
RT phosphorylated by OSR1.";
RL Biochem. Biophys. Res. Commun. 340:535-543(2006).
RN [8]
RP FUNCTION.
RX PubMed=19969290; DOI=10.1016/j.cellimm.2009.10.013;
RA Cusick J.K., Mustian A., Goldberg K., Reyland M.E.;
RT "RELT induces cellular death in HEK 293 epithelial cells.";
RL Cell. Immunol. 261:1-8(2010).
RN [9]
RP INTERACTION WITH PLSCR1, AND SUBCELLULAR LOCATION.
RX PubMed=22052202; DOI=10.1007/s11010-011-1127-4;
RA Cusick J.K., Mustian A., Jacobs A.T., Reyland M.E.;
RT "Identification of PLSCR1 as a protein that interacts with RELT family
RT members.";
RL Mol. Cell. Biochem. 362:55-63(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-223, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28688764; DOI=10.1016/j.bbrc.2017.07.022;
RA Moua P., Checketts M., Xu L.G., Shu H.B., Reyland M.E., Cusick J.K.;
RT "RELT family members activate p38 and induce apoptosis by a mechanism
RT distinct from TNFR1.";
RL Biochem. Biophys. Res. Commun. 491:25-32(2017).
RN [12]
RP FUNCTION, INVOLVEMENT IN AI3C, AND VARIANT AI3C PRO-422.
RX PubMed=30506946; DOI=10.1111/cge.13487;
RA Kim J.W., Zhang H., Seymen F., Koruyucu M., Hu Y., Kang J., Kim Y.J.,
RA Ikeda A., Kasimoglu Y., Bayram M., Zhang C., Kawasaki K., Bartlett J.D.,
RA Saunders T.L., Simmer J.P., Hu J.C.;
RT "Mutations in RELT cause autosomal recessive amelogenesis imperfecta.";
RL Clin. Genet. 95:375-383(2019).
CC -!- FUNCTION: May play a role in apoptosis (PubMed:28688764,
CC PubMed:19969290). Induces activation of MAPK14/p38 and MAPK8/JNK MAPK
CC cascades, when overexpressed (PubMed:16530727). Involved in dental
CC enamel formation (PubMed:30506946). {ECO:0000269|PubMed:16530727,
CC ECO:0000269|PubMed:19969290, ECO:0000269|PubMed:28688764,
CC ECO:0000269|PubMed:30506946}.
CC -!- SUBUNIT: Interacts with TRAF1 (PubMed:11313261). Interacts with RELL1,
CC RELL2 and OXSR1 (PubMed:16389068). Interacts with PLSCR1
CC (PubMed:22052202). Interacts with STK39 (PubMed:16530727).
CC {ECO:0000269|PubMed:11313261, ECO:0000269|PubMed:16389068,
CC ECO:0000269|PubMed:16530727, ECO:0000269|PubMed:22052202}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16389068};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:16389068}.
CC Cytoplasm {ECO:0000269|PubMed:16389068}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:22052202}.
CC -!- TISSUE SPECIFICITY: Spleen, lymph node, brain, breast and peripheral
CC blood leukocytes (at protein level) (PubMed:28688764). Expressed highly
CC in bone marrow and fetal liver. Very low levels in skeletal muscle,
CC testis and colon. Not detected in kidney and pancreas.
CC {ECO:0000269|PubMed:16389068, ECO:0000269|PubMed:28688764}.
CC -!- PTM: Phosphorylated in vitro by OXSR1 (PubMed:16389068). Phosphorylated
CC by STK39 (PubMed:16530727). {ECO:0000269|PubMed:16389068,
CC ECO:0000269|PubMed:16530727}.
CC -!- DISEASE: Amelogenesis imperfecta 3C (AI3C) [MIM:618386]: An autosomal
CC recessive form of amelogenesis imperfecta, a defect of enamel
CC formation. AI3C is characterized by generalized enamel
CC hypocalcification affecting primary and secondary dentition. The
CC surface of the enamel is rough and often stained. After eruption, the
CC occlusal enamel on the molars disappears due to attrition, leaving a
CC ring of intact enamel remaining on the sides.
CC {ECO:0000269|PubMed:30506946}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the RELT family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB84954.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF319553; AAK77356.1; -; mRNA.
DR EMBL; AK027899; BAB55441.1; -; mRNA.
DR EMBL; BC001812; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC017279; AAH17279.1; -; mRNA.
DR EMBL; BC051810; AAH51810.2; -; mRNA.
DR EMBL; AK074128; BAB84954.1; ALT_FRAME; mRNA.
DR CCDS; CCDS8222.1; -.
DR RefSeq; NP_116260.2; NM_032871.3.
DR RefSeq; NP_689408.1; NM_152222.1.
DR AlphaFoldDB; Q969Z4; -.
DR BioGRID; 124388; 75.
DR IntAct; Q969Z4; 13.
DR STRING; 9606.ENSP00000064780; -.
DR GlyGen; Q969Z4; 1 site.
DR iPTMnet; Q969Z4; -.
DR PhosphoSitePlus; Q969Z4; -.
DR BioMuta; RELT; -.
DR DMDM; 21264092; -.
DR EPD; Q969Z4; -.
DR jPOST; Q969Z4; -.
DR MassIVE; Q969Z4; -.
DR MaxQB; Q969Z4; -.
DR PaxDb; Q969Z4; -.
DR PeptideAtlas; Q969Z4; -.
DR PRIDE; Q969Z4; -.
DR ProteomicsDB; 75884; -.
DR Antibodypedia; 30960; 378 antibodies from 32 providers.
DR DNASU; 84957; -.
DR Ensembl; ENST00000064780.7; ENSP00000064780.2; ENSG00000054967.13.
DR Ensembl; ENST00000393580.2; ENSP00000377207.2; ENSG00000054967.13.
DR GeneID; 84957; -.
DR KEGG; hsa:84957; -.
DR MANE-Select; ENST00000064780.7; ENSP00000064780.2; NM_152222.2; NP_689408.1.
DR UCSC; uc001otv.4; human.
DR CTD; 84957; -.
DR DisGeNET; 84957; -.
DR GeneCards; RELT; -.
DR HGNC; HGNC:13764; RELT.
DR HPA; ENSG00000054967; Tissue enriched (bone).
DR MalaCards; RELT; -.
DR MIM; 611211; gene.
DR MIM; 618386; phenotype.
DR neXtProt; NX_Q969Z4; -.
DR OpenTargets; ENSG00000054967; -.
DR Orphanet; 100031; Hypoplastic amelogenesis imperfecta.
DR PharmGKB; PA162401092; -.
DR VEuPathDB; HostDB:ENSG00000054967; -.
DR eggNOG; ENOG502QVCC; Eukaryota.
DR GeneTree; ENSGT00940000160350; -.
DR HOGENOM; CLU_058936_0_0_1; -.
DR InParanoid; Q969Z4; -.
DR OMA; AEEVQCQ; -.
DR OrthoDB; 672843at2759; -.
DR PhylomeDB; Q969Z4; -.
DR TreeFam; TF332339; -.
DR PathwayCommons; Q969Z4; -.
DR SignaLink; Q969Z4; -.
DR BioGRID-ORCS; 84957; 20 hits in 1083 CRISPR screens.
DR ChiTaRS; RELT; human.
DR GeneWiki; RELT; -.
DR GenomeRNAi; 84957; -.
DR Pharos; Q969Z4; Tbio.
DR PRO; PR:Q969Z4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q969Z4; protein.
DR Bgee; ENSG00000054967; Expressed in monocyte and 134 other tissues.
DR ExpressionAtlas; Q969Z4; baseline and differential.
DR Genevisible; Q969Z4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0097186; P:amelogenesis; IMP:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR CDD; cd13419; TNFRSF19L; 1.
DR InterPro; IPR022248; TNF_rcpt_RELT.
DR InterPro; IPR022333; TNFR_19-like.
DR InterPro; IPR034048; TNFRSF19L_N.
DR PANTHER; PTHR47397; PTHR47397; 1.
DR Pfam; PF12606; RELT; 1.
DR PRINTS; PR01970; TNFACTORR19L.
PE 1: Evidence at protein level;
KW Amelogenesis imperfecta; Apoptosis; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:11313261,
FT ECO:0000269|PubMed:15340161"
FT CHAIN 26..430
FT /note="Tumor necrosis factor receptor superfamily member
FT 19L"
FT /id="PRO_0000034599"
FT TOPO_DOM 26..162
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..430
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 50..90
FT /note="TNFR-Cys"
FT REGION 134..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 373..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 349..352
FT /note="RFRV motif; mediates interaction with STK39"
FT /evidence="ECO:0000269|PubMed:16530727"
FT MOD_RES 223
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..65
FT /evidence="ECO:0000250"
FT DISULFID 71..90
FT /evidence="ECO:0000250"
FT VARIANT 332
FT /note="A -> V (in dbSNP:rs12362779)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_022614"
FT VARIANT 422
FT /note="R -> P (in AI3C; unknown pathological significance;
FT dbSNP:rs762816338)"
FT /evidence="ECO:0000269|PubMed:30506946"
FT /id="VAR_082198"
FT MUTAGEN 350
FT /note="F->A: Loss of interaction with STK39."
FT /evidence="ECO:0000269|PubMed:16530727"
FT CONFLICT 122
FT /note="D -> S (in Ref. 4; BAB84954)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="K -> E (in Ref. 2; BAB55441)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="H -> R (in Ref. 2; BAB55441)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 430 AA; 46092 MW; 4A5AB9AE32D36101 CRC64;
MKPSLLCRPL SCFLMLLPWP LATLTSTTLW QCPPGEEPDL DPGQGTLCRP CPPGTFSAAW
GSSPCQPHAR CSLWRRLEAQ VGMATRDTLC GDCWPGWFGP WGVPRVPCQP CSWAPLGTHG
CDEWGRRARR GVEVAAGASS GGETRQPGNG TRAGGPEETA AQYAVIAIVP VFCLMGLLGI
LVCNLLKRKG YHCTAHKEVG PGPGGGGSGI NPAYRTEDAN EDTIGVLVRL ITEKKENAAA
LEELLKEYHS KQLVQTSHRP VSKLPPAPPN VPHICPHRHH LHTVQGLASL SGPCCSRCSQ
KKWPEVLLSP EAVAATTPVP SLLPNPTRVP KAGAKAGRQG EITILSVGRF RVARIPEQRT
SSMVSEVKTI TEAGPSWGDL PDSPQPGLPP EQQALLGSGG SRTKWLKPPA ENKAEENRYV
VRLSESNLVI
