TASL_HUMAN
ID TASL_HUMAN Reviewed; 301 AA.
AC Q9HAI6;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=TLR adapter interacting with SLC15A4 on the lysosome {ECO:0000303|PubMed:32433612};
GN Name=TASL {ECO:0000303|PubMed:32433612, ECO:0000312|HGNC:HGNC:25667};
GN Synonyms=CXorf21 {ECO:0000312|HGNC:HGNC:25667};
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 [LARGE SCALE MRNA].
RC TISSUE=Embryo;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [3]
RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, AND INVOLVEMENT IN DISEASE.
RX PubMed=31001245; DOI=10.3389/fimmu.2019.00578;
RA Harris V.M., Harley I.T.W., Kurien B.T., Koelsch K.A., Scofield R.H.;
RT "Lysosomal pH Is Regulated in a Sex Dependent Manner in Immune Cells
RT Expressing CXorf21.";
RL Front. Immunol. 10:578-578(2019).
RN [4]
RP INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INVOLVEMENT IN
RP DISEASE.
RX PubMed=31092820; DOI=10.1038/s41467-019-10106-2;
RA Odhams C.A., Roberts A.L., Vester S.K., Duarte C.S.T., Beales C.T.,
RA Clarke A.J., Lindinger S., Daffern S.J., Zito A., Chen L., Jones L.L.,
RA Boteva L., Morris D.L., Small K.S., Fernando M.M.A.,
RA Cunninghame Graham D.S., Vyse T.J.;
RT "Interferon inducible X-linked gene CXorf21 may contribute to sexual
RT dimorphism in Systemic Lupus Erythematosus.";
RL Nat. Commun. 10:2164-2164(2019).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IRF5 AND SLC15A4,
RP PHOSPHORYLATION AT SER-294, AND MUTAGENESIS OF SER-294.
RX PubMed=32433612; DOI=10.1038/s41586-020-2282-0;
RA Heinz L.X., Lee J., Kapoor U., Kartnig F., Sedlyarov V., Papakostas K.,
RA Cesar-Razquin A., Essletzbichler P., Goldmann U., Stefanovic A.,
RA Bigenzahn J.W., Scorzoni S., Pizzagalli M.D., Bensimon A., Mueller A.C.,
RA King F.J., Li J., Girardi E., Mbow M.L., Whitehurst C.E., Rebsamen M.,
RA Superti-Furga G.;
RT "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9.";
RL Nature 581:316-322(2020).
CC -!- FUNCTION: Innate immune adapter that mediates the recruitment and
CC activation of IRF5 downstream of endolysosomal toll-like receptors
CC TLR7, TLR8 and TLR9 (PubMed:32433612). Following recruitment to
CC endolysosome by SLC15A4 downstream of TLR7, TLR8 and TLR9, specifically
CC recruits IRF5 transcription factor via its pLxIS motif, leading to IRF5
CC activation and subsequent expression of type I interferons
CC (PubMed:32433612). Plays a role in the regulation of endolysosomal pH
CC in immune cells such as B-cells, dendritic cells and monocytes
CC (PubMed:31001245). {ECO:0000269|PubMed:31001245,
CC ECO:0000269|PubMed:32433612}.
CC -!- SUBUNIT: Interacts (via pLxIS motif) with IRF5; leading to IRF5
CC activation (PubMed:32433612). Interacts with SLC15A4; leading to its
CC recruitment to endolysosome (PubMed:32433612).
CC {ECO:0000269|PubMed:32433612}.
CC -!- INTERACTION:
CC Q9HAI6; Q8N697: SLC15A4; NbExp=13; IntAct=EBI-21895669, EBI-4319594;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:31092820,
CC ECO:0000269|PubMed:32433612}. Endosome membrane
CC {ECO:0000269|PubMed:32433612}. Nucleus {ECO:0000269|PubMed:31092820}.
CC Cytoplasm {ECO:0000269|PubMed:31092820}. Note=Recruited to endolysosome
CC following interaction with SLC15A4 (PubMed:32433612). May colocalize
CC with TLR7 in the endosomal pathway (PubMed:31092820).
CC {ECO:0000269|PubMed:31092820, ECO:0000269|PubMed:32433612}.
CC -!- TISSUE SPECIFICITY: Highly expressed in immune cell types such as B-
CC cells, neutrophils, dendritic cells and monocytes, the expression
CC levels are two-three-fold higher in female cells compared to male cells
CC (at protein level) (PubMed:31092820, PubMed:31001245). Expressed at low
CC levels in T-cells and NK cells (PubMed:31001245).
CC {ECO:0000269|PubMed:31001245, ECO:0000269|PubMed:31092820}.
CC -!- INDUCTION: Escape from X chromosome inactivation results in an
CC increased expression in females (PubMed:31092820, PubMed:31001245). In
CC monocytes and B cells, induced by type I and type II interferons as
CC well as LPS (PubMed:31092820). {ECO:0000269|PubMed:31001245,
CC ECO:0000269|PubMed:31092820}.
CC -!- DOMAIN: The pLxIS motif constitutes an IRF5-binding motif: following
CC phosphorylation, the phosphorylated pLxIS motif of TASL recruits IRF5.
CC {ECO:0000269|PubMed:32433612}.
CC -!- PTM: The phosphorylated pLxIS motif constitutes an IRF5-binding motif,
CC leading to recruitment of the transcription factor IRF5 to induce type-
CC I interferons and other cytokines. {ECO:0000305|PubMed:32433612}.
CC -!- DISEASE: Note=Some alleles may be associated with systemic lupus
CC erythematosus (SLE); a chronic, relapsing, inflammatory, and often
CC febrile multisystemic disorder of connective tissue, characterized
CC principally by involvement of the skin, joints, kidneys and serosal
CC membranes. It is of unknown etiology, but is thought to represent a
CC failure of the regulatory mechanisms of the autoimmune system. Because
CC it evades X-chromosome inactivation, its expression is increased in
CC female immune cells which may be involved to SLE striking sex imbalance
CC towards females. {ECO:0000269|PubMed:31001245,
CC ECO:0000269|PubMed:31092820}.
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DR EMBL; AK021639; BAB13860.1; -; mRNA.
DR EMBL; BC020611; AAH20611.1; -; mRNA.
DR CCDS; CCDS14224.1; -.
DR RefSeq; NP_079435.1; NM_025159.2.
DR AlphaFoldDB; Q9HAI6; -.
DR BioGRID; 123194; 7.
DR IntAct; Q9HAI6; 2.
DR STRING; 9606.ENSP00000368245; -.
DR iPTMnet; Q9HAI6; -.
DR PhosphoSitePlus; Q9HAI6; -.
DR BioMuta; CXorf21; -.
DR MassIVE; Q9HAI6; -.
DR PaxDb; Q9HAI6; -.
DR PeptideAtlas; Q9HAI6; -.
DR PRIDE; Q9HAI6; -.
DR Antibodypedia; 379; 86 antibodies from 13 providers.
DR DNASU; 80231; -.
DR Ensembl; ENST00000378962.4; ENSP00000368245.3; ENSG00000120280.6.
DR GeneID; 80231; -.
DR KEGG; hsa:80231; -.
DR MANE-Select; ENST00000378962.4; ENSP00000368245.3; NM_025159.3; NP_079435.1.
DR UCSC; uc004dcg.3; human.
DR CTD; 80231; -.
DR DisGeNET; 80231; -.
DR GeneCards; TASL; -.
DR HGNC; HGNC:25667; TASL.
DR HPA; ENSG00000120280; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 301049; gene.
DR neXtProt; NX_Q9HAI6; -.
DR OpenTargets; ENSG00000120280; -.
DR VEuPathDB; HostDB:ENSG00000120280; -.
DR eggNOG; ENOG502QTA8; Eukaryota.
DR GeneTree; ENSGT00390000011425; -.
DR HOGENOM; CLU_081014_0_0_1; -.
DR InParanoid; Q9HAI6; -.
DR OMA; LAYWNDI; -.
DR OrthoDB; 980536at2759; -.
DR PhylomeDB; Q9HAI6; -.
DR TreeFam; TF335550; -.
DR PathwayCommons; Q9HAI6; -.
DR SignaLink; Q9HAI6; -.
DR BioGRID-ORCS; 80231; 7 hits in 679 CRISPR screens.
DR ChiTaRS; CXorf21; human.
DR GenomeRNAi; 80231; -.
DR Pharos; Q9HAI6; Tdark.
DR PRO; PR:Q9HAI6; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9HAI6; protein.
DR Bgee; ENSG00000120280; Expressed in buccal mucosa cell and 191 other tissues.
DR Genevisible; Q9HAI6; HS.
DR GO; GO:0036020; C:endolysosome membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045089; P:positive regulation of innate immune response; IDA:UniProtKB.
DR GO; GO:0034157; P:positive regulation of toll-like receptor 7 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034161; P:positive regulation of toll-like receptor 8 signaling pathway; IMP:UniProtKB.
DR GO; GO:0035751; P:regulation of lysosomal lumen pH; IDA:UniProtKB.
DR InterPro; IPR027869; TASL.
DR PANTHER; PTHR14889; PTHR14889; 1.
DR Pfam; PF15133; TASL; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endosome; Immunity; Innate immunity; Lysosome; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..301
FT /note="TLR adapter interacting with SLC15A4 on the
FT lysosome"
FT /id="PRO_0000251252"
FT MOTIF 290..294
FT /note="pLxIS motif"
FT /evidence="ECO:0000269|PubMed:32433612"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:32433612"
FT MUTAGEN 294
FT /note="S->A: Abolished ability to activate IRF5."
FT /evidence="ECO:0000269|PubMed:32433612"
FT MUTAGEN 294
FT /note="S->D: Phosphomimetic mutant; retains ability to
FT activate IRF5."
FT /evidence="ECO:0000269|PubMed:32433612"
SQ SEQUENCE 301 AA; 33894 MW; 0754B491077927C4 CRC64;
MLSEGYLSGL EYWNDIHWSC ASYNEQVAGE KEEETNSVAT LSYSSVDETQ VRSLYVSCKS
SGKFISSVHS RESQHSRSQR VTVLQTNPNP VFESPNLAAV EICRDASRET YLVPSSCKSI
CKNYNDLQIA GGQVMAINSV TTDFPSESSF EYGPLLKSSE IPLPMEDSIS TQPSDFPQKP
IQRYSSYWRI TSIKEKSSLQ MQNPISNAVL NEYLEQKVVE LYKQYIMDTV FHDSSPTQIL
ASELIMTSVD QISLQVSREK NLETSKARDI VFSRLLQLMS TEITEISTPS LHISQYSNVN
P
