LRC25_HUMAN
ID LRC25_HUMAN Reviewed; 305 AA.
AC Q8N386; Q6IQ00; Q8N9A5;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Leucine-rich repeat-containing protein 25;
DE AltName: Full=Monocyte and plasmacytoid-activated protein;
DE Flags: Precursor;
GN Name=LRRC25; Synonyms=MAPA; ORFNames=UNQ6169/PRO20174;
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], FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND
RP VARIANT SER-294.
RC TISSUE=Plasmacytoid dendritic cell;
RX PubMed=12384430; DOI=10.1182/blood-2002-02-0638;
RA Rissoan M.-C., Duhen T., Bridon J.-M., Bendriss-Vermare N., Peronne C.,
RA de Saint-Vis B.M., Briere F., Bates E.E.M.;
RT "Subtractive hybridization reveals the expression of immunoglobulin like
RT transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human
RT plasmacytoid dendritic cells.";
RL Blood 100:3295-3303(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-294.
RC TISSUE=Blood, Heart, and Lung;
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 [5]
RP FUNCTION, INTERACTION WITH RELA, AND SUBCELLULAR LOCATION.
RX PubMed=29044191; DOI=10.1038/s41598-017-12573-3;
RA Feng Y., Duan T., Du Y., Jin S., Wang M., Cui J., Wang R.F.;
RT "LRRC25 functions as an inhibitor of NF-kappaB signaling pathway by
RT promoting p65/RelA for autophagic degradation.";
RL Sci. Rep. 7:13448-13448(2017).
RN [6]
RP FUNCTION, INTERACTION WITH DDX58 AND SQSTM1, AND SUBCELLULAR LOCATION.
RX PubMed=29288164; DOI=10.15252/embj.201796781;
RA Du Y., Duan T., Feng Y., Liu Q., Lin M., Cui J., Wang R.F.;
RT "LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I
RT for autophagic degradation.";
RL EMBO J. 37:351-366(2018).
CC -!- FUNCTION: Plays a role in the inhibition of RLR-mediated type I
CC interferon signaling pathway by targeting DDX58/RIG-I for autophagic
CC degradation. Interacts specifically with ISG15-associated DDX58 to
CC promote interaction between DDX58 and the autophagic cargo receptor
CC p62/SQSTM1 to mediate DDX58 degradation via selective autophagy
CC (PubMed:29288164). Also plays a role in the inhibition of NF-kappa-B
CC signaling pathway and inflammatory response by promoting the
CC degradation of p65/RELA. {ECO:0000269|PubMed:12384430,
CC ECO:0000269|PubMed:29044191, ECO:0000269|PubMed:29288164}.
CC -!- SUBUNIT: Interacts with DDX58 (PubMed:29288164). Interacts with SQSTM1
CC (PubMed:29288164). Interacts with p65/RELA; this interaction promotes
CC the degradation of RELA through autophagy (PubMed:29044191).
CC {ECO:0000269|PubMed:29044191, ECO:0000269|PubMed:29288164}.
CC -!- INTERACTION:
CC Q8N386; Q96AP0: ACD; NbExp=2; IntAct=EBI-11304917, EBI-717666;
CC Q8N386; Q9NRZ5: AGPAT4; NbExp=3; IntAct=EBI-11304917, EBI-1754287;
CC Q8N386; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-11304917, EBI-12109402;
CC Q8N386; O95236-2: APOL3; NbExp=3; IntAct=EBI-11304917, EBI-11976321;
CC Q8N386; P27449: ATP6V0C; NbExp=3; IntAct=EBI-11304917, EBI-721179;
CC Q8N386; O95393: BMP10; NbExp=3; IntAct=EBI-11304917, EBI-3922513;
CC Q8N386; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-11304917, EBI-12244618;
CC Q8N386; P21854: CD72; NbExp=3; IntAct=EBI-11304917, EBI-307924;
CC Q8N386; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-11304917, EBI-12256978;
CC Q8N386; Q8NC01: CLEC1A; NbExp=3; IntAct=EBI-11304917, EBI-11996768;
CC Q8N386; Q9NWW5: CLN6; NbExp=3; IntAct=EBI-11304917, EBI-6165897;
CC Q8N386; A0PK11: CLRN2; NbExp=3; IntAct=EBI-11304917, EBI-12813623;
CC Q8N386; Q8TBE1: CNIH3; NbExp=3; IntAct=EBI-11304917, EBI-12208021;
CC Q8N386; Q07325: CXCL9; NbExp=3; IntAct=EBI-11304917, EBI-3911467;
CC Q8N386; Q5J5C9: DEFB121; NbExp=3; IntAct=EBI-11304917, EBI-10244198;
CC Q8N386; Q96LL9: DNAJC30; NbExp=3; IntAct=EBI-11304917, EBI-8639143;
CC Q8N386; P56851: EDDM3B; NbExp=3; IntAct=EBI-11304917, EBI-10215665;
CC Q8N386; Q92520: FAM3C; NbExp=3; IntAct=EBI-11304917, EBI-2876774;
CC Q8N386; Q969F0: FATE1; NbExp=3; IntAct=EBI-11304917, EBI-743099;
CC Q8N386; P25090: FPR2; NbExp=3; IntAct=EBI-11304917, EBI-17291771;
CC Q8N386; Q9NZD1: GPRC5D; NbExp=3; IntAct=EBI-11304917, EBI-13067820;
CC Q8N386; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-11304917, EBI-2820517;
CC Q8N386; P21145: MAL; NbExp=3; IntAct=EBI-11304917, EBI-3932027;
CC Q8N386; P35372-10: OPRM1; NbExp=3; IntAct=EBI-11304917, EBI-12807478;
CC Q8N386; Q99640-2: PKMYT1; NbExp=3; IntAct=EBI-11304917, EBI-12257782;
CC Q8N386; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-11304917, EBI-8652812;
CC Q8N386; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-11304917, EBI-8652744;
CC Q8N386; P60059: SEC61G; NbExp=3; IntAct=EBI-11304917, EBI-4402709;
CC Q8N386; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-11304917, EBI-8640191;
CC Q8N386; Q6ZMD2-2: SPNS3; NbExp=3; IntAct=EBI-11304917, EBI-17848320;
CC Q8N386; Q9BXJ8: TMEM120A; NbExp=3; IntAct=EBI-11304917, EBI-727322;
CC Q8N386; Q5SNT2-2: TMEM201; NbExp=3; IntAct=EBI-11304917, EBI-11994282;
CC Q8N386; P01375: TNF; NbExp=3; IntAct=EBI-11304917, EBI-359977;
CC Q8N386; Q9Y228: TRAF3IP3; NbExp=3; IntAct=EBI-11304917, EBI-765817;
CC Q8N386; O14817: TSPAN4; NbExp=3; IntAct=EBI-11304917, EBI-8652667;
CC Q8N386; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-11304917, EBI-10243654;
CC Q8N386; O95183: VAMP5; NbExp=3; IntAct=EBI-11304917, EBI-10191195;
CC Q8N386; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-11304917, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Cytoplasm
CC {ECO:0000269|PubMed:29044191}.
CC -!- TISSUE SPECIFICITY: Expressed in plasmacytoid dendritic cells (PDC),
CC monocyte-derived dendritic cells (MDDC), granulocytes, monocytes, B-
CC lymphocytes, peripheral blood leukocytes, spleen, bone marrow, and, to
CC a lesser extent, lymph nodes, fetal liver, and appendix but not in
CC thymus. {ECO:0000269|PubMed:12384430}.
CC -!- INDUCTION: Down-regulated in CD40-activated monocyte-derived dendritic
CC cells. {ECO:0000269|PubMed:12384430}.
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DR EMBL; AJ422148; CAD19531.1; -; mRNA.
DR EMBL; AY358151; AAQ88518.1; -; mRNA.
DR EMBL; AK095435; BAC04548.1; -; mRNA.
DR EMBL; BC071640; AAH71640.1; -; mRNA.
DR EMBL; BC093842; AAH93842.1; -; mRNA.
DR CCDS; CCDS12377.1; -.
DR RefSeq; NP_660299.2; NM_145256.2.
DR RefSeq; XP_005259796.1; XM_005259739.3.
DR AlphaFoldDB; Q8N386; -.
DR BioGRID; 125983; 214.
DR IntAct; Q8N386; 38.
DR STRING; 9606.ENSP00000340983; -.
DR GlyGen; Q8N386; 4 sites.
DR PhosphoSitePlus; Q8N386; -.
DR SwissPalm; Q8N386; -.
DR BioMuta; LRRC25; -.
DR DMDM; 47605902; -.
DR jPOST; Q8N386; -.
DR MassIVE; Q8N386; -.
DR PaxDb; Q8N386; -.
DR PeptideAtlas; Q8N386; -.
DR PRIDE; Q8N386; -.
DR ProteomicsDB; 71776; -.
DR Antibodypedia; 28033; 346 antibodies from 19 providers.
DR DNASU; 126364; -.
DR Ensembl; ENST00000339007.4; ENSP00000340983.2; ENSG00000175489.10.
DR Ensembl; ENST00000595840.1; ENSP00000472290.1; ENSG00000175489.10.
DR GeneID; 126364; -.
DR KEGG; hsa:126364; -.
DR MANE-Select; ENST00000339007.4; ENSP00000340983.2; NM_145256.3; NP_660299.2.
DR UCSC; uc002niw.4; human.
DR CTD; 126364; -.
DR DisGeNET; 126364; -.
DR GeneCards; LRRC25; -.
DR HGNC; HGNC:29806; LRRC25.
DR HPA; ENSG00000175489; Group enriched (bone marrow, lymphoid tissue).
DR MIM; 607518; gene.
DR neXtProt; NX_Q8N386; -.
DR OpenTargets; ENSG00000175489; -.
DR PharmGKB; PA134957834; -.
DR VEuPathDB; HostDB:ENSG00000175489; -.
DR eggNOG; ENOG502S9V5; Eukaryota.
DR GeneTree; ENSGT00390000004001; -.
DR HOGENOM; CLU_906014_0_0_1; -.
DR InParanoid; Q8N386; -.
DR OMA; WHNVSAF; -.
DR OrthoDB; 1374271at2759; -.
DR PhylomeDB; Q8N386; -.
DR TreeFam; TF337414; -.
DR PathwayCommons; Q8N386; -.
DR SignaLink; Q8N386; -.
DR BioGRID-ORCS; 126364; 10 hits in 1068 CRISPR screens.
DR ChiTaRS; LRRC25; human.
DR GenomeRNAi; 126364; -.
DR Pharos; Q8N386; Tbio.
DR PRO; PR:Q8N386; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8N386; protein.
DR Bgee; ENSG00000175489; Expressed in monocyte and 102 other tissues.
DR Genevisible; Q8N386; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR039243; LRRC25.
DR PANTHER; PTHR20878; PTHR20878; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Glycoprotein; Leucine-rich repeat; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..305
FT /note="Leucine-rich repeat-containing protein 25"
FT /id="PRO_0000021613"
FT TOPO_DOM 21..165
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 187..305
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 39..59
FT /note="LRR 1"
FT REPEAT 62..83
FT /note="LRR 2"
FT REPEAT 86..107
FT /note="LRR 3"
FT REGION 204..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 284
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8K1T1"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 234
FT /note="P -> T (in dbSNP:rs34439430)"
FT /id="VAR_061677"
FT VARIANT 294
FT /note="P -> S (in dbSNP:rs6512265)"
FT /evidence="ECO:0000269|PubMed:12384430,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_051109"
FT CONFLICT 40
FT /note="A -> V (in Ref. 3; BAC04548)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="A -> G (in Ref. 1; CAD19531)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="N -> S (in Ref. 3; BAC04548)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 305 AA; 33179 MW; A2851B3B8F160294 CRC64;
MGGTLAWTLL LPLLLRESDS LEPSCTVSSA DVDWNAEFSA TCLNFSGLSL SLPHNQSLRA
SNVILLDLSG NGLRELPVTF FAHLQKLEVL NVLRNPLSRV DGALAARCDL DLQADCNCAL
ESWHDIRRDN CSGQKPLLCW DTTSSQHNLS AFLEVSCAPG LASATIGAVV VSGCLLLGLA
IAGPVLAWRL WRCRVARSRE LNKPWAAQDG PKPGLGLQPR YGSRSAPKPQ VAVPSCPSTP
DYENMFVGQP AAEHQWDEQG AHPSEDNDFY INYKDIDLAS QPVYCNLQSL GQAPMDEEEY
VIPGH
