ID LRC17_HUMAN Reviewed; 441 AA. AC Q8N6Y2; Q13288; Q6UWA7; Q75MG5; DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 02-OCT-2024, entry version 163. DE RecName: Full=Leucine-rich repeat-containing protein 17; DE AltName: Full=p37NB; DE Flags: Precursor; GN Name=LRRC17; Synonyms=P37NB; ORFNames=UNQ3076/PRO9909; 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] (ISOFORM 2), TISSUE SPECIFICITY, AND VARIANT RP ALA-187. RX PubMed=8982252; DOI=10.1016/s0167-4781(96)00158-3; RA Kim D., LaQuaglia M.P., Yang S.Y.; RT "A cDNA encoding a putative 37 kDa leucine-rich repeat (LRR) protein, RT p37NB, isolated from S-type neuroblastoma cell has a differential tissue RT distribution."; RL Biochim. Biophys. Acta 1309:183-188(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 GENOMIC DNA] (ISOFORM 2). RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; 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 TISSUE SPECIFICITY. RX PubMed=19336404; DOI=10.1074/jbc.m807722200; RA Kim T., Kim K., Lee S.H., So H.-S., Lee J., Kim N., Choi Y.; RT "Identification of LRRc17 as a negative regulator of receptor activator of RT NF-kappaB ligand (RANKL)-induced osteoclast differentiation."; RL J. Biol. Chem. 284:15308-15316(2009). CC -!- FUNCTION: Involved in bone homeostasis. Acts as a negative regulator of CC RANKL-induced osteoclast precursor differentiation from bone marrow CC precursors (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8N6Y2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N6Y2-2; Sequence=VSP_011424, VSP_011425; CC -!- TISSUE SPECIFICITY: Expressed in osteoblast cell lines. Well expressed CC in ovary, heart, pancreas, skeletal muscle, lung, and fetal kidney and CC lung and only at the basal levels in the other tissues examined CC including adult kidney. More expressed in S-type neuroblastoma cells CC than in N-type neuroblastoma cells. {ECO:0000269|PubMed:19336404, CC ECO:0000269|PubMed:8982252}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U32907; AAB41565.1; -; mRNA. DR EMBL; AY358889; AAQ89248.1; -; mRNA. DR EMBL; AC073127; AAS07483.1; -; Genomic_DNA. DR EMBL; BC027903; AAH27903.1; -; mRNA. DR CCDS; CCDS34721.1; -. [Q8N6Y2-1] DR CCDS; CCDS5727.1; -. [Q8N6Y2-2] DR PIR; G02020; G02020. DR RefSeq; NP_001026862.1; NM_001031692.2. [Q8N6Y2-1] DR RefSeq; NP_005815.2; NM_005824.2. [Q8N6Y2-2] DR RefSeq; XP_005250165.1; XM_005250108.1. [Q8N6Y2-1] DR AlphaFoldDB; Q8N6Y2; -. DR SMR; Q8N6Y2; -. DR BioGRID; 115528; 23. DR IntAct; Q8N6Y2; 20. DR STRING; 9606.ENSP00000344242; -. DR GlyCosmos; Q8N6Y2; 1 site, 1 glycan. DR GlyGen; Q8N6Y2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8N6Y2; -. DR PhosphoSitePlus; Q8N6Y2; -. DR BioMuta; LRRC17; -. DR DMDM; 51701682; -. DR jPOST; Q8N6Y2; -. DR MassIVE; Q8N6Y2; -. DR PaxDb; 9606-ENSP00000344242; -. DR PeptideAtlas; Q8N6Y2; -. DR ProteomicsDB; 72249; -. [Q8N6Y2-1] DR ProteomicsDB; 72250; -. [Q8N6Y2-2] DR Antibodypedia; 31152; 66 antibodies from 16 providers. DR DNASU; 10234; -. DR Ensembl; ENST00000249377.4; ENSP00000249377.4; ENSG00000128606.13. [Q8N6Y2-2] DR Ensembl; ENST00000339431.9; ENSP00000344242.4; ENSG00000128606.13. [Q8N6Y2-1] DR GeneID; 10234; -. DR KEGG; hsa:10234; -. DR MANE-Select; ENST00000339431.9; ENSP00000344242.4; NM_001031692.3; NP_001026862.1. DR UCSC; uc003vat.4; human. [Q8N6Y2-1] DR AGR; HGNC:16895; -. DR CTD; 10234; -. DR DisGeNET; 10234; -. DR GeneCards; LRRC17; -. DR HGNC; HGNC:16895; LRRC17. DR HPA; ENSG00000128606; Tissue enhanced (ovary). DR MIM; 618749; gene. DR neXtProt; NX_Q8N6Y2; -. DR OpenTargets; ENSG00000128606; -. DR PharmGKB; PA134866295; -. DR VEuPathDB; HostDB:ENSG00000128606; -. DR eggNOG; KOG0619; Eukaryota. DR GeneTree; ENSGT00940000156400; -. DR HOGENOM; CLU_049990_0_0_1; -. DR InParanoid; Q8N6Y2; -. DR OMA; RQTQECK; -. DR OrthoDB; 5397338at2759; -. DR PhylomeDB; Q8N6Y2; -. DR PathwayCommons; Q8N6Y2; -. DR BioGRID-ORCS; 10234; 13 hits in 1139 CRISPR screens. DR ChiTaRS; LRRC17; human. DR GeneWiki; LRRC17; -. DR GenomeRNAi; 10234; -. DR Pharos; Q8N6Y2; Tdark. DR PRO; PR:Q8N6Y2; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q8N6Y2; protein. DR Bgee; ENSG00000128606; Expressed in secondary oocyte and 164 other cell types or tissues. DR ExpressionAtlas; Q8N6Y2; baseline and differential. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0048539; P:bone marrow development; ISS:UniProtKB. DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; ISS:UniProtKB. DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2. DR InterPro; IPR000483; Cys-rich_flank_reg_C. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR050541; LRR_TM_domain-containing. DR PANTHER; PTHR24369; ANTIGEN BSP, PUTATIVE-RELATED; 1. DR PANTHER; PTHR24369:SF9; LEUCINE-RICH REPEAT-CONTAINING PROTEIN 4; 1. DR Pfam; PF13855; LRR_8; 2. DR PRINTS; PR00019; LEURICHRPT. DR SMART; SM00365; LRR_SD22; 3. DR SMART; SM00369; LRR_TYP; 6. DR SMART; SM00082; LRRCT; 2. DR SUPFAM; SSF52058; L domain-like; 1. DR PROSITE; PS51450; LRR; 6. PE 1: Evidence at protein level; KW Alternative splicing; Leucine-rich repeat; Osteogenesis; KW Proteomics identification; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..441 FT /note="Leucine-rich repeat-containing protein 17" FT /id="PRO_0000021608" FT REPEAT 82..103 FT /note="LRR 1" FT REPEAT 106..127 FT /note="LRR 2" FT REPEAT 130..151 FT /note="LRR 3" FT DOMAIN 163..214 FT /note="LRRCT 1" FT DOMAIN 225..268 FT /note="LRRNT" FT REPEAT 269..290 FT /note="LRR 4" FT REPEAT 293..314 FT /note="LRR 5" FT REPEAT 317..340 FT /note="LRR 6" FT DOMAIN 350..402 FT /note="LRRCT 2" FT VAR_SEQ 310..313 FT /note="AAFL -> GSLR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8982252" FT /id="VSP_011424" FT VAR_SEQ 314..441 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8982252" FT /id="VSP_011425" FT VARIANT 95 FT /note="T -> I (in dbSNP:rs34613342)" FT /id="VAR_051103" FT VARIANT 119 FT /note="K -> E (in dbSNP:rs3800939)" FT /id="VAR_051104" FT VARIANT 187 FT /note="G -> A (in dbSNP:rs1057066)" FT /evidence="ECO:0000269|PubMed:8982252" FT /id="VAR_051105" FT CONFLICT 214 FT /note="Missing (in Ref. 2; AAQ89248)" FT /evidence="ECO:0000305" SQ SEQUENCE 441 AA; 51800 MW; F629666C807A4254 CRC64; MRVVTIVILL CFCKAAELRK ASPGSVRSRV NHGRAGGGRR GSNPVKRYAP GLPCDVYTYL HEKYLDCQER KLVYVLPGWP QDLLHMLLAR NKIRTLKNNM FSKFKKLKSL DLQQNEISKI ESEAFFGLNK LTTLLLQHNQ IKVLTEEVFI YTPLLSYLRL YDNPWHCTCE IETLISMLQI PRNRNLGNYA KCESPQEQKN KKLRQIKSEQ LCNEEEKEQL DPKPQVSGRP PVIKPEVDST FCHNYVFPIQ TLDCKRKELK KVPNNIPPDI VKLDLSYNKI NQLRPKEFED VHELKKLNLS SNGIEFIDPA AFLGLTHLEE LDLSNNSLQN FDYGVLEDLY FLKLLWLRDN PWRCDYNIHY LYYWLKHHYN VHFNGLECKT PEEYKGWSVG KYIRSYYEEC PKDKLPAYPE SFDQDTEDDE WEKKHRDHTA KKQSVIITIV G //