ID   LUM_HUMAN               Reviewed;         338 AA.
AC   P51884; B2R6R5; Q96QM7;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2002, sequence version 2.
DT   27-MAR-2024, entry version 208.
DE   RecName: Full=Lumican;
DE   AltName: Full=Keratan sulfate proteoglycan lumican;
DE            Short=KSPG lumican;
DE   Flags: Precursor;
GN   Name=LUM; Synonyms=LDC, SLRR2D;
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].
RC   TISSUE=Cartilage, Intestine, and Placenta;
RX   PubMed=7665616; DOI=10.1074/jbc.270.37.21942;
RA   Grover J., Chen X.-N., Korenberg J.R., Roughley P.J.;
RT   "The human lumican gene. Organization, chromosomal location, and expression
RT   in articular cartilage.";
RL   J. Biol. Chem. 270:21942-21949(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Cornea;
RX   PubMed=7558030; DOI=10.1006/geno.1995.1080;
RA   Chakravarti S., Stallings R.L., Sundar-Raj N., Cornuet P.K., Hassell J.R.;
RT   "Primary structure of human lumican (keratan sulfate proteoglycan) and
RT   localization of the gene (LUM) to chromosome 12q21.3-q22.";
RL   Genomics 27:481-488(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung, and Prostate;
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   [7]
RP   SULFATION, PYROGLUTAMATE FORMATION AT GLN-19, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=14551184; DOI=10.1074/jbc.m308689200;
RA   Onnerfjord P., Heathfield T.F., Heinegaard D.;
RT   "Identification of tyrosine sulfation in extracellular leucine-rich repeat
RT   proteins using mass spectrometry.";
RL   J. Biol. Chem. 279:26-33(2004).
RN   [8]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-88 AND ASN-160.
RC   TISSUE=Plasma;
RX   PubMed=14760718; DOI=10.1002/pmic.200300556;
RA   Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT   "Screening for N-glycosylated proteins by liquid chromatography mass
RT   spectrometry.";
RL   Proteomics 4:454-465(2004).
RN   [9]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-88; ASN-127; ASN-160 AND
RP   ASN-252.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [10]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-88; ASN-127; ASN-160 AND
RP   ASN-252.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   VARIANT PRO-199.
RX   PubMed=21220648; DOI=10.1001/archneurol.2010.351;
RA   Daoud H., Valdmanis P.N., Gros-Louis F., Belzil V., Spiegelman D.,
RA   Henrion E., Diallo O., Desjarlais A., Gauthier J., Camu W., Dion P.A.,
RA   Rouleau G.A.;
RT   "Resequencing of 29 candidate genes in patients with familial and sporadic
RT   amyotrophic lateral sclerosis.";
RL   Arch. Neurol. 68:587-593(2011).
CC   -!- SUBUNIT: Binds to laminin. {ECO:0000250}.
CC   -!- INTERACTION:
CC       P51884; Q92993: KAT5; NbExp=3; IntAct=EBI-725780, EBI-399080;
CC       P51884; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-725780, EBI-11742507;
CC       P51884; P50281: MMP14; NbExp=2; IntAct=EBI-725780, EBI-992788;
CC       P51884; P17252: PRKCA; NbExp=3; IntAct=EBI-725780, EBI-1383528;
CC       P51884; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-725780, EBI-9090795;
CC       P51884; P61981: YWHAG; NbExp=3; IntAct=EBI-725780, EBI-359832;
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Cornea and other tissues.
CC   -!- DEVELOPMENTAL STAGE: Present in the extracellular matrix of human
CC       articular cartilage at all ages, although its abundance is far greater
CC       in the adult. In the adult cartilage lumican exists predominantly in a
CC       glycoprotein form lacking keratan sulfate, whereas the juvenile form of
CC       the molecule is a proteoglycan.
CC   -!- PTM: Sulfated on tyrosine residue(s). {ECO:0000269|PubMed:14551184}.
CC   -!- PTM: Contains keratan sulfate. {ECO:0000250|UniProtKB:Q05443}.
CC   -!- SIMILARITY: Belongs to the small leucine-rich proteoglycan (SLRP)
CC       family. SLRP class II subfamily. {ECO:0000305}.
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DR   EMBL; U18728; AAA85268.1; -; mRNA.
DR   EMBL; U21128; AAA91639.1; -; mRNA.
DR   EMBL; BT006707; AAP35353.1; -; mRNA.
DR   EMBL; AK312682; BAG35562.1; -; mRNA.
DR   EMBL; CH471054; EAW97449.1; -; Genomic_DNA.
DR   EMBL; BC007038; AAH07038.1; -; mRNA.
DR   EMBL; BC035997; AAH35997.1; -; mRNA.
DR   CCDS; CCDS9038.1; -.
DR   RefSeq; NP_002336.1; NM_002345.3.
DR   AlphaFoldDB; P51884; -.
DR   SMR; P51884; -.
DR   BioGRID; 110238; 26.
DR   IntAct; P51884; 15.
DR   MINT; P51884; -.
DR   STRING; 9606.ENSP00000266718; -.
DR   DrugBank; DB09130; Copper.
DR   GlyConnect; 1470; 87 N-Linked glycans (4 sites).
DR   GlyCosmos; P51884; 7 sites, 99 glycans.
DR   GlyGen; P51884; 7 sites, 98 N-linked glycans (4 sites), 2 O-linked glycans (3 sites).
DR   iPTMnet; P51884; -.
DR   PhosphoSitePlus; P51884; -.
DR   BioMuta; LUM; -.
DR   DMDM; 20141464; -.
DR   EPD; P51884; -.
DR   jPOST; P51884; -.
DR   MassIVE; P51884; -.
DR   MaxQB; P51884; -.
DR   PaxDb; 9606-ENSP00000266718; -.
DR   PeptideAtlas; P51884; -.
DR   ProteomicsDB; 56448; -.
DR   TopDownProteomics; P51884; -.
DR   ABCD; P51884; 7 sequenced antibodies.
DR   Antibodypedia; 867; 422 antibodies from 34 providers.
DR   DNASU; 4060; -.
DR   Ensembl; ENST00000266718.5; ENSP00000266718.4; ENSG00000139329.5.
DR   GeneID; 4060; -.
DR   KEGG; hsa:4060; -.
DR   MANE-Select; ENST00000266718.5; ENSP00000266718.4; NM_002345.4; NP_002336.1.
DR   UCSC; uc001tbm.4; human.
DR   AGR; HGNC:6724; -.
DR   CTD; 4060; -.
DR   DisGeNET; 4060; -.
DR   GeneCards; LUM; -.
DR   HGNC; HGNC:6724; LUM.
DR   HPA; ENSG00000139329; Tissue enhanced (gallbladder, placenta).
DR   MIM; 600616; gene.
DR   neXtProt; NX_P51884; -.
DR   OpenTargets; ENSG00000139329; -.
DR   PharmGKB; PA30486; -.
DR   VEuPathDB; HostDB:ENSG00000139329; -.
DR   eggNOG; KOG0619; Eukaryota.
DR   GeneTree; ENSGT00940000158177; -.
DR   HOGENOM; CLU_000288_186_4_1; -.
DR   InParanoid; P51884; -.
DR   OMA; DCPINFP; -.
DR   OrthoDB; 521898at2759; -.
DR   PhylomeDB; P51884; -.
DR   TreeFam; TF334562; -.
DR   PathwayCommons; P51884; -.
DR   Reactome; R-HSA-2022854; Keratan sulfate biosynthesis.
DR   Reactome; R-HSA-2022857; Keratan sulfate degradation.
DR   Reactome; R-HSA-216083; Integrin cell surface interactions.
DR   Reactome; R-HSA-3000178; ECM proteoglycans.
DR   Reactome; R-HSA-3656225; Defective CHST6 causes MCDC1.
DR   Reactome; R-HSA-3656243; Defective ST3GAL3 causes MCT12 and EIEE15.
DR   Reactome; R-HSA-3656244; Defective B4GALT1 causes B4GALT1-CDG (CDG-2d).
DR   SignaLink; P51884; -.
DR   BioGRID-ORCS; 4060; 11 hits in 1142 CRISPR screens.
DR   ChiTaRS; LUM; human.
DR   GeneWiki; LUM; -.
DR   GenomeRNAi; 4060; -.
DR   Pharos; P51884; Tbio.
DR   PRO; PR:P51884; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; P51884; Protein.
DR   Bgee; ENSG00000139329; Expressed in gall bladder and 182 other cell types or tissues.
DR   ExpressionAtlas; P51884; baseline and differential.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
DR   GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:0005583; C:fibrillar collagen trimer; IDA:UniProtKB.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR   GO; GO:0005518; F:collagen binding; IDA:UniProtKB.
DR   GO; GO:0005201; F:extracellular matrix structural constituent; NAS:UniProtKB.
DR   GO; GO:0030021; F:extracellular matrix structural constituent conferring compression resistance; ISS:BHF-UCL.
DR   GO; GO:0030199; P:collagen fibril organization; NAS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0032914; P:positive regulation of transforming growth factor beta1 production; IEA:Ensembl.
DR   GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 3.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   InterPro; IPR000372; LRRNT.
DR   PANTHER; PTHR45712; AGAP008170-PA; 1.
DR   PANTHER; PTHR45712:SF6; LUMICAN; 1.
DR   Pfam; PF13516; LRR_6; 1.
DR   Pfam; PF13855; LRR_8; 3.
DR   Pfam; PF01462; LRRNT; 1.
DR   PRINTS; PR00019; LEURICHRPT.
DR   SMART; SM00364; LRR_BAC; 5.
DR   SMART; SM00365; LRR_SD22; 4.
DR   SMART; SM00369; LRR_TYP; 8.
DR   SMART; SM00013; LRRNT; 1.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   PROSITE; PS51450; LRR; 10.
DR   Genevisible; P51884; HS.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Extracellular matrix;
KW   Glycoprotein; Leucine-rich repeat; Phosphoprotein; Proteoglycan;
KW   Pyrrolidone carboxylic acid; Reference proteome; Repeat; Secreted; Signal;
KW   Sulfation.
FT   SIGNAL          1..18
FT   CHAIN           19..338
FT                   /note="Lumican"
FT                   /id="PRO_0000032733"
FT   DOMAIN          28..66
FT                   /note="LRRNT"
FT   REPEAT          67..88
FT                   /note="LRR 1"
FT   REPEAT          91..114
FT                   /note="LRR 2"
FT   REPEAT          117..137
FT                   /note="LRR 3"
FT   REPEAT          138..159
FT                   /note="LRR 4"
FT   REPEAT          160..181
FT                   /note="LRR 5"
FT   REPEAT          185..205
FT                   /note="LRR 6"
FT   REPEAT          206..227
FT                   /note="LRR 7"
FT   REPEAT          230..253
FT                   /note="LRR 8"
FT   REPEAT          255..276
FT                   /note="LRR 9"
FT   REPEAT          277..296
FT                   /note="LRR 10"
FT   REPEAT          305..326
FT                   /note="LRR 11"
FT   MOD_RES         19
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|PubMed:14551184"
FT   MOD_RES         20
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P51885"
FT   MOD_RES         21
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P51885"
FT   MOD_RES         23
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P51885"
FT   MOD_RES         30
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P51885"
FT   MOD_RES         304
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P51886"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14760718,
FT                   ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT   CARBOHYD        127
FT                   /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14760718,
FT                   ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT   CARBOHYD        252
FT                   /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        295..328
FT                   /evidence="ECO:0000250"
FT   VARIANT         199
FT                   /note="L -> P (found in patients with amyotrophic lateral
FT                   sclerosis; dbSNP:rs147975710)"
FT                   /evidence="ECO:0000269|PubMed:21220648"
FT                   /id="VAR_065763"
FT   CONFLICT        27
FT                   /note="L -> P (in Ref. 1; AAA85268)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        101
FT                   /note="L -> V (in Ref. 1; AAA85268)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   338 AA;  38429 MW;  905D2EBD370CC59D CRC64;
     MSLSAFTLFL ALIGGTSGQY YDYDFPLSIY GQSSPNCAPE CNCPESYPSA MYCDELKLKS
     VPMVPPGIKY LYLRNNQIDH IDEKAFENVT DLQWLILDHN LLENSKIKGR VFSKLKQLKK
     LHINHNNLTE SVGPLPKSLE DLQLTHNKIT KLGSFEGLVN LTFIHLQHNR LKEDAVSAAF
     KGLKSLEYLD LSFNQIARLP SGLPVSLLTL YLDNNKISNI PDEYFKRFNA LQYLRLSHNE
     LADSGIPGNS FNVSSLVELD LSYNKLKNIP TVNENLENYY LEVNQLEKFD IKSFCKILGP
     LSYSKIKHLR LDGNRISETS LPPDMYECLR VANEVTLN
//