ID   KERA_HUMAN              Reviewed;         352 AA.
AC   O60938;
DT   11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   24-JAN-2024, entry version 198.
DE   RecName: Full=Keratocan;
DE            Short=KTN;
DE   AltName: Full=Keratan sulfate proteoglycan keratocan;
DE   Flags: Precursor;
GN   Name=KERA; Synonyms=SLRR2B;
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 [GENOMIC DNA].
RX   PubMed=10565548; DOI=10.3109/10425179909033939;
RA   Tasheva E.S., Funderburgh J.L., Funderburgh M.L., Corpuz L.M., Conrad G.W.;
RT   "Structure and sequence of the gene encoding human keratocan.";
RL   DNA Seq. 10:67-74(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND VARIANT CNA2
RP   SER-247.
RX   PubMed=10802664; DOI=10.1038/75664;
RA   Pellegata N.S., Dieguez-Lucena J.L., Joensuu T., Lau S., Montgomery K.T.,
RA   Krahe R., Kivelae T., Kucherlapati R., Forsius H., de la Chapelle A.;
RT   "Mutations in KERA, encoding keratocan, cause cornea plana.";
RL   Nat. Genet. 25:91-95(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Duodenum;
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   TISSUE SPECIFICITY, AND UP-REGULATION IN KERATOCONUS CORNEAS.
RX   PubMed=11683372; DOI=10.1007/bf03401852;
RA   Wentz-Hunter K., Cheng E.L., Ueda J., Sugar J., Yue B.Y.J.T.;
RT   "Keratocan expression is increased in the stroma of keratoconus corneas.";
RL   Mol. Med. 7:470-477(2001).
RN   [5]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-298.
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   [6]
RP   VARIANT CNA2 LYS-215, AND FUNCTION.
RX   PubMed=11726611;
RA   Lehmann O.J., El-ashry M.F., Ebenezer N.D., Ocaka L., Francis P.J.,
RA   Wilkie S.E., Patel R.J., Ficker L., Jordan T., Khaw P.T.,
RA   Bhattacharya S.S.;
RT   "A novel keratocan mutation causing autosomal recessive cornea plana.";
RL   Invest. Ophthalmol. Vis. Sci. 42:3118-3122(2001).
CC   -!- FUNCTION: May be important in developing and maintaining corneal
CC       transparency and for the structure of the stromal matrix.
CC       {ECO:0000305|PubMed:10802664, ECO:0000305|PubMed:11726611}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Cornea (at protein level) (PubMed:10802664,
CC       PubMed:11683372). Increased expression in the stroma of keratoconus
CC       corneas (PubMed:11683372). Also detected in trachea, and in low levels,
CC       in intestine, skeletal muscle, ovary, lung and putamen
CC       (PubMed:10802664). {ECO:0000269|PubMed:10802664,
CC       ECO:0000269|PubMed:11683372}.
CC   -!- PTM: Binds keratan sulfate chains. {ECO:0000250}.
CC   -!- DISEASE: Cornea plana 2, autosomal recessive (CNA2) [MIM:217300]: A
CC       severe form of cornea plana, a rare ocular disorder characterized by
CC       flattened corneal curvature leading to a decrease in refraction,
CC       reduced visual activity, hyperopia, hazy corneal limbus, opacities in
CC       the corneal parenchyma, and marked arcus senilis often detected at an
CC       early age. CNA2 patients manifest extreme hyperopia and additional
CC       ocular anomalies such as malformations of the iris, a slit-like pupil,
CC       and adhesions between iris and cornea. {ECO:0000269|PubMed:10802664,
CC       ECO:0000269|PubMed:11726611}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the small leucine-rich proteoglycan (SLRP)
CC       family. SLRP class II subfamily. {ECO:0000305}.
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DR   EMBL; AF065988; AAC17741.1; -; Genomic_DNA.
DR   EMBL; AF063301; AAC16390.1; -; mRNA.
DR   EMBL; AF205403; AAF69126.1; -; mRNA.
DR   EMBL; BC032667; AAH32667.1; -; mRNA.
DR   CCDS; CCDS9037.1; -.
DR   RefSeq; NP_008966.1; NM_007035.3.
DR   AlphaFoldDB; O60938; -.
DR   SMR; O60938; -.
DR   BioGRID; 116264; 26.
DR   IntAct; O60938; 15.
DR   MINT; O60938; -.
DR   STRING; 9606.ENSP00000266719; -.
DR   GlyConnect; 1432; 2 N-Linked glycans (1 site).
DR   GlyCosmos; O60938; 4 sites, 2 glycans.
DR   GlyGen; O60938; 5 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; O60938; -.
DR   PhosphoSitePlus; O60938; -.
DR   BioMuta; KERA; -.
DR   jPOST; O60938; -.
DR   MassIVE; O60938; -.
DR   PaxDb; 9606-ENSP00000266719; -.
DR   PeptideAtlas; O60938; -.
DR   ProteomicsDB; 49681; -.
DR   Antibodypedia; 30000; 162 antibodies from 25 providers.
DR   DNASU; 11081; -.
DR   Ensembl; ENST00000266719.4; ENSP00000266719.3; ENSG00000139330.6.
DR   GeneID; 11081; -.
DR   KEGG; hsa:11081; -.
DR   MANE-Select; ENST00000266719.4; ENSP00000266719.3; NM_007035.4; NP_008966.1.
DR   UCSC; uc001tbl.4; human.
DR   AGR; HGNC:6309; -.
DR   CTD; 11081; -.
DR   DisGeNET; 11081; -.
DR   GeneCards; KERA; -.
DR   HGNC; HGNC:6309; KERA.
DR   HPA; ENSG00000139330; Not detected.
DR   MalaCards; KERA; -.
DR   MIM; 217300; phenotype.
DR   MIM; 603288; gene.
DR   neXtProt; NX_O60938; -.
DR   OpenTargets; ENSG00000139330; -.
DR   Orphanet; 53691; Congenital cornea plana.
DR   PharmGKB; PA30088; -.
DR   VEuPathDB; HostDB:ENSG00000139330; -.
DR   eggNOG; KOG0619; Eukaryota.
DR   GeneTree; ENSGT00940000158968; -.
DR   HOGENOM; CLU_000288_186_4_1; -.
DR   InParanoid; O60938; -.
DR   OMA; MECFCPP; -.
DR   OrthoDB; 521898at2759; -.
DR   PhylomeDB; O60938; -.
DR   TreeFam; TF334562; -.
DR   PathwayCommons; O60938; -.
DR   Reactome; R-HSA-2022854; Keratan sulfate biosynthesis.
DR   Reactome; R-HSA-2022857; Keratan sulfate degradation.
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; O60938; -.
DR   BioGRID-ORCS; 11081; 26 hits in 1140 CRISPR screens.
DR   GeneWiki; Keratocan; -.
DR   GenomeRNAi; 11081; -.
DR   Pharos; O60938; Tbio.
DR   PRO; PR:O60938; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; O60938; Protein.
DR   Bgee; ENSG00000139330; Expressed in calcaneal tendon and 67 other cell types or tissues.
DR   GO; GO:0031012; C:extracellular matrix; NAS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR   GO; GO:0061303; P:cornea development in camera-type eye; IEA:Ensembl.
DR   GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR   GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2.
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:SF13; KERATOCAN; 1.
DR   Pfam; PF13516; LRR_6; 2.
DR   Pfam; PF13855; LRR_8; 2.
DR   Pfam; PF01462; LRRNT; 1.
DR   SMART; SM00364; LRR_BAC; 5.
DR   SMART; SM00369; LRR_TYP; 6.
DR   SMART; SM00013; LRRNT; 1.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   PROSITE; PS51450; LRR; 11.
DR   Genevisible; O60938; HS.
PE   1: Evidence at protein level;
KW   Disease variant; Disulfide bond; Extracellular matrix; Glycoprotein;
KW   Leucine-rich repeat; Proteoglycan; Reference proteome; Repeat; Secreted;
KW   Sensory transduction; Signal; Vision.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..352
FT                   /note="Keratocan"
FT                   /id="PRO_0000032748"
FT   DOMAIN          33..71
FT                   /note="LRRNT"
FT   REPEAT          72..93
FT                   /note="LRR 1"
FT   REPEAT          96..117
FT                   /note="LRR 2"
FT   REPEAT          122..142
FT                   /note="LRR 3"
FT   REPEAT          143..164
FT                   /note="LRR 4"
FT   REPEAT          167..180
FT                   /note="LRR 5"
FT   REPEAT          193..213
FT                   /note="LRR 6"
FT   REPEAT          214..235
FT                   /note="LRR 7"
FT   REPEAT          238..258
FT                   /note="LRR 8"
FT   REPEAT          263..282
FT                   /note="LRR 9"
FT   REPEAT          283..304
FT                   /note="LRR 10"
FT   CARBOHYD        93
FT                   /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        167
FT                   /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        222
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        298
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952"
FT   DISULFID        42..48
FT                   /evidence="ECO:0000250|UniProtKB:P21793"
FT   DISULFID        46..58
FT                   /evidence="ECO:0000250|UniProtKB:P21793"
FT   DISULFID        303..343
FT                   /evidence="ECO:0000250|UniProtKB:P21793"
FT   VARIANT         215
FT                   /note="T -> K (in CNA2; dbSNP:rs121917862)"
FT                   /evidence="ECO:0000269|PubMed:11726611"
FT                   /id="VAR_012753"
FT   VARIANT         235
FT                   /note="V -> G (in dbSNP:rs737111)"
FT                   /id="VAR_013564"
FT   VARIANT         247
FT                   /note="N -> S (in CNA2; dbSNP:rs121917858)"
FT                   /evidence="ECO:0000269|PubMed:10802664"
FT                   /id="VAR_012754"
SQ   SEQUENCE   352 AA;  40509 MW;  0CF8DEC938852D28 CRC64;
     MAGTICFIMW VLFITDTVWS RSVRQVYEVH DSDDWTIHDF ECPMECFCPP SFPTALYCEN
     RGLKEIPAIP SRIWYLYLQN NLIETIPEKP FENATQLRWI NLNKNKITNY GIEKGALSQL
     KKLLFLFLED NELEEVPSPL PRSLEQLQLA RNKVSRIPQG TFSNLENLTL LDLQNNKLVD
     NAFQRDTFKG LKNLMQLNMA KNALRNMPPR LPANTMQLFL DNNSIEGIPE NYFNVIPKVA
     FLRLNHNKLS DEGLPSRGFD VSSILDLQLS HNQLTKVPRI SAHLQHLHLD HNKIKSVNVS
     VICPSPSMLP AERDSFSYGP HLRYLRLDGN EIKPPIPMAL MTCFRLLQAV II
//