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   13-FEB-2019, entry version 176.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   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
RP   CNA2 SER-247.
RX   PubMed=10802664; DOI=10.1038/75664;
RA   Pellegata N.S., Dieguez-Lucena J.L., Joensuu T., Lau S.,
RA   Montgomery K.T., Krahe R., Kivelae T., Kucherlapati R., Forsius H.,
RA   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
RT   project: 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;
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
RT   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.,
RA   Moore R.J., 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
RT   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
CC       keratoconus corneas (PubMed:11683372). Also detected in trachea,
CC       and in low levels, in intestine, skeletal muscle, ovary, lung and
CC       putamen (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]:
CC       A severe form of cornea plana, a rare ocular disorder
CC       characterized by flattened corneal curvature leading to a decrease
CC       in refraction, reduced visual activity, hyperopia, hazy corneal
CC       limbus, opacities in the corneal parenchyma, and marked arcus
CC       senilis often detected at an early age. CNA2 patients manifest
CC       extreme hyperopia and additional ocular anomalies such as
CC       malformations of the iris, a slit-like pupil, and adhesions
CC       between iris and cornea. {ECO:0000269|PubMed:10802664,
CC       ECO:0000269|PubMed:11726611}. Note=The disease is caused by
CC       mutations 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   UniGene; Hs.125750; -.
DR   ProteinModelPortal; O60938; -.
DR   SMR; O60938; -.
DR   BioGrid; 116264; 13.
DR   IntAct; O60938; 2.
DR   MINT; O60938; -.
DR   STRING; 9606.ENSP00000266719; -.
DR   GlyConnect; 1432; -.
DR   iPTMnet; O60938; -.
DR   PhosphoSitePlus; O60938; -.
DR   BioMuta; KERA; -.
DR   EPD; O60938; -.
DR   jPOST; O60938; -.
DR   PaxDb; O60938; -.
DR   PeptideAtlas; O60938; -.
DR   PRIDE; O60938; -.
DR   ProteomicsDB; 49681; -.
DR   DNASU; 11081; -.
DR   Ensembl; ENST00000266719; ENSP00000266719; ENSG00000139330.
DR   GeneID; 11081; -.
DR   KEGG; hsa:11081; -.
DR   UCSC; uc001tbl.4; human.
DR   CTD; 11081; -.
DR   DisGeNET; 11081; -.
DR   EuPathDB; HostDB:ENSG00000139330.5; -.
DR   GeneCards; KERA; -.
DR   HGNC; HGNC:6309; KERA.
DR   HPA; HPA039321; -.
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   eggNOG; KOG0619; Eukaryota.
DR   eggNOG; COG4886; LUCA.
DR   GeneTree; ENSGT00940000158968; -.
DR   HOGENOM; HOG000234447; -.
DR   HOVERGEN; HBG108061; -.
DR   InParanoid; O60938; -.
DR   KO; K08123; -.
DR   OMA; IKPPIPM; -.
DR   OrthoDB; 826997at2759; -.
DR   PhylomeDB; O60938; -.
DR   TreeFam; TF334562; -.
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   GeneWiki; Keratocan; -.
DR   GenomeRNAi; 11081; -.
DR   PRO; PR:O60938; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000139330; Expressed in 52 organ(s), highest expression level in cartilage tissue.
DR   Genevisible; O60938; HS.
DR   GO; GO:0031012; C:extracellular matrix; NAS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
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:0018146; P:keratan sulfate biosynthetic process; TAS:Reactome.
DR   GO; GO:0042340; P:keratan sulfate catabolic process; TAS:Reactome.
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; -; 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   Pfam; PF13516; LRR_6; 1.
DR   Pfam; PF13855; LRR_8; 2.
DR   SMART; SM00369; LRR_TYP; 6.
DR   SMART; SM00013; LRRNT; 1.
DR   PROSITE; PS51450; LRR; 11.
PE   1: Evidence at protein level;
KW   Complete proteome; Disease mutation; Disulfide bond;
KW   Extracellular matrix; Glycoprotein; Leucine-rich repeat; Proteoglycan;
KW   Reference proteome; Repeat; Secreted; Sensory transduction; Signal;
KW   Vision.
FT   SIGNAL        1     20       {ECO:0000255}.
FT   CHAIN        21    352       Keratocan.
FT                                /FTId=PRO_0000032748.
FT   DOMAIN       33     71       LRRNT.
FT   REPEAT       72     93       LRR 1.
FT   REPEAT       96    117       LRR 2.
FT   REPEAT      122    142       LRR 3.
FT   REPEAT      143    164       LRR 4.
FT   REPEAT      167    180       LRR 5.
FT   REPEAT      193    213       LRR 6.
FT   REPEAT      214    235       LRR 7.
FT   REPEAT      238    258       LRR 8.
FT   REPEAT      263    282       LRR 9.
FT   REPEAT      283    304       LRR 10.
FT   CARBOHYD     93     93       N-linked (GlcNAc...) (keratan sulfate)
FT                                asparagine. {ECO:0000250}.
FT   CARBOHYD    167    167       N-linked (GlcNAc...) (keratan sulfate)
FT                                asparagine. {ECO:0000250}.
FT   CARBOHYD    222    222       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    298    298       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:16335952}.
FT   DISULFID     42     48       {ECO:0000250|UniProtKB:P21793}.
FT   DISULFID     46     58       {ECO:0000250|UniProtKB:P21793}.
FT   DISULFID    303    343       {ECO:0000250|UniProtKB:P21793}.
FT   VARIANT     215    215       T -> K (in CNA2; dbSNP:rs121917862).
FT                                {ECO:0000269|PubMed:11726611}.
FT                                /FTId=VAR_012753.
FT   VARIANT     235    235       V -> G (in dbSNP:rs737111).
FT                                /FTId=VAR_013564.
FT   VARIANT     247    247       N -> S (in CNA2; dbSNP:rs121917858).
FT                                {ECO:0000269|PubMed:10802664}.
FT                                /FTId=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
//