PGCA_HUMAN
ID PGCA_HUMAN Reviewed; 2530 AA.
AC P16112; B9EK55; E7ENV9; E7EX88; H0YM81; Q13650; Q9UCD3; Q9UCP4; Q9UCP5;
AC Q9UDE0;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 3.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Aggrecan core protein;
DE AltName: Full=Cartilage-specific proteoglycan core protein;
DE Short=CSPCP;
DE AltName: Full=Chondroitin sulfate proteoglycan core protein 1;
DE Short=Chondroitin sulfate proteoglycan 1;
DE Contains:
DE RecName: Full=Aggrecan core protein 2;
DE Flags: Precursor;
GN Name=ACAN; Synonyms=AGC1, CSPG1, MSK16;
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 3), AND VARIANTS THR-913 AND VAL-1765.
RC TISSUE=Chondrocyte;
RX PubMed=1985970; DOI=10.1016/s0021-9258(17)35257-2;
RA Doege K.J., Sasaki M., Kimura T., Yamada Y.;
RT "Complete coding sequence and deduced primary structure of the human
RT cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats,
RT and additional alternatively spliced forms.";
RL J. Biol. Chem. 266:894-902(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS LEU-864;
RP ILE-930; THR-939; ALA-1080; ALA-1403; ALA-1508; VAL-1765; VAL-2079 AND
RP GLU-2373.
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 PROTEIN SEQUENCE OF 17-27 AND 393-403, AND PROTEOLYTIC PROCESSING BY
RP AGGRECANASE.
RX PubMed=7574678; DOI=10.1006/abbi.1995.1431;
RA Ilic M.Z., Mok M.T., Williamson O.D., Campbell M.A., Hughes C.E.,
RA Handley C.J.;
RT "Catabolism of aggrecan by explant cultures of human articular cartilage in
RT the presence of retinoic acid.";
RL Arch. Biochem. Biophys. 322:22-30(1995).
RN [5]
RP PROTEIN SEQUENCE OF 361-373 AND 393-409, PROTEOLYTIC PROCESSING, AND
RP GLYCOSYLATION AT THR-371 AND THR-376.
RX PubMed=1569188; DOI=10.1172/jci115742;
RA Sandy J.D., Flannery C.R., Neame P.J., Lohmander L.S.;
RT "The structure of aggrecan fragments in human synovial fluid. Evidence for
RT the involvement in osteoarthritis of a novel proteinase which cleaves the
RT Glu 373-Ala 374 bond of the interglobular domain.";
RL J. Clin. Invest. 89:1512-1516(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 350-497, AND TISSUE SPECIFICITY.
RC TISSUE=Fetal cartilage;
RX PubMed=7524681; DOI=10.1016/0167-4781(94)90220-8;
RA Glumoff V., Savontaus M., Vehanen J., Vuorio E.;
RT "Analysis of aggrecan and tenascin gene expression in mouse skeletal
RT tissues by northern and in situ hybridization using species specific cDNA
RT probes.";
RL Biochim. Biophys. Acta 1219:613-622(1994).
RN [7]
RP PROTEIN SEQUENCE OF 393-409.
RC TISSUE=Synovial fluid;
RX PubMed=8216415; DOI=10.1002/art.1780360906;
RA Lohmander L.S., Neame P.J., Sandy J.D.;
RT "The structure of aggrecan fragments in human synovial fluid. Evidence that
RT aggrecanase mediates cartilage degradation in inflammatory joint disease,
RT joint injury, and osteoarthritis.";
RL Arthritis Rheum. 36:1214-1222(1993).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 765-866.
RC TISSUE=Blood;
RX PubMed=7827755; DOI=10.1016/0945-053x(94)90198-8;
RA Barry F.P., Neame P.J., Sasse J., Pearson D.;
RT "Length variation in the keratan sulfate domain of mammalian aggrecan.";
RL Matrix Biol. 14:323-328(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1893-2530 (ISOFORM 2), AND VARIANTS VAL-2079
RP AND ARG-2500.
RC TISSUE=Chondrocyte;
RX PubMed=8611178; DOI=10.1042/bj3130933;
RA Dudhia J., Davidson C.M., Wells T.M., Vynios D.H., Hardingham T.E.,
RA Bayliss M.T.;
RT "Age-related changes in the content of the C-terminal region of aggrecan in
RT human articular cartilage.";
RL Biochem. J. 313:933-940(1996).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2051-2530 (ISOFORM 1), AND VARIANTS VAL-2079
RP AND ARG-2500.
RX PubMed=2789216; DOI=10.1016/s0021-9258(18)71537-8;
RA Baldwin C.T., Reginato A.M., Prockop D.J.;
RT "A new epidermal growth factor-like domain in the human core protein for
RT the large cartilage-specific proteoglycan. Evidence for alternative
RT splicing of the domain.";
RL J. Biol. Chem. 264:15747-15750(1989).
RN [11]
RP INVOLVEMENT IN SEDK.
RX PubMed=16080123; DOI=10.1086/444401;
RA Gleghorn L., Ramesar R., Beighton P., Wallis G.;
RT "A mutation in the variable repeat region of the aggrecan gene (AGC1)
RT causes a form of spondyloepiphyseal dysplasia associated with severe,
RT premature osteoarthritis.";
RL Am. J. Hum. Genet. 77:484-490(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-658.
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 [13]
RP INTERACTION WITH COMP.
RX PubMed=17588949; DOI=10.1074/jbc.m611390200;
RA Chen F.-H., Herndon M.E., Patel N., Hecht J.T., Tuan R.S., Lawler J.;
RT "Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with
RT aggrecan.";
RL J. Biol. Chem. 282:24591-24598(2007).
RN [14]
RP VARIANT SEMDAG ASN-2381, AND CHARACTERIZATION OF VARIANT SEMDAG ASN-2381.
RX PubMed=19110214; DOI=10.1016/j.ajhg.2008.12.001;
RA Tompson S.W., Merriman B., Funari V.A., Fresquet M., Lachman R.S.,
RA Rimoin D.L., Nelson S.F., Briggs M.D., Cohn D.H., Krakow D.;
RT "A recessive skeletal dysplasia, SEMD aggrecan type, results from a
RT missense mutation affecting the C-type lectin domain of aggrecan.";
RL Am. J. Hum. Genet. 84:72-79(2009).
RN [15]
RP VARIANT SSOAOD MET-2418, AND DETECTION OF VARIANT SSOAOD MET-2418 BY MASS
RP SPECTROMETRY.
RX PubMed=20137779; DOI=10.1016/j.ajhg.2009.12.018;
RA Stattin E.L., Wiklund F., Lindblom K., Onnerfjord P., Jonsson B.A.,
RA Tegner Y., Sasaki T., Struglics A., Lohmander S., Dahl N., Heinegard D.,
RA Aspberg A.;
RT "A missense mutation in the aggrecan C-type lectin domain disrupts
RT extracellular matrix interactions and causes dominant familial
RT osteochondritis dissecans.";
RL Am. J. Hum. Genet. 86:126-137(2010).
CC -!- FUNCTION: This proteoglycan is a major component of extracellular
CC matrix of cartilagenous tissues. A major function of this protein is to
CC resist compression in cartilage. It binds avidly to hyaluronic acid via
CC an N-terminal globular region.
CC -!- SUBUNIT: Interacts with FBLN1 (By similarity). Interacts with COMP.
CC {ECO:0000250, ECO:0000269|PubMed:17588949}.
CC -!- INTERACTION:
CC P16112; P05067: APP; NbExp=3; IntAct=EBI-9076211, EBI-77613;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P16112-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P16112-2; Sequence=VSP_003074;
CC Name=3;
CC IsoId=P16112-3; Sequence=VSP_003074, VSP_003075;
CC -!- TISSUE SPECIFICITY: Restricted to cartilages.
CC {ECO:0000269|PubMed:7524681}.
CC -!- DEVELOPMENTAL STAGE: Expression was detected in chondrocytes throughout
CC the developing skeleton.
CC -!- DOMAIN: Two globular domains, G1 and G2, comprise the N-terminus of the
CC proteoglycan, while another globular region, G3, makes up the C-
CC terminus. G1 contains Link domains and thus consists of three
CC disulfide-bonded loop structures designated as the A, B, B' motifs. G2
CC is similar to G1. The keratan sulfate (KS) and the chondroitin sulfate
CC (CS) attachment domains lie between G2 and G3.
CC -!- PTM: Contains mostly chondroitin sulfate, but also keratan sulfate
CC chains, N-linked and O-linked oligosaccharides. The release of aggrecan
CC fragments from articular cartilage into the synovial fluid at all
CC stages of human osteoarthritis is the result of cleavage by
CC aggrecanase. {ECO:0000269|PubMed:1569188, ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:7574678}.
CC -!- DISEASE: Spondyloepiphyseal dysplasia type Kimberley (SEDK)
CC [MIM:608361]: Spondyloepiphyseal dysplasias are a heterogeneous group
CC of congenital chondrodysplasias that specifically affect epiphyses and
CC vertebrae. The autosomal dominant SEDK is associated with premature
CC degenerative arthropathy. {ECO:0000269|PubMed:16080123}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Spondyloepimetaphyseal dysplasia, aggrecan type (SEMDAG)
CC [MIM:612813]: A bone disease characterized by severe short stature,
CC macrocephaly, severe midface hypoplasia, short neck, barrel chest and
CC brachydactyly. The radiological findings comprise long bones with
CC generalized irregular epiphyses with widened metaphyses, especially at
CC the knees, platyspondyly, and multiple cervical-vertebral clefts.
CC {ECO:0000269|PubMed:19110214}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Short stature and advanced bone age, with or without early-
CC onset osteoarthritis and/or osteochondritis dissecans (SSOAOD)
CC [MIM:165800]: An autosomal dominant disease characterized by short
CC stature, advanced bone maturation, early-onset osteoarthritis, and mild
CC dysmorphic features consisting of midface hypoplasia, brachydactyly,
CC broad great toes, and lumbar lordosis. Other features include
CC intervertebral disk disease and osteochondritis dissecans.
CC Osteochondritis dissecans is defined as a separation of cartilage and
CC subchondral bone from the surrounding tissue.
CC {ECO:0000269|PubMed:20137779}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the aggrecan/versican proteoglycan family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Aggrecan;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_351";
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DR EMBL; M55172; AAA62824.1; -; mRNA.
DR EMBL; AC103982; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC150624; AAI50625.1; -; mRNA.
DR EMBL; X80278; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S74659; AAC60643.2; -; Genomic_DNA.
DR EMBL; X17406; CAA35463.1; -; mRNA.
DR EMBL; J05062; AAA35726.1; -; mRNA.
DR CCDS; CCDS53970.1; -. [P16112-1]
DR CCDS; CCDS53971.1; -. [P16112-3]
DR PIR; A39086; A39086.
DR RefSeq; NP_001126.3; NM_001135.3. [P16112-3]
DR RefSeq; NP_037359.3; NM_013227.3. [P16112-1]
DR RefSeq; XP_011519616.1; XM_011521314.1. [P16112-2]
DR PDB; 4MD4; X-ray; 1.95 A; C=89-103.
DR PDBsum; 4MD4; -.
DR AlphaFoldDB; P16112; -.
DR SMR; P16112; -.
DR IntAct; P16112; 3.
DR MINT; P16112; -.
DR STRING; 9606.ENSP00000387356; -.
DR DrugBank; DB02255; Ilomastat.
DR GlyConnect; 2002; 3 N-Linked glycans (1 site).
DR GlyGen; P16112; 82 sites, 5 N-linked glycans (1 site), 8 O-linked glycans (73 sites).
DR iPTMnet; P16112; -.
DR PhosphoSitePlus; P16112; -.
DR BioMuta; ACAN; -.
DR DMDM; 129886; -.
DR jPOST; P16112; -.
DR MassIVE; P16112; -.
DR PeptideAtlas; P16112; -.
DR PRIDE; P16112; -.
DR ProteomicsDB; 17235; -.
DR ProteomicsDB; 19009; -.
DR ProteomicsDB; 40179; -.
DR ProteomicsDB; 53288; -. [P16112-1]
DR ProteomicsDB; 53289; -. [P16112-2]
DR ProteomicsDB; 53290; -. [P16112-3]
DR Antibodypedia; 4288; 547 antibodies from 32 providers.
DR DNASU; 176; -.
DR Ensembl; ENST00000352105.11; ENSP00000341615.7; ENSG00000157766.19. [P16112-3]
DR Ensembl; ENST00000439576.7; ENSP00000387356.2; ENSG00000157766.19. [P16112-1]
DR Ensembl; ENST00000559004.5; ENSP00000453499.1; ENSG00000157766.19. [P16112-2]
DR GeneID; 176; -.
DR KEGG; hsa:176; -.
DR UCSC; uc010upo.1; human.
DR CTD; 176; -.
DR DisGeNET; 176; -.
DR GeneCards; ACAN; -.
DR HGNC; HGNC:319; ACAN.
DR HPA; ENSG00000157766; Tissue enhanced (brain, seminal vesicle).
DR MalaCards; ACAN; -.
DR MIM; 155760; gene.
DR MIM; 165800; phenotype.
DR MIM; 608361; phenotype.
DR MIM; 612813; phenotype.
DR neXtProt; NX_P16112; -.
DR OpenTargets; ENSG00000157766; -.
DR Orphanet; 251262; Familial osteochondritis dissecans.
DR Orphanet; 435804; Short stature-advanced bone age-early-onset osteoarthritis syndrome.
DR Orphanet; 171866; Spondyloepimetaphyseal dysplasia, aggrecan type.
DR Orphanet; 93283; Spondyloepiphyseal dysplasia, Kimberley type.
DR PharmGKB; PA24616; -.
DR VEuPathDB; HostDB:ENSG00000157766; -.
DR eggNOG; ENOG502QUX8; Eukaryota.
DR GeneTree; ENSGT00940000155971; -.
DR InParanoid; P16112; -.
DR PhylomeDB; P16112; -.
DR TreeFam; TF332134; -.
DR PathwayCommons; P16112; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-2022854; Keratan sulfate biosynthesis.
DR Reactome; R-HSA-2022857; Keratan sulfate degradation.
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; P16112; -.
DR SIGNOR; P16112; -.
DR BioGRID-ORCS; 176; 15 hits in 1074 CRISPR screens.
DR ChiTaRS; ACAN; human.
DR GenomeRNAi; 176; -.
DR Pharos; P16112; Tbio.
DR PRO; PR:P16112; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P16112; protein.
DR Bgee; ENSG00000157766; Expressed in tibia and 149 other tissues.
DR ExpressionAtlas; P16112; baseline and differential.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
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:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:UniProtKB.
DR GO; GO:0005540; F:hyaluronic acid binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; NAS:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR CDD; cd00033; CCP; 1.
DR CDD; cd03588; CLECT_CSPGs; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.10.100.10; -; 5.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR018378; C-type_lectin_CS.
DR InterPro; IPR033987; CSPG_CTLD.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR000538; Link_dom.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR Pfam; PF00059; Lectin_C; 1.
DR Pfam; PF00084; Sushi; 1.
DR Pfam; PF07686; V-set; 1.
DR Pfam; PF00193; Xlink; 4.
DR PRINTS; PR01265; LINKMODULE.
DR SMART; SM00032; CCP; 1.
DR SMART; SM00034; CLECT; 1.
DR SMART; SM00181; EGF; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00406; IGv; 1.
DR SMART; SM00445; LINK; 4.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF56436; SSF56436; 5.
DR SUPFAM; SSF57535; SSF57535; 1.
DR PROSITE; PS00615; C_TYPE_LECTIN_1; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00290; IG_MHC; 1.
DR PROSITE; PS01241; LINK_1; 4.
DR PROSITE; PS50963; LINK_2; 4.
DR PROSITE; PS50923; SUSHI; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Direct protein sequencing;
KW Disease variant; Disulfide bond; Dwarfism; EGF-like domain;
KW Extracellular matrix; Glycoprotein; Immunoglobulin domain; Lectin;
KW Metal-binding; Proteoglycan; Reference proteome; Repeat; Secreted; Signal;
KW Sushi.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:7574678"
FT CHAIN 17..2530
FT /note="Aggrecan core protein"
FT /id="PRO_0000017505"
FT CHAIN 393..2530
FT /note="Aggrecan core protein 2"
FT /id="PRO_0000017506"
FT DOMAIN 34..147
FT /note="Ig-like V-type"
FT DOMAIN 153..248
FT /note="Link 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DOMAIN 254..350
FT /note="Link 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DOMAIN 478..573
FT /note="Link 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DOMAIN 579..675
FT /note="Link 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT REPEAT 773..778
FT /note="1-1"
FT REPEAT 779..784
FT /note="1-2"
FT REPEAT 785..790
FT /note="1-3"
FT REPEAT 791..796
FT /note="1-4"
FT REPEAT 797..802
FT /note="1-5"
FT REPEAT 803..808
FT /note="1-6"
FT REPEAT 809..814
FT /note="1-7; approximate"
FT REPEAT 815..820
FT /note="1-8; approximate"
FT REPEAT 821..826
FT /note="1-9"
FT REPEAT 827..832
FT /note="1-10; approximate"
FT REPEAT 833..838
FT /note="1-11"
FT REPEAT 839..844
FT /note="1-12"
FT REPEAT 942..960
FT /note="2-1"
FT REPEAT 961..979
FT /note="2-2"
FT REPEAT 980..998
FT /note="2-3"
FT REPEAT 999..1017
FT /note="2-4"
FT REPEAT 1018..1036
FT /note="2-5"
FT REPEAT 1037..1055
FT /note="2-6"
FT REPEAT 1056..1074
FT /note="2-7"
FT REPEAT 1075..1093
FT /note="2-8"
FT REPEAT 1094..1112
FT /note="2-9"
FT REPEAT 1113..1131
FT /note="2-10"
FT REPEAT 1132..1150
FT /note="2-11"
FT REPEAT 1151..1169
FT /note="2-12"
FT REPEAT 1170..1188
FT /note="2-13"
FT REPEAT 1189..1207
FT /note="2-14"
FT REPEAT 1208..1226
FT /note="2-15"
FT REPEAT 1227..1245
FT /note="2-16"
FT REPEAT 1246..1264
FT /note="2-17"
FT REPEAT 1265..1283
FT /note="2-18"
FT REPEAT 1284..1302
FT /note="2-19"
FT REPEAT 1303..1321
FT /note="2-20"
FT REPEAT 1322..1340
FT /note="2-21"
FT REPEAT 1341..1359
FT /note="2-22"
FT REPEAT 1360..1378
FT /note="2-23"
FT REPEAT 1379..1397
FT /note="2-24"
FT REPEAT 1398..1416
FT /note="2-25"
FT REPEAT 1417..1435
FT /note="2-26"
FT REPEAT 1436..1454
FT /note="2-27"
FT REPEAT 1455..1473
FT /note="2-28"
FT REPEAT 1475..1493
FT /note="2-29"
FT REPEAT 1494..1512
FT /note="2-30"
FT REPEAT 1513..1531
FT /note="2-31"
FT REPEAT 1533..1551
FT /note="2-32"
FT REPEAT 1553..1572
FT /note="2-33; approximate"
FT REPEAT 1574..1592
FT /note="2-34"
FT REPEAT 1594..1612
FT /note="2-35"
FT DOMAIN 2279..2314
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 2327..2441
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DOMAIN 2445..2505
FT /note="Sushi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT REGION 48..141
FT /note="G1-A"
FT REGION 152..247
FT /note="G1-B"
FT REGION 253..349
FT /note="G1-B'"
FT REGION 477..571
FT /note="G2-B"
FT REGION 578..673
FT /note="G2-B'"
FT REGION 677..849
FT /note="KS"
FT REGION 734..979
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 773..844
FT /note="12 X 6 AA approximate tandem repeats of E-[GVE]-P-
FT [SFY]-[APT]-[TSP]"
FT REGION 852..1612
FT /note="CS-1"
FT REGION 942..1612
FT /note="35 X 19 AA approximate tandem repeats of E-[IVDG]-
FT [LV]-[EV]-[GTI]-[STA]-[ATV]-[SP]-[GA]-[VIFAD]-[GEDL]-[DE]-
FT [LVI]-[SG]-[GERK]-[LV]-P-S-G"
FT REGION 1499..1526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1543..1649
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1613..2277
FT /note="CS-2"
FT REGION 1687..1772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1784..1827
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1883..1902
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1948..1977
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2048..2204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2249..2281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2278..2530
FT /note="G3"
FT REGION 2510..2530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 765..785
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 792..808
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 898..913
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1615..1629
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1709..1723
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1739..1772
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1812..1827
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2048..2077
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2093..2107
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2126..2159
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2166..2204
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2513..2530
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 2381
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 2405
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 2407
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 2408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2414
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2414
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 2415
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 2415
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 2428
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 2429
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT SITE 392..393
FT /note="Cleavage; by aggrecanase"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 371
FT /note="O-linked (Xyl...) (keratan sulfate) threonine"
FT /evidence="ECO:0000305|PubMed:1569188"
FT CARBOHYD 376
FT /note="O-linked (Xyl...) (keratan sulfate) threonine"
FT /evidence="ECO:0000305|PubMed:1569188"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 434
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 658
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 738
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2013
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..133
FT /evidence="ECO:0000250"
FT DISULFID 175..246
FT /evidence="ECO:0000250"
FT DISULFID 199..220
FT /evidence="ECO:0000250"
FT DISULFID 273..348
FT /evidence="ECO:0000250"
FT DISULFID 297..318
FT /evidence="ECO:0000250"
FT DISULFID 500..571
FT /evidence="ECO:0000250"
FT DISULFID 524..545
FT /evidence="ECO:0000250"
FT DISULFID 598..673
FT /evidence="ECO:0000250"
FT DISULFID 622..643
FT /evidence="ECO:0000250"
FT DISULFID 2283..2293
FT /evidence="ECO:0000250"
FT DISULFID 2288..2302
FT /evidence="ECO:0000250"
FT DISULFID 2304..2313
FT /evidence="ECO:0000250"
FT DISULFID 2320..2331
FT /evidence="ECO:0000250"
FT DISULFID 2348..2440
FT /evidence="ECO:0000250"
FT DISULFID 2416..2432
FT /evidence="ECO:0000250"
FT DISULFID 2447..2490
FT /evidence="ECO:0000250"
FT DISULFID 2476..2503
FT /evidence="ECO:0000250"
FT VAR_SEQ 2278..2315
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:1985970,
FT ECO:0000303|PubMed:8611178"
FT /id="VSP_003074"
FT VAR_SEQ 2445..2506
FT /note="VACGEPPVVEHARTFGQKKDRYEINSLVRYQCTEGFVQRHMPTIRCQPSGHW
FT EEPQITCTDP -> A (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1985970"
FT /id="VSP_003075"
FT VARIANT 102
FT /note="D -> E (in dbSNP:rs16942318)"
FT /id="VAR_056152"
FT VARIANT 275
FT /note="R -> Q (in dbSNP:rs34949187)"
FT /id="VAR_056153"
FT VARIANT 864
FT /note="P -> L (in dbSNP:rs3743398)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_080159"
FT VARIANT 913
FT /note="P -> T (in dbSNP:rs35430524)"
FT /evidence="ECO:0000269|PubMed:1985970"
FT /id="VAR_080160"
FT VARIANT 930
FT /note="S -> I (in dbSNP:rs938608)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_080161"
FT VARIANT 939
FT /note="S -> T (in dbSNP:rs938609)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_080162"
FT VARIANT 1080
FT /note="T -> A (in dbSNP:rs373544100)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_080163"
FT VARIANT 1403
FT /note="T -> A (in dbSNP:rs12899191)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_080164"
FT VARIANT 1508
FT /note="E -> A (in dbSNP:rs2882676)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_080165"
FT VARIANT 1765
FT /note="I -> V (in dbSNP:rs4932439)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1985970"
FT /id="VAR_080166"
FT VARIANT 2058
FT /note="P -> L (in dbSNP:rs35061438)"
FT /id="VAR_056154"
FT VARIANT 2079
FT /note="I -> V (in dbSNP:rs1042630)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2789216, ECO:0000269|PubMed:8611178"
FT /id="VAR_080167"
FT VARIANT 2120
FT /note="S -> R (in dbSNP:rs34153007)"
FT /id="VAR_056155"
FT VARIANT 2373
FT /note="D -> E (in dbSNP:rs3817428)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_080168"
FT VARIANT 2381
FT /note="D -> N (in SEMDAG; creates a functional N-
FT glycosylation site; does not adversely affect protein
FT trafficking and secretion; dbSNP:rs121913568)"
FT /evidence="ECO:0000269|PubMed:19110214"
FT /id="VAR_063053"
FT VARIANT 2418
FT /note="V -> M (in SSOAOD; dbSNP:rs779794758)"
FT /evidence="ECO:0000269|PubMed:20137779"
FT /id="VAR_063765"
FT VARIANT 2500
FT /note="Q -> R (in dbSNP:rs1126823)"
FT /evidence="ECO:0000269|PubMed:2789216,
FT ECO:0000269|PubMed:8611178"
FT /id="VAR_080169"
FT CONFLICT 285..286
FT /note="QL -> HV (in Ref. 1; AAA62824)"
FT /evidence="ECO:0000305"
FT CONFLICT 501..502
FT /note="LR -> PG (in Ref. 1; AAA62824)"
FT /evidence="ECO:0000305"
FT CONFLICT 605
FT /note="Missing (in Ref. 1; AAA62824)"
FT /evidence="ECO:0000305"
FT CONFLICT 767
FT /note="A -> E (in Ref. 1; AAA62824)"
FT /evidence="ECO:0000305"
FT CONFLICT 848
FT /note="V -> E (in Ref. 1; AAA62824)"
FT /evidence="ECO:0000305"
FT CONFLICT 999..1017
FT /note="Missing (in Ref. 3; AAI50625)"
FT /evidence="ECO:0000305"
FT CONFLICT 1075..1188
FT /note="Missing (in Ref. 1; AAA62824)"
FT /evidence="ECO:0000305"
FT CONFLICT 1548
FT /note="L -> V (in Ref. 1; AAA62824)"
FT /evidence="ECO:0000305"
FT CONFLICT 2043
FT /note="E -> A (in Ref. 9; CAA35463)"
FT /evidence="ECO:0000305"
FT CONFLICT 2185
FT /note="P -> A (in Ref. 10; AAA35726)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2530 AA; 261329 MW; 3C809F6DE829956B CRC64;
MTTLLWVFVT LRVITAAVTV ETSDHDNSLS VSIPQPSPLR VLLGTSLTIP CYFIDPMHPV
TTAPSTAPLA PRIKWSRVSK EKEVVLLVAT EGRVRVNSAY QDKVSLPNYP AIPSDATLEV
QSLRSNDSGV YRCEVMHGIE DSEATLEVVV KGIVFHYRAI STRYTLDFDR AQRACLQNSA
IIATPEQLQA AYEDGFHQCD AGWLADQTVR YPIHTPREGC YGDKDEFPGV RTYGIRDTNE
TYDVYCFAEE MEGEVFYATS PEKFTFQEAA NECRRLGARL ATTGQLYLAW QAGMDMCSAG
WLADRSVRYP ISKARPNCGG NLLGVRTVYV HANQTGYPDP SSRYDAICYT GEDFVDIPEN
FFGVGGEEDI TVQTVTWPDM ELPLPRNITE GEARGSVILT VKPIFEVSPS PLEPEEPFTF
APEIGATAFA EVENETGEAT RPWGFPTPGL GPATAFTSED LVVQVTAVPG QPHLPGGVVF
HYRPGPTRYS LTFEEAQQAC LRTGAVIASP EQLQAAYEAG YEQCDAGWLR DQTVRYPIVS
PRTPCVGDKD SSPGVRTYGV RPSTETYDVY CFVDRLEGEV FFATRLEQFT FQEALEFCES
HNATLATTGQ LYAAWSRGLD KCYAGWLADG SLRYPIVTPR PACGGDKPGV RTVYLYPNQT
GLPDPLSRHH AFCFRGISAV PSPGEEEGGT PTSPSGVEEW IVTQVVPGVA AVPVEEETTA
VPSGETTAIL EFTTEPENQT EWEPAYTPVG TSPLPGILPT WPPTGAATEE STEGPSATEV
PSASEEPSPS EVPFPSEEPS PSEEPFPSVR PFPSVELFPS EEPFPSKEPS PSEEPSASEE
PYTPSPPVPS WTELPSSGEE SGAPDVSGDF TGSGDVSGHL DFSGQLSGDR ASGLPSGDLD
SSGLTSTVGS GLPVESGLPS GDEERIEWPS TPTVGELPSG AEILEGSASG VGDLSGLPSG
EVLETSASGV GDLSGLPSGE VLETTAPGVE DISGLPSGEV LETTAPGVED ISGLPSGEVL
ETTAPGVEDI SGLPSGEVLE TTAPGVEDIS GLPSGEVLET TAPGVEDISG LPSGEVLETT
APGVEDISGL PSGEVLETAA PGVEDISGLP SGEVLETAAP GVEDISGLPS GEVLETAAPG
VEDISGLPSG EVLETAAPGV EDISGLPSGE VLETAAPGVE DISGLPSGEV LETAAPGVED
ISGLPSGEVL ETAAPGVEDI SGLPSGEVLE TAAPGVEDIS GLPSGEVLET AAPGVEDISG
LPSGEVLETA APGVEDISGL PSGEVLETAA PGVEDISGLP SGEVLETAAP GVEDISGLPS
GEVLETAAPG VEDISGLPSG EVLETAAPGV EDISGLPSGE VLETAAPGVE DISGLPSGEV
LETAAPGVED ISGLPSGEVL ETTAPGVEEI SGLPSGEVLE TTAPGVDEIS GLPSGEVLET
TAPGVEEISG LPSGEVLETS TSAVGDLSGL PSGGEVLEIS VSGVEDISGL PSGEVVETSA
SGIEDVSELP SGEGLETSAS GVEDLSRLPS GEEVLEISAS GFGDLSGLPS GGEGLETSAS
EVGTDLSGLP SGREGLETSA SGAEDLSGLP SGKEDLVGSA SGDLDLGKLP SGTLGSGQAP
ETSGLPSGFS GEYSGVDLGS GPPSGLPDFS GLPSGFPTVS LVDSTLVEVV TASTASELEG
RGTIGISGAG EISGLPSSEL DISGRASGLP SGTELSGQAS GSPDVSGEIP GLFGVSGQPS
GFPDTSGETS GVTELSGLSS GQPGISGEAS GVLYGTSQPF GITDLSGETS GVPDLSGQPS
GLPGFSGATS GVPDLVSGTT SGSGESSGIT FVDTSLVEVA PTTFKEEEGL GSVELSGLPS
GEADLSGKSG MVDVSGQFSG TVDSSGFTSQ TPEFSGLPSG IAEVSGESSR AEIGSSLPSG
AYYGSGTPSS FPTVSLVDRT LVESVTQAPT AQEAGEGPSG ILELSGAHSG APDMSGEHSG
FLDLSGLQSG LIEPSGEPPG TPYFSGDFAS TTNVSGESSV AMGTSGEASG LPEVTLITSE
FVEGVTEPTI SQELGQRPPV THTPQLFESS GKVSTAGDIS GATPVLPGSG VEVSSVPESS
SETSAYPEAG FGASAAPEAS REDSGSPDLS ETTSAFHEAN LERSSGLGVS GSTLTFQEGE
ASAAPEVSGE STTTSDVGTE APGLPSATPT ASGDRTEISG DLSGHTSQLG VVISTSIPES
EWTQQTQRPA ETHLEIESSS LLYSGEETHT VETATSPTDA SIPASPEWKR ESESTAAAPA
RSCAEEPCGA GTCKETEGHV ICLCPPGYTG EHCNIDQEVC EEGWNKYQGH CYRHFPDRET
WVDAERRCRE QQSHLSSIVT PEEQEFVNNN AQDYQWIGLN DRTIEGDFRW SDGHPMQFEN
WRPNQPDNFF AAGEDCVVMI WHEKGEWNDV PCNYHLPFTC KKGTVACGEP PVVEHARTFG
QKKDRYEINS LVRYQCTEGF VQRHMPTIRC QPSGHWEEPQ ITCTDPTTYK RRLQKRSSRH
PRRSRPSTAH
