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 27-MAR-2024, entry version 234. 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 GLYCOSYLATION. RX PubMed=32337544; DOI=10.1093/glycob/cwaa039; RA Toledo A.G., Pihl J., Spliid C.B., Persson A., Nilsson J., Pereira M.A., RA Gustavsson T., Choudhary S., Oo H.Z., Black P.C., Daugaard M., Esko J.D., RA Larson G., Salanti A., Clausen T.M.; RT "An affinity chromatography and glycoproteomics workflow to profile the RT chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in RT the placenta and in cancer."; RL Glycobiology 30:989-1002(2020). RN [15] RP TISSUE SPECIFICITY, AND GLYCOSYLATION AT SER-1530; SER-1567; SER-1601 AND RP SER-1703. RX PubMed=36213313; DOI=10.1007/s42485-022-00092-3; RA Ramarajan M.G., Saraswat M., Budhraja R., Garapati K., Raymond K., RA Pandey A.; RT "Mass spectrometric analysis of chondroitin sulfate-linked peptides."; RL J. Proteins Proteom. 13:187-203(2022). RN [16] 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 [17] 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: Detected in fibroblasts (at protein level) CC (PubMed:36213313). Restricted to cartilage (PubMed:7524681). CC {ECO:0000269|PubMed:36213313, 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:32337544, ECO:0000269|PubMed:36213313, 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"; 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; 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 CCDS; CCDS92056.1; -. [P16112-2] 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. DR PDB; 4MD4; X-ray; 1.95 A; C=89-103. DR PDB; 7RDV; X-ray; 2.90 A; H=91-101. DR PDBsum; 4MD4; -. DR PDBsum; 7RDV; -. 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 GlyCosmos; P16112; 82 sites, 13 glycans. DR GlyGen; P16112; 88 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 PaxDb; 9606-ENSP00000387356; -. DR PeptideAtlas; 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; 605 antibodies from 33 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 AGR; HGNC:319; -. DR CTD; 176; -. DR DisGeNET; 176; -. DR GeneCards; ACAN; -. DR HGNC; HGNC:319; ACAN. DR HPA; ENSG00000157766; Tissue enhanced (seminal). 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 OrthoDB; 5402504at2759; -. 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 1150 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 151 other cell types or tissues. DR ExpressionAtlas; P16112; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. 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:0072534; C:perineuronal net; IBA:GO_Central. DR GO; GO:0045202; C:synapse; IBA:GO_Central. 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:0010001; P:glial cell differentiation; IBA:GO_Central. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; 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 CDD; cd00054; EGF_CA; 1. DR CDD; cd05900; Ig_Aggrecan; 1. DR CDD; cd03517; Link_domain_CSPGs_modules_1_3; 2. DR CDD; cd03520; Link_domain_CSPGs_modules_2_4; 2. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 2.10.25.10; Laminin; 1. DR Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 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 PANTHER; PTHR22804:SF42; AGGRECAN CORE PROTEIN; 1. DR PANTHER; PTHR22804; AGGRECAN/VERSICAN PROTEOGLYCAN; 1. 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; SSF56436; C-type lectin-like; 5. DR SUPFAM; SSF57535; Complement control module/SCR domain; 1. DR SUPFAM; SSF48726; Immunoglobulin; 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 1530 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000269|PubMed:36213313" FT CARBOHYD 1567 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000269|PubMed:36213313" FT CARBOHYD 1581 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000255" FT CARBOHYD 1587 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000255" FT CARBOHYD 1591 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000255" FT CARBOHYD 1601 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000269|PubMed:36213313" FT CARBOHYD 1703 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000269|PubMed:36213313" 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 FT N-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 //