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P16112

- PGCA_HUMAN

UniProt

P16112 - PGCA_HUMAN

Protein

Aggrecan core protein

Gene

ACAN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 167 (01 Oct 2014)
      Sequence version 2 (01 Aug 1992)
      Previous versions | rss
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    Functioni

    This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei392 – 3932Cleavage; by aggrecanase
    Metal bindingi2266 – 22661Calcium 1By similarity
    Metal bindingi2270 – 22701Calcium 1By similarity
    Metal bindingi2270 – 22701Calcium 3By similarity
    Metal bindingi2290 – 22901Calcium 2By similarity
    Metal bindingi2292 – 22921Calcium 2By similarity
    Metal bindingi2293 – 22931Calcium 1By similarity
    Metal bindingi2299 – 22991Calcium 1; via carbonyl oxygenBy similarity
    Metal bindingi2299 – 22991Calcium 2By similarity
    Metal bindingi2300 – 23001Calcium 1By similarity
    Metal bindingi2300 – 23001Calcium 3By similarity
    Metal bindingi2313 – 23131Calcium 2By similarity
    Metal bindingi2314 – 23141Calcium 2By similarity
    Metal bindingi2314 – 23141Calcium 2; via carbonyl oxygenBy similarity

    GO - Molecular functioni

    1. carbohydrate binding Source: InterPro
    2. extracellular matrix structural constituent Source: UniProtKB
    3. hyaluronic acid binding Source: InterPro
    4. metal ion binding Source: UniProtKB-KW
    5. protein binding Source: UniProtKB

    GO - Biological processi

    1. carbohydrate metabolic process Source: Reactome
    2. cell adhesion Source: InterPro
    3. extracellular matrix disassembly Source: Reactome
    4. extracellular matrix organization Source: Reactome
    5. glycosaminoglycan metabolic process Source: Reactome
    6. keratan sulfate biosynthetic process Source: Reactome
    7. keratan sulfate catabolic process Source: Reactome
    8. keratan sulfate metabolic process Source: Reactome
    9. proteolysis Source: UniProtKB
    10. skeletal system development Source: UniProtKB
    11. small molecule metabolic process Source: Reactome

    Keywords - Ligandi

    Calcium, Lectin, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_118572. Degradation of the extracellular matrix.
    REACT_121120. Keratan sulfate biosynthesis.
    REACT_121313. Keratan sulfate degradation.
    REACT_163906. ECM proteoglycans.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aggrecan core protein
    Alternative name(s):
    Cartilage-specific proteoglycan core protein
    Short name:
    CSPCP
    Chondroitin sulfate proteoglycan core protein 1
    Short name:
    Chondroitin sulfate proteoglycan 1
    Cleaved into the following chain:
    Gene namesi
    Name:ACAN
    Synonyms:AGC1, CSPG1, MSK16
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Unplaced

    Organism-specific databases

    HGNCiHGNC:319. ACAN.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. Golgi lumen Source: Reactome
    3. lysosomal lumen Source: Reactome
    4. proteinaceous extracellular matrix Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Spondyloepiphyseal dysplasia type Kimberley (SEDK) [MIM:608361]: Spondyloepiphyseal dysplasias are a heterogeneous group of congenital chondrodysplasias that specifically affect epiphyses and vertebrae. The autosomal dominant SEDK is associated with premature degenerative arthropathy.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Spondyloepimetaphyseal dysplasia aggrecan type (SEMD-ACAN) [MIM:612813]: A bone disease characterized by severe short stature, macrocephaly, severe midface hypoplasia, short neck, barrel chest and brachydactyly. The radiological findings comprise long bones with generalized irregular epiphyses with widened metaphyses, especially at the knees, platyspondyly, and multiple cervical-vertebral clefts.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2266 – 22661D → N in SEMD-ACAN; creates a functional N-glycosylation site; does not adversely affect protein trafficking and secretion. 1 Publication
    VAR_063053
    Osteochondritis dissecans short stature and early-onset osteoarthritis (OD) [MIM:165800]: A type of osteochondritis defined as a separation of cartilage and subchondral bone from the surrounding tissue, primarily affecting the knee, ankle and elbow joints. It is clinically characterized by multiple osteochondritic lesions in knees and/or hips and/or elbows, disproportionate short stature and early-onset osteoarthritis.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2303 – 23031V → M in OD. 1 Publication
    VAR_063765

    Keywords - Diseasei

    Disease mutation, Dwarfism

    Organism-specific databases

    MIMi165800. phenotype.
    608361. phenotype.
    612813. phenotype.
    Orphaneti251262. Familial osteochondritis dissecans.
    171866. Spondyloepimetaphyseal dysplasia, aggrecan type.
    93283. Spondyloepiphyseal dysplasia, Kimberley type.
    PharmGKBiPA24616.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 16161 PublicationAdd
    BLAST
    Chaini17 – 24152399Aggrecan core proteinPRO_0000017505Add
    BLAST
    Chaini393 – 24152023Aggrecan core protein 2PRO_0000017506Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi51 ↔ 133By similarity
    Glycosylationi126 – 1261N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi175 ↔ 246By similarity
    Disulfide bondi199 ↔ 220By similarity
    Glycosylationi239 – 2391N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi273 ↔ 348By similarity
    Disulfide bondi297 ↔ 318By similarity
    Glycosylationi333 – 3331N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi371 – 3711O-linked (Xyl...) (keratan sulfate)1 Publication
    Glycosylationi376 – 3761O-linked (Xyl...) (keratan sulfate)1 Publication
    Glycosylationi387 – 3871N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi434 – 4341N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi500 ↔ 571By similarity
    Disulfide bondi524 ↔ 545By similarity
    Disulfide bondi598 ↔ 672By similarity
    Glycosylationi602 – 6021N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi621 ↔ 642By similarity
    Glycosylationi657 – 6571N-linked (GlcNAc...)1 Publication
    Glycosylationi737 – 7371N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1898 – 18981N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi2168 ↔ 2178By similarity
    Disulfide bondi2173 ↔ 2187By similarity
    Disulfide bondi2189 ↔ 2198By similarity
    Disulfide bondi2205 ↔ 2216By similarity
    Disulfide bondi2233 ↔ 2325By similarity
    Disulfide bondi2301 ↔ 2317By similarity
    Disulfide bondi2332 ↔ 2375By similarity
    Disulfide bondi2361 ↔ 2388By similarity

    Post-translational modificationi

    Contains mostly chondroitin sulfate, but also keratan sulfate chains, N-linked and O-linked oligosaccharides. The release of aggrecan fragments from articular cartilage into the synovial fluid at all stages of human osteoarthritis is the result of cleavage by aggrecanase.3 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Proteoglycan

    Proteomic databases

    PaxDbiP16112.
    PRIDEiP16112.

    PTM databases

    PhosphoSiteiP16112.

    Miscellaneous databases

    PMAP-CutDBP16112.

    Expressioni

    Tissue specificityi

    Restricted to cartilages.1 Publication

    Developmental stagei

    Expression was detected in chondrocytes throughout the developing skeleton.

    Gene expression databases

    CleanExiHS_ACAN.
    GenevestigatoriP16112.

    Organism-specific databases

    HPAiCAB016377.

    Interactioni

    Subunit structurei

    Interacts with FBLN1 By similarity. Interacts with COMP.By similarity1 Publication

    Protein-protein interaction databases

    IntActiP16112. 1 interaction.
    STRINGi9606.ENSP00000268134.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4MD4X-ray1.95C89-103[»]
    ProteinModelPortaliP16112.
    SMRiP16112. Positions 36-150, 154-247, 263-349, 479-572, 588-673, 2161-2200, 2203-2328.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini34 – 147114Ig-like V-typeAdd
    BLAST
    Domaini153 – 24896Link 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini254 – 35097Link 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini478 – 57396Link 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini579 – 67496Link 4PROSITE-ProRule annotationAdd
    BLAST
    Repeati772 – 77761-1
    Repeati778 – 78361-2
    Repeati784 – 78961-3
    Repeati790 – 79561-4
    Repeati796 – 80161-5
    Repeati802 – 80761-6
    Repeati808 – 81361-7; approximate
    Repeati814 – 81961-8; approximate
    Repeati820 – 82561-9
    Repeati826 – 83161-10; approximate
    Repeati832 – 83761-11
    Repeati838 – 84361-12
    Repeati941 – 959192-1Add
    BLAST
    Repeati960 – 978192-2Add
    BLAST
    Repeati979 – 997192-3Add
    BLAST
    Repeati998 – 1016192-4Add
    BLAST
    Repeati1017 – 1035192-5Add
    BLAST
    Repeati1036 – 1054192-6Add
    BLAST
    Repeati1055 – 1073192-7Add
    BLAST
    Repeati1074 – 1092192-8Add
    BLAST
    Repeati1093 – 1111192-9Add
    BLAST
    Repeati1112 – 1130192-10Add
    BLAST
    Repeati1131 – 1149192-11Add
    BLAST
    Repeati1150 – 1168192-12Add
    BLAST
    Repeati1169 – 1187192-13Add
    BLAST
    Repeati1188 – 1206192-14Add
    BLAST
    Repeati1207 – 1225192-15Add
    BLAST
    Repeati1226 – 1244192-16Add
    BLAST
    Repeati1245 – 1263192-17Add
    BLAST
    Repeati1264 – 1282192-18Add
    BLAST
    Repeati1283 – 1301192-19Add
    BLAST
    Repeati1302 – 1320192-20Add
    BLAST
    Repeati1321 – 1339192-21Add
    BLAST
    Repeati1340 – 1358192-22Add
    BLAST
    Repeati1360 – 1378192-23Add
    BLAST
    Repeati1379 – 1397192-24Add
    BLAST
    Repeati1398 – 1416192-25Add
    BLAST
    Repeati1418 – 1436192-26Add
    BLAST
    Repeati1439 – 1457192-27; approximateAdd
    BLAST
    Repeati1459 – 1477192-28Add
    BLAST
    Repeati1479 – 1497192-29Add
    BLAST
    Domaini2164 – 219936EGF-likePROSITE-ProRule annotationAdd
    BLAST
    Domaini2201 – 2327127C-type lectinPROSITE-ProRule annotationAdd
    BLAST
    Domaini2330 – 239061SushiPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni48 – 14194G1-AAdd
    BLAST
    Regioni152 – 24796G1-BAdd
    BLAST
    Regioni253 – 34997G1-B'Add
    BLAST
    Regioni477 – 57195G2-BAdd
    BLAST
    Regioni578 – 67295G2-B'Add
    BLAST
    Regioni676 – 848173KSAdd
    BLAST
    Regioni772 – 8437212 X 6 AA approximate tandem repeats of E-[GVE]-P-[SFY]-[APT]-[TSP]Add
    BLAST
    Regioni851 – 1497647CS-1Add
    BLAST
    Regioni941 – 149755729 X 19 AA approximate tandem repeats of E-[IVDG]-[LV]-[EV]-[GTI]-[STA]-[ATV]-[SP]-[GA]-[VIFAD]-[GEDL]-[DE]-[LVI]-[SG]-[GERK]-[LV]-P-S-GAdd
    BLAST
    Regioni1498 – 2162665CS-2Add
    BLAST
    Regioni2163 – 2415253G3Add
    BLAST

    Domaini

    Two globular domains, G1 and G2, comprise the N-terminus of the proteoglycan, while another globular region, G3, makes up the C-terminus. G1 contains Link domains and thus consists of three disulfide-bonded loop structures designated as the A, B, B' motifs. G2 is similar to G1. The keratan sulfate (KS) and the chondroitin sulfate (CS) attachment domains lie between G2 and G3.

    Sequence similaritiesi

    Contains 1 C-type lectin domain.PROSITE-ProRule annotation
    Contains 1 EGF-like domain.PROSITE-ProRule annotation
    Contains 4 Link domains.PROSITE-ProRule annotation
    Contains 1 Sushi (CCP/SCR) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Immunoglobulin domain, Repeat, Signal, Sushi

    Phylogenomic databases

    eggNOGiNOG12793.
    HOGENOMiHOG000168421.
    HOVERGENiHBG007982.
    InParanoidiP16112.
    PhylomeDBiP16112.

    Family and domain databases

    Gene3Di2.60.40.10. 1 hit.
    3.10.100.10. 5 hits.
    InterProiIPR001304. C-type_lectin.
    IPR016186. C-type_lectin-like.
    IPR018378. C-type_lectin_CS.
    IPR016187. C-type_lectin_fold.
    IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR003006. Ig/MHC_CS.
    IPR003599. Ig_sub.
    IPR013106. Ig_V-set.
    IPR000538. Link.
    IPR000436. Sushi_SCR_CCP.
    [Graphical view]
    PfamiPF00008. EGF. 1 hit.
    PF00059. Lectin_C. 1 hit.
    PF00084. Sushi. 1 hit.
    PF07686. V-set. 1 hit.
    PF00193. Xlink. 4 hits.
    [Graphical view]
    PRINTSiPR01265. LINKMODULE.
    SMARTiSM00032. CCP. 1 hit.
    SM00034. CLECT. 1 hit.
    SM00181. EGF. 1 hit.
    SM00409. IG. 1 hit.
    SM00445. LINK. 4 hits.
    [Graphical view]
    SUPFAMiSSF56436. SSF56436. 5 hits.
    SSF57535. SSF57535. 1 hit.
    PROSITEiPS00615. C_TYPE_LECTIN_1. 1 hit.
    PS50041. C_TYPE_LECTIN_2. 1 hit.
    PS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS50835. IG_LIKE. 1 hit.
    PS00290. IG_MHC. 1 hit.
    PS01241. LINK_1. 3 hits.
    PS50963. LINK_2. 4 hits.
    PS50923. SUSHI. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: P16112-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MTTLLWVFVT LRVITAAVTV ETSDHDNSLS VSIPQPSPLR VLLGTSLTIP     50
    CYFIDPMHPV TTAPSTAPLA PRIKWSRVSK EKEVVLLVAT EGRVRVNSAY 100
    QDKVSLPNYP AIPSDATLEV QSLRSNDSGV YRCEVMHGIE DSEATLEVVV 150
    KGIVFHYRAI STRYTLDFDR AQRACLQNSA IIATPEQLQA AYEDGFHQCD 200
    AGWLADQTVR YPIHTPREGC YGDKDEFPGV RTYGIRDTNE TYDVYCFAEE 250
    MEGEVFYATS PEKFTFQEAA NECRRLGARL ATTGHVYLAW QAGMDMCSAG 300
    WLADRSVRYP ISKARPNCGG NLLGVRTVYV HANQTGYPDP SSRYDAICYT 350
    GEDFVDIPEN FFGVGGEEDI TVQTVTWPDM ELPLPRNITE GEARGSVILT 400
    VKPIFEVSPS PLEPEEPFTF APEIGATAFA EVENETGEAT RPWGFPTPGL 450
    GPATAFTSED LVVQVTAVPG QPHLPGGVVF HYRPGPTRYS LTFEEAQQAC 500
    PGTGAVIASP EQLQAAYEAG YEQCDAGWLR DQTVRYPIVS PRTPCVGDKD 550
    SSPGVRTYGV RPSTETYDVY CFVDRLEGEV FFATRLEQFT FQEALEFCES 600
    HNATATTGQL YAAWSRGLDK CYAGWLADGS LRYPIVTPRP ACGGDKPGVR 650
    TVYLYPNQTG LPDPLSRHHA FCFRGISAVP SPGEEEGGTP TSPSGVEEWI 700
    VTQVVPGVAA VPVEEETTAV PSGETTAILE FTTEPENQTE WEPAYTPVGT 750
    SPLPGILPTW PPTGAETEES TEGPSATEVP SASEEPSPSE VPFPSEEPSP 800
    SEEPFPSVRP FPSVELFPSE EPFPSKEPSP SEEPSASEEP YTPSPPEPSW 850
    TELPSSGEES GAPDVSGDFT GSGDVSGHLD FSGQLSGDRA SGLPSGDLDS 900
    SGLTSTVGSG LTVESGLPSG DEERIEWPST PTVGELPSGA EILEGSASGV 950
    GDLSGLPSGE VLETSASGVG DLSGLPSGEV LETTAPGVED ISGLPSGEVL 1000
    ETTAPGVEDI SGLPSGEVLE TTAPGVEDIS GLPSGEVLET TAPGVEDISG 1050
    LPSGEVLETT APGVEDISGL PSGEVLETAA PGVEDISGLP SGEVLETAAP 1100
    GVEDISGLPS GEVLETAAPG VEDISGLPSG EVLETAAPGV EDISGLPSGE 1150
    VLETAAPGVE DISGLPSGEV LETAAPGVED ISGLPSGEVL ETAAPGVEDI 1200
    SGLPSGEVLE TAAPGVEDIS GLPSGEVLET AAPGVEDISG LPSGEVLETA 1250
    APGVEDISGL PSGEVLETAA PGVEDISGLP SGEVLETTAP GVEEISGLPS 1300
    GEVLETTAPG VDEISGLPSG EVLETTAPGV EEISGLPSGE VLETSTSAVG 1350
    DLSGLPSGGE VLEISVSGVE DISGLPSGEV VETSASGIED VSELPSGEGL 1400
    ETSASGVEDL SRLPSGEEVL EISASGFGDL SGVPSGGEGL ETSASEVGTD 1450
    LSGLPSGREG LETSASGAED LSGLPSGKED LVGSASGDLD LGKLPSGTLG 1500
    SGQAPETSGL PSGFSGEYSG VDLGSGPPSG LPDFSGLPSG FPTVSLVDST 1550
    LVEVVTASTA SELEGRGTIG ISGAGEISGL PSSELDISGR ASGLPSGTEL 1600
    SGQASGSPDV SGEIPGLFGV SGQPSGFPDT SGETSGVTEL SGLSSGQPGV 1650
    SGEASGVLYG TSQPFGITDL SGETSGVPDL SGQPSGLPGF SGATSGVPDL 1700
    VSGTTSGSGE SSGITFVDTS LVEVAPTTFK EEEGLGSVEL SGLPSGEADL 1750
    SGKSGMVDVS GQFSGTVDSS GFTSQTPEFS GLPSGIAEVS GESSRAEIGS 1800
    SLPSGAYYGS GTPSSFPTVS LVDRTLVESV TQAPTAQEAG EGPSGILELS 1850
    GAHSGAPDMS GEHSGFLDLS GLQSGLIEPS GEPPGTPYFS GDFASTTNVS 1900
    GESSVAMGTS GEASGLPEVT LITSEFVEGV TEPTISQELG QRPPVTHTPQ 1950
    LFESSGKVST AGDISGATPV LPGSGVEVSS VPESSSETSA YPEAGFGASA 2000
    APEASREDSG SPDLSETTSA FHEANLERSS GLGVSGSTLT FQEGEASAAP 2050
    EVSGESTTTS DVGTEAPGLP SATPTASGDR TEISGDLSGH TSQLGVVIST 2100
    SIPESEWTQQ TQRPAETHLE IESSSLLYSG EETHTVETAT SPTDASIPAS 2150
    PEWKRESEST AAAPARSCAE EPCGAGTCKE TEGHVICLCP PGYTGEHCNI 2200
    DQEVCEEGWN KYQGHCYRHF PDRETWVDAE RRCREQQSHL SSIVTPEEQE 2250
    FVNNNAQDYQ WIGLNDRTIE GDFRWSDGHP MQFENWRPNQ PDNFFAAGED 2300
    CVVMIWHEKG EWNDVPCNYH LPFTCKKGTV ACGEPPVVEH ARTFGQKKDR 2350
    YEINSLVRYQ CTEGFVQRHM PTIRCQPSGH WEEPRITCTD ATTYKRRLQK 2400
    RSSRHPRRSR PSTAH 2415
    Length:2,415
    Mass (Da):250,193
    Last modified:August 1, 1992 - v2
    Checksum:i1288937E1B98C6B6
    GO
    Isoform 2 (identifier: P16112-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         2163-2200: Missing.

    Show »
    Length:2,377
    Mass (Da):246,306
    Checksum:iCC3F3E0D74B00DAD
    GO
    Isoform 3 (identifier: P16112-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         2163-2200: Missing.
         2330-2390: Missing.

    Show »
    Length:2,316
    Mass (Da):239,235
    Checksum:i44ABD9AF85CC3612
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti766 – 7661E → A in AAC60643. (PubMed:7827755)Curated
    Sequence conflicti847 – 8471E → V in AAC60643. (PubMed:7827755)Curated
    Sequence conflicti1928 – 19281E → A in CAA35463. (PubMed:8611178)Curated
    Sequence conflicti1964 – 19641I → V in CAA35463. (PubMed:8611178)Curated
    Sequence conflicti1964 – 19641I → V in AAA35726. (PubMed:2789216)Curated
    Sequence conflicti2070 – 20701P → A in AAA35726. (PubMed:2789216)Curated
    Sequence conflicti2391 – 23911A → P in CAA35463. (PubMed:8611178)Curated
    Sequence conflicti2391 – 23911A → P in AAA35726. (PubMed:2789216)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti102 – 1021D → E.
    Corresponds to variant rs16942318 [ dbSNP | Ensembl ].
    VAR_056152
    Natural varianti275 – 2751R → Q.
    Corresponds to variant rs34949187 [ dbSNP | Ensembl ].
    VAR_056153
    Natural varianti1943 – 19431P → L.
    Corresponds to variant rs35061438 [ dbSNP | Ensembl ].
    VAR_056154
    Natural varianti2005 – 20051S → R.
    Corresponds to variant rs34153007 [ dbSNP | Ensembl ].
    VAR_056155
    Natural varianti2266 – 22661D → N in SEMD-ACAN; creates a functional N-glycosylation site; does not adversely affect protein trafficking and secretion. 1 Publication
    VAR_063053
    Natural varianti2303 – 23031V → M in OD. 1 Publication
    VAR_063765

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei2163 – 220038Missing in isoform 2 and isoform 3. 2 PublicationsVSP_003074Add
    BLAST
    Alternative sequencei2330 – 239061Missing in isoform 3. 1 PublicationVSP_003075Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M55172 mRNA. Translation: AAA62824.1.
    X80278 mRNA. No translation available.
    S74659 Genomic DNA. Translation: AAC60643.2.
    X17406 mRNA. Translation: CAA35463.1.
    J05062 mRNA. Translation: AAA35726.1.
    PIRiA39086.
    UniGeneiHs.2159.
    Hs.616395.

    Polymorphism databases

    DMDMi129886.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Functional Glycomics Gateway - Glycan Binding

    Aggrecan

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M55172 mRNA. Translation: AAA62824.1 .
    X80278 mRNA. No translation available.
    S74659 Genomic DNA. Translation: AAC60643.2 .
    X17406 mRNA. Translation: CAA35463.1 .
    J05062 mRNA. Translation: AAA35726.1 .
    PIRi A39086.
    UniGenei Hs.2159.
    Hs.616395.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4MD4 X-ray 1.95 C 89-103 [» ]
    ProteinModelPortali P16112.
    SMRi P16112. Positions 36-150, 154-247, 263-349, 479-572, 588-673, 2161-2200, 2203-2328.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P16112. 1 interaction.
    STRINGi 9606.ENSP00000268134.

    PTM databases

    PhosphoSitei P16112.

    Polymorphism databases

    DMDMi 129886.

    Proteomic databases

    PaxDbi P16112.
    PRIDEi P16112.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    GeneCardsi GC15P089346.
    H-InvDB HIX0026812.
    HGNCi HGNC:319. ACAN.
    HPAi CAB016377.
    MIMi 155760. gene.
    165800. phenotype.
    608361. phenotype.
    612813. phenotype.
    neXtProti NX_P16112.
    Orphaneti 251262. Familial osteochondritis dissecans.
    171866. Spondyloepimetaphyseal dysplasia, aggrecan type.
    93283. Spondyloepiphyseal dysplasia, Kimberley type.
    PharmGKBi PA24616.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG12793.
    HOGENOMi HOG000168421.
    HOVERGENi HBG007982.
    InParanoidi P16112.
    PhylomeDBi P16112.

    Enzyme and pathway databases

    Reactomei REACT_118572. Degradation of the extracellular matrix.
    REACT_121120. Keratan sulfate biosynthesis.
    REACT_121313. Keratan sulfate degradation.
    REACT_163906. ECM proteoglycans.

    Miscellaneous databases

    ChiTaRSi ACAN. human.
    PMAP-CutDB P16112.
    PROi P16112.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_ACAN.
    Genevestigatori P16112.

    Family and domain databases

    Gene3Di 2.60.40.10. 1 hit.
    3.10.100.10. 5 hits.
    InterProi IPR001304. C-type_lectin.
    IPR016186. C-type_lectin-like.
    IPR018378. C-type_lectin_CS.
    IPR016187. C-type_lectin_fold.
    IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR003006. Ig/MHC_CS.
    IPR003599. Ig_sub.
    IPR013106. Ig_V-set.
    IPR000538. Link.
    IPR000436. Sushi_SCR_CCP.
    [Graphical view ]
    Pfami PF00008. EGF. 1 hit.
    PF00059. Lectin_C. 1 hit.
    PF00084. Sushi. 1 hit.
    PF07686. V-set. 1 hit.
    PF00193. Xlink. 4 hits.
    [Graphical view ]
    PRINTSi PR01265. LINKMODULE.
    SMARTi SM00032. CCP. 1 hit.
    SM00034. CLECT. 1 hit.
    SM00181. EGF. 1 hit.
    SM00409. IG. 1 hit.
    SM00445. LINK. 4 hits.
    [Graphical view ]
    SUPFAMi SSF56436. SSF56436. 5 hits.
    SSF57535. SSF57535. 1 hit.
    PROSITEi PS00615. C_TYPE_LECTIN_1. 1 hit.
    PS50041. C_TYPE_LECTIN_2. 1 hit.
    PS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS50835. IG_LIKE. 1 hit.
    PS00290. IG_MHC. 1 hit.
    PS01241. LINK_1. 3 hits.
    PS50963. LINK_2. 4 hits.
    PS50923. SUSHI. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms."
      Doege K.J., Sasaki M., Kimura T., Yamada Y.
      J. Biol. Chem. 266:894-902(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
      Tissue: Chondrocyte.
    2. "Catabolism of aggrecan by explant cultures of human articular cartilage in the presence of retinoic acid."
      Ilic M.Z., Mok M.T., Williamson O.D., Campbell M.A., Hughes C.E., Handley C.J.
      Arch. Biochem. Biophys. 322:22-30(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 17-27 AND 393-403, PROTEOLYTIC PROCESSING BY AGGRECANASE.
    3. "The structure of aggrecan fragments in human synovial fluid. Evidence for the involvement in osteoarthritis of a novel proteinase which cleaves the Glu 373-Ala 374 bond of the interglobular domain."
      Sandy J.D., Flannery C.R., Neame P.J., Lohmander L.S.
      J. Clin. Invest. 89:1512-1516(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 361-373 AND 393-409, PROTEOLYTIC PROCESSING, GLYCOSYLATION AT THR-371 AND THR-376.
    4. "Analysis of aggrecan and tenascin gene expression in mouse skeletal tissues by northern and in situ hybridization using species specific cDNA probes."
      Glumoff V., Savontaus M., Vehanen J., Vuorio E.
      Biochim. Biophys. Acta 1219:613-622(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 380-497, TISSUE SPECIFICITY.
    5. "The structure of aggrecan fragments in human synovial fluid. Evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis."
      Lohmander L.S., Neame P.J., Sandy J.D.
      Arthritis Rheum. 36:1214-1222(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 393-409.
      Tissue: Synovial fluid.
    6. "Length variation in the keratan sulfate domain of mammalian aggrecan."
      Barry F.P., Neame P.J., Sasse J., Pearson D.
      Matrix Biol. 14:323-328(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 764-864.
      Tissue: Blood.
    7. "Age-related changes in the content of the C-terminal region of aggrecan in human articular cartilage."
      Dudhia J., Davidson C.M., Wells T.M., Vynios D.H., Hardingham T.E., Bayliss M.T.
      Biochem. J. 313:933-940(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1778-2415 (ISOFORM 2).
      Tissue: Chondrocyte.
    8. "A new epidermal growth factor-like domain in the human core protein for the large cartilage-specific proteoglycan. Evidence for alternative splicing of the domain."
      Baldwin C.T., Reginato A.M., Prockop D.J.
      J. Biol. Chem. 264:15747-15750(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1936-2415 (ISOFORM 1).
    9. "A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis."
      Gleghorn L., Ramesar R., Beighton P., Wallis G.
      Am. J. Hum. Genet. 77:484-490(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SEDK.
    10. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
      Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
      J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-657.
      Tissue: Plasma.
    11. "Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan."
      Chen F.-H., Herndon M.E., Patel N., Hecht J.T., Tuan R.S., Lawler J.
      J. Biol. Chem. 282:24591-24598(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH COMP.
    12. "A recessive skeletal dysplasia, SEMD aggrecan type, results from a missense mutation affecting the C-type lectin domain of aggrecan."
      Tompson S.W., Merriman B., Funari V.A., Fresquet M., Lachman R.S., Rimoin D.L., Nelson S.F., Briggs M.D., Cohn D.H., Krakow D.
      Am. J. Hum. Genet. 84:72-79(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT SEMD-ACAN ASN-2266, CHARACTERIZATION OF VARIANT SEMD-ACAN ASN-2266.
    13. "A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans."
      Stattin E.L., Wiklund F., Lindblom K., Onnerfjord P., Jonsson B.A., Tegner Y., Sasaki T., Struglics A., Lohmander S., Dahl N., Heinegard D., Aspberg A.
      Am. J. Hum. Genet. 86:126-137(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT OD MET-2303, DETECTION OF VARIANT OD MET-2303 BY MASS SPECTROMETRY.

    Entry informationi

    Entry nameiPGCA_HUMAN
    AccessioniPrimary (citable) accession number: P16112
    Secondary accession number(s): Q13650
    , Q9UCD3, Q9UCP4, Q9UCP5, Q9UDE0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: August 1, 1992
    Last modified: October 1, 2014
    This is version 167 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3