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aggrecan core protein; cartilage-specific proteoglycan core protein; CSPCP; chondroitin sulfate proteoglycan core protein 1; contains: aggrecan core protein 2 (ACAN, AGC1, CSPG1, MSK16)

Function: - major component of extracellular matrix of cartilage - role in resisting compression in cartilage - binds avidly to hyaluronic acid via an N-terminal globular region - contains mostly chondroitin sulfate, but also keratan sulfate chains, N-linked & O-linked oligosaccharides - interacts with FBLN1 (putative) Structure: - two globular domains, G1 & G2, comprise the N-terminus of the proteoglycan, while another globular region, G3, makes up the C-terminus. - G1 contains link domains & thus consists of three disulfide- bonded loop structures designated as the A, B, B' motifs. - G2 is similar to G1 - the keratan sulfate (KS) & the chondroitin sulfate (CS) attachment domains lie between G2 & G3 belongs to the aggrecan/versican proteoglycan family - contains 1 C-type lectin domain - contains 1 EGF-like domain - contains 1 Ig-like V-type domain (immunoglobulin-like) - contains 4 link domains - contains 1 Sushi (CCP/SCR) domain Compartment: - secreted, extracellular space, extracellular matrix (putative) Alternative splicing: named isoforms=3; Additional isoforms seem to exist Expression: - restricted to cartilages - detected in chondrocytes throughout the developing skeleton Pathology: - defects in ACAN are the cause of spondyloepiphyseal dysplasia type Kimberley - release of aggrecan fragments from articular cartilage into the synovial fluid at all stages of human osteoarthritis is the result of cleavage by aggrecanase [2,3]

General

matrix protein proteoglycan core protein

Properties

SIZE: entity length = 2415 aa MW = 250 kD COMPARTMENT: extracellular matrix MOTIF: signal sequence {1-16} immunoglobulin superfamily domain {34-147} MOTIF: G1-A {48-141} cysteine residue {C51} MODIFICATION: cysteine residue {C133} N-glycosylation site {N126} cysteine residue {C133} MODIFICATION: cysteine residue {C51} G1-B {152-247} Link {153-248} (4) MOTIF: cysteine residue {C175} MODIFICATION: cysteine residue {C246} cysteine residue {C199} MODIFICATION: cysteine residue {C220} cysteine residue {C220} MODIFICATION: cysteine residue {C199} N-glycosylation site {N239} cysteine residue {C246} MODIFICATION: cysteine residue {C175} G1-B' {253-349} Thr glycosylation site {T371} Thr glycosylation site {T376} N-glycosylation site {N387} peptide motif {392-393} N-glycosylation site {N434} G2-B {477-571} G2-B' {578-672} KS {676-848} MOTIF: N-glycosylation site {N737} 12 X 6 AA approximate tandem repeats of E-[GVE]-P-[SFY]-[APT]-[TSP] {772-843} (12) CS-1 {851-1497} CS-2 {1498-2162} MOTIF: N-glycosylation site {N1898} EGF domain {2164-2199} MOTIF: cysteine residue {C2168} MODIFICATION: cysteine residue {C2178} cysteine residue {C2173} MODIFICATION: cysteine residue {C2187} cysteine residue {C2178} MODIFICATION: cysteine residue {C2168} cysteine residue {C2187} MODIFICATION: cysteine residue {C2173} cysteine residue {C2189} MODIFICATION: cysteine residue {C2198} cysteine residue {C2198} MODIFICATION: cysteine residue {C2189} carbohydrate-recognition domain {2201-2327} MOTIF: cysteine residue {*1} (3) MODIFICATION: cysteine residue {*2} cysteine residue {*2} (3) MODIFICATION: cysteine residue {*1} cysteine residue {C2205} MODIFICATION: cysteine residue {C2216} cysteine residue {C2216} MODIFICATION: cysteine residue {C2205} cysteine residue {C2233} MODIFICATION: cysteine residue {C2325} cysteine residue {C2301} MODIFICATION: cysteine residue {C2317} cysteine residue {C2317} MODIFICATION: cysteine residue {C2301} cysteine residue {C2325} MODIFICATION: cysteine residue {C2233} Sushi domain {2330-2390} MOTIF: cysteine residue {C2332} MODIFICATION: cysteine residue {C2375} cysteine residue {C2361} MODIFICATION: cysteine residue {C2388} cysteine residue {C2375} MODIFICATION: cysteine residue {C2332} cysteine residue {C2388} MODIFICATION: cysteine residue {C2361}

Database Correlations

OMIM correlations UniProt P16112 PFAM correlations

References

  1. Ruoslahti E, Yamaguchi Y. Proteoglycans as modulators of growth factor activities. Cell. 1991 Mar 8;64(5):867-9. Review. PMID: 2001586
  2. UniProt :accession P16112
  3. Journal Watch 25(10):81, 2005 Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature. 2005 Mar 31;434(7033):644-8. PMID: 15800624 - Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM, Fosang AJ. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature. 2005 Mar 31;434(7033):648-52. PMID: 15800625
  4. Functional glycomics gateway - glycan binding Note: Aggrecan http://www.functionalglycomics.org/glycomics/GBPServlet?&operationtype=view&cbpId=cbp_hum_Ctlect_351