CaMPDB :: Substrate

SB0107 : Aggrecan

* Basic Information

Organism	Homo sapiens (human)
Protein Names	RecName: Full=Aggrecan core protein; AltName: Full=Cartilage-specific proteoglycan core protein; Short=CSPCP; AltName: Full=Chondroitin sulfate proteoglycan core protein 1; Short=Chondroitin sulfate proteoglycan 1; Contains: RecName: Full=Aggrecan core protein 2; Flags: Precursor; Aggrecan core protein; Cartilage-specific proteoglycan core protein; Chondroitin sulfate proteoglycan core protein 1; CSPCP; Chondroitin sulfate proteoglycan 1; Aggrecan core protein 2
Gene Names	AGC1, CSPG1, MSK16; AGC1; CSPG1; MSK16
Gene Locus	Not available
GO Function	Not available

Entrez Protein	Entrez Nucleotide	Entrez Gene	UniProt	OMIM	HGNC	HPRD	KEGG
P16112	N/A	N/A	P16112	N/A	N/A	N/A	hsa:

* Information From OMIM

Not Available.

* Structure Information

1. Primary Information

Length: 2415 aa

Average Mass: 250.190 kDa

Monoisotopic Mass: 250.040 kDa

2. Domain Information

Annotated Domains: interpro / pfam / smart / prosite

Computationally Assigned Domains (Pfam+HMMER):

domain name	begin	end	score	e-value
Immunoglobulin I-set domain 1.	114	150	54.0	0.0
Lectin C-type domain 1.	167	187	4.0	0.0
Human growth factor-like EGF 1.	198	203	3.0	0.1
Lectin C-type domain 2.	264	283	3.0	0.0
Lectin C-type domain 3.	490	512	2.0	0.0
Human growth factor-like EGF 2.	523	528	3.0	0.1
Lectin C-type domain 4.	589	604	3.0	0.1
--- cleavage 709 ---
Human growth factor-like EGF 3.	1511	1517	5.0	0.1
Human growth factor-like EGF 4.	1688	1693	6.0	0.1
Immunoglobulin V-set domain 1.	2089	2146	11.0	0.0
Nematode antimicrobial peptide 1.	2164	2189	18.0	2.8
Extracellular link domain 1.	2226	2243	16.0	0.0
Sushi repeat (SCR repeat) 1.	2332	2388	1.0	1.3

3. Sequence Information

Fasta Sequence: SB0107.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 4MD4 (X-ray; 195 A; C=89-103)

* Cleavage Information

1 [sites] cleaved by Calpain 2

Source Reference: [PubMed ID: 15175011] Oshita H, Sandy JD, Suzuki K, Akaike A, Bai Y, Sasaki T, Shimizu K, Mature bovine articular cartilage contains abundant aggrecan that is C-terminally truncated at Ala719-Ala720, a site which is readily cleaved by m-calpain. Biochem J. 2004 Aug 15;382(Pt 1):253-9.

Cleavage sites (±10aa)

[Site 1] IVTQVVPGVA⁷⁰⁹-AVPVEEETTA

Ala⁷⁰⁹ Ala

P10	P9	P8	P7	P6	P5	P4	P3	P2	P1

Ile⁷⁰⁰	Val⁷⁰¹	Thr⁷⁰²	Gln⁷⁰³	Val⁷⁰⁴	Val⁷⁰⁵	Pro⁷⁰⁶	Gly⁷⁰⁷	Val⁷⁰⁸	Ala⁷⁰⁹

P1'	P2'	P3'	P4'	P5'	P6'	P7'	P8'	P9'	P10'
Ala⁷¹⁰	Val⁷¹¹	Pro⁷¹²	Val⁷¹³	Glu⁷¹⁴	Glu⁷¹⁵	Glu⁷¹⁶	Thr⁷¹⁷	Thr⁷¹⁸	Ala⁷¹⁹

Sequence conservation (by blast) Sequence conservation (by blast)

Reference peptide (cleaved bond±30 residues)
PSPGEEEGGTPTSPSGVEEWIVTQVVPGVAAVPVEEETTAVPSGETTAILEFTTEPENQT

Summary

#	organism	max score	hits	top seq
1	N/A	112.00	4	large aggregating cartilage proteoglycan core pro
2	Contains: Aggrecan core protein 2	112.00	1	PGCA_HUMAN Aggrecan core protein precursor (Carti
3	Bos taurus	63.20	1	aggrecan 1
4	Canis lupus familiaris	62.80	1	aggrecan 1
5	Sus scrofa	62.00	1	AF314813_1 aggrecan G2 domain
6	Rattus norvegicus	59.30	1	aggrecan 1
7	Gallus gallus	33.50	1	PGCA_CHICK Aggrecan core protein precursor (Carti
8	Xanthomonas campestris pv. campestris str. ATCC 33913	32.70	1	tetracenomycin polyketide synthesis protein
9	Xanthomonas campestris pv. vesicatoria str. 85-10	31.20	1	hypothetical protein XCV1219

Top-ranked sequences

organism	matching
N/A	Query 680 PSPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 680 PSPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739
Contains: Aggrecan core protein 2	Query 680 PSPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739 \|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|#\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\|\| Query 680 PSPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739
Bos taurus	Query 680 PSPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739 \|\|\| \|\|\|\| \|\|+ \|\|\|\|+\|\|\|\| \|\|\|\|#\|\|\|+ \|\|\|\|\|+\| \|\| \|\|\|\|+\| Sbjct 690 PSPEEEEGSAPTAGPDVEEWMVTQVGPGVA#AVPIGEETTAIPG--------FTVEPENKT 741
Canis lupus familiaris	Query 680 PSPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739 \|\|\|\|\|\|\|\|\|\|\|\| \|\| \|\|+\|\| \|\|\| \| \| #+\|\|+ \| \|\|\|\|\|\|+\|\| \|\|\|\|\|\| Sbjct 699 PSPGEEEGGTPT-PSVVEDWIPTQVGPVVP#SVPMGE--------ETTAILDFTIEPENQT 749
Sus scrofa	Query 680 PSPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739 \|\|\|\|\|\|\|\|\|\|\|\|\| +\|\| \| \|\|\| \|\|\|\|#\|\|\|\| \|\|\|\| \| + \|\|\|\|\|\|\|+\| Sbjct 352 PSPGEEEGGTPTSLPDLEERIATQVGPGVA#AVPVGEETTEVAA--------FTTEPENRT 403
Rattus norvegicus	Query 680 PSPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739 \|\|\|\| \|\|\|\|\|\|\| +\|+\|\|\|\|+\| \|\|\| #\|\|\|+\| \|\|\| \|\| \|\|\|\|\|\| \|\| Sbjct 690 PSPG----GTPTSPSDIEDWIVTRVEPGVD#AVPLEPETTEVP--------YFTTEPEKQT 737
Gallus gallus	Query 697 EEWIVTQVVPGVA#AVPVEEETTAVPSGETTAILEFTTEPENQT 739 \|\| +\|\|\|++\|\|\| # +\| \|\|\|\| \|\| \| ++\|\|\|\|\|\| Sbjct 733 EEVMVTQLIPGVE#GIPSGEETTV----ET----ELSSEPENQT 767
Xanthomonas campestris pv. campestris str. ATCC 33913	Query 681 SPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAI 728 +\|\|+ \|\|\| \| ++\|+ \|\| \| # \|+ \| \|+ +\| \|\| Sbjct 29 APGDREGGPDNRHRGADQWLF--VVDGAG#EAIVDGHTQALQAGSLIAI 74
Xanthomonas campestris pv. vesicatoria str. 85-10	Query 681 SPGEEEGGTPTSPSGVEEWIVTQVVPGVA#AVPVEEETTAVPSGETTAI 728 +\|\|+ \|\|\| \| ++\|+ \|\| \| # +\| +\| \|+ +\| \|\| Sbjct 29 APGQGEGGPDNRHRGADQWLY--VVDGTG#EAVIEGQTHALQAGSLIAI 74

* References

[PubMed ID: 1985970] Doege KJ, Sasaki M, Kimura T, Yamada Y, Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms. J Biol Chem. 1991 Jan 15;266(2):894-902.

» More (12) « Hide Below

[PubMed ID: 7574678] ... Ilic MZ, Mok MT, Williamson OD, Campbell MA, Hughes CE, Handley CJ, Catabolism of aggrecan by explant cultures of human articular cartilage in the presence of retinoic acid. Arch Biochem Biophys. 1995 Sep 10;322(1):22-30.

[PubMed ID: 1569188] ... Sandy JD, Flannery CR, Neame PJ, Lohmander LS, 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. J Clin Invest. 1992 May;89(5):1512-6.

[PubMed ID: 7524681] ... Glumoff V, Savontaus M, Vehanen J, Vuorio E, Analysis of aggrecan and tenascin gene expression in mouse skeletal tissues by northern and in situ hybridization using species specific cDNA probes. Biochim Biophys Acta. 1994 Nov 22;1219(3):613-22.

[PubMed ID: 8216415] ... Lohmander LS, Neame PJ, Sandy JD, The structure of aggrecan fragments in human synovial fluid. Evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis. Arthritis Rheum. 1993 Sep;36(9):1214-22.

[PubMed ID: 7827755] ... Barry FP, Neame PJ, Sasse J, Pearson D, Length variation in the keratan sulfate domain of mammalian aggrecan. Matrix Biol. 1994 Aug;14(4):323-8.

[PubMed ID: 8611178] ... Dudhia J, Davidson CM, Wells TM, Vynios DH, Hardingham TE, Bayliss MT, Age-related changes in the content of the C-terminal region of aggrecan in human articular cartilage. Biochem J. 1996 Feb 1;313 ( Pt 3):933-40.

[PubMed ID: 2789216] ... Baldwin CT, Reginato AM, Prockop DJ, 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. J Biol Chem. 1989 Sep 25;264(27):15747-50.

[PubMed ID: 16080123] ... Gleghorn L, Ramesar R, Beighton P, Wallis G, A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis. Am J Hum Genet. 2005 Sep;77(3):484-90. Epub 2005 Jul 22.

[PubMed ID: 16335952] ... Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD, Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80.

[PubMed ID: 17588949] ... Chen FH, Herndon ME, Patel N, Hecht JT, Tuan RS, Lawler J, Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan. J Biol Chem. 2007 Aug 24;282(34):24591-8. Epub 2007 Jun 22.

[PubMed ID: 19110214] ... Tompson SW, Merriman B, Funari VA, Fresquet M, Lachman RS, Rimoin DL, Nelson SF, Briggs MD, Cohn DH, Krakow D, A recessive skeletal dysplasia, SEMD aggrecan type, results from a missense mutation affecting the C-type lectin domain of aggrecan. Am J Hum Genet. 2009 Jan;84(1):72-9. doi: 10.1016/j.ajhg.2008.12.001. Epub 2008

[PubMed ID: 20137779] ... Stattin EL, Wiklund F, Lindblom K, Onnerfjord P, Jonsson BA, Tegner Y, Sasaki T, Struglics A, Lohmander S, Dahl N, Heinegard D, Aspberg A, A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. Am J Hum Genet. 2010 Feb 12;86(2):126-37. doi: 10.1016/j.ajhg.2009.12.018. Epub