P16112 (PGCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Aggrecan core protein 2

Gene names

Name:	ACAN
Synonyms:	AGC1, CSPG1, MSK16

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	2415 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Interacts with FBLN1 By similarity. Interacts with COMP. Ref.11
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Restricted to cartilages. Ref.4
Developmental stage	Expression was detected in chondrocytes throughout the developing skeleton.
Domain	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.
Post-translational modification	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.
Involvement in disease	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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 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. Note: The disease is caused by mutations affecting the gene represented in this entry. 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Belongs to the aggrecan/versican proteoglycan family. Contains 1 C-type lectin domain. Contains 1 EGF-like domain. Contains 1 Ig-like V-type (immunoglobulin-like) domain. Contains 4 Link domains. Contains 1 Sushi (CCP/SCR) domain.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Dwarfism
Domain	EGF-like domain Immunoglobulin domain Repeat Signal Sushi
Ligand	Calcium Lectin Metal-binding
PTM	Disulfide bond Glycoprotein Proteoglycan
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement. Source: Reactome cell adhesion Inferred from electronic annotation. Source: InterPro keratan sulfate biosynthetic process Traceable author statement. Source: Reactome keratan sulfate catabolic process Traceable author statement. Source: Reactome proteolysis Non-traceable author statement Ref.3. Source: UniProtKB skeletal system development Non-traceable author statement Ref.3. Source: UniProtKB
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome lysosomal lumen Traceable author statement. Source: Reactome proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: InterPro extracellular matrix structural constituent Traceable author statement Ref.3. Source: UniProtKB hyaluronic acid binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P16112-1)

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.

Isoform 2 (identifier: P16112-2)

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

Isoform 3 (identifier: P16112-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 16	16	Ref.2
	Chain	17 – 2415	2399	Aggrecan core protein		PRO_0000017505
	Chain	393 – 2415	2023	Aggrecan core protein 2		PRO_0000017506
Regions
	Domain	34 – 147	114	Ig-like V-type
	Domain	153 – 248	96	Link 1
	Domain	254 – 350	97	Link 2
	Domain	478 – 573	96	Link 3
	Domain	579 – 674	96	Link 4
	Repeat	772 – 777	6	1-1
	Repeat	778 – 783	6	1-2
	Repeat	784 – 789	6	1-3
	Repeat	790 – 795	6	1-4
	Repeat	796 – 801	6	1-5
	Repeat	802 – 807	6	1-6
	Repeat	808 – 813	6	1-7; approximate
	Repeat	814 – 819	6	1-8; approximate
	Repeat	820 – 825	6	1-9
	Repeat	826 – 831	6	1-10; approximate
	Repeat	832 – 837	6	1-11
	Repeat	838 – 843	6	1-12
	Repeat	941 – 959	19	2-1
	Repeat	960 – 978	19	2-2
	Repeat	979 – 997	19	2-3
	Repeat	998 – 1016	19	2-4
	Repeat	1017 – 1035	19	2-5
	Repeat	1036 – 1054	19	2-6
	Repeat	1055 – 1073	19	2-7
	Repeat	1074 – 1092	19	2-8
	Repeat	1093 – 1111	19	2-9
	Repeat	1112 – 1130	19	2-10
	Repeat	1131 – 1149	19	2-11
	Repeat	1150 – 1168	19	2-12
	Repeat	1169 – 1187	19	2-13
	Repeat	1188 – 1206	19	2-14
	Repeat	1207 – 1225	19	2-15
	Repeat	1226 – 1244	19	2-16
	Repeat	1245 – 1263	19	2-17
	Repeat	1264 – 1282	19	2-18
	Repeat	1283 – 1301	19	2-19
	Repeat	1302 – 1320	19	2-20
	Repeat	1321 – 1339	19	2-21
	Repeat	1340 – 1358	19	2-22
	Repeat	1360 – 1378	19	2-23
	Repeat	1379 – 1397	19	2-24
	Repeat	1398 – 1416	19	2-25
	Repeat	1418 – 1436	19	2-26
	Repeat	1439 – 1457	19	2-27; approximate
	Repeat	1459 – 1477	19	2-28
	Repeat	1479 – 1497	19	2-29
	Domain	2164 – 2199	36	EGF-like
	Domain	2201 – 2327	127	C-type lectin
	Domain	2330 – 2390	61	Sushi
	Region	48 – 141	94	G1-A
	Region	152 – 247	96	G1-B
	Region	253 – 349	97	G1-B'
	Region	477 – 571	95	G2-B
	Region	578 – 672	95	G2-B'
	Region	676 – 848	173	KS
	Region	772 – 843	72	12 X 6 AA approximate tandem repeats of E-[GVE]-P-[SFY]-[APT]-[TSP]
	Region	851 – 1497	647	CS-1
	Region	941 – 1497	557	29 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-G
	Region	1498 – 2162	665	CS-2
	Region	2163 – 2415	253	G3
Sites
	Metal binding	2266	1	Calcium 1 By similarity
	Metal binding	2270	1	Calcium 1 By similarity
	Metal binding	2270	1	Calcium 3 By similarity
	Metal binding	2290	1	Calcium 2 By similarity
	Metal binding	2292	1	Calcium 2 By similarity
	Metal binding	2293	1	Calcium 1 By similarity
	Metal binding	2299	1	Calcium 1; via carbonyl oxygen By similarity
	Metal binding	2299	1	Calcium 2 By similarity
	Metal binding	2300	1	Calcium 1 By similarity
	Metal binding	2300	1	Calcium 3 By similarity
	Metal binding	2313	1	Calcium 2 By similarity
	Metal binding	2314	1	Calcium 2 By similarity
	Metal binding	2314	1	Calcium 2; via carbonyl oxygen By similarity
	Site	392 – 393	2	Cleavage; by aggrecanase
Amino acid modifications
	Glycosylation	126	1	N-linked (GlcNAc...) Potential
	Glycosylation	239	1	N-linked (GlcNAc...) Potential
	Glycosylation	333	1	N-linked (GlcNAc...) Potential
	Glycosylation	371	1	O-linked (Xyl...) (keratan sulfate) Probable
	Glycosylation	376	1	O-linked (Xyl...) (keratan sulfate) Probable
	Glycosylation	387	1	N-linked (GlcNAc...) Potential
	Glycosylation	434	1	N-linked (GlcNAc...) Potential
	Glycosylation	602	1	N-linked (GlcNAc...) Potential
	Glycosylation	657	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	737	1	N-linked (GlcNAc...) Potential
	Glycosylation	1898	1	N-linked (GlcNAc...) Potential
	Disulfide bond	51 ↔ 133		By similarity
	Disulfide bond	175 ↔ 246		By similarity
	Disulfide bond	199 ↔ 220		By similarity
	Disulfide bond	273 ↔ 348		By similarity
	Disulfide bond	297 ↔ 318		By similarity
	Disulfide bond	500 ↔ 571		By similarity
	Disulfide bond	524 ↔ 545		By similarity
	Disulfide bond	598 ↔ 672		By similarity
	Disulfide bond	621 ↔ 642		By similarity
	Disulfide bond	2168 ↔ 2178		By similarity
	Disulfide bond	2173 ↔ 2187		By similarity
	Disulfide bond	2189 ↔ 2198		By similarity
	Disulfide bond	2205 ↔ 2216		By similarity
	Disulfide bond	2233 ↔ 2325		By similarity
	Disulfide bond	2301 ↔ 2317		By similarity
	Disulfide bond	2332 ↔ 2375		By similarity
	Disulfide bond	2361 ↔ 2388		By similarity
Natural variations
	Alternative sequence	2163 – 2200	38	Missing in isoform 2 and isoform 3.		VSP_003074
	Alternative sequence	2330 – 2390	61	Missing in isoform 3.		VSP_003075
	Natural variant	102	1	D → E. Corresponds to variant rs16942318 [ dbSNP | Ensembl ].		VAR_056152
	Natural variant	275	1	R → Q. Corresponds to variant rs34949187 [ dbSNP | Ensembl ].		VAR_056153
	Natural variant	1943	1	P → L. Corresponds to variant rs35061438 [ dbSNP | Ensembl ].		VAR_056154
	Natural variant	2005	1	S → R. Corresponds to variant rs34153007 [ dbSNP | Ensembl ].		VAR_056155
	Natural variant	2266	1	D → N in SEMD-ACAN; creates a functional N-glycosylation site; does not adversely affect protein trafficking and secretion. Ref.12		VAR_063053
	Natural variant	2303	1	V → M in OD. Ref.13		VAR_063765
Experimental info
	Sequence conflict	766	1	E → A in AAC60643. Ref.6
	Sequence conflict	847	1	E → V in AAC60643. Ref.6
	Sequence conflict	1928	1	E → A in CAA35463. Ref.7
	Sequence conflict	1964	1	I → V in CAA35463. Ref.7
	Sequence conflict	1964	1	I → V in AAA35726. Ref.8
	Sequence conflict	2070	1	P → A in AAA35726. Ref.8
	Sequence conflict	2391	1	A → P in CAA35463. Ref.7
	Sequence conflict	2391	1	A → P in AAA35726. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1992. Version 2. Checksum: 1288937E1B98C6B6	FASTA	2,415	250,193
	10 20 30 40 50 60 MTTLLWVFVT LRVITAAVTV ETSDHDNSLS VSIPQPSPLR VLLGTSLTIP CYFIDPMHPV 70 80 90 100 110 120 TTAPSTAPLA PRIKWSRVSK EKEVVLLVAT EGRVRVNSAY QDKVSLPNYP AIPSDATLEV 130 140 150 160 170 180 QSLRSNDSGV YRCEVMHGIE DSEATLEVVV KGIVFHYRAI STRYTLDFDR AQRACLQNSA 190 200 210 220 230 240 IIATPEQLQA AYEDGFHQCD AGWLADQTVR YPIHTPREGC YGDKDEFPGV RTYGIRDTNE 250 260 270 280 290 300 TYDVYCFAEE MEGEVFYATS PEKFTFQEAA NECRRLGARL ATTGHVYLAW QAGMDMCSAG 310 320 330 340 350 360 WLADRSVRYP ISKARPNCGG NLLGVRTVYV HANQTGYPDP SSRYDAICYT GEDFVDIPEN 370 380 390 400 410 420 FFGVGGEEDI TVQTVTWPDM ELPLPRNITE GEARGSVILT VKPIFEVSPS PLEPEEPFTF 430 440 450 460 470 480 APEIGATAFA EVENETGEAT RPWGFPTPGL GPATAFTSED LVVQVTAVPG QPHLPGGVVF 490 500 510 520 530 540 HYRPGPTRYS LTFEEAQQAC PGTGAVIASP EQLQAAYEAG YEQCDAGWLR DQTVRYPIVS 550 560 570 580 590 600 PRTPCVGDKD SSPGVRTYGV RPSTETYDVY CFVDRLEGEV FFATRLEQFT FQEALEFCES 610 620 630 640 650 660 HNATATTGQL YAAWSRGLDK CYAGWLADGS LRYPIVTPRP ACGGDKPGVR TVYLYPNQTG 670 680 690 700 710 720 LPDPLSRHHA FCFRGISAVP SPGEEEGGTP TSPSGVEEWI VTQVVPGVAA VPVEEETTAV 730 740 750 760 770 780 PSGETTAILE FTTEPENQTE WEPAYTPVGT SPLPGILPTW PPTGAETEES TEGPSATEVP 790 800 810 820 830 840 SASEEPSPSE VPFPSEEPSP SEEPFPSVRP FPSVELFPSE EPFPSKEPSP SEEPSASEEP 850 860 870 880 890 900 YTPSPPEPSW TELPSSGEES GAPDVSGDFT GSGDVSGHLD FSGQLSGDRA SGLPSGDLDS 910 920 930 940 950 960 SGLTSTVGSG LTVESGLPSG DEERIEWPST PTVGELPSGA EILEGSASGV GDLSGLPSGE 970 980 990 1000 1010 1020 VLETSASGVG DLSGLPSGEV LETTAPGVED ISGLPSGEVL ETTAPGVEDI SGLPSGEVLE 1030 1040 1050 1060 1070 1080 TTAPGVEDIS GLPSGEVLET TAPGVEDISG LPSGEVLETT APGVEDISGL PSGEVLETAA 1090 1100 1110 1120 1130 1140 PGVEDISGLP SGEVLETAAP GVEDISGLPS GEVLETAAPG VEDISGLPSG EVLETAAPGV 1150 1160 1170 1180 1190 1200 EDISGLPSGE VLETAAPGVE DISGLPSGEV LETAAPGVED ISGLPSGEVL ETAAPGVEDI 1210 1220 1230 1240 1250 1260 SGLPSGEVLE TAAPGVEDIS GLPSGEVLET AAPGVEDISG LPSGEVLETA APGVEDISGL 1270 1280 1290 1300 1310 1320 PSGEVLETAA PGVEDISGLP SGEVLETTAP GVEEISGLPS GEVLETTAPG VDEISGLPSG 1330 1340 1350 1360 1370 1380 EVLETTAPGV EEISGLPSGE VLETSTSAVG DLSGLPSGGE VLEISVSGVE DISGLPSGEV 1390 1400 1410 1420 1430 1440 VETSASGIED VSELPSGEGL ETSASGVEDL SRLPSGEEVL EISASGFGDL SGVPSGGEGL 1450 1460 1470 1480 1490 1500 ETSASEVGTD LSGLPSGREG LETSASGAED LSGLPSGKED LVGSASGDLD LGKLPSGTLG 1510 1520 1530 1540 1550 1560 SGQAPETSGL PSGFSGEYSG VDLGSGPPSG LPDFSGLPSG FPTVSLVDST LVEVVTASTA 1570 1580 1590 1600 1610 1620 SELEGRGTIG ISGAGEISGL PSSELDISGR ASGLPSGTEL SGQASGSPDV SGEIPGLFGV 1630 1640 1650 1660 1670 1680 SGQPSGFPDT SGETSGVTEL SGLSSGQPGV SGEASGVLYG TSQPFGITDL SGETSGVPDL 1690 1700 1710 1720 1730 1740 SGQPSGLPGF SGATSGVPDL VSGTTSGSGE SSGITFVDTS LVEVAPTTFK EEEGLGSVEL 1750 1760 1770 1780 1790 1800 SGLPSGEADL SGKSGMVDVS GQFSGTVDSS GFTSQTPEFS GLPSGIAEVS GESSRAEIGS 1810 1820 1830 1840 1850 1860 SLPSGAYYGS GTPSSFPTVS LVDRTLVESV TQAPTAQEAG EGPSGILELS GAHSGAPDMS 1870 1880 1890 1900 1910 1920 GEHSGFLDLS GLQSGLIEPS GEPPGTPYFS GDFASTTNVS GESSVAMGTS GEASGLPEVT 1930 1940 1950 1960 1970 1980 LITSEFVEGV TEPTISQELG QRPPVTHTPQ LFESSGKVST AGDISGATPV LPGSGVEVSS 1990 2000 2010 2020 2030 2040 VPESSSETSA YPEAGFGASA APEASREDSG SPDLSETTSA FHEANLERSS GLGVSGSTLT 2050 2060 2070 2080 2090 2100 FQEGEASAAP EVSGESTTTS DVGTEAPGLP SATPTASGDR TEISGDLSGH TSQLGVVIST 2110 2120 2130 2140 2150 2160 SIPESEWTQQ TQRPAETHLE IESSSLLYSG EETHTVETAT SPTDASIPAS PEWKRESEST 2170 2180 2190 2200 2210 2220 AAAPARSCAE EPCGAGTCKE TEGHVICLCP PGYTGEHCNI DQEVCEEGWN KYQGHCYRHF 2230 2240 2250 2260 2270 2280 PDRETWVDAE RRCREQQSHL SSIVTPEEQE FVNNNAQDYQ WIGLNDRTIE GDFRWSDGHP 2290 2300 2310 2320 2330 2340 MQFENWRPNQ PDNFFAAGED CVVMIWHEKG EWNDVPCNYH LPFTCKKGTV ACGEPPVVEH 2350 2360 2370 2380 2390 2400 ARTFGQKKDR YEINSLVRYQ CTEGFVQRHM PTIRCQPSGH WEEPRITCTD ATTYKRRLQK 2410 RSSRHPRRSR PSTAH
	Isoform 2 [UniParc]. Checksum: CC3F3E0D74B00DAD	FASTA	2,377	246,306
	10 20 30 40 50 60 MTTLLWVFVT LRVITAAVTV ETSDHDNSLS VSIPQPSPLR VLLGTSLTIP CYFIDPMHPV 70 80 90 100 110 120 TTAPSTAPLA PRIKWSRVSK EKEVVLLVAT EGRVRVNSAY QDKVSLPNYP AIPSDATLEV 130 140 150 160 170 180 QSLRSNDSGV YRCEVMHGIE DSEATLEVVV KGIVFHYRAI STRYTLDFDR AQRACLQNSA 190 200 210 220 230 240 IIATPEQLQA AYEDGFHQCD AGWLADQTVR YPIHTPREGC YGDKDEFPGV RTYGIRDTNE 250 260 270 280 290 300 TYDVYCFAEE MEGEVFYATS PEKFTFQEAA NECRRLGARL ATTGHVYLAW QAGMDMCSAG 310 320 330 340 350 360 WLADRSVRYP ISKARPNCGG NLLGVRTVYV HANQTGYPDP SSRYDAICYT GEDFVDIPEN 370 380 390 400 410 420 FFGVGGEEDI TVQTVTWPDM ELPLPRNITE GEARGSVILT VKPIFEVSPS PLEPEEPFTF 430 440 450 460 470 480 APEIGATAFA EVENETGEAT RPWGFPTPGL GPATAFTSED LVVQVTAVPG QPHLPGGVVF 490 500 510 520 530 540 HYRPGPTRYS LTFEEAQQAC PGTGAVIASP EQLQAAYEAG YEQCDAGWLR DQTVRYPIVS 550 560 570 580 590 600 PRTPCVGDKD SSPGVRTYGV RPSTETYDVY CFVDRLEGEV FFATRLEQFT FQEALEFCES 610 620 630 640 650 660 HNATATTGQL YAAWSRGLDK CYAGWLADGS LRYPIVTPRP ACGGDKPGVR TVYLYPNQTG 670 680 690 700 710 720 LPDPLSRHHA FCFRGISAVP SPGEEEGGTP TSPSGVEEWI VTQVVPGVAA VPVEEETTAV 730 740 750 760 770 780 PSGETTAILE FTTEPENQTE WEPAYTPVGT SPLPGILPTW PPTGAETEES TEGPSATEVP 790 800 810 820 830 840 SASEEPSPSE VPFPSEEPSP SEEPFPSVRP FPSVELFPSE EPFPSKEPSP SEEPSASEEP 850 860 870 880 890 900 YTPSPPEPSW TELPSSGEES GAPDVSGDFT GSGDVSGHLD FSGQLSGDRA SGLPSGDLDS 910 920 930 940 950 960 SGLTSTVGSG LTVESGLPSG DEERIEWPST PTVGELPSGA EILEGSASGV GDLSGLPSGE 970 980 990 1000 1010 1020 VLETSASGVG DLSGLPSGEV LETTAPGVED ISGLPSGEVL ETTAPGVEDI SGLPSGEVLE 1030 1040 1050 1060 1070 1080 TTAPGVEDIS GLPSGEVLET TAPGVEDISG LPSGEVLETT APGVEDISGL PSGEVLETAA 1090 1100 1110 1120 1130 1140 PGVEDISGLP SGEVLETAAP GVEDISGLPS GEVLETAAPG VEDISGLPSG EVLETAAPGV 1150 1160 1170 1180 1190 1200 EDISGLPSGE VLETAAPGVE DISGLPSGEV LETAAPGVED ISGLPSGEVL ETAAPGVEDI 1210 1220 1230 1240 1250 1260 SGLPSGEVLE TAAPGVEDIS GLPSGEVLET AAPGVEDISG LPSGEVLETA APGVEDISGL 1270 1280 1290 1300 1310 1320 PSGEVLETAA PGVEDISGLP SGEVLETTAP GVEEISGLPS GEVLETTAPG VDEISGLPSG 1330 1340 1350 1360 1370 1380 EVLETTAPGV EEISGLPSGE VLETSTSAVG DLSGLPSGGE VLEISVSGVE DISGLPSGEV 1390 1400 1410 1420 1430 1440 VETSASGIED VSELPSGEGL ETSASGVEDL SRLPSGEEVL EISASGFGDL SGVPSGGEGL 1450 1460 1470 1480 1490 1500 ETSASEVGTD LSGLPSGREG LETSASGAED LSGLPSGKED LVGSASGDLD LGKLPSGTLG 1510 1520 1530 1540 1550 1560 SGQAPETSGL PSGFSGEYSG VDLGSGPPSG LPDFSGLPSG FPTVSLVDST LVEVVTASTA 1570 1580 1590 1600 1610 1620 SELEGRGTIG ISGAGEISGL PSSELDISGR ASGLPSGTEL SGQASGSPDV SGEIPGLFGV 1630 1640 1650 1660 1670 1680 SGQPSGFPDT SGETSGVTEL SGLSSGQPGV SGEASGVLYG TSQPFGITDL SGETSGVPDL 1690 1700 1710 1720 1730 1740 SGQPSGLPGF SGATSGVPDL VSGTTSGSGE SSGITFVDTS LVEVAPTTFK EEEGLGSVEL 1750 1760 1770 1780 1790 1800 SGLPSGEADL SGKSGMVDVS GQFSGTVDSS GFTSQTPEFS GLPSGIAEVS GESSRAEIGS 1810 1820 1830 1840 1850 1860 SLPSGAYYGS GTPSSFPTVS LVDRTLVESV TQAPTAQEAG EGPSGILELS GAHSGAPDMS 1870 1880 1890 1900 1910 1920 GEHSGFLDLS GLQSGLIEPS GEPPGTPYFS GDFASTTNVS GESSVAMGTS GEASGLPEVT 1930 1940 1950 1960 1970 1980 LITSEFVEGV TEPTISQELG QRPPVTHTPQ LFESSGKVST AGDISGATPV LPGSGVEVSS 1990 2000 2010 2020 2030 2040 VPESSSETSA YPEAGFGASA APEASREDSG SPDLSETTSA FHEANLERSS GLGVSGSTLT 2050 2060 2070 2080 2090 2100 FQEGEASAAP EVSGESTTTS DVGTEAPGLP SATPTASGDR TEISGDLSGH TSQLGVVIST 2110 2120 2130 2140 2150 2160 SIPESEWTQQ TQRPAETHLE IESSSLLYSG EETHTVETAT SPTDASIPAS PEWKRESEST 2170 2180 2190 2200 2210 2220 AADQEVCEEG WNKYQGHCYR HFPDRETWVD AERRCREQQS HLSSIVTPEE QEFVNNNAQD 2230 2240 2250 2260 2270 2280 YQWIGLNDRT IEGDFRWSDG HPMQFENWRP NQPDNFFAAG EDCVVMIWHE KGEWNDVPCN 2290 2300 2310 2320 2330 2340 YHLPFTCKKG TVACGEPPVV EHARTFGQKK DRYEINSLVR YQCTEGFVQR HMPTIRCQPS 2350 2360 2370 GHWEEPRITC TDATTYKRRL QKRSSRHPRR SRPSTAH
	Isoform 3 [UniParc]. Checksum: 44ABD9AF85CC3612	FASTA	2,316	239,235
	10 20 30 40 50 60 MTTLLWVFVT LRVITAAVTV ETSDHDNSLS VSIPQPSPLR VLLGTSLTIP CYFIDPMHPV 70 80 90 100 110 120 TTAPSTAPLA PRIKWSRVSK EKEVVLLVAT EGRVRVNSAY QDKVSLPNYP AIPSDATLEV 130 140 150 160 170 180 QSLRSNDSGV YRCEVMHGIE DSEATLEVVV KGIVFHYRAI STRYTLDFDR AQRACLQNSA 190 200 210 220 230 240 IIATPEQLQA AYEDGFHQCD AGWLADQTVR YPIHTPREGC YGDKDEFPGV RTYGIRDTNE 250 260 270 280 290 300 TYDVYCFAEE MEGEVFYATS PEKFTFQEAA NECRRLGARL ATTGHVYLAW QAGMDMCSAG 310 320 330 340 350 360 WLADRSVRYP ISKARPNCGG NLLGVRTVYV HANQTGYPDP SSRYDAICYT GEDFVDIPEN 370 380 390 400 410 420 FFGVGGEEDI TVQTVTWPDM ELPLPRNITE GEARGSVILT VKPIFEVSPS PLEPEEPFTF 430 440 450 460 470 480 APEIGATAFA EVENETGEAT RPWGFPTPGL GPATAFTSED LVVQVTAVPG QPHLPGGVVF 490 500 510 520 530 540 HYRPGPTRYS LTFEEAQQAC PGTGAVIASP EQLQAAYEAG YEQCDAGWLR DQTVRYPIVS 550 560 570 580 590 600 PRTPCVGDKD SSPGVRTYGV RPSTETYDVY CFVDRLEGEV FFATRLEQFT FQEALEFCES 610 620 630 640 650 660 HNATATTGQL YAAWSRGLDK CYAGWLADGS LRYPIVTPRP ACGGDKPGVR TVYLYPNQTG 670 680 690 700 710 720 LPDPLSRHHA FCFRGISAVP SPGEEEGGTP TSPSGVEEWI VTQVVPGVAA VPVEEETTAV 730 740 750 760 770 780 PSGETTAILE FTTEPENQTE WEPAYTPVGT SPLPGILPTW PPTGAETEES TEGPSATEVP 790 800 810 820 830 840 SASEEPSPSE VPFPSEEPSP SEEPFPSVRP FPSVELFPSE EPFPSKEPSP SEEPSASEEP 850 860 870 880 890 900 YTPSPPEPSW TELPSSGEES GAPDVSGDFT GSGDVSGHLD FSGQLSGDRA SGLPSGDLDS 910 920 930 940 950 960 SGLTSTVGSG LTVESGLPSG DEERIEWPST PTVGELPSGA EILEGSASGV GDLSGLPSGE 970 980 990 1000 1010 1020 VLETSASGVG DLSGLPSGEV LETTAPGVED ISGLPSGEVL ETTAPGVEDI SGLPSGEVLE 1030 1040 1050 1060 1070 1080 TTAPGVEDIS GLPSGEVLET TAPGVEDISG LPSGEVLETT APGVEDISGL PSGEVLETAA 1090 1100 1110 1120 1130 1140 PGVEDISGLP SGEVLETAAP GVEDISGLPS GEVLETAAPG VEDISGLPSG EVLETAAPGV 1150 1160 1170 1180 1190 1200 EDISGLPSGE VLETAAPGVE DISGLPSGEV LETAAPGVED ISGLPSGEVL ETAAPGVEDI 1210 1220 1230 1240 1250 1260 SGLPSGEVLE TAAPGVEDIS GLPSGEVLET AAPGVEDISG LPSGEVLETA APGVEDISGL 1270 1280 1290 1300 1310 1320 PSGEVLETAA PGVEDISGLP SGEVLETTAP GVEEISGLPS GEVLETTAPG VDEISGLPSG 1330 1340 1350 1360 1370 1380 EVLETTAPGV EEISGLPSGE VLETSTSAVG DLSGLPSGGE VLEISVSGVE DISGLPSGEV 1390 1400 1410 1420 1430 1440 VETSASGIED VSELPSGEGL ETSASGVEDL SRLPSGEEVL EISASGFGDL SGVPSGGEGL 1450 1460 1470 1480 1490 1500 ETSASEVGTD LSGLPSGREG LETSASGAED LSGLPSGKED LVGSASGDLD LGKLPSGTLG 1510 1520 1530 1540 1550 1560 SGQAPETSGL PSGFSGEYSG VDLGSGPPSG LPDFSGLPSG FPTVSLVDST LVEVVTASTA 1570 1580 1590 1600 1610 1620 SELEGRGTIG ISGAGEISGL PSSELDISGR ASGLPSGTEL SGQASGSPDV SGEIPGLFGV 1630 1640 1650 1660 1670 1680 SGQPSGFPDT SGETSGVTEL SGLSSGQPGV SGEASGVLYG TSQPFGITDL SGETSGVPDL 1690 1700 1710 1720 1730 1740 SGQPSGLPGF SGATSGVPDL VSGTTSGSGE SSGITFVDTS LVEVAPTTFK EEEGLGSVEL 1750 1760 1770 1780 1790 1800 SGLPSGEADL SGKSGMVDVS GQFSGTVDSS GFTSQTPEFS GLPSGIAEVS GESSRAEIGS 1810 1820 1830 1840 1850 1860 SLPSGAYYGS GTPSSFPTVS LVDRTLVESV TQAPTAQEAG EGPSGILELS GAHSGAPDMS 1870 1880 1890 1900 1910 1920 GEHSGFLDLS GLQSGLIEPS GEPPGTPYFS GDFASTTNVS GESSVAMGTS GEASGLPEVT 1930 1940 1950 1960 1970 1980 LITSEFVEGV TEPTISQELG QRPPVTHTPQ LFESSGKVST AGDISGATPV LPGSGVEVSS 1990 2000 2010 2020 2030 2040 VPESSSETSA YPEAGFGASA APEASREDSG SPDLSETTSA FHEANLERSS GLGVSGSTLT 2050 2060 2070 2080 2090 2100 FQEGEASAAP EVSGESTTTS DVGTEAPGLP SATPTASGDR TEISGDLSGH TSQLGVVIST 2110 2120 2130 2140 2150 2160 SIPESEWTQQ TQRPAETHLE IESSSLLYSG EETHTVETAT SPTDASIPAS PEWKRESEST 2170 2180 2190 2200 2210 2220 AADQEVCEEG WNKYQGHCYR HFPDRETWVD AERRCREQQS HLSSIVTPEE QEFVNNNAQD 2230 2240 2250 2260 2270 2280 YQWIGLNDRT IEGDFRWSDG HPMQFENWRP NQPDNFFAAG EDCVVMIWHE KGEWNDVPCN 2290 2300 2310 YHLPFTCKKG TATTYKRRLQ KRSSRHPRRS RPSTAH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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, MASS SPECTROMETRY. 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.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Aggrecan

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00793748. IPI00923424. IPI00923437.
PIR	A39086.
UniGene	Hs.2159. Hs.616395.
3D structure databases
ProteinModelPortal	P16112.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000268134.
PTM databases
PhosphoSite	P16112.
Polymorphism databases
DMDM	129886.
Proteomic databases
PaxDb	P16112.
PRIDE	P16112.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
GeneCards	GC15P089346.
H-InvDB	HIX0026812.
HGNC	HGNC:319. ACAN.
HPA	CAB016377.
MIM	155760. gene. 165800. phenotype. 608361. phenotype. 612813. phenotype.
neXtProt	NX_P16112.
Orphanet	251262. Familial osteochondritis dissecans. 171866. Spondyloepimetaphyseal dysplasia, aggrecan type. 93283. Spondyloepiphyseal dysplasia, Kimberley type.
PharmGKB	PA24616.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG12793.
HOGENOM	HOG000168421.
HOVERGEN	HBG007982.
InParanoid	P16112.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_116125. Disease.
Gene expression databases
CleanEx	HS_ACAN.
Genevestigator	P16112.
GermOnline	ENSG00000157766. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit. 3.10.100.10. 5 hits.
InterPro	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]
Pfam	PF00008. EGF. 1 hit. PF00059. Lectin_C. 1 hit. PF00084. Sushi. 1 hit. PF07686. V-set. 1 hit. PF00193. Xlink. 4 hits. [Graphical view]
PRINTS	PR01265. LINKMODULE.
SMART	SM00032. CCP. 1 hit. SM00034. CLECT. 1 hit. SM00181. EGF. 1 hit. SM00409. IG. 1 hit. SM00445. LINK. 4 hits. [Graphical view]
SUPFAM	SSF56436. C-type_lectin_fold. 5 hits. SSF57535. Complement_control_module. 1 hit.
PROSITE	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]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2904.
ChiTaRS	ACAN. human.
PMAP-CutDB	P16112.
SOURCE	Search...

Entry information

Entry name

PGCA_HUMAN

Accession

Primary (citable) accession number: P16112
Secondary accession number(s): Q13650 , Q9UCD3, Q9UCP4, Q9UCP5, Q9UDE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	August 1, 1992
Last modified:	May 1, 2013
This is version 156 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.