Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUOCW8K)

• DOT Name: Aggrecan core protein (ACAN)
• Synonyms: Cartilage-specific proteoglycan core protein; CSPCP; Chondroitin sulfate proteoglycan core protein 1; Chondroitin sulfate proteoglycan 1
• Gene Name: ACAN
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Osteochondritis dissecans
  Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans
  Spondyloepimetaphyseal dysplasia, aggrecan type
  Spondyloepiphyseal dysplasia, Kimberley type
  Stroke
  Amyloidosis
  Arteriosclerosis
  Arthritis
  Atherosclerosis
  Autism spectrum disorder
  Autoimmune disease
  Brachydactyly
  Cardiovascular disease
  Chondrosarcoma
  Colon cancer
  Developmental and epileptic encephalopathy, 39
  facioscapulohumeral muscular dystrophy
  Lhermitte-Duclos disease
  Malignant soft tissue neoplasm
  Neoplasm
  Obesity
  Osteoarthritis
  Osteochondrodysplasia
  Pneumoconiosis
  Polycystic ovarian syndrome
  Pseudoachondroplasia
  Rheumatoid arthritis
  Sarcoma
  Schizophrenia
  Spondylitis
  Spondyloepiphyseal dysplasia
  Spondyloepiphyseal dysplasia congenita
  Type 2 collagenopathy
  Type-1 diabetes
  Spondyloarthropathy
  Short stature-advanced bone age-early-onset osteoarthritis syndrome
  Dowling-Degos disease
  Hepatocellular carcinoma
  Spondyloepimetaphyseal dysplasia
  Status epilepticus seizure
• UniProt ID: PGCA_HUMAN
• PDB ID: 4MD4; 7RDV
• Pfam ID: PF00059 ; PF00084 ; PF07686 ; PF00193
• Sequence:
  MTTLLWVFVTLRVITAAVTVETSDHDNSLSVSIPQPSPLRVLLGTSLTIPCYFIDPMHPV
  TTAPSTAPLAPRIKWSRVSKEKEVVLLVATEGRVRVNSAYQDKVSLPNYPAIPSDATLEV
  QSLRSNDSGVYRCEVMHGIEDSEATLEVVVKGIVFHYRAISTRYTLDFDRAQRACLQNSA
  IIATPEQLQAAYEDGFHQCDAGWLADQTVRYPIHTPREGCYGDKDEFPGVRTYGIRDTNE
  TYDVYCFAEEMEGEVFYATSPEKFTFQEAANECRRLGARLATTGQLYLAWQAGMDMCSAG
  WLADRSVRYPISKARPNCGGNLLGVRTVYVHANQTGYPDPSSRYDAICYTGEDFVDIPEN
  FFGVGGEEDITVQTVTWPDMELPLPRNITEGEARGSVILTVKPIFEVSPSPLEPEEPFTF
  APEIGATAFAEVENETGEATRPWGFPTPGLGPATAFTSEDLVVQVTAVPGQPHLPGGVVF
  HYRPGPTRYSLTFEEAQQACLRTGAVIASPEQLQAAYEAGYEQCDAGWLRDQTVRYPIVS
  PRTPCVGDKDSSPGVRTYGVRPSTETYDVYCFVDRLEGEVFFATRLEQFTFQEALEFCES
  HNATLATTGQLYAAWSRGLDKCYAGWLADGSLRYPIVTPRPACGGDKPGVRTVYLYPNQT
  GLPDPLSRHHAFCFRGISAVPSPGEEEGGTPTSPSGVEEWIVTQVVPGVAAVPVEEETTA
  VPSGETTAILEFTTEPENQTEWEPAYTPVGTSPLPGILPTWPPTGAATEESTEGPSATEV
  PSASEEPSPSEVPFPSEEPSPSEEPFPSVRPFPSVELFPSEEPFPSKEPSPSEEPSASEE
  PYTPSPPVPSWTELPSSGEESGAPDVSGDFTGSGDVSGHLDFSGQLSGDRASGLPSGDLD
  SSGLTSTVGSGLPVESGLPSGDEERIEWPSTPTVGELPSGAEILEGSASGVGDLSGLPSG
  EVLETSASGVGDLSGLPSGEVLETTAPGVEDISGLPSGEVLETTAPGVEDISGLPSGEVL
  ETTAPGVEDISGLPSGEVLETTAPGVEDISGLPSGEVLETTAPGVEDISGLPSGEVLETT
  APGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPG
  VEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVED
  ISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISG
  LPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPS
  GEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEV
  LETAAPGVEDISGLPSGEVLETTAPGVEEISGLPSGEVLETTAPGVDEISGLPSGEVLET
  TAPGVEEISGLPSGEVLETSTSAVGDLSGLPSGGEVLEISVSGVEDISGLPSGEVVETSA
  SGIEDVSELPSGEGLETSASGVEDLSRLPSGEEVLEISASGFGDLSGLPSGGEGLETSAS
  EVGTDLSGLPSGREGLETSASGAEDLSGLPSGKEDLVGSASGDLDLGKLPSGTLGSGQAP
  ETSGLPSGFSGEYSGVDLGSGPPSGLPDFSGLPSGFPTVSLVDSTLVEVVTASTASELEG
  RGTIGISGAGEISGLPSSELDISGRASGLPSGTELSGQASGSPDVSGEIPGLFGVSGQPS
  GFPDTSGETSGVTELSGLSSGQPGISGEASGVLYGTSQPFGITDLSGETSGVPDLSGQPS
  GLPGFSGATSGVPDLVSGTTSGSGESSGITFVDTSLVEVAPTTFKEEEGLGSVELSGLPS
  GEADLSGKSGMVDVSGQFSGTVDSSGFTSQTPEFSGLPSGIAEVSGESSRAEIGSSLPSG
  AYYGSGTPSSFPTVSLVDRTLVESVTQAPTAQEAGEGPSGILELSGAHSGAPDMSGEHSG
  FLDLSGLQSGLIEPSGEPPGTPYFSGDFASTTNVSGESSVAMGTSGEASGLPEVTLITSE
  FVEGVTEPTISQELGQRPPVTHTPQLFESSGKVSTAGDISGATPVLPGSGVEVSSVPESS
  SETSAYPEAGFGASAAPEASREDSGSPDLSETTSAFHEANLERSSGLGVSGSTLTFQEGE
  ASAAPEVSGESTTTSDVGTEAPGLPSATPTASGDRTEISGDLSGHTSQLGVVISTSIPES
  EWTQQTQRPAETHLEIESSSLLYSGEETHTVETATSPTDASIPASPEWKRESESTAAAPA
  RSCAEEPCGAGTCKETEGHVICLCPPGYTGEHCNIDQEVCEEGWNKYQGHCYRHFPDRET
  WVDAERRCREQQSHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPMQFEN
  WRPNQPDNFFAAGEDCVVMIWHEKGEWNDVPCNYHLPFTCKKGTVACGEPPVVEHARTFG
  QKKDRYEINSLVRYQCTEGFVQRHMPTIRCQPSGHWEEPQITCTDPTTYKRRLQKRSSRH
  PRRSRPSTAH
• 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.
• Tissue Specificity: Detected in fibroblasts (at protein level) . Restricted to cartilage .
• Reactome Pathway:
  Keratan sulfate biosynthesis (R-HSA-2022854)
  Keratan sulfate degradation (R-HSA-2022857)
  ECM proteoglycans (R-HSA-3000178)
  Defective CHST6 causes MCDC1 (R-HSA-3656225)
  Defective ST3GAL3 causes MCT12 and EIEE15 (R-HSA-3656243)
  Defective B4GALT1 causes B4GALT1-CDG (CDG-2d) (R-HSA-3656244)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Definitive	Biomarker	[1]
Congestive heart failure	DIS32MEA	Definitive	Biomarker	[1]
Osteochondritis dissecans	DIS1FGN4	Definitive	Autosomal dominant	[2]
Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans	DISNSYSS	Definitive	Autosomal dominant	[3]
Spondyloepimetaphyseal dysplasia, aggrecan type	DISPS9HT	Definitive	Autosomal recessive	[4]
Spondyloepiphyseal dysplasia, Kimberley type	DISVYROI	Definitive	Autosomal dominant	[4]
Stroke	DISX6UHX	Definitive	Therapeutic	[5]
Amyloidosis	DISHTAI2	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[7]
Arthritis	DIST1YEL	Strong	Biomarker	[8]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[7]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[9]
Autoimmune disease	DISORMTM	Strong	Biomarker	[10]
Brachydactyly	DIS2533F	Strong	Genetic Variation	[11]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[12]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[13]
Colon cancer	DISVC52G	Strong	Altered Expression	[14]
Developmental and epileptic encephalopathy, 39	DISA15DM	Strong	Biomarker	[15]
facioscapulohumeral muscular dystrophy	DISSE0H0	Strong	Biomarker	[16]
Lhermitte-Duclos disease	DIS87XW7	Strong	Genetic Variation	[17]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Osteoarthritis	DIS05URM	Strong	Biomarker	[21]
Osteochondrodysplasia	DIS9SPWW	Strong	Biomarker	[22]
Pneumoconiosis	DISSJLBN	Strong	Biomarker	[23]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[12]
Pseudoachondroplasia	DISVJW4A	Strong	Altered Expression	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Sarcoma	DISZDG3U	Strong	Biomarker	[18]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[26]
Spondylitis	DIS3HV6E	Strong	Biomarker	[27]
Spondyloepiphyseal dysplasia	DIS1JG9A	Strong	Genetic Variation	[28]
Spondyloepiphyseal dysplasia congenita	DISLC6W8	Strong	Genetic Variation	[28]
Type 2 collagenopathy	DIS8WIDY	Strong	Biomarker	[29]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[30]
Spondyloarthropathy	DISBPYCZ	moderate	Biomarker	[31]
Short stature-advanced bone age-early-onset osteoarthritis syndrome	DISPA71J	Supportive	Autosomal dominant	[2]
Dowling-Degos disease	DISGTTEP	Limited	Biomarker	[32]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[33]
Spondyloepimetaphyseal dysplasia	DISO4L5A	Limited	Genetic Variation	[34]
Status epilepticus seizure	DISY3BIC	Limited	Biomarker	[35]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Aggrecan core protein (ACAN).	[36]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Aggrecan core protein (ACAN).	[37]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Aggrecan core protein (ACAN).	[38]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Aggrecan core protein (ACAN).	[39]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Aggrecan core protein (ACAN).	[40]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of Aggrecan core protein (ACAN).	[41]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Aggrecan core protein (ACAN).	[42]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Aggrecan core protein (ACAN).	[43]
Diacerein	DMN2Q5I	Phase 4	Diacerein increases the expression of Aggrecan core protein (ACAN).	[44]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Aggrecan core protein (ACAN).	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Aggrecan core protein (ACAN).	[47]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Aggrecan core protein (ACAN).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Aggrecan core protein (ACAN).	[46]

References

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