Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTK22NO)

• DOT Name: A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2)
• Synonyms: ADAM-TS 2; ADAM-TS2; ADAMTS-2; EC 3.4.24.14; Procollagen I N-proteinase; PC I-NP; Procollagen I/II amino propeptide-processing enzyme; Procollagen N-endopeptidase; pNPI
• Gene Name: ADAMTS2
• Related Disease:
  Anxiety
  Attention deficit hyperactivity disorder
  Delirium
  Ehlers-Danlos syndrome, dermatosparaxis type
  Language disorder
  Prostatitis
  Advanced cancer
  Alzheimer disease
  Anxiety disorder
  Atopic dermatitis
  Bone osteosarcoma
  Brain disease
  Breast cancer
  Breast carcinoma
  Chondrosarcoma
  Clear cell renal carcinoma
  Connective tissue disorder
  Cornea plana
  Dementia
  Depression
  Ehlers-Danlos syndrome
  Estrogen-receptor positive breast cancer
  Malignant mesothelioma
  Metastatic malignant neoplasm
  Mixed phenotype acute leukemia
  Myopia
  Nail-patella syndrome
  Neoplasm
  Non-insulin dependent diabetes
  Osteosarcoma
  Renal cell carcinoma
  Schizophrenia
  Sleep apnea syndrome
  Stomach cancer
  Frontotemporal dementia
  Stroke
  Cardiomyopathy
  Psychotic disorder
  Rheumatic disorder
• UniProt ID: ATS2_HUMAN
• EC Number: 3.4.24.14
• Pfam ID: PF17771 ; PF19236 ; PF05986 ; PF01562 ; PF01421 ; PF19030 ; PF00090
• Sequence:
  MDPPAGAARRLLCPALLLLLLLLPPPLLPPPPPPANARLAAAADPPGGPLGHGAERILAV
  PVRTDAQGRLVSHVVSAATSRAGVRARRAAPVRTPSFPGGNEEEPGSHLFYNVTVFGRDL
  HLRLRPNARLVAPGATMEWQGEKGTTRVEPLLGSCLYVGDVAGLAEASSVALSNCDGLAG
  LIRMEEEEFFIEPLEKGLAAQEAEQGRVHVVYRRPPTSPPLGGPQALDTGASLDSLDSLS
  RALGVLEEHANSSRRRARRHAADDDYNIEVLLGVDDSVVQFHGKEHVQKYLLTLMNIVNE
  IYHDESLGAHINVVLVRIILLSYGKSMSLIEIGNPSQSLENVCRWAYLQQKPDTGHDEYH
  DHAIFLTRQDFGPSGMQGYAPVTGMCHPVRSCTLNHEDGFSSAFVVAHETGHVLGMEHDG
  QGNRCGDEVRLGSIMAPLVQAAFHRFHWSRCSQQELSRYLHSYDCLLDDPFAHDWPALPQ
  LPGLHYSMNEQCRFDFGLGYMMCTAFRTFDPCKQLWCSHPDNPYFCKTKKGPPLDGTMCA
  PGKHCFKGHCIWLTPDILKRDGSWGAWSPFGSCSRTCGTGVKFRTRQCDNPHPANGGRTC
  SGLAYDFQLCSRQDCPDSLADFREEQCRQWDLYFEHGDAQHHWLPHEHRDAKERCHLYCE
  SRETGEVVSMKRMVHDGTRCSYKDAFSLCVRGDCRKVGCDGVIGSSKQEDKCGVCGGDNS
  HCKVVKGTFTRSPKKHGYIKMFEIPAGARHLLIQEVDATSHHLAVKNLETGKFILNEEND
  VDASSKTFIAMGVEWEYRDEDGRETLQTMGPLHGTITVLVIPVGDTRVSLTYKYMIHEDS
  LNVDDNNVLEEDSVVYEWALKKWSPCSKPCGGGSQFTKYGCRRRLDHKMVHRGFCAALSK
  PKAIRRACNPQECSQPVWVTGEWEPCSQTCGRTGMQVRSVRCIQPLHDNTTRSVHAKHCN
  DARPESRRACSRELCPGRWRAGPWSQCSVTCGNGTQERPVLCRTADDSFGICQEERPETA
  RTCRLGPCPRNISDPSKKSYVVQWLSRPDPDSPIRKISSKGHCQGDKSIFCRMEVLSRYC
  SIPGYNKLCCKSCNLYNNLTNVEGRIEPPPGKHNDIDVFMPTLPVPTVAMEVRPSPSTPL
  EVPLNASSTNATEDHPETNAVDEPYKIHGLEDEVQPPNLIPRRPSPYEKTRNQRIQELID
  EMRKKEMLGKF
• Function: Cleaves the propeptides of type I and II collagen prior to fibril assembly. Does not act on type III collagen. Cleaves lysyl oxidase LOX at a site downstream of its propeptide cleavage site to produce a short LOX form with reduced collagen-binding activity.
• Tissue Specificity: Expressed at high level in skin, bone, tendon and aorta and at low levels in thymus and brain.
• Reactome Pathway:
  Defective B3GALTL causes PpS (R-HSA-5083635)
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Definitive	Biomarker	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Definitive	Biomarker	[2]
Delirium	DIS2OKP1	Definitive	Biomarker	[1]
Ehlers-Danlos syndrome, dermatosparaxis type	DISRDFCX	Definitive	Autosomal recessive	[3]
Language disorder	DISTLKP7	Definitive	Biomarker	[1]
Prostatitis	DISL8OGN	Definitive	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[1]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[7]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[8]
Brain disease	DIS6ZC3X	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Connective tissue disorder	DISKXBS3	Strong	Biomarker	[12]
Cornea plana	DISE38HI	Strong	Biomarker	[12]
Dementia	DISXL1WY	Strong	Biomarker	[13]
Depression	DIS3XJ69	Strong	Biomarker	[14]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Genetic Variation	[15]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[16]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[18]
Mixed phenotype acute leukemia	DISNCHV9	Strong	Biomarker	[19]
Myopia	DISK5S60	Strong	Biomarker	[12]
Nail-patella syndrome	DIS8C4CT	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[21]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[8]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Schizophrenia	DISSRV2N	Strong	Biomarker	[6]
Sleep apnea syndrome	DISER6KS	Strong	Biomarker	[22]
Stomach cancer	DISKIJSX	Strong	Biomarker	[23]
Frontotemporal dementia	DISKYHXL	moderate	Biomarker	[24]
Stroke	DISX6UHX	moderate	Genetic Variation	[25]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[26]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[27]
Rheumatic disorder	DIS77ACK	Limited	Genetic Variation	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[31]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[32]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[33]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[30]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[34]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2).	[30]

References

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