Details of Drug Off-Target (DOT)

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

• DOT Name: P protein (OCA2)
• Synonyms: Melanocyte-specific transporter protein; Pink-eyed dilution protein homolog
• Gene Name: OCA2
• Related Disease:
  Metabolic disorder
  Oculocutaneous albinism type 2
  Adult glioblastoma
  Age-related macular degeneration
  Albinism
  Alzheimer disease
  Amyloidosis
  Angelman syndrome
  Autoimmune disease
  Autosomal recessive ocular albinism
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Chromosomal disorder
  Colorectal carcinoma
  Cutaneous melanoma
  Cutaneous squamous cell carcinoma
  Depression
  Familial hypercholesterolemia
  Glioblastoma multiforme
  Hepatitis B virus infection
  Hermansky-Pudlak syndrome
  Hypopigmentation of the skin
  Lung adenocarcinoma
  Lung neoplasm
  Lupus
  Melanoma
  Neoplasm
  Non-insulin dependent diabetes
  Ocular albinism
  Prader-Willi syndrome
  Rabies
  Skin cancer
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Glycine encephalopathy
  Hepatocellular carcinoma
  Neuroblastoma
  Advanced cancer
  Anxiety
  Anxiety disorder
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Uveal Melanoma
• UniProt ID: P_HUMAN
• Pfam ID: PF03600
• Sequence:
  MHLEGRDGRRYPGAPAVELLQTSVPSGLAELVAGKRRLPRGAGGADPSHSCPRGAAGQSS
  WAPAGQEFASFLTKGRSHSSLPQMSSSRSKDSCFTENTPLLRNSLQEKGSRCIPVYHPEF
  ITAEESWEDSSADWERRYLLSREVSGLSASASSEKGDLLDSPHIRLRLSKLRRCVQWLKV
  MGLFAFVVLCSILFSLYPDQGKLWQLLALSPLENYSVNLSSHVDSTLLQVDLAGALVASG
  PSRPGREEHIVVELTQADALGSRWRRPQQVTHNWTVYLNPRRSEHSVMSRTFEVLTRETV
  SISIRASLQQTQAVPLLMAHQYLRGSVETQVTIATAILAGVYALIIFEIVHRTLAAMLGS
  LAALAALAVIGDRPSLTHVVEWIDFETLALLFGMMILVAIFSETGFFDYCAVKAYRLSRG
  RVWAMIIMLCLIAAVLSAFLDNVTTMLLFTPVTIRLCEVLNLDPRQVLIAEVIFTNIGGA
  ATAIGDPPNVIIVSNQELRKMGLDFAGFTAHMFIGICLVLLVCFPLLRLLYWNRKLYNKE
  PSEIVELKHEIHVWRLTAQRISPASREETAVRRLLLGKVLALEHLLARRLHTFHRQISQE
  DKNWETNIQELQKKHRISDGILLAKCLTVLGFVIFMFFLNSFVPGIHLDLGWIAILGAIW
  LLILADIHDFEIILHRVEWATLLFFAALFVLMEALAHLHLIEYVGEQTALLIKMVPEEQR
  LIAAIVLVVWVSALASSLIDNIPFTATMIPVLLNLSHDPEVGLPAPPLMYALAFGACLGG
  NGTLIGASANVVCAGIAEQHGYGFSFMEFFRLGFPMMVVSCTVGMCYLLVAHVVVGWN
• Function: Contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation. One of the components of the mammalian pigmentary system. May serve as a key control point at which ethnic skin color variation is determined. Major determinant of brown and/or blue eye color. Seems to regulate the post-translational processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis.
• Tissue Specificity: Expressed in melanocytes and retinal pigment epithelium.
• Reactome Pathway: Melanin biosynthesis (R-HSA-5662702)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[1]
Oculocutaneous albinism type 2	DISMTYMP	Definitive	Autosomal recessive	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[4]
Albinism	DIS5D82I	Strong	Genetic Variation	[5]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[6]
Amyloidosis	DISHTAI2	Strong	Altered Expression	[6]
Angelman syndrome	DIS4QVXO	Strong	Biomarker	[7]
Autoimmune disease	DISORMTM	Strong	Biomarker	[8]
Autosomal recessive ocular albinism	DISBXXVG	Strong	Genetic Variation	[9]
B-cell neoplasm	DISVY326	Strong	Biomarker	[10]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[11]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[11]
Cervical cancer	DISFSHPF	Strong	Biomarker	[12]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[12]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[14]
Cutaneous melanoma	DIS3MMH9	Strong	Genetic Variation	[15]
Cutaneous squamous cell carcinoma	DIS3LXUG	Strong	Genetic Variation	[16]
Depression	DIS3XJ69	Strong	Biomarker	[17]
Familial hypercholesterolemia	DISC06IX	Strong	Genetic Variation	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[18]
Hermansky-Pudlak syndrome	DISCY0HQ	Strong	Biomarker	[5]
Hypopigmentation of the skin	DIS39YKC	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[19]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[20]
Lupus	DISOKJWA	Strong	Biomarker	[21]
Melanoma	DIS1RRCY	Strong	Biomarker	[22]
Neoplasm	DISZKGEW	Strong	Altered Expression	[23]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[24]
Ocular albinism	DIS5IHK1	Strong	Genetic Variation	[25]
Prader-Willi syndrome	DISYWMLU	Strong	Biomarker	[7]
Rabies	DISSC4V5	Strong	Biomarker	[26]
Skin cancer	DISTM18U	Strong	Genetic Variation	[16]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[27]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[28]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[21]
Glycine encephalopathy	DISI2XE5	moderate	Biomarker	[29]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[30]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[31]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[12]
Anxiety	DISIJDBA	Limited	Altered Expression	[32]
Anxiety disorder	DISBI2BT	Limited	Altered Expression	[32]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[33]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[34]
Uveal Melanoma	DISA7ZGL	Limited	Genetic Variation	[35]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	P protein (OCA2) affects the response to substance of Etoposide.	[42]

4 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 P protein (OCA2).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of P protein (OCA2).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of P protein (OCA2).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of P protein (OCA2).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of P protein (OCA2).	[38]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of P protein (OCA2).	[41]

References

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