Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVIRKW7)

• DOT Name: SH3 domain-binding protein 4 (SH3BP4)
• Synonyms: EH-binding protein 10; Transferrin receptor-trafficking protein
• Gene Name: SH3BP4
• Related Disease:
  Autism
  Bacteremia
  Intellectual disability
  Adenoma
  Adult lymphoma
  Advanced cancer
  Arthritis
  Autoimmune disease
  Breast cancer
  Cystic fibrosis
  Disseminated intravascular coagulation
  Endometriosis
  Familial isolated deficiency of vitamin E
  Glioblastoma multiforme
  Head-neck squamous cell carcinoma
  Hemolytic-uremic syndrome
  Hepatocellular carcinoma
  Isolated cleft lip
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lymphoma
  Neoplasm
  Pancreatic cancer
  Pediatric lymphoma
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Retinitis pigmentosa
  Retinoblastoma
  Rheumatoid arthritis
  Smallpox
  Carcinoma of liver and intrahepatic biliary tract
  Head and neck cancer
  Head and neck carcinoma
  Invasive breast carcinoma
  Liver cancer
  Small lymphocytic lymphoma
  Thrombocytopenia
  Thrombotic microangiopathy
  Congenital thrombotic thrombocytopenic purpura
  Astrocytoma
  Breast carcinoma
  Stroke
  Thrombotic thrombocytopenic purpura
• UniProt ID: SH3B4_HUMAN
• Pfam ID: PF00018 ; PF07653 ; PF00791
• Sequence:
  MAAQRIRAANSNGLPRCKSEGTLIDLSEGFSETSFNDIKVPSPSALLVDNPTPFGNAKEV
  IAIKDYCPTNFTTLKFSKGDHLYVLDTSGGEWWYAHNTTEMGYIPSSYVQPLNYRNSTLS
  DSGMIDNLPDSPDEVAKELELLGGWTDDKKVPGRMYSNNPFWNGVQTNPFLNGNVPVMPS
  LDELNPKSTVDLLLFDAGTSSFTESSSATTNSTGNIFDELPVTNGLHAEPPVRRDNPFFR
  SKRSYSLSELSVLQAKSDAPTSSSFFTGLKSPAPEQFQSREDFRTAWLNHRKLARSCHDL
  DLLGQSPGWGQTQAVETNIVCKLDSSGGAVQLPDTSISIHVPEGHVAPGETQQISMKALL
  DPPLELNSDRSCSISPVLEVKLSNLEVKTSIILEMKVSAEIKNDLFSKSTVGLQCLRSDS
  KEGPYVSVPLNCSCGDTVQAQLHNLEPCMYVAVVAHGPSILYPSTVWDFINKKVTVGLYG
  PKHIHPSFKTVVTIFGHDCAPKTLLVSEVTRQAPNPAPVALQLWGKHQFVLSRPQDLKVC
  MFSNMTNYEVKASEQAKVVRGFQLKLGKVSRLIFPITSQNPNELSDFTLRVQVKDDQEAI
  LTQFCVQTPQPPPKSAIKPSGQRRFLKKNEVGKIILSPFATTTKYPTFQDRPVSSLKFGK
  LLKTVVRQNKNHYLLEYKKGDGIALLSEERVRLRGQLWTKEWYIGYYQGRVGLVHTKNVL
  VVGRARPSLCSGPELSTSVLLEQILRPCKFLTYIYASVRTLLMENISSWRSFADALGYVN
  LPLTFFCRAELDSEPERVASVLEKLKEDCNNTENKERKSFQKELVMALLKMDCQGLVVRL
  IQDFVLLTTAVEVAQRWRELAEKLAKVSKQQMDAYESPHRDRNGVVDSEAMWKPAYDFLL
  TWSHQIGDSYRDVIQELHLGLDKMKNPITKRWKHLTGTLILVNSLDVLRAAAFSPADQDD
  FVI
• Function: May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy.
• Tissue Specificity: Expressed in all tissues tested with higher expression in pancreas. Expressed by retinal pigment epithelial cells (at protein level).
• Reactome Pathway: Amino acids regulate mTORC1 (R-HSA-9639288)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Biomarker	[1]
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[2]
Intellectual disability	DISMBNXP	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[3]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Arthritis	DIST1YEL	Strong	Biomarker	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[9]
Disseminated intravascular coagulation	DISCAVOZ	Strong	Biomarker	[10]
Endometriosis	DISX1AG8	Strong	Biomarker	[11]
Familial isolated deficiency of vitamin E	DIS53306	Strong	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[13]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[14]
Hemolytic-uremic syndrome	DISSCBGW	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[17]
leukaemia	DISS7D1V	Strong	Biomarker	[18]
Leukemia	DISNAKFL	Strong	Biomarker	[18]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Lymphoma	DISN6V4S	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Pancreatic cancer	DISJC981	Strong	Biomarker	[19]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[4]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[20]
Prostate cancer	DISF190Y	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Psoriasis	DIS59VMN	Strong	Biomarker	[6]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[21]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[22]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[23]
Smallpox	DIS9EABZ	Strong	Biomarker	[24]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Posttranslational Modification	[25]
Head and neck cancer	DISBPSQZ	moderate	Biomarker	[26]
Head and neck carcinoma	DISOU1DS	moderate	Biomarker	[26]
Invasive breast carcinoma	DISANYTW	moderate	Altered Expression	[27]
Liver cancer	DISDE4BI	moderate	Posttranslational Modification	[25]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[28]
Thrombocytopenia	DISU61YW	moderate	Biomarker	[10]
Thrombotic microangiopathy	DISLZ0VW	moderate	Biomarker	[10]
Congenital thrombotic thrombocytopenic purpura	DISC8GS9	Disputed	Genetic Variation	[29]
Astrocytoma	DISL3V18	Limited	Genetic Variation	[13]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[8]
Stroke	DISX6UHX	Limited	Biomarker	[30]
Thrombotic thrombocytopenic purpura	DIS3LDOU	Limited	Genetic Variation	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of SH3 domain-binding protein 4 (SH3BP4).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of SH3 domain-binding protein 4 (SH3BP4).	[42]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of SH3 domain-binding protein 4 (SH3BP4).	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SH3 domain-binding protein 4 (SH3BP4).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SH3 domain-binding protein 4 (SH3BP4).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SH3 domain-binding protein 4 (SH3BP4).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SH3 domain-binding protein 4 (SH3BP4).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SH3 domain-binding protein 4 (SH3BP4).	[36]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of SH3 domain-binding protein 4 (SH3BP4).	[37]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of SH3 domain-binding protein 4 (SH3BP4).	[38]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of SH3 domain-binding protein 4 (SH3BP4).	[39]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of SH3 domain-binding protein 4 (SH3BP4).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of SH3 domain-binding protein 4 (SH3BP4).	[32]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of SH3 domain-binding protein 4 (SH3BP4).	[41]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of SH3 domain-binding protein 4 (SH3BP4).	[44]

References

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