Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVIHD77)

• DOT Name: Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1)
• Synonyms: 620 kDa actin-binding protein; ABP620; Actin cross-linking family protein 7; Macrophin-1; Trabeculin-alpha
• Gene Name: MACF1
• Related Disease:
  Adult glioblastoma
  Alzheimer disease
  Bone disease
  Breast cancer
  Breast carcinoma
  Colitis
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Congenital myasthenic syndrome
  Glioblastoma multiforme
  Intellectual disability
  Intestinal disorder
  Juvenile hyaline fibromatosis
  Lissencephaly 9 with complex brainstem malformation
  Lissencephaly spectrum disorders
  Neoplasm
  Neuromuscular disease
  Non-insulin dependent diabetes
  Parkinson disease
  Peripheral arterial disease
  Renal cell carcinoma
  Schizophrenia
  Ulcerative colitis
  Advanced cancer
  Lissencephaly spectrum disorder with complex brainstem malformation
  Small-cell lung cancer
  Brain neoplasm
  Osteoporosis
• UniProt ID: MACF1_HUMAN
• PDB ID: 4Z6G; 5VE9; 5X57
• Pfam ID: PF00307 ; PF13499 ; PF02187 ; PF00681 ; PF17902 ; PF00435 ; PF18373 ; PF21019 ; PF21020 ; PF21097
• Sequence:
  MSSSDEETLSERSCRSERSCRSERSYRSERSGSLSPCPPGDTLPWNLPLHEQKKRKSQDS
  VLDPAERAVVRVADERDRVQKKTFTKWVNKHLMKVRKHINDLYEDLRDGHNLISLLEVLS
  GIKLPREKGRMRFHRLQNVQIALDFLKQRQVKLVNIRNDDITDGNPKLTLGLIWTIILHF
  QISDIYISGESGDMSAKEKLLLWTQKVTAGYTGIKCTNFSSCWSDGKMFNALIHRYRPDL
  VDMERVQIQSNRENLEQAFEVAERLGVTRLLDAEDVDVPSPDEKSVITYVSSIYDAFPKV
  PEGGEGISATEVDSRWQEYQSRVDSLIPWIKQHTILMSDKTFPQNPVELKALYNQYIHFK
  ETEILAKEREKGRIEELYKLLEVWIEFGRIKLPQGYHPNDVEEEWGKLIIEMLEREKSLR
  PAVERLELLLQIANKIQNGALNCEEKLTLAKNTLQADAAHLESGQPVQCESDVIMYIQEC
  EGLIRQLQVDLQILRDENYYQLEELAFRVMRLQDELVTLRLECTNLYRKGHFTSLELVPP
  STLTTTHLKAEPLTKATHSSSTSWFRKPMTRAELVAISSSEDEGNLRFVYELLSWVEEMQ
  MKLERAEWGNDLPSVELQLETQQHIHTSVEELGSSVKEARLYEGKMSQNFHTSYAETLGK
  LETQYCKLKETSSFRMRHLQSLHKFVSRATAELIWLNEKEEEELAYDWSDNNSNISAKRN
  YFSELTMELEEKQDVFRSLQDTAELLSLENHPAKQTVEAYSAAVQSQLQWMKQLCLCVEQ
  HVKENTAYFQFFSDARELESFLRNLQDSIKRKYSCDHNTSLSRLEDLLQDSMDEKEQLIQ
  SKSSVASLVGRSKTIVQLKPRSPDHVLKNTISVKAVCDYRQIEITICKNDECVLEDNSQR
  TKWKVISPTGNEAMVPSVCFLIPPPNKDAIEMASRVEQSYQKVMALWHQLHVNTKSLISW
  NYLRKDLDLVQTWNLEKLRSSAPGECHQIMKNLQAHYEDFLQDSRDSVLFSVADRLRLEE
  EVEACKARFQHLMKSMENEDKEETVAKMYISELKNIRLRLEEYEQRVVKRIQSLASSRTD
  RDAWQDNALRIAEQEHTQEDLQQLRSDLDAVSMKCDSFLHQSPSSSSVPTLRSELNLLVE
  KMDHVYGLSTVYLNKLKTVDVIVRSIQDAELLVKGYEIKLSQEEVVLADLSALEAHWSTL
  RHWLSDVKDKNSVFSVLDEEIAKAKVVAEQMSRLTPERNLDLERYQEKGSQLQERWHRVI
  AQLEIRQSELESIQEVLGDYRACHGTLIKWIEETTAQQEMMKPGQAEDSRVLSEQLSQQT
  ALFAEIERNQTKLDQCQKFSQQYSTIVKDYELQLMTYKAFVESQQKSPGKRRRMLSSSDA
  ITQEFMDLRTRYTALVTLTTQHVKYISDALRRLEEEEKVVEEEKQEHVEKVKELLGWVST
  LARNTQGKATSSETKESTDIEKAILEQQVLSEELTTKKEQVSEAIKTSQIFLAKHGHKLS
  EKEKKQISEQLNALNKAYHDLCDGSANQLQQLQSQLAHQTEQKECRAVAGVIDLGTVEIF
  PIFKAMQKGLLDQDTGLVLLESQVIMSGLIAPETGENLSLEEGIARNLINPQMYQQLREL
  QDALALISRLTESRGPLSVVEAIEKRIISETVGLKILEAHLATGGFSLSPSENCINLEEA
  FHQGLISAWLHSVLESYLRTSKNLIDPNTAEKIGLLDLMQRCIVHQESGFKLLPVKQLAG
  GMVSLKSGRKVSIFRAVQEGLIDRQVTVRLLEAQLFAGGIVDPRTGHRLTVEEAVRHNLI
  DQDMACAILIRQLQTGGIIDTVTGQRLTIDEAVSNDLVAAKIALVILESLWSFMGLLWPE
  SGEILPITDALEQGIVSTELAHKILSNRQHIKALFLPATTEILSWKKAIESGILDRDLAN
  NLKSICIPDVMPHMQLADSAEQNINPGAAVLPCSKSHPKATASQSENLLFQLMTHSYINV
  QNGQRLLLLDKELMETLTSRDEYQTSPPKVVEIGHQRQKTPEGLQESANVKISGTFSSGW
  TVRLPEFQFSSQNKEYPDREDCTTEKGKKTTVETEDSSVENPEQDLFVEQKERNPNIDAL
  KVINKVKLEVQRQLIGTQREDQTAVSVRENASRGHLLTIPPAEAEGVPLVVDKDVFSVET
  PKKEHQPLRNTSFTCQNEQAHTLETEYIHDETGGSHIKPQSKKLQVQVKKTLGIKLELKS
  ETDGNVHPLDKKEMLKKTFLAKDDHKESQEAQNIAGGSMMMSEKTDEEDSGREIFLSCSH
  PLELLEEATLNVLSAQLLDGGIFHEQTGQKLLLNEAISRGIVPSHTAVKLMEKLNMFQGF
  FDSQTCESLTTEEVINEGLMDEKLLHNVLMADKAISGVLDPRTQTLCSVKDAVTVGLLDK
  ETATRILERQVVTGGIIDLKRGKKVSVTLASTLGLVDVADQPELINLEKASKGRDAEKTV
  RERLISLQMETTGLIDPDSKAPLTVVQSIDRGLLEREEAVRLLTKQVVDGGIIHHISGMR
  LSVDNAFRHGLIGEDLAEKLKRVENLNIHQIFNPETKENISLPKAIKLDLITSDLKREIQ
  EVQAFTGNFVDLISGQRLTLAEAKKEGLLTNEAVLSPGMMHGIVDPENCRIVPYSELVKK
  CKIDIESGQRYLEVIPFSDIKDGVSDKVLTLSQAIQLGKVDFASTLKVLEAQANTGGIID
  TATGKRLTLASALEEKLVDENMVRIIASHQVLNGGIVDIFSDQRVTLVEAIEKRLISPEL
  ANMIQIDSSEFSDHRAQIEKQEGIEVCALQNEFLGKDMLIACNQTAEMSCNKVEESERLF
  QVENQSAQEKVKVRVSDGEQAKKSREISLKEFGCKDQRKPRMSSDAKEFISIINPHNLKG
  KSLGQVSLTHPYSECDFKLKEVARNNMGNDTNEEQEKAVTKIEIISHMKQSTSCLDSEEI
  RENQGEVILEVQETYCETSGKLPSEQVLQQPMNARVKSKREKREVIVEESIRTCKPAFLS
  EEKLYQETAIRDEHDSHIKSQPREMTSSEKGKEADTEMGFSITFKIEESSSQVVPQGISV
  KHLDALTLFSSKQANEGKVNNLSLCLTLKPEENLSREIACGAQSEPFPCMTPRPEGLHYQ
  ESDGKAQVTGPSQISKTDKSFQGTTRQETNYQDSWVTSKTKETKHQISSSNECKEKSYQE
  VSFDPARGLKLEEITVSRPDSKEVRYLEFSDRKDLHHQGSKSDDKLCGTLKSEIATQELT
  GEKFLEMANPNVAGLEAGSIEDIVTQRGSRVLGSFLPEKLFKGVSQKENTGQQNAIISPT
  VLETSEEKTVSLTVCSAVKTEKTPQEKLRESPGSEQTPFMTAPEGKGNGGVNPEPFRATQ
  NVFTRQLCLEHDEKLVSYLSLLRNIEMRTKQIQPLELNLAELQDLLCQAKVLERELKDLT
  TLVSQELECVNQIIISQPQEVPAQLLKALEKDAKNLQKSLSSVSDTWNSRLLHFQNAVEI
  EKTKVLNQHTQLEGRLQDLRAWVGNKNLILNSKGSNSEIDVDSLNLCLQQYEDLKQPMAE
  RKAQLDALAFDIQFFISEHAQDLSPQQNRQMLRLLNELQRSFQDILEQTAAQVDALQGHL
  QQMEQEALVKTLQKQQNTCHQQLEDLCSWVGQAERALAGHQGRTTQQDLSALQKNQSDLK
  DLQDDIQNRATSFATVVKDIEGFMEENQTKLSPRELTALREKLHQAKEQYEALQEETRVA
  QKELEEAVTSALQQETEKSKAAKELAENKKKIDALLDWVTSVGSSGGQLLTNLPGMEQLS
  GASLEKGALDTTDGYMGVNQAPEKLDKQCEMMKARHQELLSQQQNFILATQSAQAFLDQH
  GHNLTPEEQQMLQQKLGELKEQYSTSLAQSEAELKQVQTLQDELQKFLQDHKEFESWLER
  SEKELENMHKGGSSPETLPSLLKRQGSFSEDVISHKGDLRFVTISGQKVLDMENSFKEGK
  EPSEIGNLVKDKLKDATERYTALHSKCTRLGSHLNMLLGQYHQFQNSADSLQAWMQACEA
  NVEKLLSDTVASDPGVLQEQLATTKQLQEELAEHQVPVEKLQKVARDIMEIEGEPAPDHR
  HVQETTDSILSHFQSLSYSLAERSSLLQKAIAQSQSVQESLESLLQSIGEVEQNLEGKQV
  SSLSSGVIQEALATNMKLKQDIARQKSSLEATREMVTRFMETADSTTAAVLQGKLAEVSQ
  RFEQLCLQQQEKESSLKKLLPQAEMFEHLSGKLQQFMENKSRMLASGNQPDQDITHFFQQ
  IQELNLEMEDQQENLDTLEHLVTELSSCGFALDLCQHQDRVQNLRKDFTELQKTVKEREK
  DASSCQEQLDEFRKLVRTFQKWLKETEGSIPPTETSMSAKELEKQIEHLKSLLDDWASKG
  TLVEEINCKGTSLENLIMEITAPDSQGKTGSILPSVGSSVGSVNGYHTCKDLTEIQCDMS
  DVNLKYEKLGGVLHERQESLQAILNRMEEVHKEANSVLQWLESKEEVLKSMDAMSSPTKT
  ETVKAQAESNKAFLAELEQNSPKIQKVKEALAGLLVTYPNSQEAENWKKIQEELNSRWER
  ATEVTVARQRQLEESASHLACFQAAESQLRPWLMEKELMMGVLGPLSIDPNMLNAQKQQV
  QFMLKEFEARRQQHEQLNEAAQGILTGPGDVSLSTSQVQKELQSINQKWVELTDKLNSRS
  SQIDQAIVKSTQYQELLQDLSEKVRAVGQRLSVQSAISTQPEAVKQQLEETSEIRSDLEQ
  LDHEVKEAQTLCDELSVLIGEQYLKDELKKRLETVALPLQGLEDLAADRINRLQAALAST
  QQFQQMFDELRTWLDDKQSQQAKNCPISAKLERLQSQLQENEEFQKSLNQHSGSYEVIVA
  EGESLLLSVPPGEEKRTLQNQLVELKNHWEELSKKTADRQSRLKDCMQKAQKYQWHVEDL
  VPWIEDCKAKMSELRVTLDPVQLESSLLRSKAMLNEVEKRRSLLEILNSAADILINSSEA
  DEDGIRDEKAGINQNMDAVTEELQAKTGSLEEMTQRLREFQESFKNIEKKVEGAKHQLEI
  FDALGSQACSNKNLEKLRAQQEVLQALEPQVDYLRNFTQGLVEDAPDGSDASQLLHQAEV
  AQQEFLEVKQRVNSGCVMMENKLEGIGQFHCRVREMFSQLADLDDELDGMGAIGRDTDSL
  QSQIEDVRLFLNKIHVLKLDIEASEAECRHMLEEEGTLDLLGLKRELEALNKQCGKLTER
  GKARQEQLELTLGRVEDFYRKLKGLNDATTAAEEAEALQWVVGTEVEIINQQLADFKMFQ
  KEQVDPLQMKLQQVNGLGQGLIQSAGKDCDVQGLEHDMEEINARWNTLNKKVAQRIAQLQ
  EALLHCGKFQDALEPLLSWLADTEELIANQKPPSAEYKVVKAQIQEQKLLQRLLDDRKAT
  VDMLQAEGGRIAQSAELADREKITGQLESLESRWTELLSKAAARQKQLEDILVLAKQFHE
  TAEPISDFLSVTEKKLANSEPVGTQTAKIQQQIIRHKALNEEIVNRKKNVDQAIKNGQAL
  LKQTTGEEVLLIQEKLDGIKTRYADITVTSSKALRTLEQARQLATKFQSTYEELTGWLRE
  VEEELATSGGQSPTGEQIPQFQQRQKELKKEVMEHRLVLDTVNEVSRALLELVPWRAREG
  LDKLVSDANEQYKLVSDTIGQRVDEIDAAIQRSQQYEQAADAELAWVAETKRKLMALGPI
  RLEQDQTTAQLQVQKAFSIDIIRHKDSMDELFSHRSEIFGTCGEEQKTVLQEKTESLIQQ
  YEAISLLNSERYARLERAQVLVNQFWETYEELSPWIEETRALIAQLPSPAIDHEQLRQQQ
  EEMRQLRESIAEHKPHIDKLLKIGPQLKELNPEEGEMVEEKYQKAENMYAQIKEEVRQRA
  LALDEAVSQSTQITEFHDKIEPMLETLENLSSRLRMPPLIPAEVDKIRECISDNKSATVE
  LEKLQPSFEALKRRGEELIGRSQGADKDLAAKEIQDKLDQMVFFWEDIKARAEEREIKFL
  DVLELAEKFWYDMAALLTTIKDTQDIVHDLESPGIDPSIIKQQVEAAETIKEETDGLHEE
  LEFIRILGADLIFACGETEKPEVRKSIDEMNNAWENLNKTWKERLEKLEDAMQAAVQYQD
  TLQAMFDWLDNTVIKLCTMPPVGTDLNTVKDQLNEMKEFKVEVYQQQIEMEKLNHQGELM
  LKKATDETDRDIIREPLTELKHLWENLGEKIAHRQHKLEGALLALGQFQHALEELMSWLT
  HTEELLDAQRPISGDPKVIEVELAKHHVLKNDVLAHQATVETVNKAGNELLESSAGDDAS
  SLRSRLEAMNQCWESVLQKTEEREQQLQSTLQQAQGFHSEIEDFLLELTRMESQLSASKP
  TGGLPETAREQLDTHMELYSQLKAKEETYNQLLDKGRLMLLSRDDSGSGSKTEQSVALLE
  QKWHVVSSKMEERKSKLEEALNLATEFQNSLQEFINWLTLAEQSLNIASPPSLILNTVLS
  QIEEHKVFANEVNAHRDQIIELDQTGNQLKFLSQKQDVVLIKNLLVSVQSRWEKVVQRSI
  ERGRSLDDARKRAKQFHEAWKKLIDWLEDAESHLDSELEISNDPDKIKLQLSKHKEFQKT
  LGGKQPVYDTTIRTGRALKEKTLLPEDSQKLDNFLGEVRDKWDTVCGKSVERQHKLEEAL
  LFSGQFMDALQALVDWLYKVEPQLAEDQPVHGDLDLVMNLMDAHKVFQKELGKRTGTVQV
  LKRSGRELIENSRDDTTWVKGQLQELSTRWDTVCKLSVSKQSRLEQALKQAEVFRDTVHM
  LLEWLSEAEQTLRFRGALPDDTEALQSLIDTHKEFMKKVEEKRVDVNSAVAMGEVILAVC
  HPDCITTIKHWITIIRARFEEVLTWAKQHQQRLETALSELVANAELLEELLAWIQWAETT
  LIQRDQEPIPQNIDRVKALIAEHQTFMEEMTRKQPDVDRVTKTYKRKNIEPTHAPFIEKS
  RSGGRKSLSQPTPPPMPILSQSEAKNPRINQLSARWQQVWLLALERQRKLNDALDRLEEL
  KEFANFDFDVWRKKYMRWMNHKKSRVMDFFRRIDKDQDGKITRQEFIDGILASKFPTTKL
  EMTAVADIFDRDGDGYIDYYEFVAALHPNKDAYRPTTDADKIEDEVTRQVAQCKCAKRFQ
  VEQIGENKYRFGDSQQLRLVRILRSTVMVRVGGGWMALDEFLVKNDPCRARGRTNIELRE
  KFILPEGASQGMTPFRSRGRRSKPSSRAASPTRSSSSASQSNHSCTSMPSSPATPASGTK
  VIPSSGSKLKRPTPTFHSSRTSLAGDTSNSSSPASTGAKTNRADPKKSASRPGSRAGSRA
  GSRASSRRGSDASDFDLLETQSACSDTSESSAAGGQGNSRRGLNKPSKIPTMSKKTTTAS
  PRTPGPKR
• Function: [Isoform 2]: F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane. Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics. Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus-ends to actin filaments, regulating focal adhesion size and cell migration. May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4. Plays a key role in wound healing and epidermal cell migration. Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells. As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development.
• Tissue Specificity: Isoform 2: Ubiquitously expressed. Isoform 1: Expressed in cell lines NCI-H460, A-549 and HaCaT. Isoform 4: Expressed in heart, lung, pituitary and placenta, not found in brain, kidney, liver, pancreas or skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Bone disease	DISE1F82	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Colitis	DISAF7DD	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Genetic Variation	[6]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[6]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[6]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[6]
Congenital myasthenic syndrome	DISJLG2T	Strong	Biomarker	[7]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[8]
Intestinal disorder	DISGPMUQ	Strong	Biomarker	[9]
Juvenile hyaline fibromatosis	DISQP8V9	Strong	Genetic Variation	[10]
Lissencephaly 9 with complex brainstem malformation	DISXZUH6	Strong	Autosomal dominant	[8]
Lissencephaly spectrum disorders	DISBCZL7	Strong	Genetic Variation	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Neuromuscular disease	DISQTIJZ	Strong	Biomarker	[11]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[12]
Parkinson disease	DISQVHKL	Strong	Biomarker	[13]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[15]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[8]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[16]
Lissencephaly spectrum disorder with complex brainstem malformation	DIS7NTLK	Moderate	Autosomal dominant	[17]
Small-cell lung cancer	DISK3LZD	moderate	Genetic Variation	[18]
Brain neoplasm	DISY3EKS	Limited	Biomarker	[1]
Osteoporosis	DISF2JE0	Limited	Biomarker	[19]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1) affects the response to substance of Etoposide.	[44]
Topotecan	DMP6G8T	Approved	Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1) affects the response to substance of Topotecan.	[44]

7 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 Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[20]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[29]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[36]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[32]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[38]

20 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 Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[26]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[28]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[30]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[31]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[33]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[34]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[35]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[37]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[39]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[41]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[42]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (MACF1).	[43]

References

• [1] Microtubule actin cross-linking factor 1, a novel target in glioblastoma.Int J Oncol. 2017 Jan;50(1):310-316. doi: 10.3892/ijo.2016.3798. Epub 2016 Dec 9.
• [2] Alteration of scaffold: Possible role of MACF1 in Alzheimer's disease pathogenesis.Med Hypotheses. 2019 Sep;130:109259. doi: 10.1016/j.mehy.2019.109259. Epub 2019 Jun 5.
• [3] Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway.J Cell Mol Med. 2020 Jan;24(1):317-327. doi: 10.1111/jcmm.14729. Epub 2019 Nov 11.
• [4] Microtubule actin cross-linking factor 1, a novel potential target in cancer.Cancer Sci. 2017 Oct;108(10):1953-1958. doi: 10.1111/cas.13344. Epub 2017 Sep 21.
• [5] ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics.Nat Commun. 2017 May 25;8:15375. doi: 10.1038/ncomms15375.
• [6] Genome-wide association study of colorectal cancer in Hispanics.Carcinogenesis. 2016 Jun;37(6):547-556. doi: 10.1093/carcin/bgw046. Epub 2016 Apr 18.
• [7] MACF1 links Rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses.J Cell Biol. 2019 May 6;218(5):1686-1705. doi: 10.1083/jcb.201810023. Epub 2019 Mar 6.
• [8] MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance. Am J Hum Genet. 2018 Dec 6;103(6):1009-1021. doi: 10.1016/j.ajhg.2018.10.019. Epub 2018 Nov 21.
• [9] High fat diet exacerbates intestinal barrier dysfunction and changes gut microbiota in intestinal-specific ACF7 knockout mice.Biomed Pharmacother. 2019 Feb;110:537-545. doi: 10.1016/j.biopha.2018.11.100. Epub 2018 Dec 7.
• [10] Predictors of Hand-Foot Syndrome and Pyridoxine for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized Clinical Trial.JAMA Oncol. 2017 Nov 1;3(11):1538-1545. doi: 10.1001/jamaoncol.2017.1269.
• [11] The role of MACF1 in nervous system development and maintenance.Semin Cell Dev Biol. 2017 Sep;69:9-17. doi: 10.1016/j.semcdb.2017.05.020. Epub 2017 Jun 1.
• [12] Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nat Genet. 2018 Apr;50(4):559-571. doi: 10.1038/s41588-018-0084-1. Epub 2018 Apr 9.
• [13] Genetic Variants of Microtubule Actin Cross-linking Factor 1 (MACF1) Confer Risk for Parkinson's Disease.Mol Neurobiol. 2017 May;54(4):2878-2888. doi: 10.1007/s12035-016-9861-y. Epub 2016 Mar 28.
• [14] Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.PLoS One. 2016 Apr 15;11(4):e0152670. doi: 10.1371/journal.pone.0152670. eCollection 2016.
• [15] Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome.Int J Cancer. 2014 Sep 15;135(6):1330-42. doi: 10.1002/ijc.28768. Epub 2014 May 2.
• [16] MACF1, versatility in tissue-specific function and in human disease.Semin Cell Dev Biol. 2017 Sep;69:3-8. doi: 10.1016/j.semcdb.2017.05.017. Epub 2017 May 31.
• [17] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [18] Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors.Clin Cancer Res. 2018 Apr 1;24(7):1691-1704. doi: 10.1158/1078-0432.CCR-17-0252. Epub 2018 Jan 19.
• [19] Microtubule actin crosslinking factor 1 (MACF1) knockdown inhibits RANKL-induced osteoclastogenesis via Akt/GSK3/NFATc1 signalling pathway.Mol Cell Endocrinol. 2019 Aug 20;494:110494. doi: 10.1016/j.mce.2019.110494. Epub 2019 Jun 28.
• [20] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [21] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [22] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [23] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [24] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [25] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [26] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [27] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [28] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [29] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [30] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [31] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [32] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [33] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [34] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [35] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [36] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [37] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [38] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [39] The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells. Neurotoxicology. 2009 May;30(3):368-76.
• [40] Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
• [41] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [42] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [43] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [44] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.