MICAL1 (microtubule associated monooxygenase, calponin and LIM domain containing 1)

Gene

• Entrez ID: 64780
• Gene name: Microtubule associated monooxygenase, calponin and LIM domain containing 1
• Gene symbol: MICAL1
• Synonyms (NCBI Gene): MICAL, MICAL-1, NICAL
• Chromosome: 6
• Chromosome location: 6q21
• Summary: This gene encodes an enzyme that oxidizes methionine residues on actin, thereby promoting depolymerization of actin filaments. This protein interacts with and regulates signalling by NEDD9/CAS-L (neural precursor cell expressed, developmentally down-regul

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1447618526	CAGGGCCTCT>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023104	hsa-miR-124-3p	Microarray	18668037
MIRT045642	hsa-miR-149-5p	CLASH	23622248
MIRT2042141	hsa-miR-4708-3p	CLIP-seq
MIRT2042142	hsa-miR-4727-5p	CLIP-seq
MIRT2042143	hsa-miR-4755-3p	CLIP-seq
MIRT2042144	hsa-miR-4769-3p	CLIP-seq
MIRT2271871	hsa-miR-1245b-3p	CLIP-seq
MIRT2271872	hsa-miR-4514	CLIP-seq
MIRT2271873	hsa-miR-4645-5p	CLIP-seq
MIRT2271874	hsa-miR-4673	CLIP-seq
MIRT2271875	hsa-miR-4690-3p	CLIP-seq
MIRT2271876	hsa-miR-4692	CLIP-seq
MIRT2042142	hsa-miR-4727-5p	CLIP-seq
MIRT2042143	hsa-miR-4755-3p	CLIP-seq
MIRT2042144	hsa-miR-4769-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003779	Function	Actin binding	IDA	21864500
GO:0003779	Function	Actin binding	IEA
GO:0004497	Function	Monooxygenase activity	IDA	33393173
GO:0004497	Function	Monooxygenase activity	IEA
GO:0005515	Function	Protein binding	IPI	11827972, 28230050, 28514442, 30905672, 31413325, 32344433
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	11827972, 24440334
GO:0005737	Component	Cytoplasm	IEA
GO:0005768	Component	Endosome	IEA
GO:0005829	Component	Cytosol	IDA	32344433
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0005882	Component	Intermediate filament	NAS	11827972
GO:0005884	Component	Actin filament	IDA	33393173
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA
GO:0005929	Component	Cilium	IDA
GO:0007010	Process	Cytoskeleton organization	NAS	11827972
GO:0007165	Process	Signal transduction	NAS	11827972
GO:0010008	Component	Endosome membrane	IDA	32344433
GO:0010008	Component	Endosome membrane	IEA
GO:0015629	Component	Actin cytoskeleton	IBA
GO:0016020	Component	Membrane	IEA
GO:0016174	Function	NAD(P)H oxidase H2O2-forming activity	IDA	21864500, 26845023
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016709	Function	Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	IDA	21864500, 26845023
GO:0016709	Function	Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	IEA
GO:0017124	Function	SH3 domain binding	IPI	11827972
GO:0019417	Process	Sulfur oxidation	IEA
GO:0019417	Process	Sulfur oxidation	ISS
GO:0019901	Function	Protein kinase binding	IEA
GO:0030042	Process	Actin filament depolymerization	IDA	21864500, 28230050, 33393173
GO:0030042	Process	Actin filament depolymerization	IEA
GO:0030496	Component	Midbody	IDA	28230050
GO:0030496	Component	Midbody	IEA
GO:0031267	Function	Small GTPase binding	IEA
GO:0036064	Component	Ciliary basal body	IDA
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0045171	Component	Intercellular bridge	IDA	28230050
GO:0046872	Function	Metal ion binding	IEA
GO:0051015	Function	Actin filament binding	IBA
GO:0051017	Process	Actin filament bundle assembly	IBA
GO:0071949	Function	FAD binding	IDA	21864500
GO:0071949	Function	FAD binding	IEA
GO:0120025	Component	Plasma membrane bounded cell projection	IEA
GO:0120501	Function	F-actin monooxygenase activity	IEA
GO:1903305	Process	Regulation of regulated secretory pathway	IEA
GO:1990026	Component	Hippocampal mossy fiber expansion	IEA

Other IDs

• MIM: 607129
• HGNC: 20619
• e!Ensembl: ENSG00000135596

Protein

• UniProt ID: Q8TDZ2
• Protein name: [F-actin]-monooxygenase MICAL1 (EC 1.14.13.225) (EC 1.6.3.1) (Molecule interacting with CasL protein 1) (MICAL-1) (NEDD9-interacting protein with calponin homology and LIM domains)
• Protein function: Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization (PubMed:29343822). In t
• PDB: 1WYL, 2CO8, 2DK9, 5LE0, 5LPN, 6KU0, 8HLO, 8Y6K, 9EWY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01494	FAD_binding_3	84 → 139	FAD binding domain	Family
  PF00307	CH	508 → 613	Calponin homology (CH) domain	Domain
  PF00412	LIM	697 → 754	LIM domain	Domain
  PF12130	DUF3585	931 → 1061	Bivalent Mical/EHBP Rab binding domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the thymus, lung, spleen, kidney, testis and hematopoietic cells. {ECO:0000269|PubMed:11827972}.
• Sequence:

  MASPTSTNPAHAHFESFLQAQLCQDVLSSFQELCGALGLEPGGGLPQYHKIKDQLNYWSA
  KSLWTKLDKRAGQPVYQQGRACTSTKCLVVGAGPCGLRVAVELALLGARVVLVEKRTKFS
  RHNVLHLWPFTIHDLRALGAKKFYGRFCTGTLDHISIRQLQLLLLKVALLLGVEIHWGVT
  FTGLQPPPRKGSGWRAQLQPNPPAQLANYEFDVLISAAGGKFVPEGFKVREMRGKLAIGI
  TANFVNGRTVEETQVPEISGVARIYNQSFFQSLLKATGIDLENIVYYKDDTHYFVMTAKK
  QCLLRLGVLRQDWPDTNRLLGSANVVPEALQRFTRAAADFATHGKLGKLEFAQDAHGQPD
  VSAFDFTSMMRAESSARVQEKHGARLLLGLVGDCLVEPFWPLGTGVARGFLAAFDAAWMV
  KRWAEGAESLEVLAERESLYQLLSQTSPENMHRNVAQYGLDPATRYPNLNLRAVTPNQVR
  DLYDVLAKEPVQRNNDKTDTGMPATGSAGTQEELLRWCQEQTAGYPGVHVSDLSSSWADG
  LALCALVYRLQPGLLEPSELQGLGALEATAWALKVAENELGITPVVSAQAVVAGSDPLGL
  IAYLSHFHSAFKSMAHSPGPVSQASPGTSSAVLFLSKLQRTLQRSRAKENAEDAGGKKLR
  LEMEAETPSTEVPPDPEPGVPLTPPSQHQEAGAGDLCALCGEHLYVLERLCVNGHFFHRS
  CFRCHTCEATLWPGGYEQHPGDGHFYCLQHLPQTDHKAEGSDRGPESPELPTPSENSMPP
  GLSTPTASQEGAGPVPDPSQPTRRQIRLSSPERQRLSSLNLTPDPEMEPPPKPPRSCSAL
  ARHALESSFVGWGLPVQSPQALVAMEKEEKESPFSSEEEEEDVPLDSDVEQALQTFAKTS
  GTMNNYPTWRRTLLRRAKEEEMKRFCKAQTIQRRLNEIEAALRELEAEGVKLELALRRQS
  SSPEQQKKLWVGQLLQLVDKKNSLVAEEAELMITVQELNLEEKQWQLDQELRGYMNREEN
  LKTAADRQAEDQVLRKLVDLVNQRDALIRFQEERRLSELALGTGAQG

• Sequence length: 1067

Pathways

Reactome:

Factors involved in megakaryocyte development and platelet production

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Epilepsy, familial temporal lobe, 1	Pathogenic; Likely pathogenic	rs2115340270, rs775269055	RCV002051606 RCV003226541	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY	—	Disgenet, GenCC Disgenet, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY WITH AUDITORY FEATURES	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY, FAMILIAL TEMPORAL LOBE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Germ cell tumor of testis	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICAL1-related Lateral temporal epilepsy	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Bipolar Disorder	Bipolar disorder	Pubtator	21769101	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	27430308, 29524295		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	27430308, 29524295, 34314753	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	37248888	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	36575439	Associate	★☆☆☆☆ Found in Text Mining only
Complex partial seizure with impairment of consciousness	Dyscognitive seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Complex partial seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cone-Rod Dystrophy 2	Cone-rod dystrophy	BEFREE	16230022		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	21638339		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy, Familial Temporal Lobe 1	Epilepsy	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy, Lateral Temporal	Epilepsy	BEFREE	29394500		★☆☆☆☆ Found in Text Mining only
Epilepsy, Temporal Lobe	Epilepsy	BEFREE	21638339		★☆☆☆☆ Found in Text Mining only
Generalized tonic-clonic seizures with focal onset	Bilateral convulsive seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Kidney Neoplasms	Kidney neoplasm	Pubtator	31449970	Associate	★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	GWASCAT_DG	30219690		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of breast	Breast Cancer	BEFREE	27430308, 29524295		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	31019460		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	27430308, 31449970		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	25576923		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Stomach Carcinoma	Stomach Carcinoma	BEFREE	31019460		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	38508474	Associate	★☆☆☆☆ Found in Text Mining only