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Protein

[F-actin]-monooxygenase MICAL1

Gene

Mical1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. In the absence of actin, it also functions as a NADPH oxidase producing H2O2 (By similarity). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels. May act as Rab effector protein and play a role in vesicle trafficking.By similarity4 Publications

Caution

The reaction mechanism is subject to discussion. Some work suggest MICAL enzymes directly oxidize actin methionine residues to produce methionine-(R)-S-oxide. Other publications suggest that the enzyme functions as a NADPH oxidase producing H2O2 (EC 1.6.3.1) and that it is the produced H2O2 that is responsible for the methionine-(R)-S-oxide production.By similarity2 Publications

Catalytic activityi

[F-actin]-L-methionine + NADPH + O2 + H+ = [F-actin]-L-methionine-(R)-S-oxide + NADP+ + H2O.2 Publications

Cofactori

FAD1 Publication

Kineticsi

  1. KM=9.3 µM for actin (for a monooxygenase domain construct)1 Publication
  2. KM=28.8 µM for NADPH (for a monooxygenase domain construct)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei95FADCombined sources1 Publication1
    Binding sitei181FAD; via amide nitrogen and carbonyl oxygenCombined sources1 Publication1
    Binding sitei293FADCombined sources1 Publication1
    Binding sitei393FADCombined sources1 Publication1
    Metal bindingi683Zinc 1By similarity1
    Metal bindingi686Zinc 1By similarity1
    Metal bindingi704Zinc 1; via pros nitrogenBy similarity1
    Metal bindingi707Zinc 1By similarity1
    Metal bindingi710Zinc 2By similarity1
    Metal bindingi713Zinc 2By similarity1
    Metal bindingi733Zinc 2By similarity1
    Metal bindingi736Zinc 2; via pros nitrogenBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi114 – 116FADCombined sources1 Publication3
    Nucleotide bindingi121 – 123FADCombined sources1 Publication3

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionActin-binding, Monooxygenase, Oxidoreductase
    LigandFAD, Flavoprotein, Metal-binding, NADP, Zinc

    Enzyme and pathway databases

    ReactomeiR-MMU-983231 Factors involved in megakaryocyte development and platelet production

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    [F-actin]-monooxygenase MICAL1Curated (EC:1.14.13.2251 Publication)
    Alternative name(s):
    Molecule interacting with CasL protein 1
    Short name:
    MICAL-1
    Short name:
    mMical1
    NEDD9-interacting protein with calponin homology and LIM domains
    Gene namesi
    Name:Mical1
    Synonyms:Mical, Nical
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 10

    Organism-specific databases

    MGIiMGI:2385847 Mical1

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000758431 – 1048[F-actin]-monooxygenase MICAL1Add BLAST1048

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei475PhosphothreonineBy similarity1
    Modified residuei616PhosphoserineBy similarity1
    Modified residuei777PhosphoserineCombined sources1
    Modified residuei781PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ8VDP3
    PeptideAtlasiQ8VDP3
    PRIDEiQ8VDP3

    PTM databases

    iPTMnetiQ8VDP3
    PhosphoSitePlusiQ8VDP3

    Expressioni

    Tissue specificityi

    Expressed in the postnatal and adult hippocampus; found in dentate gyrus, the polymorphic layer, cornu ammonis (CA) 1-3 and in mossy fibers of the striatum lucidum. In adult hippocampus strongly expressed in CA3 pyramidial neurons.1 Publication

    Gene expression databases

    BgeeiENSMUSG00000019823 Expressed in 248 organ(s), highest expression level in jejunum
    ExpressionAtlasiQ8VDP3 baseline and differential
    GenevisibleiQ8VDP3 MM

    Interactioni

    Subunit structurei

    Associates with the SH3 domain of NEDD9. Interacts with VIM and PLXNA3. Interacts with RAB1B, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB1B is of low affinity compared to other Rab proteins; at least in case of RAB8A and RAB10 can bind 2 molecules of the Rab proteins simultaneously (By similarity). Interacts with STK38 and STK38L.By similarity3 Publications

    Binary interactionsi

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi228624, 1 interactor
    IntActiQ8VDP3, 4 interactors
    STRINGi10090.ENSMUSP00000019967

    Structurei

    Secondary structure

    11048
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ8VDP3
    SMRiQ8VDP3
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8VDP3

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini507 – 611Calponin-homology (CH)PROSITE-ProRule annotationAdd BLAST105
    Domaini681 – 743LIM zinc-bindingPROSITE-ProRule annotationAdd BLAST63
    Domaini905 – 1048bMERBPROSITE-ProRule annotationAdd BLAST144

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 489Monooxygenase domainAdd BLAST489

    Coiled coil

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Coiled coili847 – 867Sequence analysisAdd BLAST21
    Coiled coili906 – 949Sequence analysisAdd BLAST44
    Coiled coili974 – 1031Sequence analysisAdd BLAST58

    Domaini

    The C-terminal coiled coil part contains the plexin-interacting region.
    The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms).By similarity

    Sequence similaritiesi

    Belongs to the Mical family.Curated

    Keywords - Domaini

    Coiled coil, LIM domain

    Phylogenomic databases

    eggNOGiKOG1700 Eukaryota
    COG5069 LUCA
    GeneTreeiENSGT00760000118856
    HOGENOMiHOG000047263
    HOVERGENiHBG052474
    InParanoidiQ8VDP3
    KOiK19947
    OrthoDBiEOG091G009H
    TreeFamiTF324129

    Family and domain databases

    CDDicd00014 CH, 1 hit
    Gene3Di1.10.418.10, 1 hit
    InterProiView protein in InterPro
    IPR022735 bMERB_dom
    IPR001715 CH-domain
    IPR036872 CH_dom_sf
    IPR002938 FAD-bd
    IPR036188 FAD/NAD-bd_sf
    IPR029937 MICAL1
    IPR001781 Znf_LIM
    PANTHERiPTHR44265:SF2 PTHR44265:SF2, 1 hit
    PfamiView protein in Pfam
    PF00307 CH, 1 hit
    PF12130 DUF3585, 1 hit
    PF01494 FAD_binding_3, 1 hit
    SMARTiView protein in SMART
    SM00033 CH, 1 hit
    SM00132 LIM, 1 hit
    SUPFAMiSSF47576 SSF47576, 1 hit
    SSF51905 SSF51905, 1 hit
    PROSITEiView protein in PROSITE
    PS51848 BMERB, 1 hit
    PS50021 CH, 1 hit
    PS00478 LIM_DOMAIN_1, 1 hit
    PS50023 LIM_DOMAIN_2, 1 hit

    Sequences (3+)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q8VDP3-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MASPASTNPA HDHFETFVQA QLCQDVLSSF QGLCRALGVE SGGGLSQYHK
    60 70 80 90 100
    IKAQLNYWSA KSLWAKLDKR ASQPVYQQGQ ACTNTKCLVV GAGPCGLRAA
    110 120 130 140 150
    VELALLGARV VLVEKRIKFS RHNVLHLWPF TIHDLRALGA KKFYGRFCTG
    160 170 180 190 200
    TLDHISIRQL QLLLLKVALL LGVEIHWGVK FTGLQPPPRK GSGWRAQLQP
    210 220 230 240 250
    NPPAQLASYE FDVLISAAGG KFVPEGFTIR EMRGKLAIGI TANFVNGRTV
    260 270 280 290 300
    EETQVPEISG VARIYNQKFF QSLLKATGID LENIVYYKDE THYFVMTAKK
    310 320 330 340 350
    QCLLRLGVLR QDLSETDQLL GKANVVPEAL QRFARAAADF ATHGKLGKLE
    360 370 380 390 400
    FAQDARGRPD VAAFDFTSMM RAESSARVQE KHGARLLLGL VGDCLVEPFW
    410 420 430 440 450
    PLGTGVARGF LAAFDAAWMV KRWAEGAGPL EVLAERESLY QLLSQTSPEN
    460 470 480 490 500
    MHRNVAQYGL DPATRYPNLN LRAVTPNQVQ DLYDMMDKEH AQRKSDEPDS
    510 520 530 540 550
    RKTTTGSAGT EELLHWCQEQ TAGFPGVHVT DFSSSWADGL ALCALVHHLQ
    560 570 580 590 600
    PGLLEPSELQ GMGALEATTW ALRVAEHELG ITPVLSAQAV MAGSDPLGLI
    610 620 630 640 650
    AYLSHFHSAF KNTSHSSGLV SQPSGTPSAI LFLGKLQRSL QRTRAKVDEE
    660 670 680 690 700
    TPSTEEPPVS EPSMSPNTPE LSEHQEAGAE ELCELCGKHL YILERFCVDG
    710 720 730 740 750
    HFFHRSCFCC HTCEATLWPG GYGQHPGDGH FYCLQHLPQE DQKEADNNGS
    760 770 780 790 800
    LESQELPTPG DSNMQPDPSS PPVTRVSPVP SPSQPARRLI RLSSLERLRL
    810 820 830 840 850
    SSLNIIPDSG AEPPPKPPRS CSDLARESLK SSFVGWGVPV QAPQVPEAIE
    860 870 880 890 900
    KGDDEEEEEE EEEEEEEPLP PLEPELEQTL LTLAKNPGAM TKYPTWRRTL
    910 920 930 940 950
    MRRAKEEEMK RFCKAQAIQR RLNEIEATMR ELEAEGTKLE LALRKESSSP
    960 970 980 990 1000
    EQQKKLWLDQ LLRLIQKKNS LVTEEAELMI TVQELDLEEK QRQLDHELRG
    1010 1020 1030 1040
    YMNREETMKT EADLQSENQV LRKLLEVVNQ RDALIQFQEE RRLREMPA
    Length:1,048
    Mass (Da):116,785
    Last modified:March 1, 2002 - v1
    Checksum:iC31A392A4AE222FC
    GO
    Isoform 2 (identifier: Q8VDP3-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         87-159: Missing.

    Show »
    Length:975
    Mass (Da):108,692
    Checksum:iB2D2BF964B034CBC
    GO
    Isoform 3 (identifier: Q8VDP3-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         192-192: S → D

    Show »
    Length:1,048
    Mass (Da):116,813
    Checksum:iAF50CC8B1FBBBAE2
    GO

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    E9PUI4E9PUI4_MOUSE
    [F-actin]-monooxygenase MICAL1
    Mical1
    939Annotation score:
    D3Z5P6D3Z5P6_MOUSE
    [F-actin]-monooxygenase MICAL1
    Mical1
    43Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti871P → H in BAE35027 (PubMed:16141072).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_04259187 – 159Missing in isoform 2. 1 PublicationAdd BLAST73
    Alternative sequenceiVSP_042592192S → D in isoform 3. Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK159369 mRNA Translation: BAE35027.1
    AK170881 mRNA Translation: BAE42090.1
    AK171234 mRNA Translation: BAE42330.1
    AK171411 mRNA Translation: BAE42437.1
    AK171429 mRNA Translation: BAE42447.1
    AK171479 mRNA Translation: BAE42481.1
    AC153360 Genomic DNA No translation available.
    BC021477 mRNA Translation: AAH21477.1
    BC034682 mRNA Translation: AAH34682.1
    CCDSiCCDS35888.1 [Q8VDP3-1]
    CCDS48547.1 [Q8VDP3-2]
    RefSeqiNP_001157905.1, NM_001164433.1 [Q8VDP3-2]
    NP_612188.1, NM_138315.2 [Q8VDP3-1]
    XP_011241439.1, XM_011243137.2 [Q8VDP3-1]
    UniGeneiMm.290431

    Genome annotation databases

    EnsembliENSMUST00000019967; ENSMUSP00000019967; ENSMUSG00000019823 [Q8VDP3-1]
    ENSMUST00000099934; ENSMUSP00000097519; ENSMUSG00000019823 [Q8VDP3-2]
    ENSMUST00000119962; ENSMUSP00000113783; ENSMUSG00000019823 [Q8VDP3-3]
    GeneIDi171580
    KEGGimmu:171580
    UCSCiuc007exn.2 mouse [Q8VDP3-1]
    uc007exp.2 mouse [Q8VDP3-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK159369 mRNA Translation: BAE35027.1
    AK170881 mRNA Translation: BAE42090.1
    AK171234 mRNA Translation: BAE42330.1
    AK171411 mRNA Translation: BAE42437.1
    AK171429 mRNA Translation: BAE42447.1
    AK171479 mRNA Translation: BAE42481.1
    AC153360 Genomic DNA No translation available.
    BC021477 mRNA Translation: AAH21477.1
    BC034682 mRNA Translation: AAH34682.1
    CCDSiCCDS35888.1 [Q8VDP3-1]
    CCDS48547.1 [Q8VDP3-2]
    RefSeqiNP_001157905.1, NM_001164433.1 [Q8VDP3-2]
    NP_612188.1, NM_138315.2 [Q8VDP3-1]
    XP_011241439.1, XM_011243137.2 [Q8VDP3-1]
    UniGeneiMm.290431

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2BRAX-ray2.00A/B1-484[»]
    2BRYX-ray1.45A/B1-489[»]
    2C4CX-ray2.90A/B1-489[»]
    4TXIX-ray2.31A2-615[»]
    4TXKX-ray2.88A2-615[»]
    ProteinModelPortaliQ8VDP3
    SMRiQ8VDP3
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi228624, 1 interactor
    IntActiQ8VDP3, 4 interactors
    STRINGi10090.ENSMUSP00000019967

    PTM databases

    iPTMnetiQ8VDP3
    PhosphoSitePlusiQ8VDP3

    Proteomic databases

    PaxDbiQ8VDP3
    PeptideAtlasiQ8VDP3
    PRIDEiQ8VDP3

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000019967; ENSMUSP00000019967; ENSMUSG00000019823 [Q8VDP3-1]
    ENSMUST00000099934; ENSMUSP00000097519; ENSMUSG00000019823 [Q8VDP3-2]
    ENSMUST00000119962; ENSMUSP00000113783; ENSMUSG00000019823 [Q8VDP3-3]
    GeneIDi171580
    KEGGimmu:171580
    UCSCiuc007exn.2 mouse [Q8VDP3-1]
    uc007exp.2 mouse [Q8VDP3-2]

    Organism-specific databases

    CTDi64780
    MGIiMGI:2385847 Mical1

    Phylogenomic databases

    eggNOGiKOG1700 Eukaryota
    COG5069 LUCA
    GeneTreeiENSGT00760000118856
    HOGENOMiHOG000047263
    HOVERGENiHBG052474
    InParanoidiQ8VDP3
    KOiK19947
    OrthoDBiEOG091G009H
    TreeFamiTF324129

    Enzyme and pathway databases

    ReactomeiR-MMU-983231 Factors involved in megakaryocyte development and platelet production

    Miscellaneous databases

    ChiTaRSiMical1 mouse
    EvolutionaryTraceiQ8VDP3
    PROiPR:Q8VDP3
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000019823 Expressed in 248 organ(s), highest expression level in jejunum
    ExpressionAtlasiQ8VDP3 baseline and differential
    GenevisibleiQ8VDP3 MM

    Family and domain databases

    CDDicd00014 CH, 1 hit
    Gene3Di1.10.418.10, 1 hit
    InterProiView protein in InterPro
    IPR022735 bMERB_dom
    IPR001715 CH-domain
    IPR036872 CH_dom_sf
    IPR002938 FAD-bd
    IPR036188 FAD/NAD-bd_sf
    IPR029937 MICAL1
    IPR001781 Znf_LIM
    PANTHERiPTHR44265:SF2 PTHR44265:SF2, 1 hit
    PfamiView protein in Pfam
    PF00307 CH, 1 hit
    PF12130 DUF3585, 1 hit
    PF01494 FAD_binding_3, 1 hit
    SMARTiView protein in SMART
    SM00033 CH, 1 hit
    SM00132 LIM, 1 hit
    SUPFAMiSSF47576 SSF47576, 1 hit
    SSF51905 SSF51905, 1 hit
    PROSITEiView protein in PROSITE
    PS51848 BMERB, 1 hit
    PS50021 CH, 1 hit
    PS00478 LIM_DOMAIN_1, 1 hit
    PS50023 LIM_DOMAIN_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiMICA1_MOUSE
    AccessioniPrimary (citable) accession number: Q8VDP3
    Secondary accession number(s): D3Z4C6
    , E9PXR1, Q3TB77, Q3TBH9, Q3TX89
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
    Last sequence update: March 1, 2002
    Last modified: November 7, 2018
    This is version 146 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
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