MICA2_HUMAN
ID MICA2_HUMAN Reviewed; 1957 AA.
AC O94851; A0A2R8YFA9; B4DGZ0; B7Z849; D3DQW5; G3XAC8; Q5KTR3; Q5KTR4; Q6ZW33;
AC Q7RTP7; Q7Z3A8; Q96JU6;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=[F-actin]-monooxygenase MICAL2 {ECO:0000305};
DE EC=1.14.13.225 {ECO:0000269|PubMed:24440334, ECO:0000269|PubMed:29343822, ECO:0000269|PubMed:34106209};
DE AltName: Full=MICAL C-terminal-like protein;
DE Short=Mical-cL;
DE AltName: Full=Molecule interacting with CasL protein 2;
DE Short=MICAL-2;
GN Name=MICAL2 {ECO:0000312|HGNC:HGNC:24693};
GN Synonyms=KIAA0750, MICAL2PV1, MICAL2PV2, MICALCL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 6).
RC TISSUE=Prostate;
RX PubMed=16675569; DOI=10.1158/1078-0432.ccr-05-1995;
RA Ashida S., Furihata M., Katagiri T., Tamura K., Anazawa Y., Yoshioka H.,
RA Miki T., Fujioka T., Shuin T., Nakamura Y., Nakagawa H.;
RT "Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer
RT variants), increases with high Gleason score and prostate cancer
RT progression.";
RL Clin. Cancer Res. 12:2767-2773(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1228-1957 (ISOFORM 7), AND VARIANTS
RP PRO-1106; ILE-1332; SER-1355; THR-1567; GLY-1575; GLU-1631 AND PRO-1733.
RC TISSUE=Brain, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon endothelium, and Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP GENE STRUCTURE.
RX PubMed=12110185; DOI=10.1016/s0092-8674(02)00794-8;
RA Terman J.R., Mao T., Pasterkamp R.J., Yu H.-H., Kolodkin A.L.;
RT "MICALs, a family of conserved flavoprotein oxidoreductases, function in
RT plexin-mediated axonal repulsion.";
RL Cell 109:887-900(2002).
RN [9]
RP INTERACTION WITH RAB1B.
RX PubMed=15694364; DOI=10.1016/j.bbrc.2004.12.182;
RA Fischer J., Weide T., Barnekow A.;
RT "The MICAL proteins and rab1: a possible link to the cytoskeleton?";
RL Biochem. Biophys. Res. Commun. 328:415-423(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-631, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION
RP SIGNAL, MUTAGENESIS OF GLY-95 AND 677-LYS--LYS-681, AND ACTIVITY
RP REGULATION.
RX PubMed=24440334; DOI=10.1016/j.cell.2013.12.035;
RA Lundquist M.R., Storaska A.J., Liu T.C., Larsen S.D., Evans T.,
RA Neubig R.R., Jaffrey S.R.;
RT "Redox modification of nuclear actin by MICAL-2 regulates SRF signaling.";
RL Cell 156:563-576(2014).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29343822; DOI=10.1038/s41598-017-17943-5;
RA Wu H., Yesilyurt H.G., Yoon J., Terman J.R.;
RT "The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved
RT from Drosophila to Humans.";
RL Sci. Rep. 8:937-937(2018).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH CORO1C.
RX PubMed=34106209; DOI=10.1083/jcb.202102043;
RA Galloni C., Carra D., Abella J.V.G., Kjaer S., Singaravelu P., Barry D.J.,
RA Kogata N., Guerin C., Blanchoin L., Way M.;
RT "MICAL2 enhances branched actin network disassembly by oxidizing Arp3B-
RT containing Arp2/3 complexes.";
RL J. Cell Biol. 220:0-0(2021).
RN [15]
RP STRUCTURE BY NMR OF 511-629.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the CH domain from human MICAL-2.";
RL Submitted (JUL-2007) to the PDB data bank.
RN [16] {ECO:0007744|PDB:2E9K}
RP STRUCTURE BY NMR OF 516-629.
RA Tomizawa T., Tochio N., Koshiba S., Watanabe S., Harada T., Kigawa T.,
RA Yokoyama S.;
RT "Solution structure of the CH domain from human MICAL-2.";
RL Submitted (JAN-2007) to the PDB data bank.
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1796-1945 IN COMPLEX WITH RAB1B,
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 1796-1945 IN COMPLEX WITH RAB8A,
RP X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) OF 1796-1945 IN COMPLEX WITH RAB10,
RP INTERACTION WITH RAB13; RAB15 AND RAB35, AND DOMAIN.
RX PubMed=27552051; DOI=10.7554/elife.18675;
RA Rai A., Oprisko A., Campos J., Fu Y., Friese T., Itzen A., Goody R.S.,
RA Gazdag E.M., Muller M.P.;
RT "bMERB domains are bivalent Rab8 family effectors evolved by gene
RT duplication.";
RL Elife 5:E18675-E18675(2016).
CC -!- FUNCTION: Methionine monooxygenase that promotes depolymerization of F-
CC actin by mediating oxidation of residues 'Met-44' and 'Met-47' on actin
CC to form methionine-sulfoxide, resulting in actin filament disassembly
CC and preventing repolymerization (PubMed:24440334, PubMed:29343822).
CC Regulates the disassembly of branched actin networks also by oxidizing
CC ARP3B-containing ARP2/3 complexes leading to ARP3B dissociation from
CC the network (PubMed:34106209). Acts as a key regulator of the SRF
CC signaling pathway elicited by nerve growth factor and serum: mediates
CC oxidation and subsequent depolymerization of nuclear actin, leading to
CC increase MKL1/MRTF-A presence in the nucleus and promote SRF:MKL1/MRTF-
CC A-dependent gene transcription. Does not activate SRF:MKL1/MRTF-A
CC through RhoA (PubMed:24440334). {ECO:0000269|PubMed:24440334,
CC ECO:0000269|PubMed:29343822, ECO:0000269|PubMed:34106209}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-methionyl-[F-actin] + NADPH + O2 = H2O + L-methionyl-
CC (R)-S-oxide-[F-actin] + NADP(+); Xref=Rhea:RHEA:51308, Rhea:RHEA-
CC COMP:12953, Rhea:RHEA-COMP:12956, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16044,
CC ChEBI:CHEBI:45764, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.14.13.225; Evidence={ECO:0000269|PubMed:24440334,
CC ECO:0000269|PubMed:29343822, ECO:0000269|PubMed:34106209};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q8TDZ2};
CC -!- ACTIVITY REGULATION: Specifically inhibited by CCG-1423, a small
CC molecule inhibitor of SRF:MKL1/MRTF-A-dependent transcription.
CC {ECO:0000269|PubMed:24440334}.
CC -!- SUBUNIT: Interacts with PLXNA4 (By similarity). Interacts with RAB1B
CC (PubMed:15694364, PubMed:27552051). Interacts with MAPK1/ERK2 (By
CC similarity). Interacts with RAB35, RAB8A, RAB10, RAB13 and RAB15 (in
CC their GTP-bound forms); binding to RAB35 is of low affinity compared to
CC other Rab proteins; at least in case of RAB8A may bind 2 molecules of
CC RAB8A simultaneously through a high and a low affinity binding site,
CC respectively (PubMed:27552051). May interact with MAPK1/ERK2 (By
CC similarity). Interacts with CORO1C; this interaction recruits MICAL2 to
CC the actin filaments (PubMed:34106209). {ECO:0000250|UniProtKB:Q8BML1,
CC ECO:0000269|PubMed:15694364, ECO:0000269|PubMed:27552051,
CC ECO:0000269|PubMed:34106209}.
CC -!- INTERACTION:
CC O94851; P05067: APP; NbExp=3; IntAct=EBI-2804835, EBI-77613;
CC O94851; Q9UBB4: ATXN10; NbExp=3; IntAct=EBI-2804835, EBI-702390;
CC O94851; P54252: ATXN3; NbExp=3; IntAct=EBI-2804835, EBI-946046;
CC O94851; P14136: GFAP; NbExp=3; IntAct=EBI-2804835, EBI-744302;
CC O94851; P42858: HTT; NbExp=3; IntAct=EBI-2804835, EBI-466029;
CC O94851; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2804835, EBI-1055254;
CC O94851; P29474: NOS3; NbExp=3; IntAct=EBI-2804835, EBI-1391623;
CC O94851; P49810: PSEN2; NbExp=3; IntAct=EBI-2804835, EBI-2010251;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24440334}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8BML1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=7;
CC IsoId=O94851-7; Sequence=Displayed;
CC Name=1;
CC IsoId=O94851-1; Sequence=VSP_061297, VSP_061298;
CC Name=2;
CC IsoId=O94851-2; Sequence=VSP_061291, VSP_061292, VSP_061296,
CC VSP_061299;
CC Name=3;
CC IsoId=O94851-3; Sequence=VSP_061294, VSP_061297, VSP_061298;
CC Name=4;
CC IsoId=O94851-4; Sequence=VSP_061293, VSP_061295, VSP_061296,
CC VSP_061299;
CC Name=5;
CC IsoId=O94851-5; Sequence=VSP_061293, VSP_061297, VSP_061298;
CC Name=6;
CC IsoId=O94851-6; Sequence=VSP_061292, VSP_061296, VSP_061299;
CC -!- DOMAIN: The C-terminal RAB-binding domain (RBD) (1796-1945), also
CC described as bivalent Mical/EHBP Rab binding (bMERB) domain, mediates
CC binding to predominantly RAB8A, RAB10, RAB13 and RAB15 (in their GTP-
CC bound forms). {ECO:0000269|PubMed:27552051}.
CC -!- SIMILARITY: Belongs to the Mical family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA34470.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55422.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB110785; BAD83656.1; -; mRNA.
DR EMBL; AB110786; BAD83657.1; -; mRNA.
DR EMBL; AB018293; BAA34470.2; ALT_INIT; mRNA.
DR EMBL; AK027872; BAB55422.1; ALT_INIT; mRNA.
DR EMBL; AK123671; BAC85674.1; -; mRNA.
DR EMBL; AK294845; BAG57951.1; -; mRNA.
DR EMBL; AK302893; BAH13835.1; -; mRNA.
DR EMBL; BX538021; CAD97967.1; -; mRNA.
DR EMBL; BX641163; CAE46072.1; -; mRNA.
DR EMBL; AC025106; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025300; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455321; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68528.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68529.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68531.1; -; Genomic_DNA.
DR EMBL; BC044577; AAH44577.1; -; mRNA.
DR EMBL; BK000462; DAA01341.1; -; mRNA.
DR EMBL; BK000463; DAA01342.1; -; mRNA.
DR CCDS; CCDS60726.1; -. [O94851-3]
DR CCDS; CCDS60727.1; -. [O94851-5]
DR CCDS; CCDS60728.1; -. [O94851-4]
DR CCDS; CCDS7809.1; -. [O94851-1]
DR RefSeq; NP_001269592.1; NM_001282663.1. [O94851-1]
DR RefSeq; NP_001269593.1; NM_001282664.1. [O94851-3]
DR RefSeq; NP_001269594.1; NM_001282665.1. [O94851-5]
DR RefSeq; NP_001269595.1; NM_001282666.1. [O94851-4]
DR RefSeq; NP_001269596.1; NM_001282667.1. [O94851-6]
DR RefSeq; NP_001333221.1; NM_001346292.1. [O94851-1]
DR RefSeq; NP_001333222.1; NM_001346293.1. [O94851-3]
DR RefSeq; NP_001333223.1; NM_001346294.1. [O94851-3]
DR RefSeq; NP_001333224.1; NM_001346295.1. [O94851-3]
DR RefSeq; NP_001333225.1; NM_001346296.1. [O94851-3]
DR RefSeq; NP_001333226.1; NM_001346297.1. [O94851-3]
DR RefSeq; NP_001333227.1; NM_001346298.1. [O94851-3]
DR RefSeq; NP_001333228.1; NM_001346299.1. [O94851-3]
DR RefSeq; NP_055447.1; NM_014632.3. [O94851-1]
DR RefSeq; XP_016874078.1; XM_017018589.1.
DR RefSeq; XP_016874079.1; XM_017018590.1.
DR RefSeq; XP_016874080.1; XM_017018591.1.
DR PDB; 2E9K; NMR; -; A=516-629.
DR PDB; 5SZH; X-ray; 2.30 A; A=1796-1945.
DR PDB; 5SZI; X-ray; 2.85 A; B=1796-1945.
DR PDB; 5SZJ; X-ray; 2.66 A; B=1796-1945.
DR PDB; 5SZK; X-ray; 2.80 A; A=1796-1945.
DR PDBsum; 2E9K; -.
DR PDBsum; 5SZH; -.
DR PDBsum; 5SZI; -.
DR PDBsum; 5SZJ; -.
DR PDBsum; 5SZK; -.
DR AlphaFoldDB; O94851; -.
DR SMR; O94851; -.
DR BioGRID; 115003; 28.
DR BioGRID; 124385; 1.
DR IntAct; O94851; 21.
DR MINT; O94851; -.
DR STRING; 9606.ENSP00000256186; -.
DR iPTMnet; O94851; -.
DR PhosphoSitePlus; O94851; -.
DR BioMuta; MICAL2; -.
DR BioMuta; MICALCL; -.
DR DMDM; 296439303; -.
DR EPD; O94851; -.
DR jPOST; O94851; -.
DR MassIVE; O94851; -.
DR MaxQB; O94851; -.
DR PaxDb; O94851; -.
DR PeptideAtlas; O94851; -.
DR PRIDE; O94851; -.
DR ProteomicsDB; 50480; -. [O94851-1]
DR ProteomicsDB; 50481; -. [O94851-2]
DR ProteomicsDB; 50482; -. [O94851-3]
DR ProteomicsDB; 50483; -. [O94851-4]
DR ProteomicsDB; 50484; -. [O94851-5]
DR ProteomicsDB; 50485; -. [O94851-6]
DR Antibodypedia; 24509; 162 antibodies from 24 providers.
DR DNASU; 84953; -.
DR DNASU; 9645; -.
DR Ensembl; ENST00000256194.8; ENSP00000256194.4; ENSG00000133816.18. [O94851-1]
DR Ensembl; ENST00000527546.5; ENSP00000433965.1; ENSG00000133816.18. [O94851-5]
DR Ensembl; ENST00000528931.5; ENSP00000499778.1; ENSG00000133816.18. [O94851-6]
DR Ensembl; ENST00000646065.1; ENSP00000494982.1; ENSG00000133816.18. [O94851-7]
DR Ensembl; ENST00000675839.1; ENSP00000502351.1; ENSG00000133816.18. [O94851-3]
DR Ensembl; ENST00000683283.1; ENSP00000507067.1; ENSG00000133816.18. [O94851-1]
DR GeneID; 9645; -.
DR KEGG; hsa:9645; -.
DR MANE-Select; ENST00000683283.1; ENSP00000507067.1; NM_001282663.2; NP_001269592.1. [O94851-1]
DR UCSC; uc001mjz.5; human. [O94851-7]
DR CTD; 9645; -.
DR DisGeNET; 9645; -.
DR GeneCards; MICAL2; -.
DR GeneCards; MICALCL; -.
DR HGNC; HGNC:24693; MICAL2.
DR HPA; ENSG00000133816; Tissue enhanced (brain).
DR MIM; 608881; gene.
DR neXtProt; NX_O94851; -.
DR OpenTargets; ENSG00000133816; -.
DR PharmGKB; PA142671453; -.
DR VEuPathDB; HostDB:ENSG00000133816; -.
DR eggNOG; ENOG502QWDX; Eukaryota.
DR eggNOG; KOG1700; Eukaryota.
DR GeneTree; ENSGT00940000158780; -.
DR HOGENOM; CLU_000329_0_1_1; -.
DR InParanoid; O94851; -.
DR OMA; RRIVPKS; -.
DR OrthoDB; 1029138at2759; -.
DR PhylomeDB; O94851; -.
DR TreeFam; TF324129; -.
DR TreeFam; TF336446; -.
DR PathwayCommons; O94851; -.
DR SignaLink; O94851; -.
DR BioGRID-ORCS; 84953; 14 hits in 1066 CRISPR screens.
DR BioGRID-ORCS; 9645; 9 hits in 1073 CRISPR screens.
DR ChiTaRS; MICAL2; human.
DR ChiTaRS; MICALCL; human.
DR EvolutionaryTrace; O94851; -.
DR GeneWiki; MICAL2; -.
DR GenomeRNAi; 9645; -.
DR Pharos; O94851; Tbio.
DR PRO; PR:Q6ZW33; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O94851; protein.
DR Bgee; ENSG00000133816; Expressed in cerebellar hemisphere and 213 other tissues.
DR ExpressionAtlas; O94851; baseline and differential.
DR Genevisible; O94851; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISS:UniProtKB.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; IEA:Ensembl.
DR GO; GO:0043914; F:NADPH:sulfur oxidoreductase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0016709; F: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; ISS:UniProtKB.
DR GO; GO:0030042; P:actin filament depolymerization; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0001947; P:heart looping; ISS:UniProtKB.
DR GO; GO:0010735; P:positive regulation of transcription via serum response element binding; IMP:UniProtKB.
DR GO; GO:0019417; P:sulfur oxidation; ISS:UniProtKB.
DR CDD; cd00014; CH; 1.
DR Gene3D; 1.10.418.10; -; 1.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR022735; bMERB_dom.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR029939; MICAL2.
DR InterPro; IPR016103; ProQ/FinO.
DR InterPro; IPR001781; Znf_LIM.
DR PANTHER; PTHR23167:SF39; PTHR23167:SF39; 1.
DR Pfam; PF00307; CH; 1.
DR Pfam; PF12130; DUF3585; 1.
DR Pfam; PF01494; FAD_binding_3; 1.
DR Pfam; PF00412; LIM; 1.
DR SMART; SM00033; CH; 1.
DR SMART; SM00132; LIM; 1.
DR SMART; SM00945; ProQ; 1.
DR SUPFAM; SSF47576; SSF47576; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR PROSITE; PS51848; BMERB; 1.
DR PROSITE; PS50021; CH; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 1.
DR PROSITE; PS50023; LIM_DOMAIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Coiled coil; Cytoplasm;
KW FAD; Flavoprotein; LIM domain; Metal-binding; Monooxygenase; NADP; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..1957
FT /note="[F-actin]-monooxygenase MICAL2"
FT /id="PRO_0000075844"
FT DOMAIN 516..619
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 1000..1062
FT /note="LIM zinc-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 1796..1945
FT /note="bMERB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01195"
FT REGION 2..494
FT /note="Monooxygenase domain"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT REGION 660..714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 886..942
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1070..1143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1168..1243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1258..1345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1324..1363
FT /note="Interaction with MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q8BML1"
FT REGION 1361..1431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1467..1626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1675..1779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 660..681
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:24440334"
FT COMPBIAS 665..685
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 686..714
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1070..1091
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1168..1182
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1274..1321
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1411..1431
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1564..1578
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1586..1602
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1675..1691
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1715..1736
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1745..1768
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 97
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 116..118
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 123..125
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 183
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 298
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 398
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 1002
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 1005
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 1023
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 1026
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 1029
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 1032
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 1052
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 1055
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1688
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4G091"
FT VAR_SEQ 1..171
FT /note="Missing (in isoform 2)"
FT /id="VSP_061291"
FT VAR_SEQ 740..986
FT /note="Missing (in isoform 6 and isoform 2)"
FT /id="VSP_061292"
FT VAR_SEQ 740..929
FT /note="Missing (in isoform 4 and isoform 5)"
FT /id="VSP_061293"
FT VAR_SEQ 929..949
FT /note="Missing (in isoform 3)"
FT /id="VSP_061294"
FT VAR_SEQ 950..985
FT /note="Missing (in isoform 4)"
FT /id="VSP_061295"
FT VAR_SEQ 1112..1202
FT /note="DEPTSPKRPKSISEPQHSDAEGDAASPLPSEWTSVRISPGEEAAGQDVLAVR
FT VLVTSEDSSSDTESDYGGSEGSHTEPCEEKPWRPGSPHL -> GISTSFFRKVLGWPLR
FT LPRDLCNWMQGLLQAAGLHIRDNAYNYCYMYELLSLGLPLLWAFSEVLAAMYRESEGSL
FT ESICNWVLRCFPVKLR (in isoform 4, isoform 6 and isoform 2)"
FT /id="VSP_061296"
FT VAR_SEQ 1112..1124
FT /note="DEPTSPKRPKSIS -> VHFSLPVLHPLLG (in isoform 1,
FT isoform 3 and isoform 5)"
FT /id="VSP_061297"
FT VAR_SEQ 1125..1957
FT /note="Missing (in isoform 1, isoform 3 and isoform 5)"
FT /id="VSP_061298"
FT VAR_SEQ 1203..1957
FT /note="Missing (in isoform 4, isoform 6 and isoform 2)"
FT /id="VSP_061299"
FT VARIANT 145
FT /note="F -> L (in dbSNP:rs2706656)"
FT /id="VAR_050155"
FT VARIANT 220
FT /note="I -> V (in dbSNP:rs2306727)"
FT /id="VAR_021992"
FT VARIANT 687
FT /note="D -> E (in dbSNP:rs3794084)"
FT /id="VAR_050156"
FT VARIANT 1089
FT /note="R -> Q (in dbSNP:rs2270515)"
FT /id="VAR_020257"
FT VARIANT 1106
FT /note="L -> P (in dbSNP:rs1027335)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_024523"
FT VARIANT 1110
FT /note="P -> S (in dbSNP:rs35518829)"
FT /id="VAR_050157"
FT VARIANT 1332
FT /note="V -> I (in dbSNP:rs10741578)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_056936"
FT VARIANT 1355
FT /note="Y -> S (in dbSNP:rs12574273)"
FT /id="VAR_056937"
FT VARIANT 1567
FT /note="A -> T (in dbSNP:rs1493953)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_056938"
FT VARIANT 1575
FT /note="S -> G (in dbSNP:rs1493954)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_056939"
FT VARIANT 1631
FT /note="D -> E (in dbSNP:rs3812753)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_056940"
FT VARIANT 1733
FT /note="T -> P (in dbSNP:rs3812754)"
FT /id="VAR_061684"
FT MUTAGEN 95
FT /note="G->V: Blocks FAD binding and abolishes catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:24440334"
FT MUTAGEN 677..681
FT /note="KRRRK->AAAAA: In MICAL-2NLSMut; abolishes nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:24440334"
FT CONFLICT 19
FT /note="F -> S (in Ref. 3; BAG57951)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="D -> G (in Ref. 4; CAD97967)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="T -> A (in Ref. 4; CAD97967)"
FT /evidence="ECO:0000305"
FT CONFLICT 529
FT /note="Q -> H (in Ref. 3; BAG57951)"
FT /evidence="ECO:0000305"
FT CONFLICT 563
FT /note="I -> V (in Ref. 3; BAG57951)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="S -> Y (in Ref. 4; CAD97967)"
FT /evidence="ECO:0000305"
FT CONFLICT 1732
FT /note="P -> PP (in Ref. 3; BAC85674)"
FT /evidence="ECO:0000305"
FT HELIX 520..530
FT /evidence="ECO:0007829|PDB:2E9K"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:2E9K"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:2E9K"
FT STRAND 546..548
FT /evidence="ECO:0007829|PDB:2E9K"
FT HELIX 549..558
FT /evidence="ECO:0007829|PDB:2E9K"
FT TURN 560..562
FT /evidence="ECO:0007829|PDB:2E9K"
FT TURN 565..567
FT /evidence="ECO:0007829|PDB:2E9K"
FT HELIX 570..572
FT /evidence="ECO:0007829|PDB:2E9K"
FT HELIX 573..586
FT /evidence="ECO:0007829|PDB:2E9K"
FT HELIX 596..601
FT /evidence="ECO:0007829|PDB:2E9K"
FT HELIX 607..621
FT /evidence="ECO:0007829|PDB:2E9K"
FT HELIX 1796..1834
FT /evidence="ECO:0007829|PDB:5SZH"
FT HELIX 1845..1894
FT /evidence="ECO:0007829|PDB:5SZH"
FT HELIX 1897..1899
FT /evidence="ECO:0007829|PDB:5SZH"
FT HELIX 1902..1939
FT /evidence="ECO:0007829|PDB:5SZH"
SQ SEQUENCE 1957 AA; 219061 MW; 701E811AD201304F CRC64;
MGENEDEKQA QAGQVFENFV QASTCKGTLQ AFNILTRHLD LDPLDHRNFY SKLKSKVTTW
KAKALWYKLD KRGSHKEYKR GKSCTNTKCL IVGGGPCGLR TAIELAYLGA KVVVVEKRDS
FSRNNVLHLW PFTIHDLRGL GAKKFYGKFC AGSIDHISIR QLQLILFKVA LMLGVEIHVN
VEFVKVLEPP EDQENQKIGW RAEFLPTDHS LSEFEFDVII GADGRRNTLE GFRRKEFRGK
LAIAITANFI NRNSTAEAKV EEISGVAFIF NQKFFQDLKE ETGIDLENIV YYKDCTHYFV
MTAKKQSLLD KGVIINDYID TEMLLCAENV NQDNLLSYAR EAADFATNYQ LPSLDFAMNH
YGQPDVAMFD FTCMYASENA ALVRERQAHQ LLVALVGDSL LEPFWPMGTG CARGFLAAFD
TAWMVKSWNQ GTPPLELLAE RESLYRLLPQ TTPENINKNF EQYTLDPGTR YPNLNSHCVR
PHQVKHLYIT KELEHYPLER LGSVRRSVNL SRKESDIRPS KLLTWCQQQT EGYQHVNVTD
LTTSWRSGLA LCAIIHRFRP ELINFDSLNE DDAVENNQLA FDVAEREFGI PPVTTGKEMA
SAQEPDKLSM VMYLSKFYEL FRGTPLRPVD SWRKNYGENA DLSLAKSSIS NNYLNLTFPR
KRTPRVDGQT GENDMNKRRR KGFTNLDEPS NFSSRSLGSN QECGSSKEGG NQNKVKSMAN
QLLAKFEEST RNPSLMKQER RVSGIGKPVL CSSSGPPVHS CCPKPEEATP SPSPPLKRQF
PSVVVTGHVL RELKQVSAGS ECLSRPWRAR AKSDLQLGGT ENFATLPSTR PRAQALSGVL
WRLQQVEEKI LQKRAQNLAN REFHTKNIKE KAAHLASMFG HGDFPQNKLL SKGLSHTHPP
SPPSRLPSPD PAASSSPSTV DSASPARKEK KSPSGFHFHP SHLRTVHPQL TVGKVSSGIG
AAAEVLVNLY MNDHRPKAQA TSPDLESMRK SFPLNLGGSD TCYFCKKRVY VMERLSAEGH
FFHRECFRCS ICATTLRLAA YTFDCDEGKF YCKPHFIHCK TNSKQRKRRA ELKQQREEEA
TWQEQEAPRR DTPTESSCAV AAIGTLEGSP PDEPTSPKRP KSISEPQHSD AEGDAASPLP
SEWTSVRISP GEEAAGQDVL AVRVLVTSED SSSDTESDYG GSEGSHTEPC EEKPWRPGSP
HLPHTSLGEA LSRAVSPQCP EEPRAVHAAL QRANSFQSPT PSKYQNWRRE FWWSLTPVNK
RTMSPPKDPS PSLPLPSSSS HSSSPPSSSS TSVSGNAPDG SSPPQMTASE PLSQVSRGHP
SPPTPNFRRR AVAQGAPREI PLYLPHHPKP EWAEYCLVSP GEDGLSDPAE MTSDECQPAE
APLGDIGSNH RDPHPIWGKD RSWTGQELSP LAGEDREKGS TGARKEEEGG PVLVKEKLGL
KKLVLTQEQK TMLLDWNDSI PESVHLKAGE RISQKSAENG RGGRVLKPVR PLLLPRAAGE
PLPTQRGAQE KMGTPAEQAQ GERNVPPPKS PLRLIANAIR RSLEPLLSNS EGGKKAWAKQ
ESKTLPAQAC TRSFSLRKTN SNKDGDQHSP GRNQSSAFSP PDPALRTHSL PNRPSKVFPA
LRSPPCSKIE DVPTLLEKVS LQENFPDASK PPKKRISLFS SLRLKDKSFE SFLQESRQRK
DIRDLFGSPK RKVLPEDSAQ ALEKLLQPFK STSLRQAAPP PPPPPPPPPP PPTAGGADSK
NFPLRAQVTE ASSSASSTSS SSADEEFDPQ LSLQLKEKKT LRRRKKLEKA MKQLVKQEEL
KRLYKAQAIQ RQLEEVEERQ RASEIQGVRL EKALRGEADS GTQDEAQLLQ EWFKLVLEKN
KLMRYESELL IMAQELELED HQSRLEQKLR EKMLKEESQK DEKDLNEEQE VFTELMQVIE
QRDKLVDSLE EQRIREKAED QHFESFVFSR GCQLSRT
