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 27-MAR-2024, entry version 191. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; CCDS7809.1; -. [O94851-1] DR CCDS; CCDS91442.1; -. [O94851-7] DR CCDS; CCDS91443.1; -. [O94851-6] 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; 37. DR BioGRID; 124385; 2. DR IntAct; O94851; 22. DR MINT; O94851; -. DR STRING; 9606.ENSP00000256194; -. DR GlyGen; O94851; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O94851; -. DR PhosphoSitePlus; O94851; -. DR SwissPalm; O94851; -. DR BioMuta; MICAL2; -. DR BioMuta; MICALCL; -. DR DMDM; 296439303; -. DR EPD; O94851; -. DR jPOST; O94851; -. DR MassIVE; O94851; -. DR MaxQB; O94851; -. DR PaxDb; 9606-ENSP00000256186; -. DR PeptideAtlas; 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 ProteomicsDB; 68455; -. DR Pumba; O94851; -. DR Antibodypedia; 24509; 174 antibodies from 24 providers. DR DNASU; 84953; -. DR DNASU; 9645; -. DR Ensembl; ENST00000256194.8; ENSP00000256194.4; ENSG00000133816.19. [O94851-1] DR Ensembl; ENST00000527546.5; ENSP00000433965.1; ENSG00000133816.19. [O94851-5] DR Ensembl; ENST00000528931.5; ENSP00000499778.1; ENSG00000133816.19. [O94851-6] DR Ensembl; ENST00000646065.1; ENSP00000494982.1; ENSG00000133816.19. [O94851-7] DR Ensembl; ENST00000675839.1; ENSP00000502351.1; ENSG00000133816.19. [O94851-3] DR Ensembl; ENST00000683283.1; ENSP00000507067.1; ENSG00000133816.19. [O94851-1] DR Ensembl; ENST00000707072.1; ENSP00000516723.1; ENSG00000133816.19. [O94851-4] 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 AGR; HGNC:24693; -. DR DisGeNET; 9645; -. DR GeneCards; MICAL2; -. DR HGNC; HGNC:24693; MICAL2. DR HPA; ENSG00000133816; Tissue enriched (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; CEHEQSG; -. DR OrthoDB; 5399346at2759; -. DR PhylomeDB; O94851; -. DR TreeFam; TF324129; -. DR TreeFam; TF336446; -. DR PathwayCommons; O94851; -. DR SignaLink; O94851; -. DR BioGRID-ORCS; 84953; 16 hits in 1142 CRISPR screens. DR BioGRID-ORCS; 9645; 9 hits in 1150 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:O94851; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O94851; Protein. DR Bgee; ENSG00000133816; Expressed in cerebellar hemisphere and 215 other cell types or tissues. DR ExpressionAtlas; O94851; baseline and differential. DR GO; GO:0005884; C:actin filament; IDA:UniProt. 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:0004497; F:monooxygenase activity; IDA:UniProt. DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; IEA:Ensembl. 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:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0019417; P:sulfur oxidation; ISS:UniProtKB. DR CDD; cd21195; CH_MICAL2_3-like; 1. DR CDD; cd09439; LIM_Mical; 1. DR Gene3D; 1.10.418.10; Calponin-like domain; 1. DR Gene3D; 2.10.110.10; Cysteine Rich Protein; 1. DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1. DR InterPro; IPR022735; bMERB_dom. DR InterPro; IPR001715; CH_dom. DR InterPro; IPR036872; CH_dom_sf. DR InterPro; IPR002938; FAD-bd. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR InterPro; IPR016103; ProQ/FinO. DR InterPro; IPR001781; Znf_LIM. DR PANTHER; PTHR23167:SF39; [F-ACTIN]-MONOOXYGENASE MICAL2; 1. DR PANTHER; PTHR23167; CALPONIN HOMOLOGY DOMAIN-CONTAINING PROTEIN DDB_G0272472-RELATED; 1. DR Pfam; PF12130; bMERB_dom; 1. DR Pfam; PF00307; CH; 1. DR Pfam; PF01494; FAD_binding_3; 1. DR Pfam; PF00412; LIM; 1. DR PRINTS; PR00420; RNGMNOXGNASE. DR SMART; SM00033; CH; 1. DR SMART; SM01203; DUF3585; 1. DR SMART; SM00132; LIM; 1. DR SMART; SM00945; ProQ; 1. DR SUPFAM; SSF47576; Calponin-homology domain, CH-domain; 1. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1. DR SUPFAM; SSF101447; Formin homology 2 domain (FH2 domain); 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 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. DR Genevisible; O94851; HS. 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 //