MCA2B_DANRE
ID MCA2B_DANRE Reviewed; 1679 AA.
AC F1RA39; A0A0A0MPT7; E5F2M5; F6P3I3; J9XHI3; J9XHS8; J9XJU2; J9XNZ0;
DT 11-JUN-2014, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=[F-actin]-monooxygenase mical2b {ECO:0000250|UniProtKB:O94851};
DE EC=1.14.13.225 {ECO:0000250|UniProtKB:O94851};
DE AltName: Full=Molecule interacting with CasL protein 2B;
DE Short=MICAL-2;
GN Name=mical2b {ECO:0000250|UniProtKB:O94851}; Synonyms=si:ch211-192p3.1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RA Ji X., Du S.;
RT "microtubule associated monoxygenase calponin and LIM domain containing 2b
RT play a vital role in myofibril organization in zebrafish.";
RL Submitted (JUL-2012) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 93-1571 (ISOFORM 1).
RC STRAIN=Tuebingen;
RX PubMed=21035094; DOI=10.1016/s1673-8527(09)60086-2;
RA Xue Y., Kuok C., Xiao A., Zhu Z., Lin S., Zhang B.;
RT "Identification and expression analysis of mical family genes in
RT zebrafish.";
RL J. Genet. Genomics 37:685-693(2010).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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).
CC -!- FUNCTION: Nuclear monooxygenase that promotes depolymerization of F-
CC actin by mediating oxidation of specific methionine residues on actin
CC and regulates the srf signaling. Acts by modifying nuclear actin
CC subunits through the addition of oxygen to form methionine-sulfoxide,
CC leading to promote actin filament severing and prevent repolymerization
CC (By similarity). Acts as a key regulator of the srf signaling pathway
CC elicited by nerve growth factor and serum: mediates oxidation and
CC subsequent depolymerization of nuclear actin, leading to increase
CC mkl1/mrtf-a presence in the nucleus and promote srf:mkl1/mrtf-a-
CC dependent gene transcription (PubMed:24440334).
CC {ECO:0000250|UniProtKB:O94851, ECO:0000269|PubMed:24440334}.
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:0000250|UniProtKB:O94851};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q8TDZ2};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O94851}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8BML1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=5;
CC IsoId=F1RA39-5; Sequence=Displayed;
CC Name=1;
CC IsoId=F1RA39-1; Sequence=VSP_061325;
CC Name=2; Synonyms=S1;
CC IsoId=F1RA39-2; Sequence=VSP_061327, VSP_061330;
CC Name=3; Synonyms=S3;
CC IsoId=F1RA39-3; Sequence=VSP_061328, VSP_061329;
CC Name=4; Synonyms=S2;
CC IsoId=F1RA39-4; Sequence=VSP_061326, VSP_061328, VSP_061329;
CC -!- DISRUPTION PHENOTYPE: Small hearts that fail to undergo normal looping
CC at 24 hours post-fertilization (hpf) with thin, linear morphology
CC compared to wild-type hearts at 48 hpf. moreover, cardiomyocytes hearts
CC are spatially disorganized. Defects in srf:mkl1/mrtf-a-dependent gene
CC transcription. {ECO:0000269|PubMed:24440334}.
CC -!- SIMILARITY: Belongs to the Mical family. {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; JX291154; AFS28883.1; -; mRNA.
DR EMBL; JX291155; AFS28884.1; -; mRNA.
DR EMBL; JX291156; AFS28885.1; -; mRNA.
DR EMBL; JX291157; AFS28886.1; -; mRNA.
DR EMBL; BX908400; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR388031; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759887; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; HM151006; ADQ13088.1; -; mRNA.
DR RefSeq; NP_001258842.1; NM_001271913.1. [F1RA39-1]
DR RefSeq; XP_005174399.1; XM_005174342.3. [F1RA39-1]
DR RefSeq; XP_005174402.1; XM_005174345.1. [F1RA39-3]
DR AlphaFoldDB; F1RA39; -.
DR STRING; 7955.ENSDARP00000119970; -.
DR PaxDb; F1RA39; -.
DR PRIDE; F1RA39; -.
DR Ensembl; ENSDART00000109672; ENSDARP00000099449; ENSDARG00000020395. [F1RA39-2]
DR Ensembl; ENSDART00000139013; ENSDARP00000119970; ENSDARG00000020395. [F1RA39-5]
DR Ensembl; ENSDART00000141994; ENSDARP00000116980; ENSDARG00000020395. [F1RA39-1]
DR Ensembl; ENSDART00000158582; ENSDARP00000134150; ENSDARG00000020395. [F1RA39-1]
DR Ensembl; ENSDART00000185592; ENSDARP00000148540; ENSDARG00000020395. [F1RA39-3]
DR Ensembl; ENSDART00000190093; ENSDARP00000153343; ENSDARG00000020395. [F1RA39-4]
DR GeneID; 569564; -.
DR KEGG; dre:569564; -.
DR CTD; 569564; -.
DR ZFIN; ZDB-GENE-061207-15; mical2b.
DR eggNOG; KOG1700; Eukaryota.
DR GeneTree; ENSGT00940000158780; -.
DR HOGENOM; CLU_000329_3_0_1; -.
DR OMA; RRIVPKS; -.
DR OrthoDB; 430978at2759; -.
DR TreeFam; TF324129; -.
DR PRO; PR:F1RA39; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 25.
DR Bgee; ENSDARG00000020395; Expressed in heart and 47 other tissues.
DR ExpressionAtlas; F1RA39; baseline.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0043914; F:NADPH:sulfur oxidoreductase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:UniProtKB.
DR GO; GO:0030042; P:actin filament depolymerization; ISS:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0001947; P:heart looping; IMP:UniProtKB.
DR GO; GO:0010735; P:positive regulation of transcription via serum response element binding; 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; 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 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 2: Evidence at transcript level;
KW Actin-binding; Alternative splicing; Cytoplasm; FAD; Flavoprotein;
KW LIM domain; Metal-binding; Monooxygenase; NADP; Nucleus; Oxidoreductase;
KW Reference proteome; Zinc.
FT CHAIN 1..1679
FT /note="[F-actin]-monooxygenase mical2b"
FT /id="PRO_0000429476"
FT DOMAIN 516..619
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 1011..1073
FT /note="LIM zinc-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 1517..1667
FT /note="bMERB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01195"
FT REGION 2..494
FT /note="Monooxygenase domain"
FT /evidence="ECO:0000250"
FT REGION 661..772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 818..838
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 874..907
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1073..1163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1194..1247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1259..1283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1302..1342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1473..1509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 658..679
FT /note="Nuclear localization signal"
FT COMPBIAS 661..685
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 731..745
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1085..1127
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1220..1242
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1266..1283
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1307..1323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1473..1489
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1490..1509
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 97..125
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 97
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 116
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 118
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 123
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 125
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 398
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT VAR_SEQ 731..996
FT /note="Missing (in isoform 1)"
FT /id="VSP_061325"
FT VAR_SEQ 886..997
FT /note="TDESSPAVSPSSPPQTIPESSTLSCLLSPAPSLTHKQCSEASETHLKADKHT
FT EIRRVERLDPSKQRTVGKVSSAIGVKAATLAILYETDHRPNNPITLSLTEARRCAESGL
FT V -> V (in isoform 4)"
FT /id="VSP_061326"
FT VAR_SEQ 1108..1120
FT /note="GGEFDSSTQQDLQ -> VCFKFPMLQALIG (in isoform 2)"
FT /id="VSP_061327"
FT VAR_SEQ 1108..1119
FT /note="GGEFDSSTQQDL -> EAAFLSQSHSFP (in isoform 4 and
FT isoform 3)"
FT /id="VSP_061328"
FT VAR_SEQ 1120..1679
FT /note="Missing (in isoform 4 and isoform 3)"
FT /id="VSP_061329"
FT VAR_SEQ 1121..1679
FT /note="Missing (in isoform 2)"
FT /id="VSP_061330"
FT CONFLICT 879
FT /note="G -> D (in Ref. 1; AFS28886)"
FT /evidence="ECO:0000305"
FT CONFLICT 1088
FT /note="S -> P (in Ref. 3; ADQ13088)"
FT /evidence="ECO:0000305"
FT CONFLICT 1224
FT /note="S -> A (in Ref. 3; ADQ13088)"
FT /evidence="ECO:0000305"
FT CONFLICT 1314
FT /note="Q -> E (in Ref. 3; ADQ13088)"
FT /evidence="ECO:0000305"
FT CONFLICT 1327
FT /note="H -> Y (in Ref. 3; ADQ13088)"
FT /evidence="ECO:0000305"
FT CONFLICT 1485
FT /note="K -> E (in Ref. 3; ADQ13088)"
FT /evidence="ECO:0000305"
FT CONFLICT 1502
FT /note="G -> D (in Ref. 3; ADQ13088)"
FT /evidence="ECO:0000305"
FT CONFLICT 1511
FT /note="I -> M (in Ref. 3; ADQ13088)"
FT /evidence="ECO:0000305"
FT CONFLICT F1RA39-3:879
FT /note="G -> D (in Ref. 1; AFS28886)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1679 AA; 189361 MW; 03C2EBFAB5857EB9 CRC64;
MGETEEERTS QAGQLFENFI QATTCKGTLQ AFSVLCRQLE LNPSDHRGFY SSLKTAVTFW
KAKGLWGKLD KRAGHKEYSK GRACADTRCL IIGGGPCGFR TAIELALLGA KVVVIEKRDT
FSRNNVLHLW PYTIHDLRNL GAKKFYGKFC AGSIDHISIR QLQLMLLKIA LIVGVEVHVN
VEFVKLLEPP EDQSTDGQGW RAEIRPADNP VSDYEFDVII GADGRRSTLD GFRRKEFRGK
LAIAITANFV NRNTTAEAKV EEISGVAFIF NQKFFLELKE ETGIDLENIV YYKDNTHYFV
MTAKKQSLLD KGVIINDYIE TERLLAFDNV NQEALLSYAR EAADFGTNYQ LPSLDYAINH
YGQPDVAMFD FTCMYASENA ALVREKSHRQ LLVALVGDSL LEPFWPMGTG CARGFLAAFD
TAWMIKGWAQ GKEPLDLLSE RESIYRLLPQ TTAENISKNF EQYTIDPATR YPNLNSSCVR
PHQVRHLFIS GEQDLSSLER SGQTRRSVSI SRRESEVRPG RLLLWCQNQT QDYRGVNVTD
LNTSWRSGLA LCALIHRQRP ELIDFDSLNE ADCAKNNQLA FDVAEREFGI QPVTTGKEMD
AERGPDKLIM VLYLSKFYEM FHKSTQSVTG LPKEIDANNG DCSSKTANSL YNSINHARKR
IPKLDKKLEE SDVNRKRKKA SSHHEELMSC QTAPPAGERE EQKENKVRSM ATQLLARFEE
NAPSCALRRQ SDSESDSDAD RPVSLDLTEN PRFARPKIEP THPSTTPDKA KWQPSPYLRL
LESNTRSETL HTEHYVESQS SHRLTEIQSE CQYSSVSSAY KSSERRPRSP LIPFTPTLSP
MMHCLQQLEE QVIQQRKREP LNRKSIKERA QKLSSLFTGN PAQPQTDESS PAVSPSSPPQ
TIPESSTLSC LLSPAPSLTH KQCSEASETH LKADKHTEIR RVERLDPSKQ RTVGKVSSAI
GVKAATLAIL YETDHRPNNP ITLSLTEARR CAESGLVSVR KEFSASLGGS DTCVFCQKRV
YIMERLSAEG FFFHRECFRC HICGCSLRLG AHTFDSQQGT FYCKMHFSQR KTSTRHRRGE
IQDGGIRSSS ITISNHTSTD GTRGQPSGGE FDSSTQQDLQ TLPDSKEIIS VSEVKDSSKK
ADPADSAPAC PDSPLQKVKR STAKGEITNK NILWKKKIRS TLPLVLMKKF HRGKPEDKTE
VLAEEDGNSD FEEIHESLSS KKPSNPSTDS NCLPTKDNSS TPLDEIPKIP LYRTHVLPEY
PKPSSSSPEP IVTSISSDPI SFSPKKKLTL SLSEKEKLLN WDLTNPGKSG AEEQQQQHVK
PSISLQHDHP EPTHPQPEPA PPLFGFQQWA NNLRKSFSKG SNPVVLRRNR PMKARPLSEG
SFNVGAVFQD EERCGSLVDE GEARPRTESE IASLLEQVAL GSKTSRGTKD DMASLPPRKL
NFFSSLRIKR VEGAEQSRGE GQKDILSILS RFRNKASAQQ QQQQKSNSSS EDEQEPKLTH
SGALQKKKEK IAIRQTKSDE LKRLHRAQVI QRQLEEVEEK QRSLEEKGVA LEKVLRGENG
DDGSTDEAAL LQTWFKLVLE KNKLSRYESE LMIFAQELEL EDTQSRLQQD LRRRMATEDC
EKSASELVEE QNILVEIMKV VEKRDKLVSL LEEQRLKEKA EDRDLESLIL SRGYQFHWT
