MICA1_RAT
ID MICA1_RAT Reviewed; 1047 AA.
AC D3ZBP4; D3ZJD1;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=[F-actin]-monooxygenase MICAL1 {ECO:0000305};
DE EC=1.14.13.225 {ECO:0000250|UniProtKB:Q8TDZ2};
DE EC=1.6.3.1 {ECO:0000250|UniProtKB:Q8TDZ2};
DE AltName: Full=Molecule interacting with CasL protein 1;
DE Short=MICAL-1;
GN Name=Mical1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-475, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Monooxygenase that promotes depolymerization of F-actin by
CC mediating oxidation of specific methionine residues on actin to form
CC methionine-sulfoxide, resulting in actin filament disassembly and
CC preventing repolymerization. In the absence of actin, it also functions
CC as a NADPH oxidase producing H(2)O(2). Acts as a cytoskeletal regulator
CC that connects NEDD9 to intermediate filaments. Also acts as a negative
CC regulator of apoptosis via its interaction with STK38 and STK38L; acts
CC by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in
CC regulation of lamina-specific connectivity in the nervous system such
CC as the development of lamina-restricted hippocampal connections.
CC Through redox regulation of the actin cytoskeleton controls the
CC intracellular distribution of secretory vesicles containing
CC L1/neurofascin/NgCAM family proteins in neurons, thereby regulating
CC their cell surface levels. May act as Rab effector protein and play a
CC role in vesicle trafficking. {ECO:0000250|UniProtKB:Q8TDZ2}.
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:Q8TDZ2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 = H2O2 + NADP(+); Xref=Rhea:RHEA:11260,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.6.3.1;
CC Evidence={ECO:0000250|UniProtKB:Q8TDZ2};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q8TDZ2};
CC -!- SUBUNIT: Interacts with STK38 and STK38L. Associates with the SH3
CC domain of NEDD9. Interacts with VIM and PLXNA3. Interacts with RAB1B,
CC RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to
CC RAB1B is of low affinity compared to other Rab proteins; at least in
CC case of RAB8A and RAB10 can bind 2 molecules of the Rab proteins
CC simultaneously. {ECO:0000250|UniProtKB:Q8TDZ2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8TDZ2}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q8TDZ2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=D3ZBP4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=D3ZBP4-2; Sequence=VSP_042607, VSP_042608;
CC -!- DOMAIN: The C-terminal coiled coil part contains the plexin-interacting
CC region. {ECO:0000250|UniProtKB:Q8TDZ2}.
CC -!- DOMAIN: The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates
CC binding to predominantly Rab8, Rab10, Rab10, Rab13 and Rab15 (in their
CC GTP-bound forms). {ECO:0000250|UniProtKB:Q8TDZ2}.
CC -!- SIMILARITY: Belongs to the Mical family. {ECO:0000305}.
CC -!- CAUTION: The reaction mechanism is subject to discussion. Some work
CC suggest MICAL enzymes directly oxidize actin methionine residues to
CC produce methionine-(R)-S-oxide. Other publications suggest that the
CC enzyme functions as a NADPH oxidase producing H(2)O(2) (EC 1.6.3.1) and
CC that it is the produced H(2)O(2) that is responsible for the
CC methionine-(R)-S-oxide production. {ECO:0000250|UniProtKB:Q86BA1,
CC ECO:0000250|UniProtKB:Q8TDZ2, ECO:0000250|UniProtKB:Q8VDP3}.
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DR EMBL; CH474025; EDL99736.1; -; Genomic_DNA.
DR RefSeq; NP_001099867.1; NM_001106397.1. [D3ZBP4-1]
DR AlphaFoldDB; D3ZBP4; -.
DR SMR; D3ZBP4; -.
DR IntAct; D3ZBP4; 1.
DR STRING; 10116.ENSRNOP00000000337; -.
DR iPTMnet; D3ZBP4; -.
DR PhosphoSitePlus; D3ZBP4; -.
DR PaxDb; D3ZBP4; -.
DR PRIDE; D3ZBP4; -.
DR Ensembl; ENSRNOT00000000337; ENSRNOP00000000337; ENSRNOG00000000307. [D3ZBP4-1]
DR GeneID; 294520; -.
DR KEGG; rno:294520; -.
DR CTD; 64780; -.
DR RGD; 1309386; Mical1.
DR eggNOG; KOG1700; Eukaryota.
DR GeneTree; ENSGT00940000159117; -.
DR HOGENOM; CLU_000329_0_0_1; -.
DR InParanoid; D3ZBP4; -.
DR OMA; CKAQSIQ; -.
DR OrthoDB; 430978at2759; -.
DR TreeFam; TF324129; -.
DR PRO; PR:D3ZBP4; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Proteomes; UP000234681; Chromosome 20.
DR Bgee; ENSRNOG00000000307; Expressed in thymus and 19 other tissues.
DR Genevisible; D3ZBP4; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:1990026; C:hippocampal mossy fiber expansion; ISO:RGD.
DR GO; GO:0045171; C:intercellular bridge; ISO:RGD.
DR GO; GO:0030496; C:midbody; ISO:RGD.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; ISO:RGD.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; ISO:RGD.
DR GO; GO:0106294; F:NADPH oxidase H202-forming activity; IEA:RHEA.
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:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0017124; F:SH3 domain binding; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0030042; P:actin filament depolymerization; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:1903305; P:regulation of regulated secretory pathway; ISO:RGD.
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; IPR001781; Znf_LIM.
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 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Coiled coil; Cytoplasm; Cytoskeleton;
KW FAD; Flavoprotein; LIM domain; Metal-binding; Monooxygenase; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..1047
FT /note="[F-actin]-monooxygenase MICAL1"
FT /id="PRO_0000416299"
FT DOMAIN 507..611
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 679..741
FT /note="LIM zinc-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 905..1047
FT /note="bMERB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01195"
FT REGION 1..489
FT /note="Monooxygenase domain"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT REGION 644..672
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 739..787
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 849..872
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 912..996
FT /evidence="ECO:0000255"
FT COMPBIAS 747..770
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 849..871
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 95
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 114..116
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 121..123
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 181
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 293
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 393
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT BINDING 681
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 684
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 702
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 705
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 708
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 711
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 731
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT BINDING 734
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT MOD_RES 475
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 616
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDZ2"
FT MOD_RES 777
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT MOD_RES 781
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT VAR_SEQ 87..159
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042607"
FT VAR_SEQ 192
FT /note="S -> N (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042608"
SQ SEQUENCE 1047 AA; 116672 MW; B74E4A60CBB65A5B CRC64;
MASPTSTNPA HDHFETFVQA QLCQDVLSSF QGLCRALGVE SGGGLPQYHK IKAQLNYWSA
KSLWAKLDKR ASQPAYQQGQ ACTNTKCLVV GAGPCGLRAA VELALLGARV VLVEKRTKFS
RHNVLHLWPF TIHDLRALGA KKFYGRFCTG TLDHISIRQL QLLLLKVALL LGVEIHWGFT
FTGLQPPPKK GSGWRARIQP SPPAQLASYE FDVLISAGGG KFVPEGFTIR EMRGKLAIGI
TANFVNGRTV EETQVPEISG VARIYNQKFF QSLLKATGID LENIVYYKDD THYFVMTAKK
QCLLRLGVLR QDLPETDQLL GKANVVPEAL QQFARAAADF ATQGKLGKLE FAQDARGRPD
VAAFDFTSMM RSESSARIQE KHGARLLLGL VGDCLVEPFW PLGTGVARGF LAAFDAAWMV
KRWAEGTGPL ELLAERESLY QLLSQTSPEN MHRNVAQYGL DPATRYPNLN LRAVTPNQVQ
DLYDIMDKEH ARKKSDETDA RKTTTGSAGT EELLHWCQEQ TAGFPGVSVT DFSSSWADGR
ALCALVHRLQ PGLLEPSELQ GMSALEATAW ALRVAEYELG IIPVLSAQAV VAGSDPLGLI
AYLSHFHSAF KNTPHSSGLV SQPHGTPSAI LFLGKLQRSL QRTRTKVEEE TPCTEEPPVS
EPSVPPALPS EHEEAGAEDV CELCGKRLYI LERFCVDGHF FHRGCFCCRT CEATLRPGGY
GQYPGDGYFY CLQHLPQEDQ KEADNNGSPE NQELPTPGDS TTQSGPSSPV PPVTEASPVP
SPSQPARRLI RLSSVERLRL SSLNIIPDSG VEPPPKPPRS CLDLAQESLK SSFMGWGVLR
APQVPEAIEK GEEEEEEEEE EEEEEEELPP PLALEVEQSL LTLAKNSGDM TKYPTWRRTL
MRRAKEEEMK RFCKAQAIQR RLNEIEAAMR ELETEGMKLE VALRKESSSP EKQKKLWLEQ
LLQLIQKKNS LVTEEAELMI TVQELDLEEK QRQLDHEFRG INREETLKTQ ADRLSEDRVL
RKLLDVVNQR DALIQFQEER RLREMPV
