MICA1_HUMAN
ID MICA1_HUMAN Reviewed; 1067 AA.
AC Q8TDZ2; B7Z3R5; E1P5F0; Q7Z633; Q8IVS9; Q96G47; Q9H6X6; Q9H7I0; Q9HAA1;
AC Q9UFF7;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=[F-actin]-monooxygenase MICAL1 {ECO:0000305};
DE EC=1.14.13.225 {ECO:0000269|PubMed:29343822};
DE EC=1.6.3.1 {ECO:0000269|PubMed:21864500, ECO:0000269|PubMed:26845023, ECO:0000269|PubMed:29343822};
DE AltName: Full=Molecule interacting with CasL protein 1;
DE Short=MICAL-1;
DE AltName: Full=NEDD9-interacting protein with calponin homology and LIM domains;
GN Name=MICAL1; Synonyms=MICAL, NICAL;
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] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INTERACTION WITH NEDD9 AND VIM, AND VARIANT LYS-758.
RX PubMed=11827972; DOI=10.1074/jbc.m111842200;
RA Suzuki T., Nakamoto T., Ogawa S., Seo S., Matsumura T., Tachibana K.,
RA Morimoto C., Hirai H.;
RT "MICAL, a novel CasL interacting molecule, associates with vimentin.";
RL J. Biol. Chem. 277:14933-14941(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Spleen;
RX PubMed=11214971; DOI=10.1093/dnares/7.6.357;
RA Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen.";
RL DNA Res. 7:357-366(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND VARIANTS
RP LYS-758 AND LYS-758.
RC TISSUE=Colon mucosa, Embryo, Spleen, and Thalamus;
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 GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP CYS-453; THR-624 AND LYS-758.
RC TISSUE=Blood, Lymph, and Uterus;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 422-1067 (ISOFORMS 1/2).
RC TISSUE=Testis;
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 [8]
RP INTERACTION WITH PLXNA3.
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 ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP INTERACTION WITH VIM.
RX PubMed=12788069; DOI=10.1016/s0006-291x(03)00918-5;
RA Weide T., Teuber J., Bayer M., Barnekow A.;
RT "MICAL-1 isoforms, novel rab1 interacting proteins.";
RL Biochem. Biophys. Res. Commun. 306:79-86(2003).
RN [10]
RP INTERACTION WITH RAB1B, AND SUBCELLULAR LOCATION.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-872, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION.
RX PubMed=18305261; DOI=10.1523/jneurosci.5646-07.2008;
RA Schmidt E.F., Shim S.O., Strittmatter S.M.;
RT "Release of MICAL autoinhibition by semaphorin-plexin signaling promotes
RT interaction with collapsin response mediator protein.";
RL J. Neurosci. 28:2287-2297(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617; SER-875 AND SER-876, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, CAUTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=21864500; DOI=10.1016/j.abb.2011.08.004;
RA Zucchini D., Caprini G., Pasterkamp R.J., Tedeschi G., Vanoni M.A.;
RT "Kinetic and spectroscopic characterization of the putative monooxygenase
RT domain of human MICAL-1.";
RL Arch. Biochem. Biophys. 515:1-13(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-872; SER-875 AND SER-876, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617 AND SER-1057, AND
RP IDENTIFICATION BY 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 [18]
RP SUBCELLULAR LOCATION.
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 [19]
RP FUNCTION AS NADPH OXIDASE, BIOPHYSICOCHEMICAL PROPERTIES, CAUTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=26845023; DOI=10.1016/j.abb.2016.01.016;
RA Vitali T., Maffioli E., Tedeschi G., Vanoni M.A.;
RT "Properties and catalytic activities of MICAL1, the flavoenzyme involved in
RT cytoskeleton dynamics, and modulation by its CH, LIM and C-terminal
RT domains.";
RL Arch. Biochem. Biophys. 593:24-37(2016).
RN [20]
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 [21]
RP STRUCTURE BY NMR OF 506-613.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the CH domain of human NEDD9-interacting protein
RT with calponin homology and LIM domains.";
RL Submitted (AUG-2005) to the PDB data bank.
RN [22]
RP STRUCTURE BY NMR OF 506-614.
RX PubMed=17043746; DOI=10.1007/s10858-006-9062-5;
RA Sun H., Dai H., Zhang J., Jin X., Xiong S., Xu J., Wu J., Shi Y.;
RT "Solution structure of calponin homology domain of Human MICAL-1.";
RL J. Biomol. NMR 36:295-300(2006).
RN [23]
RP STRUCTURE BY NMR OF 506-614.
RX PubMed=17662518; DOI=10.1016/j.bpc.2007.06.008;
RA Jin X., Zhang J., Dai H., Sun H., Wang D., Wu J., Shi Y.;
RT "Investigation of the four cooperative unfolding units existing in the
RT MICAL-1 CH domain.";
RL Biophys. Chem. 129:269-278(2007).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 918-1067 IN COMPLEX WITH RAB10,
RP INTERACTION WITH RAB1B; RAB8A; RAB13 AND RAB15, DOMAIN, AND FUNCTION.
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).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 918-1067, FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH RAB35.
RX PubMed=28230050; DOI=10.1038/ncomms14528;
RA Fremont S., Hammich H., Bai J., Wioland H., Klinkert K., Rocancourt M.,
RA Kikuti C., Stroebel D., Romet-Lemonne G., Pylypenko O., Houdusse A.,
RA Echard A.;
RT "Oxidation of F-actin controls the terminal steps of cytokinesis.";
RL Nat. Commun. 8:14528-14528(2017).
RN [26]
RP VARIANT [LARGE SCALE ANALYSIS] MET-309.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
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 (PubMed:29343822). In the absence of actin,
CC it also functions as a NADPH oxidase producing H(2)O(2)
CC (PubMed:21864500, PubMed:26845023, PubMed:29343822). Acts as a
CC cytoskeletal regulator that connects NEDD9 to intermediate filaments.
CC Also acts as a negative regulator of apoptosis via its interaction with
CC STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by
CC MST1/STK4. Involved in regulation of lamina-specific connectivity in
CC the nervous system such as the development of lamina-restricted
CC hippocampal connections. Through redox regulation of the actin
CC cytoskeleton controls the intracellular distribution of secretory
CC vesicles containing L1/neurofascin/NgCAM family proteins in neurons,
CC thereby regulating their cell surface levels (By similarity). May act
CC as Rab effector protein and play a role in vesicle trafficking.
CC {ECO:0000250|UniProtKB:Q8VDP3, ECO:0000269|PubMed:18305261,
CC ECO:0000269|PubMed:21864500, ECO:0000269|PubMed:26845023,
CC ECO:0000269|PubMed:28230050, ECO:0000269|PubMed:29343822,
CC ECO:0000305|PubMed:27552051}.
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:29343822};
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:0000269|PubMed:21864500, ECO:0000269|PubMed:26845023,
CC ECO:0000269|PubMed:29343822};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:21864500};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.7 uM for F-actin (at saturating NADPH concentration)
CC {ECO:0000269|PubMed:21864500};
CC KM=375 uM for NADPH (for the NADPH oxidase reaction)
CC {ECO:0000269|PubMed:26845023};
CC Note=kcat is 0.28 sec(-1) for NADPH for the NADPH oxidase reaction.
CC {ECO:0000269|PubMed:26845023};
CC -!- SUBUNIT: Interacts with STK38 and STK38L (By similarity). Interacts
CC with RAB1B, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms);
CC binding to RAB1B is of low affinity compared to other Rab proteins; at
CC least in case of RAB8A and RAB10 can bind 2 molecules of the Rab
CC proteins simultaneously; ternary complex formation of RAB8A, RAB13 and
CC MICAL1 is possible. Associates with the SH3 domain of NEDD9. Interacts
CC with VIM and PLXNA3. Interacts with RAB1B. {ECO:0000250,
CC ECO:0000269|PubMed:11827972, ECO:0000269|PubMed:12110185,
CC ECO:0000269|PubMed:12788069, ECO:0000269|PubMed:15694364,
CC ECO:0000269|PubMed:27552051}.
CC -!- INTERACTION:
CC Q8TDZ2; Q9NQ75-2: CASS4; NbExp=2; IntAct=EBI-7153876, EBI-12270182;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. Midbody
CC {ECO:0000269|PubMed:28230050}. Note=Accumulates transiently at the
CC abscission site before abscission occurs.
CC {ECO:0000269|PubMed:28230050}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=MICAL-1a;
CC IsoId=Q8TDZ2-1; Sequence=Displayed;
CC Name=2; Synonyms=MICAL-1b;
CC IsoId=Q8TDZ2-2; Sequence=VSP_009639;
CC Name=3;
CC IsoId=Q8TDZ2-3; Sequence=VSP_009637, VSP_009638;
CC Name=4;
CC IsoId=Q8TDZ2-4; Sequence=VSP_042590;
CC -!- TISSUE SPECIFICITY: Expressed in the thymus, lung, spleen, kidney,
CC testis and hematopoietic cells. {ECO:0000269|PubMed:11827972}.
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:0000269|PubMed:27552051}.
CC -!- DOMAIN: The C-terminal coiled coil part contains the plexin-interacting
CC region.
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:Q8VDP3, ECO:0000269|PubMed:21864500,
CC ECO:0000269|PubMed:26845023}.
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DR EMBL; AB048948; BAB86289.1; -; mRNA.
DR EMBL; AK024500; BAB15790.1; -; mRNA.
DR EMBL; AK021999; BAB13949.1; -; mRNA.
DR EMBL; AK025392; BAB15124.1; -; mRNA.
DR EMBL; AK296284; BAH12301.1; -; mRNA.
DR EMBL; AL109947; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48344.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48345.1; -; Genomic_DNA.
DR EMBL; BC009972; AAH09972.2; -; mRNA.
DR EMBL; BC042144; AAH42144.1; -; mRNA.
DR EMBL; BC052983; AAH52983.1; -; mRNA.
DR EMBL; AL122098; CAB59266.1; -; mRNA.
DR CCDS; CCDS5076.1; -. [Q8TDZ2-1]
DR CCDS; CCDS55047.1; -. [Q8TDZ2-2]
DR CCDS; CCDS69170.1; -. [Q8TDZ2-4]
DR PIR; T34532; T34532.
DR RefSeq; NP_001152763.1; NM_001159291.1. [Q8TDZ2-2]
DR RefSeq; NP_001273542.1; NM_001286613.1. [Q8TDZ2-4]
DR RefSeq; NP_073602.3; NM_022765.3. [Q8TDZ2-1]
DR PDB; 1WYL; NMR; -; A=510-612.
DR PDB; 2CO8; NMR; -; A=687-755.
DR PDB; 2DK9; NMR; -; A=506-614.
DR PDB; 5LE0; X-ray; 3.30 A; B=918-1067.
DR PDB; 5LPN; X-ray; 2.80 A; B=918-1067.
DR PDB; 6KU0; X-ray; 1.60 A; B/D=799-822.
DR PDBsum; 1WYL; -.
DR PDBsum; 2CO8; -.
DR PDBsum; 2DK9; -.
DR PDBsum; 5LE0; -.
DR PDBsum; 5LPN; -.
DR PDBsum; 6KU0; -.
DR AlphaFoldDB; Q8TDZ2; -.
DR BMRB; Q8TDZ2; -.
DR SASBDB; Q8TDZ2; -.
DR SMR; Q8TDZ2; -.
DR BioGRID; 122290; 73.
DR CORUM; Q8TDZ2; -.
DR IntAct; Q8TDZ2; 24.
DR MINT; Q8TDZ2; -.
DR STRING; 9606.ENSP00000351664; -.
DR GlyGen; Q8TDZ2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TDZ2; -.
DR MetOSite; Q8TDZ2; -.
DR PhosphoSitePlus; Q8TDZ2; -.
DR BioMuta; MICAL1; -.
DR DMDM; 45593495; -.
DR EPD; Q8TDZ2; -.
DR jPOST; Q8TDZ2; -.
DR MassIVE; Q8TDZ2; -.
DR MaxQB; Q8TDZ2; -.
DR PaxDb; Q8TDZ2; -.
DR PeptideAtlas; Q8TDZ2; -.
DR PRIDE; Q8TDZ2; -.
DR ProteomicsDB; 74376; -. [Q8TDZ2-1]
DR ProteomicsDB; 74377; -. [Q8TDZ2-2]
DR ProteomicsDB; 74378; -. [Q8TDZ2-3]
DR ProteomicsDB; 74379; -. [Q8TDZ2-4]
DR Antibodypedia; 32258; 289 antibodies from 24 providers.
DR DNASU; 64780; -.
DR Ensembl; ENST00000358577.7; ENSP00000351385.3; ENSG00000135596.18. [Q8TDZ2-2]
DR Ensembl; ENST00000358807.8; ENSP00000351664.3; ENSG00000135596.18. [Q8TDZ2-1]
DR Ensembl; ENST00000630715.2; ENSP00000486901.1; ENSG00000135596.18. [Q8TDZ2-4]
DR GeneID; 64780; -.
DR KEGG; hsa:64780; -.
DR MANE-Select; ENST00000358807.8; ENSP00000351664.3; NM_022765.4; NP_073602.3.
DR UCSC; uc003ptk.4; human. [Q8TDZ2-1]
DR CTD; 64780; -.
DR DisGeNET; 64780; -.
DR GeneCards; MICAL1; -.
DR GeneReviews; MICAL1; -.
DR HGNC; HGNC:20619; MICAL1.
DR HPA; ENSG00000135596; Low tissue specificity.
DR MalaCards; MICAL1; -.
DR MIM; 607129; gene.
DR neXtProt; NX_Q8TDZ2; -.
DR OpenTargets; ENSG00000135596; -.
DR PharmGKB; PA134900249; -.
DR VEuPathDB; HostDB:ENSG00000135596; -.
DR eggNOG; KOG1700; Eukaryota.
DR GeneTree; ENSGT00940000159117; -.
DR HOGENOM; CLU_000329_0_0_1; -.
DR InParanoid; Q8TDZ2; -.
DR OMA; CKAQSIQ; -.
DR OrthoDB; 430978at2759; -.
DR PhylomeDB; Q8TDZ2; -.
DR TreeFam; TF324129; -.
DR BRENDA; 1.14.13.225; 2681.
DR PathwayCommons; Q8TDZ2; -.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SABIO-RK; Q8TDZ2; -.
DR SignaLink; Q8TDZ2; -.
DR BioGRID-ORCS; 64780; 10 hits in 1078 CRISPR screens.
DR ChiTaRS; MICAL1; human.
DR EvolutionaryTrace; Q8TDZ2; -.
DR GeneWiki; MICAL1; -.
DR GenomeRNAi; 64780; -.
DR Pharos; Q8TDZ2; Tbio.
DR PRO; PR:Q8TDZ2; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8TDZ2; protein.
DR Bgee; ENSG00000135596; Expressed in right coronary artery and 151 other tissues.
DR ExpressionAtlas; Q8TDZ2; baseline and differential.
DR Genevisible; Q8TDZ2; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1990026; C:hippocampal mossy fiber expansion; IEA:Ensembl.
DR GO; GO:0045171; C:intercellular bridge; IDA:UniProtKB.
DR GO; GO:0005882; C:intermediate filament; NAS:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0051017; P:actin filament bundle assembly; IBA:GO_Central.
DR GO; GO:0030042; P:actin filament depolymerization; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:1903305; P:regulation of regulated secretory pathway; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS: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; IPR045268; LIMA-like.
DR InterPro; IPR029937; MICAL1.
DR InterPro; IPR001781; Znf_LIM.
DR PANTHER; PTHR24206; PTHR24206; 1.
DR PANTHER; PTHR24206:SF59; PTHR24206:SF59; 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 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Coiled coil; Cytoplasm;
KW Cytoskeleton; FAD; Flavoprotein; LIM domain; Metal-binding; Monooxygenase;
KW NADP; Oxidoreductase; Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..1067
FT /note="[F-actin]-monooxygenase MICAL1"
FT /id="PRO_0000075842"
FT DOMAIN 508..612
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 695..757
FT /note="LIM zinc-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 918..1067
FT /note="bMERB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01195,
FT ECO:0000269|PubMed:27552051, ECO:0000269|PubMed:28230050"
FT REGION 1..489
FT /note="Monooxygenase domain"
FT /evidence="ECO:0000250|UniProtKB:Q8VDP3"
FT REGION 645..688
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 755..838
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 867..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 646..666
FT /evidence="ECO:0000255"
FT COILED 919..962
FT /evidence="ECO:0000255"
FT COILED 999..1027
FT /evidence="ECO:0000255"
FT COMPBIAS 645..665
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..795
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 802..821
FT /note="Polar 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 697
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:2CO8"
FT BINDING 700
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:2CO8"
FT BINDING 718
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:2CO8"
FT BINDING 721
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:2CO8"
FT BINDING 724
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:2CO8"
FT BINDING 727
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:2CO8"
FT BINDING 747
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:2CO8"
FT BINDING 750
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:2CO8"
FT MOD_RES 475
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:D3ZBP4"
FT MOD_RES 617
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 872
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 875
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 876
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1057
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..735
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_009637"
FT VAR_SEQ 1
FT /note="M -> MSCLSHSSLPSCCPPQEASM (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042590"
FT VAR_SEQ 312..397
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009639"
FT VAR_SEQ 736..768
FT /note="YEQHPGDGHFYCLQHLPQTDHKAEGSDRGPESP -> MPRLTFAPKGWPHPP
FT TSLHPGQVTDQTTWWLFQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_009638"
FT VARIANT 12
FT /note="A -> S (in dbSNP:rs4946977)"
FT /id="VAR_067063"
FT VARIANT 12
FT /note="A -> T (in dbSNP:rs4946977)"
FT /id="VAR_050153"
FT VARIANT 153
FT /note="D -> A (in dbSNP:rs34726911)"
FT /id="VAR_050154"
FT VARIANT 195
FT /note="R -> H (in dbSNP:rs34699467)"
FT /id="VAR_067064"
FT VARIANT 309
FT /note="L -> M (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036191"
FT VARIANT 453
FT /note="R -> C (in dbSNP:rs17854785)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_067065"
FT VARIANT 624
FT /note="A -> T (in dbSNP:rs17850590)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_067066"
FT VARIANT 758
FT /note="A -> E (in dbSNP:rs9320288)"
FT /id="VAR_017903"
FT VARIANT 758
FT /note="A -> K (requires 2 nucleotide substitutions;
FT dbSNP:rs35260632)"
FT /evidence="ECO:0000269|PubMed:11827972,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_067067"
FT VARIANT 758
FT /note="A -> S (in dbSNP:rs59056467)"
FT /id="VAR_067068"
FT VARIANT 758
FT /note="A -> T (in dbSNP:rs59056467)"
FT /id="VAR_061355"
FT CONFLICT 767
FT /note="S -> C (in Ref. 3; BAB15124)"
FT /evidence="ECO:0000305"
FT CONFLICT 816
FT /note="L -> S (in Ref. 3; BAH12301)"
FT /evidence="ECO:0000305"
FT CONFLICT 877
FT /note="E -> V (in Ref. 3; BAH12301)"
FT /evidence="ECO:0000305"
FT CONFLICT 887
FT /note="S -> L (in Ref. 7; CAB59266)"
FT /evidence="ECO:0000305"
FT CONFLICT 981
FT /note="K -> N (in Ref. 3; BAB13949)"
FT /evidence="ECO:0000305"
FT HELIX 511..524
FT /evidence="ECO:0007829|PDB:1WYL"
FT TURN 533..538
FT /evidence="ECO:0007829|PDB:1WYL"
FT HELIX 541..550
FT /evidence="ECO:0007829|PDB:1WYL"
FT HELIX 552..554
FT /evidence="ECO:0007829|PDB:2DK9"
FT HELIX 560..562
FT /evidence="ECO:0007829|PDB:1WYL"
FT HELIX 565..578
FT /evidence="ECO:0007829|PDB:1WYL"
FT HELIX 588..593
FT /evidence="ECO:0007829|PDB:1WYL"
FT HELIX 597..610
FT /evidence="ECO:0007829|PDB:1WYL"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:2CO8"
FT TURN 706..708
FT /evidence="ECO:0007829|PDB:2CO8"
FT TURN 719..721
FT /evidence="ECO:0007829|PDB:2CO8"
FT STRAND 725..727
FT /evidence="ECO:0007829|PDB:2CO8"
FT STRAND 735..737
FT /evidence="ECO:0007829|PDB:2CO8"
FT TURN 740..742
FT /evidence="ECO:0007829|PDB:2CO8"
FT TURN 748..750
FT /evidence="ECO:0007829|PDB:2CO8"
FT HELIX 810..817
FT /evidence="ECO:0007829|PDB:6KU0"
FT HELIX 919..959
FT /evidence="ECO:0007829|PDB:5LPN"
FT HELIX 963..972
FT /evidence="ECO:0007829|PDB:5LPN"
FT HELIX 974..1013
FT /evidence="ECO:0007829|PDB:5LPN"
FT HELIX 1027..1059
FT /evidence="ECO:0007829|PDB:5LPN"
SQ SEQUENCE 1067 AA; 117875 MW; 78C1BBF3E3CCD56B CRC64;
MASPTSTNPA HAHFESFLQA QLCQDVLSSF QELCGALGLE PGGGLPQYHK IKDQLNYWSA
KSLWTKLDKR AGQPVYQQGR ACTSTKCLVV GAGPCGLRVA VELALLGARV VLVEKRTKFS
RHNVLHLWPF TIHDLRALGA KKFYGRFCTG TLDHISIRQL QLLLLKVALL LGVEIHWGVT
FTGLQPPPRK GSGWRAQLQP NPPAQLANYE FDVLISAAGG KFVPEGFKVR EMRGKLAIGI
TANFVNGRTV EETQVPEISG VARIYNQSFF QSLLKATGID LENIVYYKDD THYFVMTAKK
QCLLRLGVLR QDWPDTNRLL GSANVVPEAL QRFTRAAADF ATHGKLGKLE FAQDAHGQPD
VSAFDFTSMM RAESSARVQE KHGARLLLGL VGDCLVEPFW PLGTGVARGF LAAFDAAWMV
KRWAEGAESL EVLAERESLY QLLSQTSPEN MHRNVAQYGL DPATRYPNLN LRAVTPNQVR
DLYDVLAKEP VQRNNDKTDT GMPATGSAGT QEELLRWCQE QTAGYPGVHV SDLSSSWADG
LALCALVYRL QPGLLEPSEL QGLGALEATA WALKVAENEL GITPVVSAQA VVAGSDPLGL
IAYLSHFHSA FKSMAHSPGP VSQASPGTSS AVLFLSKLQR TLQRSRAKEN AEDAGGKKLR
LEMEAETPST EVPPDPEPGV PLTPPSQHQE AGAGDLCALC GEHLYVLERL CVNGHFFHRS
CFRCHTCEAT LWPGGYEQHP GDGHFYCLQH LPQTDHKAEG SDRGPESPEL PTPSENSMPP
GLSTPTASQE GAGPVPDPSQ PTRRQIRLSS PERQRLSSLN LTPDPEMEPP PKPPRSCSAL
ARHALESSFV GWGLPVQSPQ ALVAMEKEEK ESPFSSEEEE EDVPLDSDVE QALQTFAKTS
GTMNNYPTWR RTLLRRAKEE EMKRFCKAQT IQRRLNEIEA ALRELEAEGV KLELALRRQS
SSPEQQKKLW VGQLLQLVDK KNSLVAEEAE LMITVQELNL EEKQWQLDQE LRGYMNREEN
LKTAADRQAE DQVLRKLVDL VNQRDALIRF QEERRLSELA LGTGAQG
