MYO3A_MOUSE
ID MYO3A_MOUSE Reviewed; 1613 AA.
AC Q8K3H5;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Myosin-IIIa;
DE EC=2.7.11.1;
GN Name=Myo3a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ;
RX PubMed=12032315; DOI=10.1073/pnas.102091699;
RA Walsh T., Walsh V., Vreugde S., Hertzano R., Shahin H., Haika S., Lee M.K.,
RA Kanaan M., King M.-C., Avraham K.B.;
RT "From flies' eyes to our ears: mutations in a human class III myosin cause
RT progressive nonsyndromic hearing loss DFNB30.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7518-7523(2002).
RN [2]
RP FUNCTION.
RX PubMed=19287378; DOI=10.1038/ncb1851;
RA Salles F.T., Merritt R.C. Jr., Manor U., Dougherty G.W., Sousa A.D.,
RA Moore J.E., Yengo C.M., Dose A.C., Kachar B.;
RT "Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to
RT the plus ends of actin filaments.";
RL Nat. Cell Biol. 11:443-450(2009).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH MORN4, TISSUE SPECIFICITY,
RP AND SUBCELLULAR LOCATION.
RX PubMed=26754646; DOI=10.1083/jcb.201509017;
RA Lelli A., Michel V., Boutet de Monvel J., Cortese M., Bosch-Grau M.,
RA Aghaie A., Perfettini I., Dupont T., Avan P., El-Amraoui A., Petit C.;
RT "Class III myosins shape the auditory hair bundles by limiting microvilli
RT and stereocilia growth.";
RL J. Cell Biol. 212:231-244(2016).
RN [4]
RP INTERACTION WITH ESPN AND ESPNL.
RX PubMed=26926603; DOI=10.1038/ncomms10833;
RA Ebrahim S., Avenarius M.R., Grati M., Krey J.F., Windsor A.M., Sousa A.D.,
RA Ballesteros A., Cui R., Millis B.A., Salles F.T., Baird M.A.,
RA Davidson M.W., Jones S.M., Choi D., Dong L., Raval M.H., Yengo C.M.,
RA Barr-Gillespie P.G., Kachar B.;
RT "Stereocilia-staircase spacing is influenced by myosin III motors and their
RT cargos espin-1 and espin-like.";
RL Nat. Commun. 7:10833-10833(2016).
CC -!- FUNCTION: Probable actin-based motor with a protein kinase activity.
CC Probably plays a role in vision and hearing (By similarity). Required
CC for normal cochlear hair bundle development and hearing. Plays an
CC important role in the early steps of cochlear hair bundle
CC morphogenesis. Influences the number and lengths of stereocilia to be
CC produced and limits the growth of microvilli within the forming
CC auditory hair bundles thereby contributing to the architecture of the
CC hair bundle, including its staircase pattern (PubMed:26754646).
CC Involved in the elongation of actin in stereocilia tips by transporting
CC the actin regulatory factor ESPN to the plus ends of actin filaments
CC (PubMed:19287378). {ECO:0000250|UniProtKB:Q8NEV4,
CC ECO:0000269|PubMed:19287378, ECO:0000269|PubMed:26754646}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Interacts with MORN4 (PubMed:26754646). Interacts (via C-
CC terminus) with ESPN and ESPNL (PubMed:26926603).
CC {ECO:0000269|PubMed:26754646, ECO:0000269|PubMed:26926603}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm
CC {ECO:0000269|PubMed:26754646}. Cell projection, filopodium tip
CC {ECO:0000250|UniProtKB:Q8NEV4}. Cell projection, stereocilium
CC {ECO:0000269|PubMed:26754646}. Note=Increased localization at the
CC filodium tip seen in the presence of MORN4.
CC {ECO:0000250|UniProtKB:Q8NEV4}.
CC -!- TISSUE SPECIFICITY: Expressed in the cochlear hair cells (at protein
CC level) (PubMed:26754646). Expressed in utricle hair bundles (at protein
CC level) (PubMed:26926603). {ECO:0000269|PubMed:26754646,
CC ECO:0000269|PubMed:26926603}.
CC -!- DISRUPTION PHENOTYPE: MYO3A single knockout mice do not exhibit early
CC hearing impairment whereas mice with a double knockout of MYO3A and
CC MYO3B are profoundly deaf at 1 month of age. Cochlear hair bundles have
CC abnormally long stereocilia and show dynamic shape defects during
CC development. {ECO:0000269|PubMed:26754646}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the TRAFAC class
CC myosin-kinesin ATPase superfamily. Myosin family. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the protein kinase
CC superfamily. STE Ser/Thr protein kinase family. {ECO:0000305}.
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DR EMBL; AY101368; AAM34501.1; -; mRNA.
DR AlphaFoldDB; Q8K3H5; -.
DR SMR; Q8K3H5; -.
DR STRING; 10090.ENSMUSP00000046329; -.
DR iPTMnet; Q8K3H5; -.
DR PhosphoSitePlus; Q8K3H5; -.
DR PaxDb; Q8K3H5; -.
DR PRIDE; Q8K3H5; -.
DR ProteomicsDB; 287585; -.
DR MGI; MGI:2183924; Myo3a.
DR eggNOG; KOG0587; Eukaryota.
DR eggNOG; KOG4229; Eukaryota.
DR InParanoid; Q8K3H5; -.
DR PhylomeDB; Q8K3H5; -.
DR ChiTaRS; Myo3a; mouse.
DR PRO; PR:Q8K3H5; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8K3H5; protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031941; C:filamentous actin; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0032433; C:filopodium tip; IDA:MGI.
DR GO; GO:0016459; C:myosin complex; IEA:UniProtKB-KW.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:MGI.
DR GO; GO:0032426; C:stereocilium tip; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IDA:MGI.
DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0000146; F:microfilament motor activity; IDA:MGI.
DR GO; GO:0060002; F:plus-end directed microfilament motor activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IMP:MGI.
DR GO; GO:0090103; P:cochlea morphogenesis; IMP:UniProtKB.
DR GO; GO:0048839; P:inner ear development; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:MGI.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IGI:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0030832; P:regulation of actin filament length; IMP:MGI.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd01379; MYSc_Myo3; 1.
DR Gene3D; 3.40.850.10; -; 1.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR036961; Kinesin_motor_dom_sf.
DR InterPro; IPR001609; Myosin_head_motor_dom.
DR InterPro; IPR036083; MYSc_Myo3.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00612; IQ; 1.
DR Pfam; PF00063; Myosin_head; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR00193; MYOSINHEAVY.
DR SMART; SM00015; IQ; 2.
DR SMART; SM00242; MYSc; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50096; IQ; 2.
DR PROSITE; PS51456; MYOSIN_MOTOR; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Actin-binding; ATP-binding; Cell projection; Cytoplasm; Cytoskeleton;
KW Hearing; Kinase; Motor protein; Myosin; Nucleotide-binding;
KW Reference proteome; Repeat; Sensory transduction;
KW Serine/threonine-protein kinase; Transferase; Vision.
FT CHAIN 1..1613
FT /note="Myosin-IIIa"
FT /id="PRO_0000086414"
FT DOMAIN 21..287
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 338..1052
FT /note="Myosin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00782"
FT DOMAIN 1054..1083
FT /note="IQ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 1081..1110
FT /note="IQ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 933..955
FT /note="Actin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00782"
FT REGION 1136..1168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1398..1476
FT /note="Interaction with MORN4"
FT /evidence="ECO:0000250|UniProtKB:Q8NEV4"
FT REGION 1476..1506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1137..1162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 27..35
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 1613 AA; 184730 MW; 19DFD980BF7B8847 CRC64;
MLPLIGKTII FDNFPDPSDT WEIIETIGKG TYGKVFKVLN KKSGQKAAVK ILDPIHDIDE
EIEAEYNILR TLSDHPNVVR FYGIYFKKDK INGDKLWLVL ELCNGGSVTD LVKGFLKRGE
RMSEPVIAYI LHEALMGLQH LHSNKTIHRD VKGNNILLTT EGGVKLVDFG VSAQLSSTRH
RLNTSVGTPF WMAPEVIACE QQLDTTYDAR CDTWSLGITA IELGDGDPPL AELHPMRALF
KIPRNPPPKL RQPELWSAEF NDFISKCLTK DYEKRPTVSD LLKHKFITQI EGKDVILQKQ
LMEFIDIHQC LGSTEKARHE RIHTKKGNLN RSLISSLKDV DDLATLDVLD EPTASPHLHP
CHSRDQIHIH VADILIALNP FQSLGIYSPK LSRLYIGAKR TANPPHIFAM ADLGYQSMVT
YNADQCIVIS GESGAGKTES AHLLVQQLTV LGKANNRTLQ EKILQMNNLV EAFGNACTII
NDNSSRFGKY LEMKFTSSGA VVGAQISEYL LEKSRVIHQA MGEKNFHIFY YIYGGLAEKK
KLALYKSPEH KPPRYLQNDN LRTVQDMMNN SFYKSQYELI EQCFKVIGFT MEQLASVYSV
LAAILNVGNI EFSSVATEYQ MDKSYICNHT ALENCASLLC IQADELQEAL TSHCVVTRGE
TIIRPNTVEK AADVRDAMAK TLYGRLFSCI VNCINSLLKH DTSPSGDEEL NIGILDIFGF
ENFKRNSFEQ LCINIANEQI QYYFNQHVFA WEQNEYLNED VDARVIEYED NRPLLDMFLQ
KPMGLLSLLD EESRFPKATD QTLIEKFEDN LKSQYFWRPK RMELSFGIHH YAGKVLYSAS
GFLAKNRDTF PTDIVLPLRS SENSVIRQLV NHPLTKTGNL PLSKTKNIVN YQMWNSEKST
NLTKGETRDV TCHACETTNV KTQTVSSYFR YSLMDLLSKM VVGQPHFVRC IKPNNERQAR
KYDKEKVLLQ LRCTGILETA RIRRLGYSHR ILFANFIKRY YILCYKSSEE PPVSPDTCAA
ILEKAGLDNW ALGKTKVFLK YYHVEQLNLM RKEATNKLVL IQASVRAFLG ARRYQELQQK
RKSSAVIIQS AARGHLVRKQ RKEIVDMKNT AVTTIQTSDQ EFDYKKNFEN TRESFVKKQT
ENAVPTNESN TSTPNNKESP SAGKTAPFIA ESKATNVESN NRRYHTQKKM SNVYAEGQNQ
ELYIVEDTWA EVSPRQKYVQ DLEESRKMRK EEKGDAVIQS YCQWYTEGSN FEESKATCLE
GRETWERTSC PGLWLTEEIY LRKTLDPTLS QKSVYQNADG KEKEHKVSVV TQNAPLGNLE
RDYHLLGFLG EEDTGPVPQA QEEHKAVSIH SKYQSSKKKQ QLGKDRLAPP FKNQKILSSS
TEVAKTTHNV YPCPTKQEGV HHSKMVDERD SKMASKKEAW DLAMFSRQIS KLSEEYFILQ
KNLNEIILAQ QLKPFYLGIY RHKPINRHVS THQYLSGVSK GEEPKILRPP RRPRKPKTLN
NPEDSTYYYL LHKSTQEEKR RPGKDSQGKL LGLEDFYYKE FLPTHYGPKA HSSNAREWKA
LKEPQAQPIE SNERCWTTSE NESLEEERIS ANPYDYRRLL RKTSQRQRLV QQL
