MYO6_CHICK
ID MYO6_CHICK Reviewed; 1276 AA.
AC Q9I8D1;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Unconventional myosin-VI;
DE AltName: Full=Unconventional myosin-6;
GN Name=MYO6; Synonyms=CMY6;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Intestine;
RX PubMed=9852149; DOI=10.1083/jcb.143.6.1535;
RA Buss F., Kendrick-Jones J., Lionne C., Knight A.E., Cote G.P.,
RA Paul Luzio J.;
RT "The localization of myosin VI at the Golgi complex and leading edge of
RT fibroblasts and its phosphorylation and recruitment into membrane ruffles
RT of A431 cells after growth factor stimulation.";
RL J. Cell Biol. 143:1535-1545(1998).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=11447109; DOI=10.1093/emboj/20.14.3676;
RA Buss F., Arden S.D., Lindsay M., Luzio J.P., Kendrick-Jones J.;
RT "Myosin VI isoform localized to clathrin-coated vesicles with a role in
RT clathrin-mediated endocytosis.";
RL EMBO J. 20:3676-3684(2001).
RN [3]
RP SUBCELLULAR LOCATION, INTERACTION WITH OPTN, PHOSPHORYLATION AT THR-1088
RP AND THR-1091, AND MUTAGENESIS OF THR-1088 AND THR-1091.
RX PubMed=15837803; DOI=10.1083/jcb.200501162;
RA Sahlender D.A., Roberts R.C., Arden S.D., Spudich G., Taylor M.J.,
RA Luzio J.P., Kendrick-Jones J., Buss F.;
RT "Optineurin links myosin VI to the Golgi complex and is involved in Golgi
RT organization and exocytosis.";
RL J. Cell Biol. 169:285-295(2005).
CC -!- FUNCTION: Myosins are actin-based motor molecules with ATPase activity
CC (By similarity). Unconventional myosins serve in intracellular
CC movements (By similarity). Myosin 6 is a reverse-direction motor
CC protein that moves towards the minus-end of actin filaments (By
CC similarity). Has slow rate of actin-activated ADP release due to weak
CC ATP binding (By similarity). Functions in a variety of intracellular
CC processes such as vesicular membrane trafficking and cell migration (By
CC similarity). Required for the structural integrity of the Golgi
CC apparatus via the p53-dependent pro-survival pathway (By similarity).
CC Appears to be involved in a very early step of clathrin-mediated
CC endocytosis in polarized epithelial cells (By similarity). May act as a
CC regulator of F-actin dynamics (By similarity). May play a role in
CC transporting DAB2 from the plasma membrane to specific cellular targets
CC (By similarity). May play a role in the extension and network
CC organization of neurites (By similarity). Modulates RNA polymerase II-
CC dependent transcription (By similarity). {ECO:0000250|UniProtKB:Q29122,
CC ECO:0000250|UniProtKB:Q64331, ECO:0000250|UniProtKB:Q9UM54}.
CC -!- SUBUNIT: Homodimer; dimerization seems to implicate the unfolding of
CC the three-helix bundle region creating an additional calmodulin binding
CC site, and cargo binding (By similarity). Able to function as a monomer
CC under specific conditions in vitro (By similarity). Forms a complex
CC with CFTR and DAB2 in the apical membrane of epithelial cells (By
CC similarity). Binding to calmodulin through a unique insert, not found
CC in other myosins, located in the neck region between the motor domain
CC and the IQ domain appears to contribute to the directionality reversal
CC (By similarity). This interaction occurs only if the C-terminal lobe of
CC calmodulin is occupied by calcium (By similarity). Interaction with F-
CC actin/ACTN1 occurs only at the apical brush border domain of the
CC proximal tubule cells (By similarity). Interacts with DAB2 (By
CC similarity). In vitro, the C-terminal globular tail binds a C-terminal
CC region of DAB2 (By similarity). Interacts with CFTR (By similarity).
CC Interacts with OPTN (PubMed:15837803). Interacts with CABP5 (By
CC similarity). {ECO:0000250|UniProtKB:E1BPK6,
CC ECO:0000250|UniProtKB:Q29122, ECO:0000250|UniProtKB:Q64331,
CC ECO:0000250|UniProtKB:Q9UM54, ECO:0000269|PubMed:15837803}.
CC -!- INTERACTION:
CC Q9I8D1; P98078: Dab2; Xeno; NbExp=2; IntAct=EBI-6307292, EBI-1391846;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:11447109}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11447109}. Golgi apparatus
CC {ECO:0000269|PubMed:11447109, ECO:0000269|PubMed:15837803}. Nucleus
CC {ECO:0000250|UniProtKB:Q9UM54}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q9UM54}. Membrane, clathrin-coated pit
CC {ECO:0000250|UniProtKB:Q9UM54}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000250|UniProtKB:Q9UM54}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:Q9UM54}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:11447109}. Cell projection, microvillus
CC {ECO:0000250|UniProtKB:Q9UM54}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q29122}. Note=Also present in endocyctic
CC vesicles (By similarity). Translocates from membrane ruffles, endocytic
CC vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and
CC nucleus through induction by p53 and p53-induced DNA damage (By
CC similarity). Recruited into membrane ruffles from cell surface by EGF-
CC stimulation (By similarity). Colocalizes with DAB2 in clathrin-coated
CC pits/vesicles (By similarity). Colocalizes with OPTN at the Golgi
CC complex and in vesicular structures close to the plasma membrane
CC (PubMed:15837803). {ECO:0000250|UniProtKB:Q9UM54,
CC ECO:0000269|PubMed:15837803}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasmic vesicle, clathrin-coated
CC vesicle membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9I8D1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9I8D1-2; Sequence=VSP_022331;
CC -!- DOMAIN: Divided into three regions: a N-terminal motor (head) domain,
CC followed by a neck domain consisting of a calmodulin-binding linker
CC domain and a single IQ motif, and a C-terminal tail region with a
CC three-helix bundle region, a SAH domain and a unique globular domain
CC required for interaction with other proteins such as cargo-binding.
CC {ECO:0000250|UniProtKB:Q29122}.
CC -!- DOMAIN: The SAH (single alpha-helix) region is characterized by a high
CC content of charged residues which are predicted to stabilize the alpha-
CC helical structure by ionic bonds (By similarity). Its contribution to
CC the mechanism confering the myosin movement on actin filaments is
CC debated (By similarity). {ECO:0000250|UniProtKB:Q9UM54}.
CC -!- PTM: Phosphorylation in the motor domain, induced by EGF, results in
CC translocation of MYO6 from the cell surface to membrane ruffles.
CC Phosphorylated in vitro by p21-activated kinase (PAK).
CC {ECO:0000269|PubMed:15837803}.
CC -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase
CC superfamily. Myosin family. {ECO:0000305}.
CC -!- CAUTION: Represents an unconventional myosin. This protein should not
CC be confused with the conventional myosin-6 (MYH6). {ECO:0000305}.
CC -!- CAUTION: Originally predicted to contain a coiled coil domain but
CC generally accepted to contain a stable SAH domain instead.
CC {ECO:0000305}.
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DR EMBL; AJ278608; CAB96536.1; -; mRNA.
DR RefSeq; NP_990066.1; NM_204735.1. [Q9I8D1-1]
DR AlphaFoldDB; Q9I8D1; -.
DR SMR; Q9I8D1; -.
DR IntAct; Q9I8D1; 4.
DR STRING; 9031.ENSGALP00000025573; -.
DR iPTMnet; Q9I8D1; -.
DR PaxDb; Q9I8D1; -.
DR PRIDE; Q9I8D1; -.
DR GeneID; 395487; -.
DR KEGG; gga:395487; -.
DR CTD; 4646; -.
DR VEuPathDB; HostDB:geneid_395487; -.
DR eggNOG; KOG0163; Eukaryota.
DR InParanoid; Q9I8D1; -.
DR PhylomeDB; Q9I8D1; -.
DR PRO; PR:Q9I8D1; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0005884; C:actin filament; IDA:UniProtKB.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central.
DR GO; GO:0031941; C:filamentous actin; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; IBA:GO_Central.
DR GO; GO:0016459; C:myosin complex; IEA:UniProtKB-KW.
DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016591; C:RNA polymerase II, holoenzyme; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
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:0003774; F:cytoskeletal motor activity; ISS:UniProtKB.
DR GO; GO:0000146; F:microfilament motor activity; IBA:GO_Central.
DR GO; GO:0060002; F:plus-end directed microfilament motor activity; IDA:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0030048; P:actin filament-based movement; ISS:UniProtKB.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IBA:GO_Central.
DR GO; GO:0042472; P:inner ear morphogenesis; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0051046; P:regulation of secretion; ISS:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR GO; GO:0030050; P:vesicle transport along actin filament; IBA:GO_Central.
DR CDD; cd01382; MYSc_Myo6; 1.
DR Gene3D; 2.30.30.360; -; 1.
DR Gene3D; 3.40.850.10; -; 2.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR036961; Kinesin_motor_dom_sf.
DR InterPro; IPR032412; Myosin-VI_CBD.
DR InterPro; IPR001609; Myosin_head_motor_dom.
DR InterPro; IPR004009; Myosin_N.
DR InterPro; IPR008989; Myosin_S1_N.
DR InterPro; IPR036114; MYSc_Myo6.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF16521; Myosin-VI_CBD; 1.
DR Pfam; PF00063; Myosin_head; 1.
DR PRINTS; PR00193; MYOSINHEAVY.
DR SMART; SM00242; MYSc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50096; IQ; 1.
DR PROSITE; PS51456; MYOSIN_MOTOR; 1.
DR PROSITE; PS51844; SH3_LIKE; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; ATP-binding; Calmodulin-binding;
KW Cell membrane; Cell projection; Coated pit; Cytoplasm; Cytoplasmic vesicle;
KW Endocytosis; Golgi apparatus; Hearing; Membrane; Motor protein; Myosin;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..1276
FT /note="Unconventional myosin-VI"
FT /id="PRO_0000271747"
FT DOMAIN 2..53
FT /note="Myosin N-terminal SH3-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01190"
FT DOMAIN 57..771
FT /note="Myosin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00782"
FT DOMAIN 813..842
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 273..317
FT /note="Responsible for slow ATPase activity"
FT /evidence="ECO:0000250|UniProtKB:Q29122"
FT REGION 665..672
FT /note="Actin-binding"
FT /evidence="ECO:0000255"
FT REGION 782..810
FT /note="Required for binding calmodulin"
FT /evidence="ECO:0000250|UniProtKB:Q29122"
FT REGION 835..916
FT /note="Three-helix bundle"
FT /evidence="ECO:0000250|UniProtKB:Q29122"
FT REGION 917..984
FT /note="SAH"
FT /evidence="ECO:0000250|UniProtKB:Q9UM54"
FT REGION 934..957
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1107..1109
FT /note="Interaction with OPTN"
FT /evidence="ECO:0000269|PubMed:15837803"
FT REGION 1117..1151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1130..1151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 151..158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 405
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 1088
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:15837803"
FT MOD_RES 1091
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:15837803"
FT VAR_SEQ 1036..1058
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9852149"
FT /id="VSP_022331"
FT MUTAGEN 1088
FT /note="T->A: No effect on binding to OPTN; when associated
FT with A-1091."
FT /evidence="ECO:0000269|PubMed:15837803"
FT MUTAGEN 1088
FT /note="T->E: Abolishes binding to OPTN; when associated
FT with E-1091."
FT /evidence="ECO:0000269|PubMed:15837803"
FT MUTAGEN 1091
FT /note="T->A: No effect on binding to OPTN; when associated
FT with A-1088."
FT /evidence="ECO:0000269|PubMed:15837803"
FT MUTAGEN 1091
FT /note="T->E: Abolishes binding to OPTN; when associated
FT with E-1088."
FT /evidence="ECO:0000269|PubMed:15837803"
SQ SEQUENCE 1276 AA; 147604 MW; 5F6AEE43A6FB260F CRC64;
MEDGKPVWAP HPTDGFQMGM IVDIGTDYLT IEPLNQKGKT FQAAINQVFP AEEDSKKDVE
DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKFYSSD AIKKYQGRSL
GTLPPHVFAI ADKAYRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD
RIVEANPLLE AFGNAKTIRN NNSSRFGKFV EIHFNEKNSV VGGFVSHYLL EKSRICVQGK
EERNYHIFYR LCAGAPEDIR EKLYLSSPDS FRYLNRGCTR YFATKETDKQ ILQNRKSPEY
LKAGSLKDPL LDDHGDFNRM CTAMKKIGLD DAEKLDLFRV VAGVLHLGNI DFEEAGSTSG
GCTLKAQSQP ALECCAALLG LDEEDLRVSL TTRVMLTTAG GAKGTVIKVP LKVEQANNAR
DALAKTVYSH LFDHVVNRVN QCFPFETSSF FIGVLDIAGF EYFEHNSFEQ FCINYCNEKL
QQFFNERILK EEQELYQKEG LGVNEVRYVD NQDCIDLIEA KLIGVLDILD EENRLPQPSD
QHFTSVVHQK HKDHFRLSIP RKSKLAVHRN VRDDEGFIIR HFAGAVCYET TQFVEKNNDA
LHMSLESLIC ESKDKFVRQL FESNTNNNKD PKQKAGKLSF ISVGNKFKTQ LNLLLEKLHS
TGSSFIRCIF PNLKMTSHHF EGGQILSQLQ CSGMVSVLDL MQGGFPSRAS FHELYNMYKK
YLPEKLARLD PRLFCKALFK ALGLNEIDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAEL
VKRVNHWLIC SRWKKVQWCS LSVIKLKNKI KYRASACIKI QKTIRMWLCK RKHKPRIDGL
IKVRTLKKRL DKFNEVVSAL KEGKAETSKQ IKELEYSIDA SMTKIKTTMM TREQIMKEYD
ALVRSSEQLL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEEEKRRRKE EEERRLKSEI
EAKRKQEEEE RKKREEEEKR IQAEIEAQLA REREEETQHQ AILEQERRDR ELAMRIAQTG
AELSTEETKL DVGLCRANGT KLQMTAEQMA KEMSEMLSRG PAVQATKAAA GAKKHDLSKW
KYAELRDTIN TSCDIELLAA CREEFHRRLK VYHAWKSKNK KRNAETEQRA PKSVTDYAQQ
NPTAQLPMRQ QEIEINRQQR YFRIPFIRPM DQYKDPQNKK KGWWYAHFDG PWIARQMELH
PDKAPILLVA GKDDMDMCEL NLEETGLTRK RGAEILPRQF EEIWERCGGI QYLQNAIESR
QARPTYATAM LQNLLK
