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Protein

Unconventional myosin-VI

Gene

Myo6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi151 – 158ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

  • auditory receptor cell differentiation Source: MGI
  • cellular response to electrical stimulus Source: MGI
  • chemical synaptic transmission Source: MGI
  • dendrite development Source: MGI
  • DNA damage response, signal transduction by p53 class mediator Source: MGI
  • endocytosis Source: MGI
  • glutamate secretion Source: MGI
  • inner ear development Source: MGI
  • inner ear morphogenesis Source: MGI
  • locomotory behavior Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein targeting Source: MGI
  • regulation of secretion Source: MGI
  • regulation of synaptic plasticity Source: MGI
  • sensory perception of sound Source: MGI
  • synapse assembly Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Motor protein, Myosin

Keywords - Biological processi

Endocytosis, Hearing, Protein transport, Transport

Keywords - Ligandi

Actin-binding, ATP-binding, Calmodulin-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Unconventional myosin-VI
Alternative name(s):
Unconventional myosin-6
Gene namesi
Name:Myo6
Synonyms:Sv
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:104785. Myo6.

Subcellular locationi

GO - Cellular componenti

  • axon Source: MGI
  • brush border Source: UniProtKB
  • cell-cell adherens junction Source: MGI
  • clathrin-coated pit Source: UniProtKB-SubCell
  • cytoplasm Source: MGI
  • cytoplasmic, membrane-bounded vesicle Source: MGI
  • DNA-directed RNA polymerase II, holoenzyme Source: MGI
  • extracellular exosome Source: MGI
  • filamentous actin Source: MGI
  • Golgi apparatus Source: MGI
  • membrane Source: MGI
  • myosin complex Source: UniProtKB-KW
  • neuronal cell body Source: MGI
  • nuclear membrane Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • perinuclear region of cytoplasm Source: MGI
  • plasma membrane Source: MGI
  • ruffle Source: MGI
  • synapse Source: MGI
  • vesicle membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Coated pit, Cytoplasm, Cytoplasmic vesicle, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Myo6 are the cause of Snell's waltzer, a condition characterized by circling, head-tossing, deafness and hyperactivity.

Keywords - Diseasei

Deafness, Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001234651 – 1265Unconventional myosin-VIAdd BLAST1265

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei267PhosphoserineBy similarity1
Modified residuei406PhosphothreonineBy similarity1
Modified residuei607PhosphoserineCombined sources1
Modified residuei1028PhosphoserineCombined sources1
Modified residuei1126PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles and affects F-actin dynamics. Phosphorylated in vitro by p21-activated kinase (PAK) (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ64331.
PeptideAtlasiQ64331.
PRIDEiQ64331.

PTM databases

iPTMnetiQ64331.
PhosphoSitePlusiQ64331.

Expressioni

Tissue specificityi

Widely expressed. Within the cochlea, expressed specifically within the sensory hair cells.

Gene expression databases

CleanExiMM_MYO6.

Interactioni

Subunit structurei

Homodimer; dimerization seems to implicate the unfolding of the three-helix bundle region creating an additional calmodulin binding site, and cargo binding (By similarity). Binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain and the IQ domain appears to contribute to the directionality reversal. This interaction occurs only if the C-terminal lobe of calmodulin is occupied by calcium. Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells (By similarity). Interacts with DAB2. In vitro, the C-terminal globular tail binds a C-terminal region of DAB2. Interacts with CFTR. Forms a complex with CFTR and DAB2 in the apical membrane of epithelial cells. Interacts with OPTN (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ64331. 6 interactors.
MINTiMINT-4102874.

Structurei

Secondary structure

11265
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi843 – 861Combined sources19
Helixi867 – 889Combined sources23
Helixi895 – 922Combined sources28
Helixi1138 – 1142Combined sources5
Beta strandi1147 – 1156Combined sources10
Helixi1158 – 1160Combined sources3
Helixi1165 – 1167Combined sources3
Beta strandi1170 – 1178Combined sources9
Beta strandi1181 – 1188Combined sources8
Beta strandi1190 – 1192Combined sources3
Beta strandi1195 – 1198Combined sources4
Turni1199 – 1205Combined sources7
Helixi1211 – 1214Combined sources4
Helixi1216 – 1218Combined sources3
Turni1220 – 1222Combined sources3
Helixi1226 – 1235Combined sources10
Helixi1238 – 1247Combined sources10
Helixi1255 – 1263Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KIANMR-A1137-1265[»]
2LD3NMR-A843-925[»]
3H8DX-ray2.20A/B/C/D1137-1265[»]
ProteinModelPortaliQ64331.
SMRiQ64331.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ64331.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini57 – 774Myosin motorAdd BLAST718
Domaini817 – 837IQAdd BLAST21

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni273 – 317Responsible for slow ATPase activityBy similarityAdd BLAST45
Regioni668 – 675Actin-bindingSequence analysis8
Regioni785 – 813Required for binding calmodulinBy similarityAdd BLAST29
Regioni838 – 919Three-helix bundleBy similarityAdd BLAST82
Regioni920 – 987SAHBy similarityAdd BLAST68
Regioni1087 – 1089Interaction with OPTN3

Domaini

Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a three-helix bundle region, a SAH domain and a unique globular domain required for interaction with other proteins such as cargo-binding.Curated
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds. Its contribution to the mechanism confering the myosin movement on actin filaments is debated.By similarity

Sequence similaritiesi

Contains 1 IQ domain.Curated
Contains 1 myosin motor domain.Curated

Phylogenomic databases

HOGENOMiHOG000007806.
HOVERGENiHBG003523.
InParanoidiQ64331.
PhylomeDBiQ64331.

Family and domain databases

InterProiIPR032412. Myosin-VI_CBD.
IPR001609. Myosin_head_motor_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF16521. Myosin-VI_CBD. 1 hit.
PF00063. Myosin_head. 1 hit.
[Graphical view]
PRINTSiPR00193. MYOSINHEAVY.
SMARTiSM00242. MYSc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS51456. MYOSIN_MOTOR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q64331-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FGALINQVFP
60 70 80 90 100
AEEDSKKDVE DNCSLMYLNE ATLLHNVKVR YSKDRIYTYV ANILIAVNPY
110 120 130 140 150
FDIPKIYSSD TIKSYQGKSL GTMPPHVFGI ADKAFRDMKV LKMSQSIIVS
160 170 180 190 200
GESGAGKTEN TKFGSKIPDR ILWTGQDIDD RIVEANPLLE AFGNAKTVRN
210 220 230 240 250
NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK EERNHHIFYR
260 270 280 290 300
LCAGASEDIR EKLHLSSPDN FRYLNRGCTR FFANKETDKQ ILQNRKSPEY
310 320 330 340 350
VKAGSLEGSS IRRPWRFYQD VHSHEKNWFG MMKKNFDLFR VVAGVLHLGN
360 370 380 390 400
IDLEEAGSTS GGCNLKNKSA PSLEYCAELL GLDQDDLRVS LTTRVMLTTA
410 420 430 440 450
GGTKGTVIKV PLKVEQANNA RDALAKTVYS HLFDHVVNRV NQCFPFETSS
460 470 480 490 500
YFIGVLDIAG FEYFEHNSFE QFCINYCNEK LQQFFNERIL KEEQELYQKE
510 520 530 540 550
GLGVNEVHYV DNQDCIELIE VKLVGILDIL DEENRLPQPS DQHFTSVVHQ
560 570 580 590 600
KHKDHFRLTI PRKSKLAVHR NLRDDEGFII RQLCRGRVLR RQPQYGGGKN
610 620 630 640 650
NDALHMSLES LICESRDKFI RALFESSTNN SKDTKQKAGK LSFISVGNKF
660 670 680 690 700
KTQLNLLLDK LRSTGASFIR CIKPNLKMAS HHFEGAQILS QLQCSGMVSV
710 720 730 740 750
LDLMQGGFPS RASFHELYNM YKKYMPEKLP RLDPRLFCKP LFKALGLNEV
760 770 780 790 800
DYKFGLTQVF FRPGKFAEFD QIMKSDPDHL AELVKRVNLW LVCSRWKKVQ
810 820 830 840 850
WCSLSVIKLK NKIKYRAEAC IKMQKPIRMW LCKRRHNPRI DGLVKVGTLK
860 870 880 890 900
KRLDKFNEVV SALKDGKPEV NRQIKNLEIS IDALMAKFTS TMMTREQIQK
910 920 930 940 950
EYDALVKSSE DLLSALQKKK QQEEEAERLR RIQEEMEKER KRREEDEERR
960 970 980 990 1000
RKEEEERRMK LEMEPKRKQE EEERKKREDD EKRIQSEVEA QLARQREEES
1010 1020 1030 1040 1050
QQQAVLAQEC RDRELALRIA QNESELISDE AQGDMALRRG PAVQATKAAS
1060 1070 1080 1090 1100
GTKKHDLSKW KYAELRDTIN TSCDIELLAA CREEFHRRLK VYHAWKSKNK
1110 1120 1130 1140 1150
KRNTETEQRA PKSVTDYDFA PFLNNSPQQN PAAQLPARQQ EIDMKRQQRF
1160 1170 1180 1190 1200
FRIPFIRPAD QYKDPQNKKK GWWYAHFDGP WIARQMELHP DKPPILLVAG
1210 1220 1230 1240 1250
KDDMEMCELN LEETGLTRKR GAEILPRQFE EIWERCGGIQ YLQSAIESRQ
1260
ARPTYATAML QNLLK
Length:1,265
Mass (Da):146,409
Last modified:November 1, 1996 - v1
Checksum:i4F51ABC72463148C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti766 – 1265Missing in Snell's waltzer. Add BLAST500

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U49739 mRNA. Translation: AAB00194.1.
PIRiA59299.
UniGeneiMm.4040.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U49739 mRNA. Translation: AAB00194.1.
PIRiA59299.
UniGeneiMm.4040.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KIANMR-A1137-1265[»]
2LD3NMR-A843-925[»]
3H8DX-ray2.20A/B/C/D1137-1265[»]
ProteinModelPortaliQ64331.
SMRiQ64331.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ64331. 6 interactors.
MINTiMINT-4102874.

PTM databases

iPTMnetiQ64331.
PhosphoSitePlusiQ64331.

Proteomic databases

MaxQBiQ64331.
PeptideAtlasiQ64331.
PRIDEiQ64331.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:104785. Myo6.

Phylogenomic databases

HOGENOMiHOG000007806.
HOVERGENiHBG003523.
InParanoidiQ64331.
PhylomeDBiQ64331.

Miscellaneous databases

ChiTaRSiMyo6. mouse.
EvolutionaryTraceiQ64331.
PROiQ64331.
SOURCEiSearch...

Gene expression databases

CleanExiMM_MYO6.

Family and domain databases

InterProiIPR032412. Myosin-VI_CBD.
IPR001609. Myosin_head_motor_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF16521. Myosin-VI_CBD. 1 hit.
PF00063. Myosin_head. 1 hit.
[Graphical view]
PRINTSiPR00193. MYOSINHEAVY.
SMARTiSM00242. MYSc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS51456. MYOSIN_MOTOR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMYO6_MOUSE
AccessioniPrimary (citable) accession number: Q64331
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Represents an unconventional myosin. This protein should not be confused with the conventional myosin-6 (MYH6).Curated
Originally predicted to contain a coiled coil domain but generally accepted to contain a stable SAH domain instead.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.