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Protein

Unconventional myosin-VI

Gene

Myo6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.

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

Regions

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActin-binding, Calmodulin-binding, Motor protein, Myosin
Biological processEndocytosis, Hearing, Protein transport, Transport
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:104785 Myo6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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, 10 interactors
MINTiQ64331

Structurei

Secondary structure

11265
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ64331
SMRiQ64331
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ64331

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 53Myosin N-terminal SH3-likePROSITE-ProRule annotationAdd BLAST52
Domaini57 – 774Myosin motorPROSITE-ProRule annotationAdd 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

Phylogenomic databases

HOGENOMiHOG000007806
HOVERGENiHBG003523
InParanoidiQ64331
PhylomeDBiQ64331

Family and domain databases

CDDicd01382 MYSc_Myo6, 1 hit
Gene3Di2.30.30.360, 1 hit
3.40.850.10, 1 hit
InterProiView protein in InterPro
IPR036961 Kinesin_motor_dom_sf
IPR032412 Myosin-VI_CBD
IPR001609 Myosin_head_motor_dom
IPR004009 Myosin_N
IPR008989 Myosin_S1_N
IPR036114 MYSc_Myo6
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF16521 Myosin-VI_CBD, 1 hit
PF00063 Myosin_head, 1 hit
PRINTSiPR00193 MYOSINHEAVY
SMARTiView protein in SMART
SM00242 MYSc, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51456 MYOSIN_MOTOR, 1 hit
PS51844 SH3_LIKE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9Q3L1E9Q3L1_MOUSE
Unconventional myosin-VI
Myo6
1,262Annotation score:
E9Q175E9Q175_MOUSE
Unconventional myosin-VI
Myo6
1,253Annotation score:
V9GX76V9GX76_MOUSE
Unconventional myosin-VI
Myo6
1,294Annotation score:
E9PVU0E9PVU0_MOUSE
Unconventional myosin-VI
Myo6
1,266Annotation score:
E9Q174E9Q174_MOUSE
Unconventional myosin-VI
Myo6
1,284Annotation score:
V9GXM4V9GXM4_MOUSE
Unconventional myosin-VI
Myo6
1,285Annotation score:

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

Similar proteinsi

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[»]
5V6EX-ray3.51B/D/F/H/J1055-1099[»]
5V6HX-ray3.60B/D/F/H/J1055-1099[»]
ProteinModelPortaliQ64331
SMRiQ64331
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ64331, 10 interactors
MINTiQ64331

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
PROiPR:Q64331
SOURCEiSearch...

Gene expression databases

CleanExiMM_MYO6

Family and domain databases

CDDicd01382 MYSc_Myo6, 1 hit
Gene3Di2.30.30.360, 1 hit
3.40.850.10, 1 hit
InterProiView protein in InterPro
IPR036961 Kinesin_motor_dom_sf
IPR032412 Myosin-VI_CBD
IPR001609 Myosin_head_motor_dom
IPR004009 Myosin_N
IPR008989 Myosin_S1_N
IPR036114 MYSc_Myo6
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF16521 Myosin-VI_CBD, 1 hit
PF00063 Myosin_head, 1 hit
PRINTSiPR00193 MYOSINHEAVY
SMARTiView protein in SMART
SM00242 MYSc, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51456 MYOSIN_MOTOR, 1 hit
PS51844 SH3_LIKE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMYO6_MOUSE
AccessioniPrimary (citable) accession number: Q64331
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

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