Descriptions

Myosin VI (Myo6) is the only minus-end directed nanomotor on actin and is essential for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. The N-terminal region of the SAH domain folds back on the 3HB domain, thus adopting Myo6 to an elongated conformation that inhibits its activity. Notably, not all partners are capable of relieving the autoinhibition of Myo6. TOM1 and Dab2 are unable to bind the off-state of Myo6, while GIPC1 binds Myo6, releases its autoinhibition, and triggers proximal dimerization. The L926Q deafness mutation also disrupts the autoinhibition of Myo6 and indirectly impairs its proximal dimerization.

Autoinhibitory domains (AIDs)

Target domain

834-917 (3HB domain)

Relief mechanism

Partner binding, Others

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q9I8D1

Entry ID Method Resolution Chain Position Source
AF-Q9I8D1-F1 Predicted AlphaFoldDB

No variants for Q9I8D1

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9I8D1

No associated diseases with Q9I8D1

6 regional properties for Q9I8D1

Type Name Position InterPro Accession
domain Forkhead-associated (FHA) domain 470 - 534 IPR000253
domain Kinesin motor domain 3 - 360 IPR001752
conserved_site Kinesin motor domain, conserved site 246 - 257 IPR019821
domain Kinesin-like KIF1-type 748 - 792 IPR022140
domain Kinesin-like 1209 - 1268 IPR022164
domain Kinesin-associated 391 - 468 IPR032405

Functions

Description
EC Number
Subcellular Localization
  • Golgi apparatus, trans-Golgi network membrane ; Peripheral membrane protein
  • Golgi apparatus
  • Nucleus
  • Cytoplasm, perinuclear region
  • Membrane, clathrin-coated pit
  • Cytoplasmic vesicle, clathrin-coated vesicle
  • Cell projection, filopodium
  • Cell projection, ruffle membrane
  • Cell projection, microvillus
  • Cytoplasm, cytosol
  • Also present in endocyctic vesicles (By similarity)
  • Translocates from membrane ruffles, endocytic vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and nucleus through induction by p53 and p53-induced DNA damage (By similarity)
  • Recruited into membrane ruffles from cell surface by EGF-stimulation (By similarity)
  • Colocalizes with DAB2 in clathrin-coated pits/vesicles (By similarity)
  • Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane (PubMed:15837803)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

22 GO annotations of cellular component

Name Definition
actin cytoskeleton The part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins. Includes actin cytoskeleton-associated complexes.
actin filament A filamentous structure formed of a two-stranded helical polymer of the protein actin and associated proteins. Actin filaments are a major component of the contractile apparatus of skeletal muscle and the microfilaments of the cytoskeleton of eukaryotic cells. The filaments, comprising polymerized globular actin molecules, appear as flexible structures with a diameter of 5-9 nm. They are organized into a variety of linear bundles, two-dimensional networks, and three dimensional gels. In the cytoskeleton they are most highly concentrated in the cortex of the cell just beneath the plasma membrane.
cell cortex The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
clathrin-coated pit A part of the endomembrane system in the form of an invagination of a membrane upon which a clathrin coat forms, and that can be converted by vesicle budding into a clathrin-coated vesicle. Coated pits form on the plasma membrane, where they are involved in receptor-mediated selective transport of many proteins and other macromolecules across the cell membrane, in the trans-Golgi network, and on some endosomes.
clathrin-coated vesicle A vesicle with a coat formed of clathrin connected to the membrane via one of the clathrin adaptor complexes.
clathrin-coated vesicle membrane The lipid bilayer surrounding a clathrin-coated vesicle.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic vesicle A vesicle found in the cytoplasm of a cell.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
endocytic vesicle A membrane-bounded intracellular vesicle formed by invagination of the plasma membrane around an extracellular substance. Endocytic vesicles fuse with early endosomes to deliver the cargo for further sorting.
filamentous actin A two-stranded helical polymer of the protein actin.
filopodium Thin, stiff, actin-based protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal or dendritic growth cone, or a dendritic shaft.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
microvillus Thin cylindrical membrane-covered projections on the surface of an animal cell containing a core bundle of actin filaments. Present in especially large numbers on the absorptive surface of intestinal cells.
myosin complex A protein complex, formed of one or more myosin heavy chains plus associated light chains and other proteins, that functions as a molecular motor; uses the energy of ATP hydrolysis to move actin filaments or to move vesicles or other cargo on fixed actin filaments; has magnesium-ATPase activity and binds actin. Myosin classes are distinguished based on sequence features of the motor, or head, domain, but also have distinct tail regions that are believed to bind specific cargoes.
nuclear membrane Either of the lipid bilayers that surround the nucleus and form the nuclear envelope; excludes the intermembrane space.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
ruffle Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork.
ruffle membrane The portion of the plasma membrane surrounding a ruffle.

8 GO annotations of molecular function

Name Definition
actin binding Binding to monomeric or multimeric forms of actin, including actin filaments.
actin filament binding Binding to an actin filament, also known as F-actin, a helical filamentous polymer of globular G-actin subunits.
ADP binding Binding to ADP, adenosine 5'-diphosphate.
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
calmodulin binding Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
cytoskeletal motor activity Generation of force resulting in movement, for example along a microfilament or microtubule, or in torque resulting in membrane scission or rotation of a flagellum. The energy required is obtained either from the hydrolysis of a nucleoside triphosphate or by an electrochemical proton gradient (proton-motive force).
microfilament motor activity A motor activity that generates movement along a microfilament, driven by ATP hydrolysis.
plus-end directed microfilament motor activity A motor activity that generates movement along a microfilament towards the plus end, driven by ATP hydrolysis. The minus end of an actin filament is the end that does not preferentially add actin monomers.

10 GO annotations of biological process

Name Definition
actin filament organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments. Includes processes that control the spatial distribution of actin filaments, such as organizing filaments into meshworks, bundles, or other structures, as by cross-linking.
actin filament-based movement Movement of organelles or other particles along actin filaments, or sliding of actin filaments past each other, mediated by motor proteins.
DNA damage response, signal transduction by p53 class mediator A cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage.
endocytosis A vesicle-mediated transport process in which cells take up external materials or membrane constituents by the invagination of a part of the plasma membrane to form a new membrane-bounded vesicle.
inner ear auditory receptor cell differentiation The process in which a relatively unspecialized inner cell acquires specialized features of an auditory hair cell.
inner ear morphogenesis The process in which the anatomical structures of the inner ear are generated and organized. The inner ear is the structure in vertebrates that contains the organs of balance and hearing. It consists of soft hollow sensory structures (the membranous labyrinth) containing fluid (endolymph) surrounded by fluid (perilymph) and encased in a bony cavity (the bony labyrinth). It consists of two chambers, the sacculus and utriculus, from which arise the cochlea and semicircular canals respectively.
intracellular protein transport The directed movement of proteins in a cell, including the movement of proteins between specific compartments or structures within a cell, such as organelles of a eukaryotic cell.
regulation of secretion Any process that modulates the frequency, rate or extent of the controlled release of a substance from a cell or a tissue.
sensory perception of sound The series of events required for an organism to receive an auditory stimulus, convert it to a molecular signal, and recognize and characterize the signal. Sonic stimuli are detected in the form of vibrations and are processed to form a sound.
vesicle transport along actin filament Movement of a vesicle along an actin filament, mediated by motor proteins.

6 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
E1BPK6 MYO6 Unconventional myosin-VI Bos taurus (Bovine) SS
Q02440 MYO5A Unconventional myosin-Va Gallus gallus (Chicken) SS
Q9UM54 MYO6 Unconventional myosin-VI Homo sapiens (Human) EV
Q64331 Myo6 Unconventional myosin-VI Mus musculus (Mouse) SS
Q29122 MYO6 Unconventional myosin-VI Sus scrofa (Pig) SS
Q9M2K0 XI-J Myosin-16 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MEDGKPVWAP HPTDGFQMGM IVDIGTDYLT IEPLNQKGKT FQAAINQVFP AEEDSKKDVE
70 80 90 100 110 120
DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKFYSSD AIKKYQGRSL
130 140 150 160 170 180
GTLPPHVFAI ADKAYRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD
190 200 210 220 230 240
RIVEANPLLE AFGNAKTIRN NNSSRFGKFV EIHFNEKNSV VGGFVSHYLL EKSRICVQGK
250 260 270 280 290 300
EERNYHIFYR LCAGAPEDIR EKLYLSSPDS FRYLNRGCTR YFATKETDKQ ILQNRKSPEY
310 320 330 340 350 360
LKAGSLKDPL LDDHGDFNRM CTAMKKIGLD DAEKLDLFRV VAGVLHLGNI DFEEAGSTSG
370 380 390 400 410 420
GCTLKAQSQP ALECCAALLG LDEEDLRVSL TTRVMLTTAG GAKGTVIKVP LKVEQANNAR
430 440 450 460 470 480
DALAKTVYSH LFDHVVNRVN QCFPFETSSF FIGVLDIAGF EYFEHNSFEQ FCINYCNEKL
490 500 510 520 530 540
QQFFNERILK EEQELYQKEG LGVNEVRYVD NQDCIDLIEA KLIGVLDILD EENRLPQPSD
550 560 570 580 590 600
QHFTSVVHQK HKDHFRLSIP RKSKLAVHRN VRDDEGFIIR HFAGAVCYET TQFVEKNNDA
610 620 630 640 650 660
LHMSLESLIC ESKDKFVRQL FESNTNNNKD PKQKAGKLSF ISVGNKFKTQ LNLLLEKLHS
670 680 690 700 710 720
TGSSFIRCIF PNLKMTSHHF EGGQILSQLQ CSGMVSVLDL MQGGFPSRAS FHELYNMYKK
730 740 750 760 770 780
YLPEKLARLD PRLFCKALFK ALGLNEIDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAEL
790 800 810 820 830 840
VKRVNHWLIC SRWKKVQWCS LSVIKLKNKI KYRASACIKI QKTIRMWLCK RKHKPRIDGL
850 860 870 880 890 900
IKVRTLKKRL DKFNEVVSAL KEGKAETSKQ IKELEYSIDA SMTKIKTTMM TREQIMKEYD
910 920 930 940 950 960
ALVRSSEQLL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEEEKRRRKE EEERRLKSEI
970 980 990 1000 1010 1020
EAKRKQEEEE RKKREEEEKR IQAEIEAQLA REREEETQHQ AILEQERRDR ELAMRIAQTG
1030 1040 1050 1060 1070 1080
AELSTEETKL DVGLCRANGT KLQMTAEQMA KEMSEMLSRG PAVQATKAAA GAKKHDLSKW
1090 1100 1110 1120 1130 1140
KYAELRDTIN TSCDIELLAA CREEFHRRLK VYHAWKSKNK KRNAETEQRA PKSVTDYAQQ
1150 1160 1170 1180 1190 1200
NPTAQLPMRQ QEIEINRQQR YFRIPFIRPM DQYKDPQNKK KGWWYAHFDG PWIARQMELH
1210 1220 1230 1240 1250 1260
PDKAPILLVA GKDDMDMCEL NLEETGLTRK RGAEILPRQF EEIWERCGGI QYLQNAIESR
1270
QARPTYATAM LQNLLK