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 E1BPK6

Entry ID Method Resolution Chain Position Source
AF-E1BPK6-F1 Predicted AlphaFoldDB

214 variants for E1BPK6

Variant ID(s) Position Change Description Diseaes Association Provenance
rs435383039 3 D>G No EVA
rs720486438 4 G>R No EVA
rs453886260 4 G>V No EVA
rs472301189 6 P>S No EVA
rs432815473 7 V>G No EVA
rs451271469 8 W>G No EVA
rs451271469 8 W>R No EVA
rs476281291 9 A>T No EVA
rs463309238 11 H>L No EVA
rs443186024 11 H>N No EVA
rs475057392 11 H>Q No EVA
rs451835764 13 T>P No EVA
rs442195078 13 T>R No EVA
rs460553166 14 E>K No EVA
rs478993385 15 G>A No EVA
rs473649255 17 Q>H No EVA
rs446140707 17 Q>R No EVA
rs458159980 18 M>I No EVA
rs483113266 19 G>D No EVA
rs483113266 19 G>V No EVA
rs435444440 31 I>S No EVA
rs465992501 33 P>H No EVA
rs133952752 35 G>D No EVA
rs1117960497 35 G>S No EVA
rs133952752 35 G>V No EVA
rs475132573 39 K>N No EVA
rs455214000 39 K>R No EVA
rs449519268 40 T>P No EVA
rs434968301 45 I>L No EVA
rs453478716 46 N>K No EVA
rs471866725 48 V>G No EVA
rs432384936 49 F>V No EVA
rs457301757 58 D>E No EVA
rs442704981 61 D>G No EVA
rs437382034 88 T>S No EVA
rs455873112 90 V>L No EVA
rs467821661 97 V>L No EVA
rs453254964 115 Y>* No EVA
rs457064746 116 Q>H No EVA
rs471754046 116 Q>K No EVA
rs438720587 116 Q>L No EVA
rs475455664 118 K>R No EVA
rs460890867 122 T>M No EVA
rs440014689 125 P>S No EVA
rs445599918 127 V>E No EVA
rs477027994 127 V>M No EVA
rs470472249 128 F>L No EVA
rs482415800 131 A>P No EVA
rs482415800 131 A>S No EVA
rs455799517 137 D>V No EVA
rs448342919 138 M>V No EVA
rs466904046 139 K>Q No EVA
rs478918794 161 T>I No EVA
rs454284340 167 Y>N No EVA
rs472757302 167 Y>S No EVA
rs433293486 169 T>A No EVA
rs433293486 169 T>S No EVA
rs451816775 170 E>V No EVA
rs476647945 171 S>P No EVA
rs455559718 172 Y>* No EVA
rs443597769 172 Y>D No EVA
rs474089297 173 G>V No EVA
rs459575890 174 S>C No EVA
rs438501048 176 Q>P No EVA
rs481634238 177 D>V No EVA
rs463239427 177 D>Y No EVA
rs448832866 179 D>V No EVA
rs468876395 180 D>V No EVA
rs480981351 181 R>S No EVA
rs447873777 182 I>M No EVA
rs451824976 184 E>D No EVA
rs433352301 184 E>K No EVA
rs470235814 185 A>P No EVA
rs443996152 192 F>V No EVA
rs457646629 199 R>G No EVA
rs443090834 209 F>L No EVA
rs480043120 211 E>G No EVA
rs440514312 212 I>R No EVA
rs458833128 214 F>C No EVA
rs477221075 217 K>E No EVA
rs433513777 259 I>L No EVA
rs459297434 285 K>N No EVA
rs471281123 295 R>L No EVA
rs471281123 295 R>P No EVA
rs453083754 340 V>G No EVA
rs471412863 344 V>G No EVA
rs457843103 412 K>N No EVA
rs482802888 413 V>L No EVA
rs449691094 453 G>A No EVA
rs3423603813 520 A>G No EVA
rs457296521 563 S>P No EVA
rs475742492 567 V>G No EVA
rs442885721 568 H>P No EVA
rs454966112 568 H>Q No EVA
rs473339670 570 N>D No EVA
rs473339670 570 N>Y No EVA
rs440296018 573 D>E No EVA
rs458744325 574 D>G No EVA
rs477218912 575 E>G No EVA
rs444275994 576 G>A No EVA
rs460155236 584 G>W No EVA
rs478605707 585 A>T No EVA
rs208833933 606 E>G No EVA
rs481745213 642 S>I No EVA
rs478729682 658 L>V No EVA
rs438789573 677 S>R No EVA
rs482213612 678 H>P No EVA
rs442691695 678 H>Q No EVA
rs463572783 678 H>Y No EVA
rs1114227815 687 S>F No EVA
rs439195093 699 D>E No EVA
rs450802942 699 D>N No EVA
rs443649582 763 F>S No EVA
rs441089065 774 P>R No EVA
rs477891749 785 N>K No EVA
rs445139229 790 C>* No EVA
rs445068347 796 V>G No EVA
rs469965943 798 W>G No EVA
rs442661414 807 K>N No EVA
rs211487253 824 I>V No EVA
rs443434200 836 R>L No EVA
rs437719425 842 K>R No EVA
rs456190749 843 V>A No EVA
rs470779431 851 D>H No EVA
rs719601649 852 K>Q No EVA
rs441580725 853 F>I No EVA
rs459933107 854 N>Y No EVA
rs473502925 857 V>G No EVA
rs459119353 867 M>T No EVA
rs211513012 868 N>S No EVA
rs450968567 870 Q>K No EVA
rs463078262 870 Q>R No EVA
rs481474004 876 I>M No EVA
rs518765759 877 S>F No EVA
rs448495417 878 I>T No EVA
rs466966478 882 M>L No EVA
rs480245025 887 S>T No EVA
rs481874538 912 A>E No EVA
rs447367566 917 K>T No EVA
rs465710062 922 E>* No EVA
rs451331238 930 Q>E No EVA
rs469755788 938 K>T No EVA
rs456806128 946 R>H No EVA
rs456806128 946 R>P No EVA
rs521711477 951 E>D No EVA
rs471673691 983 A>G No EVA
rs471673691 983 A>V No EVA
rs438596078 984 E>A No EVA
rs438596078 984 E>G No EVA
rs463516777 985 V>E No EVA
rs463516777 985 V>G No EVA
rs481961792 986 E>V No EVA
rs448988222 987 A>E No EVA
rs460975278 988 Q>* No EVA
rs460975278 988 Q>E No EVA
rs479381288 989 L>P No EVA
rs446403781 990 A>D No EVA
rs446403781 990 A>G No EVA
rs466437496 992 Q>L No EVA
rs445439519 993 R>P No EVA
rs470203486 994 E>V No EVA
rs437294695 996 E>G No EVA
rs455653453 997 S>A No EVA
rs455653453 997 S>T No EVA
rs467676940 999 Q>E No EVA
rs434762428 999 Q>H No EVA
rs453240562 1000 Q>P No EVA
rs438681605 1004 E>D No EVA
rs457115240 1005 Q>E No EVA
rs475582191 1008 R>L No EVA
rs442568380 1014 L>I No EVA
rs479467322 1015 R>G No EVA
rs458548781 1020 E>A No EVA
rs478589147 1022 E>D No EVA
rs135198034 1025 I>S No EVA
rs470240360 1030 A>P No EVA
rs482246908 1031 D>A No EVA
rs434830415 1034 A>E No EVA
rs467713716 1034 A>T No EVA
rs437579599 1065 E>* No EVA
rs447407698 1070 G>A No EVA
rs458606679 1074 Q>K No EVA
rs43588600 1097 D>G No EVA
rs477897130 1102 S>A No EVA
rs436112374 1104 D>E No EVA
rs444897816 1104 D>N No EVA
rs473037375 1131 K>N No EVA
rs458478090 1140 A>S No EVA
rs471945786 1143 S>Y No EVA
rs463820153 1145 T>A No EVA
rs482247187 1145 T>N No EVA
rs452727785 1148 D>E No EVA
rs444529616 1154 N>K No EVA
rs462990325 1156 S>P No EVA
rs462393104 1160 N>I No EVA
rs480866351 1161 P>T No EVA
rs466104750 1170 Q>H No EVA
rs445235411 1174 M>T No EVA
rs437152539 1201 G>R No EVA
rs455640488 1203 W>G No EVA
rs471531613 1219 H>R No EVA
rs453127139 1219 H>Y No EVA
rs438499824 1222 K>Q No EVA
rs463374823 1222 K>T No EVA
rs475464261 1227 L>P No EVA
rs439927516 1234 M>T No EVA
rs453492600 1237 C>F No EVA
rs471861889 1245 G>C No EVA
rs463914486 1248 R>P No EVA
rs442871468 1255 L>P No EVA
rs461422745 1256 P>L No EVA
rs479822566 1261 E>V No EVA
rs446820407 1264 E>A No EVA
rs465266952 1265 R>P No EVA

No associated diseases with E1BPK6

5 regional properties for E1BPK6

Type Name Position InterPro Accession
domain Myosin head, motor domain 51 - 772 IPR001609
domain Myosin, N-terminal, SH3-like 2 - 53 IPR004009
domain Myosin VI, cargo binding domain 1178 - 1268 IPR032412
domain Class VI myosin, motor domain 71 - 759 IPR036114
domain Myosin VI, lever arm 770 - 917 IPR049016

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 endocytic 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
  • Recruited into membrane ruffles from cell surface by EGF-stimulation
  • 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 (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

17 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.
clathrin-coated endocytic vesicle A clathrin-coated, membrane-bounded intracellular vesicle formed by invagination of the plasma membrane around an extracellular substance.
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.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
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.
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.

4 GO annotations of molecular function

Name Definition
actin filament binding Binding to an actin filament, also known as F-actin, a helical filamentous polymer of globular G-actin subunits.
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.
microfilament motor activity A motor activity that generates movement along a microfilament, driven by ATP hydrolysis.

11 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.
protein localization Any process in which a protein is transported to, or maintained in, a specific location.
protein transport The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
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.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9I8D1 MYO6 Unconventional myosin-VI 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
MEDGRPVWAP HPTEGFQMGN IVDIGPDSLT IEPLGQKGKT FLALINQVFP AEEDSKKDVE
70 80 90 100 110 120
DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKIYSSD SIKSYQGKSL
130 140 150 160 170 180
GTMPPHVFAI ADKAFRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGSGQDIDD
190 200 210 220 230 240
RIVEANPLLE AFGNAKTVRN NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK
250 260 270 280 290 300
EERNYHIFYR LCAGASEDIR ERLHLSSPDN FRYLNRGCTR YFANKETDKQ ILQNRKTPEH
310 320 330 340 350 360
LKAGSLKDPL LDDHGDFVRM CTAMKKIGLD DEEKLDLFRV VAGVLHLGNI DFEEAGSTSG
370 380 390 400 410 420
GCNLKNKSTQ SLEYCAELLG LDQDDLRVSL TTRVMLTTAG GTKGTVIKVP LKVEQANNAR
430 440 450 460 470 480
DALAKTVYSH LFDHVVNRVN QCFPFETSSY FIGVLDIAGF EYFEHNSFEQ FCINYCNEKL
490 500 510 520 530 540
QQFFNERILK EEQELYQKEG LGVNEVHYVD NQDCIDLIEA KLMGILDILD EENRLPQPSD
550 560 570 580 590 600
QHFTSAVHQK HKDHFRLSIP RKSKLAVHRN IRDDEGFIVR HFAGAVCYET TQFVEKNNDA
610 620 630 640 650 660
LHMSLESLIC ESRDKFIREL FESSTNNNKD TKQKAGKLSF ISVGNKFKTQ LNLLLDKLRS
670 680 690 700 710 720
TGASFIRCIK PNLKMTSHDF EGAQILSQLQ CSGMVSVLDL MQGGFPSRAS FHELYNMYKK
730 740 750 760 770 780
YMPDKLARLD PRLFCKALFK ALGLNEVDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAQL
790 800 810 820 830 840
VKRVNHWLIC SRWKKVQWCS LSVIKLKNKI KYRAEACIKM QKTIRMWLCK RRHKPRIDGL
850 860 870 880 890 900
VKVGTLKKRL DKFNEVVSAL KDGKAEMNKQ VKDLEISIDA LMAKIKSTMM TREQIQKEYD
910 920 930 940 950 960
ALVKSSEVLL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEDEQRRRKE EEERRMKLEM
970 980 990 1000 1010 1020
EAKRKQEEEE RKKREDDEKR IQAEVEAQLA RQREEESQQQ AVLEQERRDR ELALRIARSE
1030 1040 1050 1060 1070 1080
AELIIDEAQA DPAALRSLDF HPVTSKINGT RRTMTPEQMA KEMSEILSRG PAVQATKAAA
1090 1100 1110 1120 1130 1140
GTKKHDLSKW KYAELRDTIN TSCDIELLAA CREEFHRRLK VYHAWKSKNK KRNTETEQRA
1150 1160 1170 1180 1190 1200
PKSVTDYDFA PFLNNSPQQN PAAQLPARQQ EIEMNRQQRF FRIPFIRPAD QYKDPQNKKK
1210 1220 1230 1240 1250 1260
GWWYAHFDGP WIARQMELHP DKPPILLVAG KDDMEMCELN LEETGLTRKR GAEILPRQFE
1270 1280 1290
EIWERCGGIQ YLQSAIESRQ ARPTYATAML QNLLK