Reviewed, UniProtKB/Swiss-Prot Q9UM54 (MYO6_HUMAN)

Names and origin

Protein names

Recommended name:
    Myosin-VI
Alternative name(s):
    Unconventional myosin VI

Gene names

Name:	MYO6
Synonyms:	KIAA0389

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1294 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 By similarity.
Subunit structure	Homodimer. 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.
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein. Nucleus. Cytoplasm › perinuclear region. Membrane › clathrin-coated pit. Cell projection › ruffle membrane; Peripheral membrane protein. Note: Also present in endocyctic vesicles, and membrane ruffles. 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. Ref.7 Ref.12 Isoform 3: Cytoplasmic vesicle › clathrin-coated vesicle membrane. Ref.7 Ref.12 Isoform 4: Cytoplasmic vesicle › clathrin-coated vesicle membrane. Cell projection › ruffle membrane. Ref.7 Ref.12
Tissue specificity	Expressed in most tissues examined including heart, brain, placenta, pancreas, spleen, thymus, prostate, testis, ovary, small intestine and colon. Highest levels in brain, pancreas, testis and small intestine. Also expressed in fetal brain and cochlea. Isoform 1 and isoform 2, containing the small insert, and isoform 4, containing neither insert, are expressed in unpolarized epithelial cells. Ref.1
Domain	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 coiled-coil and a unique globular domain required for interaction with other proteins.
Post-translational modification	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.
Involvement in disease	Defects in MYO6 are the cause of non-syndromic sensorineural deafness autosomal dominant type 22 (DFNA22) [MIM:606346]. DFNA22 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA22 is progressive and postlingual, with onset during childhood. By the age of approximately 50 years, affected individuals invariably have profound sensorineural deafness. Ref.13 Defects in MYO6 are the cause of non-syndromic sensorineural deafness autosomal recessive type 37 (DFNB37) [MIM:607821]. Defects in MYO6 are the cause of sensorineural deafness with hypertrophic cardiomyopathy (DFNHCM) [MIM:606346]. Ref.15
Sequence similarities	Contains 1 IQ domain. Contains 1 myosin head-like domain.

Ontologies

Keywords
Biological process	Endocytosis Hearing Protein transport Transport
Cellular component	Cell membrane Cell projection Coated pit Cytoplasm Cytoplasmic vesicle Golgi apparatus Membrane Nucleus
Coding sequence diversity	Alternative splicing
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Coiled coil
Ligand	ATP-binding Actin-binding Calmodulin-binding Nucleotide-binding
Molecular function	Motor protein Myosin
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator Ref.12 Inferred from direct assay. Source: UniProtKB actin filament-based movement Ref.6 Non-traceable author statement. Source: UniProtKB endocytosis Ref.9 Inferred from mutant phenotype. Source: UniProtKB intracellular protein transport Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Ref.11 Inferred from mutant phenotype. Source: UniProtKB regulation of secretion Inferred from mutant phenotype. Source: UniProtKB sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	DNA-directed RNA polymerase II, holoenzyme Ref.11 Inferred from direct assay. Source: UniProtKB Golgi apparatus Ref.12 Inferred from direct assay. Source: UniProtKB cell cortex Inferred from sequence or structural similarity. Source: UniProtKB clathrin coated vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell coated pit Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from Experiment. Source: Reactome extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell filamentous actin Inferred from direct assay. Source: UniProtKB nuclear membrane Ref.12 Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB ruffle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell unconventional myosin complex Ref.1 Traceable author statement. Source: UniProtKB
Molecular function	ADP binding Inferred from sequence or structural similarity. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW actin filament binding Inferred from direct assay. Source: UniProtKB calmodulin binding Traceable author statement. Source: UniProtKB minus-end directed microfilament motor activity Ref.6 Non-traceable author statement. Source: UniProtKB protein binding Ref.7 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GIPC1	O14908	1	EBI-350606,EBI-373132
RPS27A	P62988	1	EBI-350606,EBI-413034

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 3 (identifier: Q9UM54-3)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: Q9UM54-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1037-1045: Missing.

Isoform 2 (identifier: Q9UM54-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1037-1068: Missing.

Isoform 4 (identifier: Q9UM54-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1147-1155: Missing.

Isoform 5 (identifier: Q9UM54-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1037-1068: Missing.
     1147-1155: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1294	1294	Myosin-VI		PRO_0000123464
Regions
	Domain	1 – 759	759	Myosin head-like
	Domain	814 – 834	21	IQ
	Nucleotide binding	151 – 158	8	ATP Potential
	Region	273 – 317	45	Responsible for slow ATPase activity By similarity
	Region	665 – 672	8	Actin-binding Potential
	Region	782 – 810	29	Required for binding calmodulin By similarity
	Coiled coil	864 – 1023	160	Potential
	Compositional bias	920 – 1027	108	Glu-rich
Amino acid modifications
	Modified residue	405	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	1037 – 1068	32	Missing in isoform 2 and isoform 5.		VSP_007985
	Alternative sequence	1037 – 1045	9	Missing in isoform 1.		VSP_022332
	Alternative sequence	1147 – 1155	9	Missing in isoform 4 and isoform 5.		VSP_022333
	Natural variant	216	1	E → V in DFNB37. Ref.14		VAR_016209
	Natural variant	246	1	H → R in DFNHCM. Ref.15		VAR_029988
	Natural variant	442	1	C → Y in DFNA22. Ref.13		VAR_012110
Experimental info
	Sequence conflict	1156	1	P → A in CAI42826. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 3 [UniParc]. Last modified January 9, 2007. Version 4. Checksum: 3A8966E6864B8576	FASTA	1,294	149,691
	10 20 30 40 50 60 MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE 70 80 90 100 110 120 DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKIYSSE AIKSYQGKSL 130 140 150 160 170 180 GTRPPHVFAI ADKAFRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD 190 200 210 220 230 240 RIVEANPLLE AFGNAKTVRN NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK 250 260 270 280 290 300 EERNYHIFYR LCAGASEDIR EKLHLSSPDN FRYLNRGCTR YFANKETDKQ ILQNRKSPEY 310 320 330 340 350 360 LKAGSMKDPL LDDHGDFIRM CTAMKKIGLD DEEKLDLFRV VAGVLHLGNI DFEEAGSTSG 370 380 390 400 410 420 GCNLKNKSAQ 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 KLVGILDILD EENRLPQPSD 550 560 570 580 590 600 QHFTSAVHQK HKDHFRLTIP RKSKLAVHRN IRDDEGFIIR HFAGAVCYET TQFVEKNNDA 610 620 630 640 650 660 LHMSLESLIC ESRDKFIREL FESSTNNNKD TKQKAGKLSF ISVGNKFKTQ LNLLLDKLRS 670 680 690 700 710 720 TGASFIRCIK PNLKMTSHHF EGAQILSQLQ CSGMVSVLDL MQGGYPSRAS FHELYNMYKK 730 740 750 760 770 780 YMPDKLARLD PRLFCKALFK ALGLNENDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAEL 790 800 810 820 830 840 VKRVNHWLTC SRWKKVQWCS LSVIKLKNKI KYRAEACIKM QKTIRMWLCK RRHKPRIDGL 850 860 870 880 890 900 VKVGTLKKRL DKFNEVVSVL KDGKPEMNKQ IKNLEISIDT LMAKIKSTMM TQEQIQKEYD 910 920 930 940 950 960 ALVKSSEELL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEDEKRRRKE EEERRMKLEM 970 980 990 1000 1010 1020 EAKRKQEEEE RKKREDDEKR IQAEVEAQLA RQKEEESQQQ AVLEQERRDR ELALRIAQSE 1030 1040 1050 1060 1070 1080 AELISDEAQA DLALRRSLDS YPVSKNDGTR PKMTPEQMAK EMSEFLSRGP AVLATKAAAG 1090 1100 1110 1120 1130 1140 TKKYDLSKWK YAELRDTINT SCDIELLAAC REEFHRRLKV YHAWKSKNKK RNTETEQRAP 1150 1160 1170 1180 1190 1200 KSVTDYDFAP FLNNSPQQNP AAQIPARQRE IEMNRQQRFF RIPFIRPADQ YKDPQSKKKG 1210 1220 1230 1240 1250 1260 WWYAHFDGPW IARQMELHPD KPPILLVAGK DDMEMCELNL EETGLTRKRG AEILPRQFEE 1270 1280 1290 IWERCGGIQY LQNAIESRQA RPTYATAMLQ SLLK
	Isoform 1. Checksum: BCB4FDFE920712CD	FASTA	1,285	148,714
	10 20 30 40 50 60 MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE 70 80 90 100 110 120 DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKIYSSE AIKSYQGKSL 130 140 150 160 170 180 GTRPPHVFAI ADKAFRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD 190 200 210 220 230 240 RIVEANPLLE AFGNAKTVRN NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK 250 260 270 280 290 300 EERNYHIFYR LCAGASEDIR EKLHLSSPDN FRYLNRGCTR YFANKETDKQ ILQNRKSPEY 310 320 330 340 350 360 LKAGSMKDPL LDDHGDFIRM CTAMKKIGLD DEEKLDLFRV VAGVLHLGNI DFEEAGSTSG 370 380 390 400 410 420 GCNLKNKSAQ 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 KLVGILDILD EENRLPQPSD 550 560 570 580 590 600 QHFTSAVHQK HKDHFRLTIP RKSKLAVHRN IRDDEGFIIR HFAGAVCYET TQFVEKNNDA 610 620 630 640 650 660 LHMSLESLIC ESRDKFIREL FESSTNNNKD TKQKAGKLSF ISVGNKFKTQ LNLLLDKLRS 670 680 690 700 710 720 TGASFIRCIK PNLKMTSHHF EGAQILSQLQ CSGMVSVLDL MQGGYPSRAS FHELYNMYKK 730 740 750 760 770 780 YMPDKLARLD PRLFCKALFK ALGLNENDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAEL 790 800 810 820 830 840 VKRVNHWLTC SRWKKVQWCS LSVIKLKNKI KYRAEACIKM QKTIRMWLCK RRHKPRIDGL 850 860 870 880 890 900 VKVGTLKKRL DKFNEVVSVL KDGKPEMNKQ IKNLEISIDT LMAKIKSTMM TQEQIQKEYD 910 920 930 940 950 960 ALVKSSEELL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEDEKRRRKE EEERRMKLEM 970 980 990 1000 1010 1020 EAKRKQEEEE RKKREDDEKR IQAEVEAQLA RQKEEESQQQ AVLEQERRDR ELALRIAQSE 1030 1040 1050 1060 1070 1080 AELISDEAQA DLALRRNDGT RPKMTPEQMA KEMSEFLSRG PAVLATKAAA GTKKYDLSKW 1090 1100 1110 1120 1130 1140 KYAELRDTIN TSCDIELLAA CREEFHRRLK VYHAWKSKNK KRNTETEQRA PKSVTDYDFA 1150 1160 1170 1180 1190 1200 PFLNNSPQQN PAAQIPARQR EIEMNRQQRF FRIPFIRPAD QYKDPQSKKK GWWYAHFDGP 1210 1220 1230 1240 1250 1260 WIARQMELHP DKPPILLVAG KDDMEMCELN LEETGLTRKR GAEILPRQFE EIWERCGGIQ 1270 1280 YLQNAIESRQ ARPTYATAML QSLLK
	Isoform 2. Checksum: CF1FA35796FC1C60	FASTA	1,262	146,048
	10 20 30 40 50 60 MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE 70 80 90 100 110 120 DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKIYSSE AIKSYQGKSL 130 140 150 160 170 180 GTRPPHVFAI ADKAFRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD 190 200 210 220 230 240 RIVEANPLLE AFGNAKTVRN NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK 250 260 270 280 290 300 EERNYHIFYR LCAGASEDIR EKLHLSSPDN FRYLNRGCTR YFANKETDKQ ILQNRKSPEY 310 320 330 340 350 360 LKAGSMKDPL LDDHGDFIRM CTAMKKIGLD DEEKLDLFRV VAGVLHLGNI DFEEAGSTSG 370 380 390 400 410 420 GCNLKNKSAQ 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 KLVGILDILD EENRLPQPSD 550 560 570 580 590 600 QHFTSAVHQK HKDHFRLTIP RKSKLAVHRN IRDDEGFIIR HFAGAVCYET TQFVEKNNDA 610 620 630 640 650 660 LHMSLESLIC ESRDKFIREL FESSTNNNKD TKQKAGKLSF ISVGNKFKTQ LNLLLDKLRS 670 680 690 700 710 720 TGASFIRCIK PNLKMTSHHF EGAQILSQLQ CSGMVSVLDL MQGGYPSRAS FHELYNMYKK 730 740 750 760 770 780 YMPDKLARLD PRLFCKALFK ALGLNENDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAEL 790 800 810 820 830 840 VKRVNHWLTC SRWKKVQWCS LSVIKLKNKI KYRAEACIKM QKTIRMWLCK RRHKPRIDGL 850 860 870 880 890 900 VKVGTLKKRL DKFNEVVSVL KDGKPEMNKQ IKNLEISIDT LMAKIKSTMM TQEQIQKEYD 910 920 930 940 950 960 ALVKSSEELL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEDEKRRRKE EEERRMKLEM 970 980 990 1000 1010 1020 EAKRKQEEEE RKKREDDEKR IQAEVEAQLA RQKEEESQQQ AVLEQERRDR ELALRIAQSE 1030 1040 1050 1060 1070 1080 AELISDEAQA DLALRRGPAV LATKAAAGTK KYDLSKWKYA ELRDTINTSC DIELLAACRE 1090 1100 1110 1120 1130 1140 EFHRRLKVYH AWKSKNKKRN TETEQRAPKS VTDYDFAPFL NNSPQQNPAA QIPARQREIE 1150 1160 1170 1180 1190 1200 MNRQQRFFRI PFIRPADQYK DPQSKKKGWW YAHFDGPWIA RQMELHPDKP PILLVAGKDD 1210 1220 1230 1240 1250 1260 MEMCELNLEE TGLTRKRGAE ILPRQFEEIW ERCGGIQYLQ NAIESRQARP TYATAMLQSL LK
	Isoform 4. Checksum: F68A79F74AB9170C	FASTA	1,285	148,685
	10 20 30 40 50 60 MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE 70 80 90 100 110 120 DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKIYSSE AIKSYQGKSL 130 140 150 160 170 180 GTRPPHVFAI ADKAFRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD 190 200 210 220 230 240 RIVEANPLLE AFGNAKTVRN NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK 250 260 270 280 290 300 EERNYHIFYR LCAGASEDIR EKLHLSSPDN FRYLNRGCTR YFANKETDKQ ILQNRKSPEY 310 320 330 340 350 360 LKAGSMKDPL LDDHGDFIRM CTAMKKIGLD DEEKLDLFRV VAGVLHLGNI DFEEAGSTSG 370 380 390 400 410 420 GCNLKNKSAQ 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 KLVGILDILD EENRLPQPSD 550 560 570 580 590 600 QHFTSAVHQK HKDHFRLTIP RKSKLAVHRN IRDDEGFIIR HFAGAVCYET TQFVEKNNDA 610 620 630 640 650 660 LHMSLESLIC ESRDKFIREL FESSTNNNKD TKQKAGKLSF ISVGNKFKTQ LNLLLDKLRS 670 680 690 700 710 720 TGASFIRCIK PNLKMTSHHF EGAQILSQLQ CSGMVSVLDL MQGGYPSRAS FHELYNMYKK 730 740 750 760 770 780 YMPDKLARLD PRLFCKALFK ALGLNENDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAEL 790 800 810 820 830 840 VKRVNHWLTC SRWKKVQWCS LSVIKLKNKI KYRAEACIKM QKTIRMWLCK RRHKPRIDGL 850 860 870 880 890 900 VKVGTLKKRL DKFNEVVSVL KDGKPEMNKQ IKNLEISIDT LMAKIKSTMM TQEQIQKEYD 910 920 930 940 950 960 ALVKSSEELL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEDEKRRRKE EEERRMKLEM 970 980 990 1000 1010 1020 EAKRKQEEEE RKKREDDEKR IQAEVEAQLA RQKEEESQQQ AVLEQERRDR ELALRIAQSE 1030 1040 1050 1060 1070 1080 AELISDEAQA DLALRRSLDS YPVSKNDGTR PKMTPEQMAK EMSEFLSRGP AVLATKAAAG 1090 1100 1110 1120 1130 1140 TKKYDLSKWK YAELRDTINT SCDIELLAAC REEFHRRLKV YHAWKSKNKK RNTETEQRAP 1150 1160 1170 1180 1190 1200 KSVTDYPQQN PAAQIPARQR EIEMNRQQRF FRIPFIRPAD QYKDPQSKKK GWWYAHFDGP 1210 1220 1230 1240 1250 1260 WIARQMELHP DKPPILLVAG KDDMEMCELN LEETGLTRKR GAEILPRQFE EIWERCGGIQ 1270 1280 YLQNAIESRQ ARPTYATAML QSLLK
	Isoform 5. Checksum: DD739BA2DD557EEF	FASTA	1,253	145,042
	10 20 30 40 50 60 MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE 70 80 90 100 110 120 DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKIYSSE AIKSYQGKSL 130 140 150 160 170 180 GTRPPHVFAI ADKAFRDMKV LKMSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD 190 200 210 220 230 240 RIVEANPLLE AFGNAKTVRN NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK 250 260 270 280 290 300 EERNYHIFYR LCAGASEDIR EKLHLSSPDN FRYLNRGCTR YFANKETDKQ ILQNRKSPEY 310 320 330 340 350 360 LKAGSMKDPL LDDHGDFIRM CTAMKKIGLD DEEKLDLFRV VAGVLHLGNI DFEEAGSTSG 370 380 390 400 410 420 GCNLKNKSAQ 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 KLVGILDILD EENRLPQPSD 550 560 570 580 590 600 QHFTSAVHQK HKDHFRLTIP RKSKLAVHRN IRDDEGFIIR HFAGAVCYET TQFVEKNNDA 610 620 630 640 650 660 LHMSLESLIC ESRDKFIREL FESSTNNNKD TKQKAGKLSF ISVGNKFKTQ LNLLLDKLRS 670 680 690 700 710 720 TGASFIRCIK PNLKMTSHHF EGAQILSQLQ CSGMVSVLDL MQGGYPSRAS FHELYNMYKK 730 740 750 760 770 780 YMPDKLARLD PRLFCKALFK ALGLNENDYK FGLTKVFFRP GKFAEFDQIM KSDPDHLAEL 790 800 810 820 830 840 VKRVNHWLTC SRWKKVQWCS LSVIKLKNKI KYRAEACIKM QKTIRMWLCK RRHKPRIDGL 850 860 870 880 890 900 VKVGTLKKRL DKFNEVVSVL KDGKPEMNKQ IKNLEISIDT LMAKIKSTMM TQEQIQKEYD 910 920 930 940 950 960 ALVKSSEELL SALQKKKQQE EEAERLRRIQ EEMEKERKRR EEDEKRRRKE EEERRMKLEM 970 980 990 1000 1010 1020 EAKRKQEEEE RKKREDDEKR IQAEVEAQLA RQKEEESQQQ AVLEQERRDR ELALRIAQSE 1030 1040 1050 1060 1070 1080 AELISDEAQA DLALRRGPAV LATKAAAGTK KYDLSKWKYA ELRDTINTSC DIELLAACRE 1090 1100 1110 1120 1130 1140 EFHRRLKVYH AWKSKNKKRN TETEQRAPKS VTDYPQQNPA AQIPARQREI EMNRQQRFFR 1150 1160 1170 1180 1190 1200 IPFIRPADQY KDPQSKKKGW WYAHFDGPWI ARQMELHPDK PPILLVAGKD DMEMCELNLE 1210 1220 1230 1240 1250 ETGLTRKRGA EILPRQFEEI WERCGGIQYL QNAIESRQAR PTYATAMLQS LLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice." Avraham K.B., Hasson T., Sobe T., Balsara B., Testa J.R., Skvorak A.B., Morton C.C., Copeland N.G., Jenkins N.A. Hum. Mol. Genet. 6:1225-1231(1997) [PubMed: 9259267] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Brain.
[2]	Avraham K.B. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Genomic organization of the human myosin VI gene (MYO6), a candidate gene for neurosensory and storage disorders." Kuehn M.H., Hageman G.S. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed: 9205841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1; 2 AND 5).
[6]	"Myosin VI is an actin-based motor that moves backwards." Wells A.L., Lin A.W., Chen L.-Q., Safer D., Cain S.M., Hasson T., Carragher B.O., Milligan R.A., Sweeney H.L. Nature 401:505-508(1999) [PubMed: 10519557] [Abstract] Cited for: FUNCTION.
[7]	"Myosin VI isoform localized to clathrin-coated vesicles with a role in clathrin-mediated endocytosis." Buss F., Arden S.D., Lindsay M., Luzio J.P., Kendrick-Jones J. EMBO J. 20:3676-3684(2001) [PubMed: 11447109] [Abstract] Cited for: FUNCTION IN ENDOCYTOSIS, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
[8]	"Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton." Morris S.M., Arden S.D., Roberts R.C., Kendrick-Jones J., Cooper J.A., Luzio J.P., Buss F. Traffic 3:331-341(2002) [PubMed: 11967127] [Abstract] Cited for: INTERACTION WITH DAB2.
[9]	"Myosin VI regulates endocytosis of the cystic fibrosis transmembrane conductance regulator." Swiatecka-Urban A., Boyd C., Coutermarsh B., Karlson K.H., Barnaby R., Aschenbrenner L., Langford G.M., Hasson T., Stanton B.A. J. Biol. Chem. 279:38025-38031(2004) [PubMed: 15247260] [Abstract] Cited for: INTERACTION WITH CFTR.
[10]	"A monomeric myosin VI with a large working stroke." Lister I., Schmitz S., Walker M., Trinick J., Buss F., Veigel C., Kendrick-Jones J. EMBO J. 23:1729-1738(2004) [PubMed: 15044955] [Abstract] Cited for: SUBUNIT.
[11]	"Nuclear myosin VI enhances RNA polymerase II-dependent transcription." Vreugde S., Ferrai C., Miluzio A., Hauben E., Marchisio P.C., Crippa M.P., Bussi M., Biffo S. Mol. Cell 23:749-755(2006) [PubMed: 16949370] [Abstract] Cited for: FUNCTION.
[12]	"Myosin VI is a mediator of the p53-dependent cell survival pathway." Jung E.J., Liu G., Zhou W., Chen X. Mol. Cell. Biol. 26:2175-2186(2006) [PubMed: 16507995] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[13]	"MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss." Melchionda S., Ahituv N., Bisceglia L., Sobe T., Glaser F., Rabionet R., Arbones M.L., Notarangelo A., Di Iorio E., Carella M., Zelante L., Estivill X., Avraham K.B., Gasparini P. Am. J. Hum. Genet. 69:635-640(2001) [PubMed: 11468689] [Abstract] Cited for: VARIANT DFNA22 TYR-442.
[14]	"Mutations of MYO6 are associated with recessive deafness, DFNB37." Ahmed Z.M., Morell R.J., Riazuddin S., Gropman A., Shaukat S., Ahmad M.M., Mohiddin S.A., Fananapazir L., Caruso R.C., Husnain T., Khan S.N., Riazuddin S., Griffith A.J., Friedman T.B., Wilcox E.R. Am. J. Hum. Genet. 72:1315-1322(2003) [PubMed: 12687499] [Abstract] Cited for: VARIANT DFNB37 VAL-216.
[15]	"Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6)." Mohiddin S.A., Ahmed Z.M., Griffith A.J., Tripodi D., Friedman T.B., Fananapazir L., Morell R.J. J. Med. Genet. 41:309-314(2004) [PubMed: 15060111] [Abstract] Cited for: VARIANT DFNHCM ARG-246.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U90236 mRNA. Translation: AAC51654.2. AF229111 , AF229082, AF229083, AF229084, AF229085, AF229086, AF229087, AF229088, AF229089, AF229090, AF229091, AF229092, AF229093, AF229094, AF229095, AF229096, AF229097, AF229098, AF229099, AF229100, AF229101, AF229102, AF229103, AF229104, AF229105, AF229106, AF229107, AF229108, AF229109, AF229110 Genomic DNA. Translation: AAK00229.1. AL109897, AL136093 Genomic DNA. Translation: CAI19520.1. AL109897, AL136093 Genomic DNA. Translation: CAI19521.1. AL109897, AL136093 Genomic DNA. Translation: CAI19522.1. AL136093, AL109897 Genomic DNA. Translation: CAI42824.1. AL136093, AL109897 Genomic DNA. Translation: CAI42825.1. AL136093, AL109897 Genomic DNA. Translation: CAI42826.1. AB002387 mRNA. Translation: BAA20843.2. Different initiation.
IPI	IPI00008455. IPI00069126. IPI00642722. IPI00816452. IPI00816461.
RefSeq	NP_004990.3.
UniGene	Hs.149387
3D structure databases
HSSP	HSSP built from PDB template 1MND based on UniProtKB P08799.
SMR	Q9UM54. Positions 4-812.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UM54. 10 interactions.
STRING	Q9UM54.
PTM databases
PhosphoSite	Q9UM54.
Proteomic databases
PRIDE	Q9UM54.
Genome annotation databases
Ensembl	ENST00000369975; ENSP00000358992; ENSG00000196586; Homo sapiens. [Genome view] ENST00000369977; ENSP00000358994; ENSG00000196586; Homo sapiens. [Genome view] ENST00000369978; ENSP00000358995; ENSG00000196586; Homo sapiens. [Genome view] ENST00000369981; ENSP00000358998; ENSG00000196586; Homo sapiens. [Genome view] ENST00000369985; ENSP00000359002; ENSG00000196586; Homo sapiens. [Genome view] ENST00000428345; ENSP00000412500; ENSG00000196586; Homo sapiens. [Genome view] ENST00000430435; ENSP00000399406; ENSG00000196586; Homo sapiens. [Genome view]
GeneID	4646.
KEGG	hsa:4646.
UCSC	uc003pig.1. human. uc003pih.1. human. uc003pii.1. human.
Organism-specific databases
CTD	4646.
GeneCards	GC06P076515.
H-InvDB	HIX0006018.
HGNC	HGNC:7605. MYO6.
HPA	CAB010762.
MIM	600970. gene. 606346. phenotype. 607821. phenotype.
Orphanet	99739. Cardiomyopathy, familial, hypertrophic. 90635. Deafness, autosomal dominant, nonsyndromic, sensorineural, type DFNA. 90636. Deafness, autosomal recessive, nonsyndromic, sensorineural, type DFNB.
PharmGKB	PA31410.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9UM54.
HOVERGEN	Q9UM54.
OMA	TINTSCD.
Enzyme and pathway databases
Reactome	REACT_13685. Synaptic Transmission. REACT_9480. Gap junction trafficking and regulation.
Gene expression databases
ArrayExpress	Q9UM54.
Bgee	Q9UM54.
CleanEx	HS_MYO6.
Genevestigator	Q9UM54.
GermOnline	ENSG00000196586. Homo sapiens.
Family and domain databases
InterPro	IPR000048. IQ_CaM_bd_region. IPR001609. Myosin_head. [Graphical view]
Pfam	PF00612. IQ. 1 hit. PF00063. Myosin_head. 1 hit. [Graphical view]
PRINTS	PR00193. MYOSINHEAVY.
ProDom	PD000355. Myosin_head. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00015. IQ. 1 hit. SM00242. MYSc. 1 hit. [Graphical view]
PROSITE	PS50096. IQ. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	17908.
SOURCE	Search...

Entry information

Entry name

MYO6_HUMAN

Accession

Primary (citable) accession number: Q9UM54
Secondary accession number(s): Q5TEM5 , Q5TEM6, Q5TEM7, Q9BZZ7, Q9UEG2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	January 9, 2007
Last modified:	November 3, 2009
This is version 98 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.