Unconventional myosin-VI - Sus scrofa (Pig)

Preferred order of sections

Names and origin

Protein names

Recommended name:
Unconventional myosin-VI

Alternative name(s):
Unconventional myosin-6

Gene names

Name:

MYO6

Organism

Sus scrofa (Pig) [Reference proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	1254 AA.
Sequence status	Complete.
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. Ref.6
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. 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. Ref.1
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein By similarity. Golgi apparatus By similarity. Nucleus By similarity. Cytoplasm › perinuclear region By similarity. 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 OPTN at the Golgi complex and in vesicular structures close to the plasma membrane By similarity. Ref.1 Ref.6
Tissue specificity	Expressed in all tissues examined including kidney cortex, intestinal mucosa, liver, lung, heart, jowl muscle, brain cortex and medulla, and in the epithelial cell line, LLC-PK1. In the kidney, located to the brush border of adult kidney proximal tubule cells. Ref.1
Developmental stage	Locates to the apical domain only during the final stages of kidney proximal tubule development.
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). Ref.4
Sequence similarities	Contains 1 IQ domain. Contains 1 myosin head-like domain.
Caution	Represents a unconventional myosin. This protein should not be confused with the conventional myosin-6 (MYH6).

Ontologies

Keywords
Biological process	Endocytosis Hearing Protein transport Transport
Cellular component	Cytoplasm Golgi apparatus Membrane Nucleus
Domain	Coiled coil
Ligand	ATP-binding Actin-binding Calmodulin-binding Nucleotide-binding
Molecular function	Motor protein Myosin
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator Inferred from sequence or structural similarity. Source: UniProtKB actin filament-based movement Inferred from direct assay PubMed 10519557. Source: UniProtKB endocytosis Inferred from mutant phenotype PubMed 12857860. Source: UniProtKB intracellular protein transport Inferred from mutant phenotype PubMed 12857860. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB regulation of secretion Inferred from sequence or structural similarity. Source: UniProtKB sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	DNA-directed RNA polymerase II, holoenzyme Inferred from sequence or structural similarity. Source: UniProtKB Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB cell cortex Inferred from direct assay PubMed 12857860. Source: UniProtKB cytoplasmic membrane-bounded vesicle Inferred from sequence or structural similarity. Source: UniProtKB filamentous actin Inferred from direct assay PubMed 10519557. Source: UniProtKB myosin complex Inferred from electronic annotation. Source: UniProtKB-KW nuclear membrane Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay PubMed 12857860. Source: UniProtKB ruffle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ADP binding Inferred from direct assay PubMed 10519557. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW actin filament binding Inferred from direct assay PubMed 10519557. Source: UniProtKB calmodulin binding Non-traceable author statement PubMed 10519557. Source: UniProtKB motor activity Inferred from direct assay PubMed 10519557. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1254

1254

Unconventional myosin-VI

PRO_0000271746

Regions

Domain

59 – 760

702

Myosin head-like

Domain

814 – 843

30

IQ

Nucleotide binding

151 – 158

8

ATP Potential

Region

273 – 317

45

Responsible for slow ATPase activity

Region

666 – 673

8

Actin-binding Potential

Region

783 – 811

29

Required for binding calmodulin

Region

1085 – 1087

3

Interaction with OPTN

Coiled coil

847 – 1024

178

Potential

Compositional bias

921 – 1028

108

Glu-rich

Amino acid modifications

Modified residue

406

1

Phosphothreonine Ref.4

Experimental info

Mutagenesis

406

1

T → E: Greatly reduced phosphorylation. Transports uncoated endocytic vesicles to clusters at distinct peripheral sites and alters actin filament structure. Ref.4 Ref.6

Secondary structure

1

.

1254

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q29122 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 0A72C1A7991CF763
Show »

FASTA

1,254

144,859

        10         20         30         40         50         60 
MEDGKPVWAP HPTDGFQVGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE 

        70         80         90        100        110        120 
DNCSLMYLNE ATLLHNIKVR YSKDRIYTYV ANILIAVNPY FDIPKIYSSE TIKSYQGKSL 

       130        140        150        160        170        180 
GTMPPHVFAI ADKAFRDMKV LKLSQSIIVS GESGAGKTEN TKFVLRYLTE SYGTGQDIDD 

       190        200        210        220        230        240 
RIVEANPLLE AFGNAKTVRN NNSSRFGKFV EIHFNEKSSV VGGFVSHYLL EKSRICVQGK 

       250        260        270        280        290        300 
EERNYHIFYR LCAGASEDIR ERLHLSSPDN FRYLNRGCTR YFANKETDKQ ILQNRKSPEY 

       310        320        330        340        350        360 
LKAGSLKDPL LDDHGDFIRM CTAMKKIGLD DEEKLDLFRV VAGVLHLGNI DFEEAGSTSG 

       370        380        390        400        410        420 
GCNLKNKSTQ ALEYCAEKLL GLDQDDLRVS LTTRVMLTTA GGAKGTVIKV PLKVEQANNA 

       430        440        450        460        470        480 
RDALAKTVYS HLFDHVVNRV NQCFPFETSS YFIGVLDIAG FEYFEHNSFE QFCINYCNEK 

       490        500        510        520        530        540 
LQQFFNERIL KEEQELYQKE GLGVNEVHYV DNQDCIDLIE ARLVGILDIL DEENRLPQPS 

       550        560        570        580        590        600 
DQHFTSAGHQ KHKDHFRLSI PRKSKLAIHR NIAYDEGFII RHFAGAVCYE TTQFVEKNND 

       610        620        630        640        650        660 
ALHMSLESLI CESRDKFIRE LFESSTNNNK DTKQKAGKLS FISVGNKFKT QLNLLLDKLR 

       670        680        690        700        710        720 
STGASFIRCI KPNLKMTSHH FEGAQILSQL QCSGMVSVLD LMQGGFPSRA SFHEVYNMYK 

       730        740        750        760        770        780 
KSLPDKLARL DPRLFCKALF KALGLNEIDY KFGLTKVFFR PGKFAEFDQI MKSDPDHLAE 

       790        800        810        820        830        840 
LVKRVNHWLI CSRWKKVQWC SLSVIKLKNK IKYRAEACIK MQKTIRMWLC KRRHKPRIDG 

       850        860        870        880        890        900 
LVKVGTLKKR LDKFNEVVSA LKDGKQEMSK QVKDLEISID ALMAKIKSTM MTREQIQKEY 

       910        920        930        940        950        960 
DALVKSSAVL LSALQKKKQQ EEEAERLRRI QEEMEKERKR REEDEQRRRK EEEERRMKLE 

       970        980        990       1000       1010       1020 
MEAKRKQEEE ERKKREDDEK RIQAEVEAQL ARQREEESQQ QAVLEQERRD RELALRIAQS 

      1030       1040       1050       1060       1070       1080 
EAELISDEAQ ADPGLRRGPA VQATKAAAGT KKYDLSKWKY AELRDTINTS CDIELLAACR 

      1090       1100       1110       1120       1130       1140 
EEFHRRLKVY HAWKSKNKKR NTETEQRAPK SVTDYAQQNP AVQLPARQQE IEMNRQQRFF 

      1150       1160       1170       1180       1190       1200 
RIPFIRSADQ YKDPQNKKKG WWYAHFDGPW IARQMELHPD KPPILLVAGK DDMEMCELNL 

      1210       1220       1230       1240       1250 
EETGLTRKRG AEILPRQFEE IWERCGGIQY LQNAIESRQA RPTYATAMLQ NLLK

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References

[1]	"Porcine myosin-VI: characterization of a new mammalian unconventional myosin." Hasson T., Mooseker M.S. J. Cell Biol. 127:425-440(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH ACTN1, SUBCELLULAR LOCATION. Tissue: Kidney.
[2]	"Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types." Bement W.M., Hasson T., Wirth J.A., Cheney R.E., Mooseker M.S. Proc. Natl. Acad. Sci. U.S.A. 91:6549-6553(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[3]	Erratum Bement W.M., Hasson T., Wirth J.A., Cheney R.E., Mooseker M.S. Proc. Natl. Acad. Sci. U.S.A. 91:11767-11767(1994) [PubMed] [Europe PMC] [Abstract]
[4]	"Calcium functionally uncouples the heads of myosin VI." Morris C.A., Wells A.L., Yang Z., Chen L.Q., Baldacchino C.V., Sweeney H.L. J. Biol. Chem. 278:23324-23330(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-406, CALCIUM-BINDING, MUTAGENESIS OF THR-406.
[5]	"The unique insert in myosin VI is a structural calcium-calmodulin binding site." Bahloul A., Chevreux G., Wells A.L., Martin D., Nolt J., Yang Z., Chen L.-Q., Potier N., van Dorsselaer A., Rosenfeld S., Houdusse A., Sweeney H.L. Proc. Natl. Acad. Sci. U.S.A. 101:4787-4792(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CALCIUM-CALMODULIN BINDING SITE.
[6]	"Myosin VI altered at threonine 406 stabilizes actin filaments in vivo." Naccache S.N., Hasson T. Cell Motil. Cytoskeleton 63:633-645(2006) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF THR-406, POSSIBLE FUNCTION, SUBCELLULAR LOCATION.
[7]	"The structure of the myosin VI motor reveals the mechanism of directionality reversal." Menetrey J., Bahloul A., Wells A.L., Yengo C.M., Morris C.A., Sweeney H.L., Houdusse A. Nature 435:779-785(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-859 IN COMPLEX WITH CALMODULIN, ATPASE ACTIVITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z35331 mRNA. Translation: CAA84559.1.

PIR

A54818.

RefSeq

NP_999186.1. NM_214021.1.

UniGene

Ssc.94.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BKH	X-ray	2.40	A	2-816	[»]
2BKI	X-ray	2.90	A	1-859	[»]
2V26	X-ray	1.75	A	5-789	[»]
2VAS	X-ray	2.40	A	2-816	[»]
2VB6	X-ray	2.30	A	2-816	[»]
2X51	X-ray	2.20	A	1-816	[»]
3GN4	X-ray	2.70	A/E	771-918	[»]
3L9I	X-ray	2.20	A	2-816	[»]
4ANJ	X-ray	2.60	A	1-817	[»]
4DBP	X-ray	2.20	A	2-816	[»]
4DBQ	X-ray	2.60	A	2-816	[»]
4DBR	X-ray	1.95	A	5-790	[»]

ProteinModelPortal

Q29122.

SMR

Q29122. Positions 2-826.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48994N.

Proteomic databases

PaxDb

Q29122.

PRIDE

Q29122.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

397085.

KEGG

ssc:397085.

Organism-specific databases

CTD

4646.

Phylogenomic databases

eggNOG

COG5022.

HOGENOM

HOG000007806.

HOVERGEN

HBG003523.

KO

K10358.

OrthoDB

EOG46HG8W.

Family and domain databases

InterPro

IPR000048. IQ_motif_EF-hand-BS.
IPR001609. Myosin_head_motor_dom.
[Graphical view]

Pfam

PF00063. Myosin_head. 1 hit.
[Graphical view]

PRINTS

PR00193. MYOSINHEAVY.

SMART

SM00015. IQ. 1 hit.
SM00242. MYSc. 1 hit.
[Graphical view]

PROSITE

PS50096. IQ. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q29122.

Entry information

Entry name

MYO6_PIG

Accession

Primary (citable) accession number: Q29122

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families