MYMK_MOUSE
ID MYMK_MOUSE Reviewed; 221 AA.
AC Q9D1N4;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Protein myomaker {ECO:0000303|PubMed:23868259};
DE AltName: Full=Myoblast fusion maker {ECO:0000303|PubMed:23868259};
DE AltName: Full=Transmembrane protein 8C;
GN Name=Mymk {ECO:0000312|MGI:MGI:1913389};
GN Synonyms=Tmem8c {ECO:0000312|MGI:MGI:1913389};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Jaw, and Limb;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=23868259; DOI=10.1038/nature12343;
RA Millay D.P., O'Rourke J.R., Sutherland L.B., Bezprozvannaya S.,
RA Shelton J.M., Bassel-Duby R., Olson E.N.;
RT "Myomaker is a membrane activator of myoblast fusion and muscle
RT formation.";
RL Nature 499:301-305(2013).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=25085416; DOI=10.1101/gad.247205.114;
RA Millay D.P., Sutherland L.B., Bassel-Duby R., Olson E.N.;
RT "Myomaker is essential for muscle regeneration.";
RL Genes Dev. 28:1641-1646(2014).
RN [6]
RP INDUCTION.
RX PubMed=28579197; DOI=10.1016/j.abb.2017.05.020;
RA He J., Wang F., Zhang P., Li W., Wang J., Li J., Liu H., Chen X.;
RT "miR-491 inhibits skeletal muscle differentiation through targeting
RT myomaker.";
RL Arch. Biochem. Biophys. 625:30-38(2017).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28186492; DOI=10.7554/elife.20007;
RA Goh Q., Millay D.P.;
RT "Requirement of myomaker-mediated stem cell fusion for skeletal muscle
RT hypertrophy.";
RL Elife 6:0-0(2017).
RN [8]
RP SUBCELLULAR LOCATION, TOPOLOGY, PALMITOYLATION AT CYS-217 AND CYS-218, AND
RP MUTAGENESIS OF GLY-2; 215-THR--VAL-221; 216-LEU--VAL-221; 217-CYS--CYS-220;
RP 217-CYS-CYS-218; 218-CYS--CYS-220 AND 219-THR--VAL-221.
RX PubMed=28860190; DOI=10.1074/jbc.m117.811372;
RA Gamage D.G., Leikina E., Quinn M.E., Ratinov A., Chernomordik L.V.,
RA Millay D.P.;
RT "Insights into the localization and function of myomaker during myoblast
RT fusion.";
RL J. Biol. Chem. 292:17272-17289(2017).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28681861; DOI=10.1038/ncomms16077;
RG Moebius Syndrome Research Consortium;
RA Di Gioia S.A., Connors S., Matsunami N., Cannavino J., Rose M.F.,
RA Gilette N.M., Artoni P., de Macena Sobreira N.L., Chan W.M., Webb B.D.,
RA Robson C.D., Cheng L., Van Ryzin C., Ramirez-Martinez A., Mohassel P.,
RA Leppert M., Scholand M.B., Grunseich C., Ferreira C.R., Hartman T.,
RA Hayes I.M., Morgan T., Markie D.M., Fagiolini M., Swift A., Chines P.S.,
RA Speck-Martins C.E., Collins F.S., Jabs E.W., Boennemann C.G., Olson E.N.,
RA Carey J.C., Robertson S.P., Manoli I., Engle E.C.;
RT "A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.";
RL Nat. Commun. 8:16077-16077(2017).
RN [10]
RP FUNCTION, AND INTERACTION WITH MYMX.
RX PubMed=28386024; DOI=10.1126/science.aam9361;
RA Bi P., Ramirez-Martinez A., Li H., Cannavino J., McAnally J.R.,
RA Shelton J.M., Sanchez-Ortiz E., Bassel-Duby R., Olson E.N.;
RT "Control of muscle formation by the fusogenic micropeptide myomixer.";
RL Science 356:323-327(2017).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30197239; DOI=10.1016/j.devcel.2018.08.006;
RA Leikina E., Gamage D.G., Prasad V., Goykhberg J., Crowe M., Diao J.,
RA Kozlov M.M., Chernomordik L.V., Millay D.P.;
RT "Myomaker and Myomerger work independently to control distinct steps of
RT membrane remodeling during myoblast fusion.";
RL Dev. Cell 46:767-780(2018).
CC -!- FUNCTION: Myoblast-specific protein that mediates myoblast fusion, an
CC essential step for the formation of multi-nucleated muscle fibers
CC (PubMed:23868259, PubMed:28386024, PubMed:28681861, PubMed:30197239).
CC Actively participates in the membrane fusion reaction by mediating the
CC mixing of cell membrane lipids (hemifusion) upstream of MYMX
CC (PubMed:30197239). Acts independently of MYMX (PubMed:30197239).
CC Involved in skeletal muscle regeneration in response to injury by
CC mediating the fusion of satellite cells, a population of muscle stem
CC cells, with injured myofibers (PubMed:25085416). Also involved in
CC skeletal muscle hypertrophy, probably by mediating the fusion of
CC satellite cells with myofibers (PubMed:28186492).
CC {ECO:0000269|PubMed:23868259, ECO:0000269|PubMed:25085416,
CC ECO:0000269|PubMed:28186492, ECO:0000269|PubMed:28386024,
CC ECO:0000269|PubMed:28681861, ECO:0000269|PubMed:30197239}.
CC -!- SUBUNIT: Interacts with MYMX (PubMed:28386024).
CC {ECO:0000269|PubMed:28386024}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23868259,
CC ECO:0000269|PubMed:28860190}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:23868259}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:28860190}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:28860190}. Note=Localizes on the plasma membrane of
CC myoblasts, where it mediates myoblasts fusion (PubMed:23868259,
CC PubMed:28860190). Also localizes in the Golgi apparatus and post-Golgi
CC following palmitoylation; the role of Golgi localization is unclear
CC (PubMed:28860190). {ECO:0000269|PubMed:23868259,
CC ECO:0000269|PubMed:28860190}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in skeletal muscle during
CC embryogenesis and adult muscle regeneration.
CC {ECO:0000269|PubMed:23868259, ECO:0000269|PubMed:28681861}.
CC -!- DEVELOPMENTAL STAGE: During embryogenesis, highly expressed in the
CC myotome compartment of the somites, and later in limb buds and axial
CC skeletal muscles. Specifically expressed in skeletal muscle, and not in
CC other muscle tissues or non-muscle tissues. Expression is down-
CC regulated postnatally. {ECO:0000269|PubMed:23868259}.
CC -!- INDUCTION: Expression is induced in muscles in response to muscle
CC injury (PubMed:25085416). Expression is induced in muscle progenitors
CC response to muscle overload (PubMed:28186492). Down-regulated by in
CC microRNA miR-491, which binds specifically to its 3' untranslated
CC region of Mymk leading to its down-regulation (PubMed:28579197).
CC {ECO:0000269|PubMed:25085416, ECO:0000269|PubMed:28186492,
CC ECO:0000269|PubMed:28579197}.
CC -!- PTM: Palmitoylated at the C-terminus; palmitoylation promotes
CC localization to the Golgi apparatus. {ECO:0000269|PubMed:28860190}.
CC -!- DISRUPTION PHENOTYPE: Perinatal death due to an absence of multi-
CC nucleated muscle fibers (PubMed:23868259). Mice are observed at normal
CC Mendelian ratios at 15 dpc and 17.5 dpc, full-term embryos are alive
CC but are paralyzed and kyphotic with flaccid limbs due to skeletal
CC muscle deficiency (PubMed:23868259). They show a complete absence of
CC differentiated muscle tissue in the trunk, limbs or head
CC (PubMed:23868259). Myoblasts can activate muscle-specific gene
CC expression and differentiate, but lack the ability to fuse
CC (PubMed:23868259). Defects are caused by impaired lipid mixing of cell
CC membranes (PubMed:30197239). Conditional deletion in adult satellite
CC cells, a population of muscle stem cells, completely abolishes muscle
CC regeneration after injury, resulting in severe muscle destruction
CC (PubMed:25085416). Conditional deletion in adult satellite cells
CC impairs skeletal muscle hypertrophy in response to exercise
CC (PubMed:28186492). {ECO:0000269|PubMed:23868259,
CC ECO:0000269|PubMed:25085416, ECO:0000269|PubMed:28186492,
CC ECO:0000269|PubMed:30197239}.
CC -!- SIMILARITY: Belongs to the TMEM8 family. {ECO:0000305}.
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DR EMBL; AK003298; BAB22699.1; -; mRNA.
DR EMBL; AL845266; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062145; AAH62145.1; -; mRNA.
DR CCDS; CCDS15823.1; -.
DR RefSeq; NP_001153074.1; NM_001159602.1.
DR RefSeq; NP_079652.1; NM_025376.3.
DR AlphaFoldDB; Q9D1N4; -.
DR STRING; 10090.ENSMUSP00000009358; -.
DR PhosphoSitePlus; Q9D1N4; -.
DR PaxDb; Q9D1N4; -.
DR PRIDE; Q9D1N4; -.
DR Antibodypedia; 67468; 8 antibodies from 4 providers.
DR DNASU; 66139; -.
DR Ensembl; ENSMUST00000009358; ENSMUSP00000009358; ENSMUSG00000009214.
DR GeneID; 66139; -.
DR KEGG; mmu:66139; -.
DR UCSC; uc008iwz.2; mouse.
DR CTD; 389827; -.
DR MGI; MGI:1913389; Mymk.
DR VEuPathDB; HostDB:ENSMUSG00000009214; -.
DR eggNOG; ENOG502REE6; Eukaryota.
DR GeneTree; ENSGT00940000160710; -.
DR HOGENOM; CLU_084233_0_0_1; -.
DR InParanoid; Q9D1N4; -.
DR OMA; QFHMEAM; -.
DR OrthoDB; 704708at2759; -.
DR PhylomeDB; Q9D1N4; -.
DR BioGRID-ORCS; 66139; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q9D1N4; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9D1N4; protein.
DR Bgee; ENSMUSG00000009214; Expressed in internal carotid artery and 34 other tissues.
DR ExpressionAtlas; Q9D1N4; baseline and differential.
DR Genevisible; Q9D1N4; MM.
DR GO; GO:0030173; C:integral component of Golgi membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0007520; P:myoblast fusion; IDA:UniProtKB.
DR GO; GO:0014905; P:myoblast fusion involved in skeletal muscle regeneration; IMP:MGI.
DR GO; GO:0045026; P:plasma membrane fusion; IDA:UniProtKB.
DR GO; GO:1904206; P:positive regulation of skeletal muscle hypertrophy; IDA:UniProtKB.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IMP:MGI.
DR InterPro; IPR021910; NGX6/PGAP6/MYMK.
DR PANTHER; PTHR14319; PTHR14319; 1.
DR Pfam; PF12036; DUF3522; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Golgi apparatus; Lipoprotein; Membrane; Myogenesis;
KW Palmitate; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..221
FT /note="Protein myomaker"
FT /id="PRO_0000319063"
FT TOPO_DOM 1..3
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..29
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 30..50
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 51..64
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 94..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..113
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28860190"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28860190"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT LIPID 217
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:28860190"
FT LIPID 218
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:28860190"
FT MUTAGEN 2
FT /note="G->A: Does not affect subcellular localization."
FT /evidence="ECO:0000269|PubMed:28860190"
FT MUTAGEN 215..221
FT /note="TLCCTCV->AAAAAAA: Abolished localization to the
FT Golgi apparatus."
FT /evidence="ECO:0000269|PubMed:28860190"
FT MUTAGEN 215..221
FT /note="TLCCTCV->AACCACA: Does not affect subcellular
FT localization."
FT /evidence="ECO:0000269|PubMed:28860190"
FT MUTAGEN 216..221
FT /note="LCCTCV->ACCACA: Does not affect subcellular
FT localization."
FT /evidence="ECO:0000269|PubMed:28860190"
FT MUTAGEN 217..220
FT /note="CCTC->AATA,SSTS: Abolished localization to the Golgi
FT apparatus."
FT /evidence="ECO:0000269|PubMed:28860190"
FT MUTAGEN 217..218
FT /note="CC->SS: Abolished localization to the Golgi
FT apparatus."
FT /evidence="ECO:0000269|PubMed:28860190"
FT MUTAGEN 218..220
FT /note="CTC->STS: Abolished localization to the Golgi
FT apparatus."
FT /evidence="ECO:0000269|PubMed:28860190"
FT MUTAGEN 219..221
FT /note="TCV->AAA: Does not affect subcellular localization."
FT /evidence="ECO:0000269|PubMed:28860190"
SQ SEQUENCE 221 AA; 24792 MW; 6D3C885770201FC4 CRC64;
MGTVVAKLLL PTLSSLAFLP TVSIATKRRF YMEAMVYLFT MFFVAFSHAC DGPGLSVLCF
MRRDILEYFS IYGTALSMWV SLMALADFDE PQRSTFTMLG VLTIAVRTFH DRWGYGVYSG
PIGTATLIIA VKWLKKMKEK KGLYPDKSIY TQQIGPGLCF GALALMLRFF FEEWDYTYVH
SFYHCALAMS FVLLLPKVNK KAGNAGAPAK LTFSTLCCTC V
