MYMK_HUMAN
ID MYMK_HUMAN Reviewed; 221 AA.
AC A6NI61;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Protein myomaker {ECO:0000250|UniProtKB:Q9D1N4};
DE AltName: Full=Myoblast fusion maker {ECO:0000250|UniProtKB:Q9D1N4};
DE AltName: Full=Transmembrane protein 226;
DE AltName: Full=Transmembrane protein 8C;
GN Name=MYMK {ECO:0000312|HGNC:HGNC:33778};
GN Synonyms=TMEM226 {ECO:0000312|HGNC:HGNC:33778},
GN TMEM8C {ECO:0000312|HGNC:HGNC:33778};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP VARIANTS CFZS THR-91; SER-100; THR-154 AND ARG-185, FUNCTION, AND
RP SUBCELLULAR LOCATION.
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 [3]
RP VARIANTS CFZS ARG-79 AND THR-91.
RX PubMed=30065953; DOI=10.1212/nxg.0000000000000254;
RA Hedberg-Oldfors C., Lindberg C., Oldfors A.;
RT "Carey-Fineman-Ziter syndrome with mutations in the myomaker gene and
RT muscle fiber hypertrophy.";
RL Neurol. Genet. 4:E254-E254(2018).
CC -!- FUNCTION: Myoblast-specific protein that mediates myoblast fusion, an
CC essential step for the formation of multi-nucleated muscle fibers
CC (PubMed:28681861). Actively participates in the membrane fusion
CC reaction by mediating the mixing of cell membrane lipids (hemifusion)
CC upstream of MYMX. Acts independently of MYMX (By similarity). Involved
CC in skeletal muscle regeneration in response to injury by mediating the
CC fusion of satellite cells, a population of muscle stem cells, with
CC injured myofibers (By similarity). Also involved in skeletal muscle
CC hypertrophy, probably by mediating the fusion of satellite cells with
CC myofibers (By similarity). {ECO:0000250|UniProtKB:Q9D1N4,
CC ECO:0000269|PubMed:28681861}.
CC -!- SUBUNIT: Interacts with MYMX. {ECO:0000250|UniProtKB:Q9D1N4}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9D1N4};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9D1N4}. Golgi
CC apparatus membrane {ECO:0000250|UniProtKB:Q9D1N4}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:Q9D1N4}. Note=Localizes on the plasma
CC membrane of myoblasts, where it mediates myoblasts fusion. Also
CC localizes in the Golgi apparatus and post-Golgi following
CC palmitoylation; the role of Golgi localization is unclear.
CC {ECO:0000250|UniProtKB:Q9D1N4}.
CC -!- PTM: Palmitoylated at the C-terminus; palmitoylation promotes
CC localization to the Golgi apparatus. {ECO:0000250|UniProtKB:Q9D1N4}.
CC -!- DISEASE: Carey-Fineman-Ziter syndrome (CFZS) [MIM:254940]: An autosomal
CC recessive multisystem disorder characterized by hypotonia, bilateral
CC congenital facial palsy with impairment of ocular abduction (Moebius
CC sequence), micrognathia, glossoptosis and high-arched or cleft palate
CC (Pierre Robin complex), delayed motor milestones, and failure to
CC thrive. {ECO:0000269|PubMed:28681861, ECO:0000269|PubMed:30065953}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the TMEM8 family. {ECO:0000305}.
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DR EMBL; BX324209; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS35170.1; -.
DR RefSeq; NP_001073952.1; NM_001080483.2.
DR AlphaFoldDB; A6NI61; -.
DR STRING; 9606.ENSP00000419712; -.
DR TCDB; 1.N.2.1.1; the myoblast fusion complex (mfc) family.
DR iPTMnet; A6NI61; -.
DR PhosphoSitePlus; A6NI61; -.
DR BioMuta; MYMK; -.
DR PaxDb; A6NI61; -.
DR PRIDE; A6NI61; -.
DR Antibodypedia; 67468; 8 antibodies from 4 providers.
DR DNASU; 389827; -.
DR Ensembl; ENST00000339996.4; ENSP00000419712.2; ENSG00000187616.5.
DR GeneID; 389827; -.
DR KEGG; hsa:389827; -.
DR MANE-Select; ENST00000339996.4; ENSP00000419712.2; NM_001080483.3; NP_001073952.1.
DR UCSC; uc011mdk.2; human.
DR CTD; 389827; -.
DR DisGeNET; 389827; -.
DR GeneCards; MYMK; -.
DR HGNC; HGNC:33778; MYMK.
DR HPA; ENSG00000187616; Tissue enhanced (brain).
DR MalaCards; MYMK; -.
DR MIM; 254940; phenotype.
DR MIM; 615345; gene.
DR neXtProt; NX_A6NI61; -.
DR OpenTargets; ENSG00000187616; -.
DR Orphanet; 1358; Carey-Fineman-Ziter syndrome.
DR PharmGKB; PA165586306; -.
DR VEuPathDB; HostDB:ENSG00000187616; -.
DR eggNOG; ENOG502REE6; Eukaryota.
DR GeneTree; ENSGT00940000160710; -.
DR HOGENOM; CLU_084233_0_0_1; -.
DR InParanoid; A6NI61; -.
DR OMA; QFHMEAM; -.
DR OrthoDB; 704708at2759; -.
DR PhylomeDB; A6NI61; -.
DR PathwayCommons; A6NI61; -.
DR SignaLink; A6NI61; -.
DR BioGRID-ORCS; 389827; 11 hits in 1066 CRISPR screens.
DR GenomeRNAi; 389827; -.
DR Pharos; A6NI61; Tdark.
DR PRO; PR:A6NI61; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; A6NI61; protein.
DR Bgee; ENSG00000187616; Expressed in tibial nerve and 55 other tissues.
DR GO; GO:0030173; C:integral component of Golgi membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS: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; IEA:Ensembl.
DR GO; GO:0045026; P:plasma membrane fusion; ISS:UniProtKB.
DR GO; GO:1904206; P:positive regulation of skeletal muscle hypertrophy; ISS:UniProtKB.
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; Disease variant; Golgi apparatus; Lipoprotein; Membrane;
KW Myogenesis; Palmitate; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..221
FT /note="Protein myomaker"
FT /id="PRO_0000319062"
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..34
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 35..55
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 56..64
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..92
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 93..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..113
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9D1N4"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9D1N4"
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:0000250|UniProtKB:Q9D1N4"
FT LIPID 218
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9D1N4"
FT VARIANT 79
FT /note="W -> R (in CFZS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:30065953"
FT /id="VAR_081291"
FT VARIANT 91
FT /note="P -> T (in CFZS; unknown pathological significance;
FT supports cell fusion in a heterologous cell fusion assay in
FT vitro; decreased localization at the plasma membrane;
FT partially rescues of mymk knockout fish; primary myoblasts
FT from a compound heterozygote associating T-91 and R-185
FT exhibit no difference in their capability to differentiate
FT compared to control myoblasts, but show a significant
FT difference in the fusion index, with a higher percentage of
FT singly-nucleated relative to multinucleated cells in
FT compound heterozygous compared to control myoblasts;
FT dbSNP:rs137868995)"
FT /evidence="ECO:0000269|PubMed:28681861,
FT ECO:0000269|PubMed:30065953"
FT /id="VAR_079262"
FT VARIANT 100
FT /note="G -> S (in CFZS; loss of localization at the plasma
FT membrane; loss of cell fusion in a heterologous cell fusion
FT assay in vitro; no rescue of mymk knockout fish;
FT dbSNP:rs964335184)"
FT /evidence="ECO:0000269|PubMed:28681861"
FT /id="VAR_079263"
FT VARIANT 154
FT /note="I -> T (in CFZS; decreased localization at the
FT plasma membrane; reduced cell fusion in a heterologous cell
FT fusion assay in vitro compared to wild-type; partially
FT rescues of mymk knockout fish; dbSNP:rs1131692249)"
FT /evidence="ECO:0000269|PubMed:28681861"
FT /id="VAR_079264"
FT VARIANT 185
FT /note="C -> R (in CFZS; loss of localization at the plasma
FT membrane; loss of cell fusion in a heterologous cell fusion
FT assay in vitro; no rescue of mymk knockout fish; primary
FT myoblasts from a compound heterozygote associating T-91 and
FT R-185 exhibit no difference in their capability to
FT differentiate compared to control myoblasts, but show a
FT significant difference in the fusion index, with a higher
FT percentage of singly-nucleated relative to multinucleated
FT cells in compound heterozygous compared to control
FT myoblasts; dbSNP:rs1131692247)"
FT /evidence="ECO:0000269|PubMed:28681861"
FT /id="VAR_079265"
SQ SEQUENCE 221 AA; 24699 MW; 8A163CD15CC25290 CRC64;
MGTLVAKLLL PTLSSLAFLP TVSIAAKRRF HMEAMVYLFT LFFVALHHAC NGPGLSVLCF
MRHDILEYFS VYGTALSMWV SLMALADFDE PKRSTFVMFG VLTIAVRIYH DRWGYGVYSG
PIGTAILIIA AKWLQKMKEK KGLYPDKSVY TQQIGPGLCF GALALMLRFF FEDWDYTYVH
SFYHCALAMS FVLLLPKVNK KAGSPGTPAK LDCSTLCCAC V
