MYOF_HUMAN
ID MYOF_HUMAN Reviewed; 2061 AA.
AC Q9NZM1; B3KQN5; Q5VWW2; Q5VWW3; Q5VWW4; Q5VWW5; Q7Z642; Q8IWH0; Q9HBU3;
AC Q9NZM0; Q9ULL3; Q9Y4U4;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Myoferlin;
DE AltName: Full=Fer-1-like protein 3;
GN Name=MYOF; Synonyms=FER1L3, KIAA1207;
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 [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Heart, and Lung;
RX PubMed=10607832; DOI=10.1093/hmg/9.2.217;
RA Davis D.B., Delmonte A.J., Ly C.T., McNally E.M.;
RT "Myoferlin, a candidate gene and potential modifier of muscular
RT dystrophy.";
RL Hum. Mol. Genet. 9:217-226(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), AND ALTERNATIVE SPLICING.
RC TISSUE=Placenta;
RX PubMed=10995573; DOI=10.1006/geno.2000.6290;
RA Britton S., Freeman T., Vafiadaki E., Keers S., Harrison R., Bushby K.M.D.,
RA Bashir R.;
RT "The third human FER-1-like protein is highly similar to dysferlin.";
RL Genomics 68:313-321(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 8).
RC TISSUE=Lung;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 621-2061 (ISOFORM 3).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1389-2061 (ISOFORMS 1/2).
RC TISSUE=Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11959863; DOI=10.1074/jbc.m201858200;
RA Davis D.B., Doherty K.R., Delmonte A.J., McNally E.M.;
RT "Calcium-sensitive phospholipid binding properties of normal and mutant
RT ferlin C2 domains.";
RL J. Biol. Chem. 277:22883-22888(2002).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=17702744; DOI=10.1074/jbc.m704798200;
RA Bernatchez P.N., Acevedo L., Fernandez-Hernando C., Murata T., Chalouni C.,
RA Kim J., Erdjument-Bromage H., Shah V., Gratton J.-P., McNally E.M.,
RA Tempst P., Sessa W.C.;
RT "Myoferlin regulates vascular endothelial growth factor receptor-2
RT stability and function.";
RL J. Biol. Chem. 282:30745-30753(2007).
RN [11]
RP INTERACTION WITH EHD2, MUTAGENESIS OF 238-ASN--PHE-240, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18502764; DOI=10.1074/jbc.m802306200;
RA Doherty K.R., Demonbreun A.R., Wallace G.Q., Cave A., Posey A.D.,
RA Heretis K., Pytel P., McNally E.M.;
RT "The endocytic recycling protein EHD2 interacts with myoferlin to regulate
RT myoblast fusion.";
RL J. Biol. Chem. 283:20252-20260(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-884, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1915, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729 AND SER-1915, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP INTERACTION WITH RIPOR2.
RX PubMed=24687993; DOI=10.1096/fj.13-246470;
RA Balasubramanian A., Kawahara G., Gupta V.A., Rozkalne A., Beauvais A.,
RA Kunkel L.M., Gussoni E.;
RT "Fam65b is important for formation of the HDAC6-dysferlin protein complex
RT during myogenic cell differentiation.";
RL FASEB J. 28:2955-2969(2014).
RN [18]
RP STRUCTURE BY NMR OF 1-127.
RG RIKEN structural genomics initiative (RSGI);
RT "The solution structure of the first C2 domain of human myoferlin.";
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [19]
RP STRUCTURE BY NMR OF 923-1040.
RX PubMed=18495154; DOI=10.1016/j.jmb.2008.04.046;
RA Patel P., Harris R., Geddes S.M., Strehle E.-M., Watson J.D., Bashir R.,
RA Bushby K., Driscoll P.C., Keep N.H.;
RT "Solution structure of the inner DysF domain of myoferlin and implications
RT for limb girdle muscular dystrophy type 2b.";
RL J. Mol. Biol. 379:981-990(2008).
RN [20]
RP VARIANT HAE7 SER-217, AND INVOLVEMENT IN HAE7.
RX PubMed=32542751; DOI=10.1111/all.14454;
RA Ariano A., D'Apolito M., Bova M., Bellanti F., Loffredo S., D'Andrea G.,
RA Intrieri M., Petraroli A., Maffione A.B., Spadaro G., Santacroce R.,
RA Margaglione M.;
RT "A myoferlin gain-of-function variant associates with a new type of
RT hereditary angioedema.";
RL Allergy 75:2989-2992(2020).
CC -!- FUNCTION: Calcium/phospholipid-binding protein that plays a role in the
CC plasmalemma repair mechanism of endothelial cells that permits rapid
CC resealing of membranes disrupted by mechanical stress. Involved in
CC endocytic recycling. Implicated in VEGF signal transduction by
CC regulating the levels of the receptor KDR (By similarity).
CC {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds Ca(2+). The ions are bound to the C2 1 domain.
CC {ECO:0000250};
CC -!- SUBUNIT: Interacts with DNM2 and KDR. Interacts with EHD1 (By
CC similarity). Interacts with EHD2; the interaction is direct
CC (PubMed:18502764). Interacts with RIPOR2 (PubMed:24687993).
CC {ECO:0000250|UniProtKB:Q69ZN7, ECO:0000269|PubMed:18502764,
CC ECO:0000269|PubMed:24687993}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein. Nucleus membrane; Single-pass type II membrane protein.
CC Cytoplasmic vesicle membrane; Single-pass type II membrane protein.
CC Note=Concentrated at the membrane sites of both myoblast-myoblast and
CC myoblast-myotube fusions. Detected at the plasmalemma in endothelial
CC cells lining intact blood vessels (By similarity). Found at nuclear and
CC plasma membranes. Enriched in undifferentiated myoblasts near the
CC plasma membrane in puncate structures. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1;
CC IsoId=Q9NZM1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NZM1-2; Sequence=VSP_001515;
CC Name=3;
CC IsoId=Q9NZM1-3; Sequence=VSP_001516, VSP_001517;
CC Name=4;
CC IsoId=Q9NZM1-4; Sequence=VSP_023797, VSP_023798;
CC Name=5;
CC IsoId=Q9NZM1-5; Sequence=VSP_023802;
CC Name=6;
CC IsoId=Q9NZM1-6; Sequence=VSP_023801;
CC Name=7;
CC IsoId=Q9NZM1-7; Sequence=VSP_023800;
CC Name=8;
CC IsoId=Q9NZM1-8; Sequence=VSP_023796, VSP_023799;
CC -!- TISSUE SPECIFICITY: Expressed in myoblast and endothelial cells (at
CC protein level). Highly expressed in cardiac and skeletal muscles. Also
CC present in lung, and at very low levels in kidney, placenta and brain.
CC {ECO:0000269|PubMed:11959863, ECO:0000269|PubMed:17702744,
CC ECO:0000269|PubMed:18502764}.
CC -!- DOMAIN: The C2 domain 1 associates with lipid membranes in a calcium-
CC dependent manner.
CC -!- DISEASE: Angioedema, hereditary, 7 (HAE7) [MIM:619366]: A form of
CC angioedema, a disorder characterized by episodic local swelling
CC involving subcutaneous or submucous tissue of the upper respiratory and
CC gastrointestinal tracts, face, extremities, and genitalia. HAE7 is an
CC autosomal dominant form characterized by onset of recurrent swelling of
CC the face, lips, and oral mucosa in the second decade.
CC {ECO:0000269|PubMed:32542751}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ferlin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH40110.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAG52097.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF182316; AAF27176.1; -; mRNA.
DR EMBL; AF182317; AAF27177.1; -; mRNA.
DR EMBL; AF207990; AAG23737.1; -; mRNA.
DR EMBL; AB033033; BAA86521.2; -; mRNA.
DR EMBL; AL360229; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365364; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC040110; AAH40110.1; ALT_SEQ; mRNA.
DR EMBL; BC052617; AAH52617.1; -; mRNA.
DR EMBL; AL096713; CAB46370.1; -; mRNA.
DR EMBL; AK075258; BAG52097.1; ALT_INIT; mRNA.
DR CCDS; CCDS41550.1; -. [Q9NZM1-6]
DR CCDS; CCDS41551.1; -. [Q9NZM1-1]
DR PIR; T12449; T12449.
DR RefSeq; NP_038479.1; NM_013451.3. [Q9NZM1-1]
DR RefSeq; NP_579899.1; NM_133337.2. [Q9NZM1-6]
DR PDB; 2DMH; NMR; -; A=1-127.
DR PDB; 2K2O; NMR; -; A=923-1040.
DR PDB; 6EEL; X-ray; 1.93 A; A/B/C=1-125.
DR PDBsum; 2DMH; -.
DR PDBsum; 2K2O; -.
DR PDBsum; 6EEL; -.
DR AlphaFoldDB; Q9NZM1; -.
DR BMRB; Q9NZM1; -.
DR SMR; Q9NZM1; -.
DR BioGRID; 117715; 110.
DR IntAct; Q9NZM1; 58.
DR MINT; Q9NZM1; -.
DR STRING; 9606.ENSP00000352208; -.
DR BindingDB; Q9NZM1; -.
DR ChEMBL; CHEMBL4523476; -.
DR TCDB; 1.F.1.2.2; the synaptosomal vesicle fusion pore (svf-pore) family.
DR GlyConnect; 2941; 1 N-Linked glycan (1 site).
DR GlyGen; Q9NZM1; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q9NZM1; -.
DR MetOSite; Q9NZM1; -.
DR PhosphoSitePlus; Q9NZM1; -.
DR SwissPalm; Q9NZM1; -.
DR BioMuta; MYOF; -.
DR DMDM; 20139241; -.
DR CPTAC; CPTAC-545; -.
DR CPTAC; CPTAC-546; -.
DR EPD; Q9NZM1; -.
DR jPOST; Q9NZM1; -.
DR MassIVE; Q9NZM1; -.
DR MaxQB; Q9NZM1; -.
DR PaxDb; Q9NZM1; -.
DR PeptideAtlas; Q9NZM1; -.
DR PRIDE; Q9NZM1; -.
DR ProteomicsDB; 83437; -. [Q9NZM1-1]
DR ProteomicsDB; 83438; -. [Q9NZM1-2]
DR ProteomicsDB; 83439; -. [Q9NZM1-3]
DR ProteomicsDB; 83440; -. [Q9NZM1-4]
DR ProteomicsDB; 83441; -. [Q9NZM1-5]
DR ProteomicsDB; 83442; -. [Q9NZM1-6]
DR ProteomicsDB; 83443; -. [Q9NZM1-7]
DR ProteomicsDB; 83444; -. [Q9NZM1-8]
DR Antibodypedia; 2467; 98 antibodies from 28 providers.
DR DNASU; 26509; -.
DR Ensembl; ENST00000358334.9; ENSP00000351094.5; ENSG00000138119.17. [Q9NZM1-6]
DR Ensembl; ENST00000359263.9; ENSP00000352208.4; ENSG00000138119.17. [Q9NZM1-1]
DR Ensembl; ENST00000371488.3; ENSP00000360543.3; ENSG00000138119.17. [Q9NZM1-4]
DR Ensembl; ENST00000371489.5; ENSP00000360544.1; ENSG00000138119.17. [Q9NZM1-7]
DR GeneID; 26509; -.
DR KEGG; hsa:26509; -.
DR MANE-Select; ENST00000359263.9; ENSP00000352208.4; NM_013451.4; NP_038479.1.
DR UCSC; uc001kin.4; human. [Q9NZM1-1]
DR CTD; 26509; -.
DR DisGeNET; 26509; -.
DR GeneCards; MYOF; -.
DR HGNC; HGNC:3656; MYOF.
DR HPA; ENSG00000138119; Low tissue specificity.
DR MIM; 604603; gene.
DR MIM; 619366; phenotype.
DR neXtProt; NX_Q9NZM1; -.
DR OpenTargets; ENSG00000138119; -.
DR Orphanet; 599418; Hereditary angioedema with normal C1Inh not related to F12 or PLG variant.
DR PharmGKB; PA164723288; -.
DR VEuPathDB; HostDB:ENSG00000138119; -.
DR eggNOG; KOG1326; Eukaryota.
DR GeneTree; ENSGT00940000154741; -.
DR HOGENOM; CLU_001183_2_1_1; -.
DR InParanoid; Q9NZM1; -.
DR OMA; YENQAFM; -.
DR OrthoDB; 20162at2759; -.
DR PhylomeDB; Q9NZM1; -.
DR TreeFam; TF316871; -.
DR PathwayCommons; Q9NZM1; -.
DR SignaLink; Q9NZM1; -.
DR SIGNOR; Q9NZM1; -.
DR BioGRID-ORCS; 26509; 13 hits in 1068 CRISPR screens.
DR ChiTaRS; MYOF; human.
DR EvolutionaryTrace; Q9NZM1; -.
DR GeneWiki; FER1L3; -.
DR GenomeRNAi; 26509; -.
DR Pharos; Q9NZM1; Tchem.
DR PRO; PR:Q9NZM1; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9NZM1; protein.
DR Bgee; ENSG00000138119; Expressed in skin of hip and 200 other tissues.
DR ExpressionAtlas; Q9NZM1; baseline and differential.
DR Genevisible; Q9NZM1; HS.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005635; C:nuclear envelope; TAS:ProtInc.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR GO; GO:0061025; P:membrane fusion; IBA:GO_Central.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0007520; P:myoblast fusion; IEA:InterPro.
DR GO; GO:0007009; P:plasma membrane organization; IBA:GO_Central.
DR GO; GO:0001778; P:plasma membrane repair; ISS:UniProtKB.
DR GO; GO:0033292; P:T-tubule organization; IBA:GO_Central.
DR CDD; cd08373; C2A_Ferlin; 1.
DR CDD; cd04011; C2B_Ferlin; 1.
DR CDD; cd04018; C2C_Ferlin; 1.
DR CDD; cd04017; C2D_Ferlin; 1.
DR CDD; cd04037; C2E_Ferlin; 1.
DR CDD; cd08374; C2F_Ferlin; 1.
DR Gene3D; 2.60.40.150; -; 6.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037726; C2A_Ferlin.
DR InterPro; IPR037720; C2B_Ferlin.
DR InterPro; IPR037722; C2C_Ferlin.
DR InterPro; IPR037723; C2D_Ferlin.
DR InterPro; IPR037724; C2E_Ferlin.
DR InterPro; IPR037725; C2F_Ferlin.
DR InterPro; IPR012968; FerIin_dom.
DR InterPro; IPR037721; Ferlin.
DR InterPro; IPR012560; Ferlin_A-domain.
DR InterPro; IPR012561; Ferlin_B-domain.
DR InterPro; IPR032362; Ferlin_C.
DR InterPro; IPR029999; Myoferlin.
DR InterPro; IPR006614; Peroxin/Ferlin.
DR PANTHER; PTHR12546; PTHR12546; 1.
DR PANTHER; PTHR12546:SF55; PTHR12546:SF55; 1.
DR Pfam; PF00168; C2; 7.
DR Pfam; PF08165; FerA; 1.
DR Pfam; PF08150; FerB; 1.
DR Pfam; PF08151; FerI; 1.
DR Pfam; PF16165; Ferlin_C; 1.
DR SMART; SM00239; C2; 7.
DR SMART; SM00694; DysFC; 2.
DR SMART; SM00693; DysFN; 2.
DR SMART; SM01200; FerA; 1.
DR SMART; SM01201; FerB; 1.
DR SMART; SM01202; FerI; 1.
DR SUPFAM; SSF49562; SSF49562; 7.
DR PROSITE; PS50004; C2; 7.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Calcium; Cell membrane;
KW Cytoplasmic vesicle; Membrane; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..2061
FT /note="Myoferlin"
FT /id="PRO_0000057884"
FT TOPO_DOM 1..2025
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2026..2046
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2047..2061
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 1..101
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 181..300
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 339..474
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1123..1251
FT /note="C2 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1282..1410
FT /note="C2 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1536..1654
FT /note="C2 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1772..1920
FT /note="C2 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 123..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 186..281
FT /note="Necessary for interaction with EHD2"
FT /evidence="ECO:0000269|PubMed:18502764"
FT REGION 323..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 938..967
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..342
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 396
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 444
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 444
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 446
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 446
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 452
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1155
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1161
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1217
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1219
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1569
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1575
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1624
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1626
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1891
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1894
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1897
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 553
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q69ZN7"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 884
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1507
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q69ZN7"
FT MOD_RES 1915
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..87
FT /note="MLRVIVESASNIPKTKFGKPDPIVSVIFKDEKKKTKKVDNELNPVWNEILEF
FT DLRGIPLDFSSSLGIIVKDFETIGQNKLIGTATVA -> MRPPKEGSGSNICCSAIFAV
FT LQPPLVISRQTRSGMDLQQTPTDLQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10607832"
FT /id="VSP_001515"
FT VAR_SEQ 1..29
FT /note="MLRVIVESASNIPKTKFGKPDPIVSVIFK -> MIPPNSPPNRT (in
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023796"
FT VAR_SEQ 146..160
FT /note="DGEEDEGDEDRLDNA -> KLTLLKAQPPPGGGC (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_023797"
FT VAR_SEQ 161..2061
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_023798"
FT VAR_SEQ 438..2061
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023799"
FT VAR_SEQ 446..2061
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_023800"
FT VAR_SEQ 473..485
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10995573"
FT /id="VSP_023801"
FT VAR_SEQ 1224..1707
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023802"
FT VAR_SEQ 1442
FT /note="K -> KCLSSMSTALSKMASPATVH (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_001516"
FT VAR_SEQ 1757..1787
FT /note="QGKLQMWVDVFPKSLGPPGPPFNITPRKAKK -> R (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_001517"
FT VARIANT 217
FT /note="R -> S (in HAE7; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:32542751"
FT /id="VAR_085819"
FT VARIANT 1136
FT /note="V -> I (in dbSNP:rs36032890)"
FT /id="VAR_049058"
FT VARIANT 1198
FT /note="Y -> F (in dbSNP:rs12256834)"
FT /id="VAR_031250"
FT VARIANT 1399
FT /note="R -> C (in dbSNP:rs11187393)"
FT /id="VAR_031251"
FT VARIANT 1701
FT /note="G -> A (in dbSNP:rs34000599)"
FT /id="VAR_049059"
FT VARIANT 1783
FT /note="R -> Q (in dbSNP:rs11594445)"
FT /id="VAR_031252"
FT MUTAGEN 238..240
FT /note="NPF->SPL: Reduces interaction with EHD2."
FT /evidence="ECO:0000269|PubMed:18502764"
FT CONFLICT 251
FT /note="M -> T (in Ref. 2; AAG23737)"
FT /evidence="ECO:0000305"
FT CONFLICT 621
FT /note="R -> W (in Ref. 7; CAB46370)"
FT /evidence="ECO:0000305"
FT CONFLICT 659
FT /note="T -> A (in Ref. 2; AAG23737 and 7; CAB46370)"
FT /evidence="ECO:0000305"
FT CONFLICT 846
FT /note="E -> A (in Ref. 1; AAF27177)"
FT /evidence="ECO:0000305"
FT CONFLICT 1136
FT /note="V -> D (in Ref. 7; CAB46370)"
FT /evidence="ECO:0000305"
FT CONFLICT 1163
FT /note="Y -> F (in Ref. 7; CAB46370)"
FT /evidence="ECO:0000305"
FT CONFLICT 1544
FT /note="E -> G (in Ref. 2; AAG23737 and 7; CAB46370)"
FT /evidence="ECO:0000305"
FT CONFLICT 1574
FT /note="C -> R (in Ref. 7; CAB46370)"
FT /evidence="ECO:0000305"
FT CONFLICT 1723
FT /note="P -> H (in Ref. 1; AAF27177)"
FT /evidence="ECO:0000305"
FT CONFLICT 1834
FT /note="H -> R (in Ref. 7; CAB46370)"
FT /evidence="ECO:0000305"
FT CONFLICT 1946..1952
FT /note="MKGWWPC -> IRMVAM (in Ref. 1; AAF27177)"
FT /evidence="ECO:0000305"
FT STRAND 1..10
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 22..28
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 45..53
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 79..87
FT /evidence="ECO:0007829|PDB:6EEL"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:2DMH"
FT STRAND 97..107
FT /evidence="ECO:0007829|PDB:6EEL"
FT STRAND 113..124
FT /evidence="ECO:0007829|PDB:6EEL"
FT TURN 924..927
FT /evidence="ECO:0007829|PDB:2K2O"
FT STRAND 929..939
FT /evidence="ECO:0007829|PDB:2K2O"
FT STRAND 942..944
FT /evidence="ECO:0007829|PDB:2K2O"
FT STRAND 947..954
FT /evidence="ECO:0007829|PDB:2K2O"
FT TURN 964..966
FT /evidence="ECO:0007829|PDB:2K2O"
FT STRAND 977..979
FT /evidence="ECO:0007829|PDB:2K2O"
FT STRAND 985..987
FT /evidence="ECO:0007829|PDB:2K2O"
FT STRAND 994..996
FT /evidence="ECO:0007829|PDB:2K2O"
FT STRAND 1017..1028
FT /evidence="ECO:0007829|PDB:2K2O"
FT TURN 1030..1034
FT /evidence="ECO:0007829|PDB:2K2O"
SQ SEQUENCE 2061 AA; 234709 MW; 61D9E9447B40781C CRC64;
MLRVIVESAS NIPKTKFGKP DPIVSVIFKD EKKKTKKVDN ELNPVWNEIL EFDLRGIPLD
FSSSLGIIVK DFETIGQNKL IGTATVALKD LTGDQSRSLP YKLISLLNEK GQDTGATIDL
VIGYDPPSAP HPNDLSGPSV PGMGGDGEED EGDEDRLDNA VRGPGPKGPV GTVSEAQLAR
RLTKVKNSRR MLSNKPQDFQ IRVRVIEGRQ LSGNNIRPVV KVHVCGQTHR TRIKRGNNPF
FDELFFYNVN MTPSELMDEI ISIRVYNSHS LRADCLMGEF KIDVGFVYDE PGHAVMRKWL
LLNDPEDTSS GSKGYMKVSM FVLGTGDEPP PERRDRDNDS DDVESNLLLP AGIALRWVTF
LLKIYRAEDI PQMDDAFSQT VKEIFGGNAD KKNLVDPFVE VSFAGKKVCT NIIEKNANPE
WNQVVNLQIK FPSVCEKIKL TIYDWDRLTK NDVVGTTYLH LSKIAASGGE VEDFSSSGTG
AASYTVNTGE TEVGFVPTFG PCYLNLYGSP REYTGFPDPY DELNTGKGEG VAYRGRILVE
LATFLEKTPP DKKLEPISND DLLVVEKYQR RRKYSLSAVF HSATMLQDVG EAIQFEVSIG
NYGNKFDTTC KPLASTTQYS RAVFDGNYYY YLPWAHTKPV VTLTSYWEDI SHRLDAVNTL
LAMAERLQTN IEALKSGIQG KIPANQLAEL WLKLIDEVIE DTRYTLPLTE GKANVTVLDT
QIRKLRSRSL SQIHEAAVRM RSEATDVKST LAEIEDWLDK LMQLTEEPQN SMPDIIIWMI
RGEKRLAYAR IPAHQVLYST SGENASGKYC GKTQTIFLKY PQEKNNGPKV PVELRVNIWL
GLSAVEKKFN SFAEGTFTVF AEMYENQALM FGKWGTSGLV GRHKFSDVTG KIKLKREFFL
PPKGWEWEGE WIVDPERSLL TEADAGHTEF TDEVYQNESR YPGGDWKPAE DTYTDANGDK
AASPSELTCP PGWEWEDDAW SYDINRAVDE KGWEYGITIP PDHKPKSWVA AEKMYHTHRR
RRLVRKRKKD LTQTASSTAR AMEELQDQEG WEYASLIGWK FHWKQRSSDT FRRRRWRRKM
APSETHGAAA IFKLEGALGA DTTEDGDEKS LEKQKHSATT VFGANTPIVS CNFDRVYIYH
LRCYVYQARN LLALDKDSFS DPYAHICFLH RSKTTEIIHS TLNPTWDQTI IFDEVEIYGE
PQTVLQNPPK VIMELFDNDQ VGKDEFLGRS IFSPVVKLNS EMDITPKLLW HPVMNGDKAC
GDVLVTAELI LRGKDGSNLP ILPPQRAPNL YMVPQGIRPV VQLTAIEILA WGLRNMKNFQ
MASITSPSLV VECGGERVES VVIKNLKKTP NFPSSVLFMK VFLPKEELYM PPLVIKVIDH
RQFGRKPVVG QCTIERLDRF RCDPYAGKED IVPQLKASLL SAPPCRDIVI EMEDTKPLLA
SKLTEKEEEI VDWWSKFYAS SGEHEKCGQY IQKGYSKLKI YNCELENVAE FEGLTDFSDT
FKLYRGKSDE NEDPSVVGEF KGSFRIYPLP DDPSVPAPPR QFRELPDSVP QECTVRIYIV
RGLELQPQDN NGLCDPYIKI TLGKKVIEDR DHYIPNTLNP VFGRMYELSC YLPQEKDLKI
SVYDYDTFTR DEKVGETIID LENRFLSRFG SHCGIPEEYC VSGVNTWRDQ LRPTQLLQNV
ARFKGFPQPI LSEDGSRIRY GGRDYSLDEF EANKILHQHL GAPEERLALH ILRTQGLVPE
HVETRTLHST FQPNISQGKL QMWVDVFPKS LGPPGPPFNI TPRKAKKYYL RVIIWNTKDV
ILDEKSITGE EMSDIYVKGW IPGNEENKQK TDVHYRSLDG EGNFNWRFVF PFDYLPAEQL
CIVAKKEHFW SIDQTEFRIP PRLIIQIWDN DKFSLDDYLG FLELDLRHTI IPAKSPEKCR
LDMIPDLKAM NPLKAKTASL FEQKSMKGWW PCYAEKDGAR VMAGKVEMTL EILNEKEADE
RPAGKGRDEP NMNPKLDLPN RPETSFLWFT NPCKTMKFIV WRRFKWVIIG LLFLLILLLF
VAVLLYSLPN YLSMKIVKPN V
