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 27-MAR-2024, entry version 203. 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; Evidence={ECO:0000255|PROSITE- CC 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; 127. DR IntAct; Q9NZM1; 60. 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 GlyCosmos; Q9NZM1; 1 site, 1 glycan. DR GlyGen; Q9NZM1; 4 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (3 sites). 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; 9606-ENSP00000352208; -. DR PeptideAtlas; 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 Pumba; Q9NZM1; -. DR Antibodypedia; 2467; 122 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 AGR; HGNC:3656; -. DR CTD; 26509; -. DR DisGeNET; 26509; -. DR GeneCards; MYOF; -. DR HGNC; HGNC:3656; MYOF. DR HPA; ENSG00000138119; Low tissue specificity. DR MalaCards; MYOF; -. 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; DLLVVEX; -. DR OrthoDB; 991411at2759; -. DR PhylomeDB; Q9NZM1; -. DR TreeFam; TF316871; -. DR PathwayCommons; Q9NZM1; -. DR SignaLink; Q9NZM1; -. DR SIGNOR; Q9NZM1; -. DR BioGRID-ORCS; 26509; 13 hits in 1152 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 202 other cell types or tissues. DR ExpressionAtlas; Q9NZM1; baseline and differential. DR GO; GO:0005901; C:caveola; ISS:UniProtKB. DR GO; GO:0034451; C:centriolar satellite; IDA:HPA. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. 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:0030672; C:synaptic vesicle membrane; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB. DR GO; GO:0008015; P:blood circulation; TAS:ProtInc. DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc. DR GO; GO:0001778; P:plasma membrane repair; ISS:UniProtKB. DR GO; GO:0046928; P:regulation of neurotransmitter secretion; 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; C2 domain; 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; IPR006614; Peroxin/Ferlin. DR PANTHER; PTHR12546; FER-1-LIKE; 1. DR PANTHER; PTHR12546:SF60; MISFIRE, ISOFORM F; 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; C2 domain (Calcium/lipid-binding domain, CaLB); 7. DR PROSITE; PS50004; C2; 7. DR Genevisible; Q9NZM1; HS. 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; uncertain significance; FT dbSNP:rs1256778304)" 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 //