MEG10_HUMAN
ID MEG10_HUMAN Reviewed; 1140 AA.
AC Q96KG7; Q68DE5; Q8WUL3;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Multiple epidermal growth factor-like domains protein 10 {ECO:0000312|HGNC:HGNC:29634};
DE Short=Multiple EGF-like domains protein 10 {ECO:0000305};
DE Flags: Precursor;
GN Name=MEGF10 {ECO:0000312|HGNC:HGNC:29634}; Synonyms=KIAA1780;
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 MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retina;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Muscle;
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 [5]
RP INTERACTION WITH GULP1 AND ABCA1, MUTAGENESIS OF ASN-927 AND TYR-930, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17205124; DOI=10.1371/journal.pone.0000120;
RA Hamon Y., Trompier D., Ma Z., Venegas V., Pophillat M., Mignotte V.,
RA Zhou Z., Chimini G.;
RT "Cooperation between engulfment receptors: the case of ABCA1 and MEGF10.";
RL PLoS ONE 1:E120-E120(2006).
RN [6]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17498693; DOI=10.1016/j.yexcr.2007.03.041;
RA Suzuki E., Nakayama M.;
RT "The mammalian Ced-1 ortholog MEGF10/KIAA1780 displays a novel adhesion
RT pattern.";
RL Exp. Cell Res. 313:2451-2464(2007).
RN [7]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH AP2M1 AND
RP GULP1, PHOSPHORYLATION, AND UBIQUITINATION.
RX PubMed=17643423; DOI=10.1016/j.yexcr.2007.06.015;
RA Suzuki E., Nakayama M.;
RT "MEGF10 is a mammalian ortholog of CED-1 that interacts with clathrin
RT assembly protein complex 2 medium chain and induces large vacuole
RT formation.";
RL Exp. Cell Res. 313:3729-3742(2007).
RN [8]
RP FUNCTION IN ENDOCYTOSIS.
RX PubMed=20828568; DOI=10.1016/j.febslet.2010.08.050;
RA Singh T.D., Park S.Y., Bae J.S., Yun Y., Bae Y.C., Park R.W., Kim I.S.;
RT "MEGF10 functions as a receptor for the uptake of amyloid-beta.";
RL FEBS Lett. 584:3936-3942(2010).
RN [9]
RP FUNCTION IN MYOGENESIS, AND VARIANT EMARDD ARG-774.
RX PubMed=22101682; DOI=10.1038/ng.995;
RA Logan C.V., Lucke B., Pottinger C., Abdelhamed Z.A., Parry D.A.,
RA Szymanska K., Diggle C.P., Riesen A., Morgan J.E., Markham G., Ellis I.,
RA Manzur A.Y., Markham A.F., Shires M., Helliwell T., Scoto M., Hubner C.,
RA Bonthron D.T., Taylor G.R., Sheridan E., Muntoni F., Carr I.M.,
RA Schuelke M., Johnson C.A.;
RT "Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early
RT onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD).";
RL Nat. Genet. 43:1189-1192(2011).
RN [10]
RP VARIANTS EMARDD TRP-71; ARG-326 AND ARG-774.
RX PubMed=22371254; DOI=10.1007/s10048-012-0315-z;
RA Boyden S.E., Mahoney L.J., Kawahara G., Myers J.A., Mitsuhashi S.,
RA Estrella E.A., Duncan A.R., Dey F., Dechene E.T., Blasko-Goehringer J.M.,
RA Bonnemann C.G., Darras B.T., Mendell J.R., Lidov H.G., Nishino I.,
RA Beggs A.H., Kunkel L.M., Kang P.B.;
RT "Mutations in the satellite cell gene MEGF10 cause a recessive congenital
RT myopathy with minicores.";
RL Neurogenetics 13:115-124(2012).
RN [11]
RP CHARACTERIZATION OF VARIANTS EMARDD ARG-326 AND ARG-774, MUTAGENESIS OF
RP TYR-1030, AND PHOSPHORYLATION AT TYR-1030.
RX PubMed=23954233; DOI=10.1016/j.febslet.2013.08.002;
RA Mitsuhashi S., Mitsuhashi H., Alexander M.S., Sugimoto H., Kang P.B.;
RT "Cysteine mutations cause defective tyrosine phosphorylation in MEGF10
RT myopathy.";
RL FEBS Lett. 587:2952-2957(2013).
RN [12]
RP CHARACTERIZATION OF VARIANTS EMARDD ARG-326 AND ARG-774, FUNCTION,
RP INTERACTION WITH COMPLEMENT C1Q, AND SUBCELLULAR LOCATION.
RX PubMed=27170117; DOI=10.1523/jneurosci.3850-15.2016;
RA Iram T., Ramirez-Ortiz Z., Byrne M.H., Coleman U.A., Kingery N.D.,
RA Means T.K., Frenkel D., El Khoury J.;
RT "Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by
RT Astrocytes.";
RL J. Neurosci. 36:5185-5192(2016).
RN [13]
RP CHARACTERIZATION OF VARIANTS EMARDD ARG-326 AND ARG-774, FUNCTION, AND
RP INTERACTION WITH NOTCH1.
RX PubMed=28498977; DOI=10.1093/hmg/ddx189;
RA Saha M., Mitsuhashi S., Jones M.D., Manko K., Reddy H.M., Bruels C.,
RA Cho K.A., Pacak C.A., Draper I., Kang P.B.;
RT "Consequences of MEGF10 deficiency on myoblast function and Notch1
RT interactions.";
RL Hum. Mol. Genet. 26:2984-3000(2017).
RN [14]
RP INVOLVEMENT IN MEG10 MYOPATHY, VARIANTS EMARDD ARG-326 AND ARG-774, VARIANT
RP CYS-1030, AND FUNCTION.
RX DOI=10.1093/hmg/ddz064;
RA Saha M., Rizzo S.A., Ramanathan M., Hightower R.M., Santostefano K.E.,
RA Terada N., Finkel R.S., Berg J.S., Chahin N., Pacak C.A., Wagner R.E.,
RA Alexander M.S., Draper I., Kang P.B.;
RT "Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy.";
RL Hum. Mol. Genet. 2019:0-0(2019).
CC -!- FUNCTION: Membrane receptor involved in phagocytosis by macrophages and
CC astrocytes of apoptotic cells. Receptor for C1q, an eat-me signal, that
CC binds phosphatidylserine expressed on the surface of apoptotic cells
CC (PubMed:27170117). Cooperates with ABCA1 within the process of
CC engulfment. Promotes the formation of large intracellular vacuoles and
CC may be responsible for the uptake of amyloid-beta peptides
CC (PubMed:20828568, PubMed:17643423). Necessary for astrocyte-dependent
CC apoptotic neuron clearance in the developing cerebellum
CC (PubMed:27170117). Plays role in muscle cell proliferation, adhesion
CC and motility. Is also an essential factor in the regulation of
CC myogenesis. Controls the balance between skeletal muscle satellite
CC cells proliferation and differentiation through regulation of the notch
CC signaling pathway (PubMed:28498977, Ref.14). May also function in the
CC mosaic spacing of specific neuron subtypes in the retina through
CC homotypic retinal neuron repulsion. Mosaics provide a mechanism to
CC distribute each cell type evenly across the retina, ensuring that all
CC parts of the visual field have access to a full set of processing
CC elements (PubMed:17498693, PubMed:17643423, PubMed:20828568,
CC PubMed:22101682, PubMed:27170117, PubMed:28498977).
CC {ECO:0000269|PubMed:17205124, ECO:0000269|PubMed:17498693,
CC ECO:0000269|PubMed:17643423, ECO:0000269|PubMed:20828568,
CC ECO:0000269|PubMed:22101682, ECO:0000269|PubMed:27170117,
CC ECO:0000269|PubMed:28498977, ECO:0000269|Ref.14}.
CC -!- SUBUNIT: Homomer (Probable). Interacts with GULP1 and ABCA1. Interacts
CC with AP2M1 (PubMed:17643423). Does not interact with MEGF11
CC (PubMed:17498693). Binds with high affinity to complement C1q
CC (PubMed:27170117). Interacts (via the cytoplasmic domain) with NOTCH1
CC (via NICD domain) (PubMed:28498977). {ECO:0000269|PubMed:17205124,
CC ECO:0000269|PubMed:17498693, ECO:0000269|PubMed:17643423,
CC ECO:0000269|PubMed:27170117, ECO:0000269|PubMed:28498977}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27170117};
CC Single-pass type I membrane protein. Cell projection, phagocytic cup
CC {ECO:0000269|PubMed:17205124}. Note=Enriched at the sites of contact
CC with apoptotic thymocyte cells (PubMed:17205124). Forms an irregular,
CC mosaic-like adhesion pattern in region of the cell surface that becomes
CC firmely fixed to the substrate. Expressed at the cell surface in
CC clusters around cell corpses during engulfment. During the engulfment
CC of apoptotic thymocytes, recruited at the bottom of the forming
CC phagocytic cup (PubMed:17498693). Colocalizes with ABCA1 in absence of
CC any phagocytic challenge (PubMed:17205124). Does not localize within
CC lamellipodia (PubMed:17498693). Does not localize with MEGF11
CC (PubMed:17498693). {ECO:0000269|PubMed:17205124,
CC ECO:0000269|PubMed:17498693}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96KG7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96KG7-2; Sequence=VSP_029244, VSP_029245;
CC -!- DOMAIN: The EMI and EGF-like domains work in concert to promote self-
CC assembly.
CC -!- PTM: Phosphorylated on tyrosine residues. Phosphorylation at Tyr-1030
CC may be important for muscle cell proliferation.
CC {ECO:0000269|PubMed:17643423, ECO:0000269|PubMed:23954233}.
CC -!- PTM: Ubiquitinated; mono- and polyubiquitinated forms are detected.
CC {ECO:0000269|PubMed:17643423}.
CC -!- DISEASE: Myopathy, early-onset, areflexia, respiratory distress, and
CC dysphagia (EMARDD) [MIM:614399]: An autosomal recessive congenital
CC myopathy characterized by onset at birth, or early in infancy, of
CC respiratory distress caused by diaphragmatic weakness. Additional
CC features are dysphagia resulting in poor feeding, failure to thrive,
CC poor head control, facial weakness, cleft palate, contractures and
CC scoliosis. Affected individuals become ventilator-dependent, and most
CC require feeding by gastrostomy. The disorder results in severe muscle
CC weakness and most patients never achieve walking. Death from
CC respiratory failure in childhood occurs in about half of patients.
CC Muscle biopsies from affected individuals show myopathic changes,
CC replacement of myofibers with fatty tissue, small and incompletely
CC fused muscle fibers, and variation in fiber size. Short regions of
CC sarcomeric disorganization with few or no mitochondria (minicores) have
CC been observed in some cases. {ECO:0000269|PubMed:22101682,
CC ECO:0000269|PubMed:22371254, ECO:0000269|PubMed:23954233,
CC ECO:0000269|PubMed:27170117, ECO:0000269|PubMed:28498977,
CC ECO:0000269|Ref.14}. Note=The disease is caused by variants affecting
CC the gene represented in this entry.
CC -!- DISEASE: Note=An adult onset form of MEG10 myopathy, a condition
CC characterized by muscle weakness and respiratory distress. Additional
CC features include a palatal midline ridge, bilateral scapular winging,
CC pes cavus, lumbar lordosis and protruded abdomen. Muscle weakness is
CC proximal more than distal with diffusely absent deep tendon reflexes.
CC Affected individuals become ventilator-dependent and have poor exercise
CC tolerance. Muscle biopsies from affected individuals show myopathic
CC changes such as fiber atrophy and the presence of core-like structures.
CC Prior to onset of symptoms, affected individuals do not display any
CC significant respiratory or motor symptoms. {ECO:0000269|Ref.14}.
CC -!- SIMILARITY: Belongs to the MEGF family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47409.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB058676; BAB47409.2; ALT_INIT; mRNA.
DR EMBL; CR749437; CAH18275.1; -; mRNA.
DR EMBL; CH471062; EAW62406.1; -; Genomic_DNA.
DR EMBL; BC020198; AAH20198.1; -; mRNA.
DR EMBL; BC152478; AAI52479.1; -; mRNA.
DR CCDS; CCDS4142.1; -. [Q96KG7-1]
DR CCDS; CCDS78055.1; -. [Q96KG7-2]
DR RefSeq; NP_001243474.1; NM_001256545.1. [Q96KG7-1]
DR RefSeq; NP_001295048.1; NM_001308119.1. [Q96KG7-2]
DR RefSeq; NP_001295050.1; NM_001308121.1. [Q96KG7-2]
DR RefSeq; NP_115822.1; NM_032446.2. [Q96KG7-1]
DR RefSeq; XP_011541996.1; XM_011543694.1. [Q96KG7-1]
DR AlphaFoldDB; Q96KG7; -.
DR BioGRID; 124099; 14.
DR IntAct; Q96KG7; 27.
DR MINT; Q96KG7; -.
DR STRING; 9606.ENSP00000274473; -.
DR GlyGen; Q96KG7; 5 sites.
DR iPTMnet; Q96KG7; -.
DR PhosphoSitePlus; Q96KG7; -.
DR BioMuta; MEGF10; -.
DR DMDM; 74716908; -.
DR EPD; Q96KG7; -.
DR jPOST; Q96KG7; -.
DR MassIVE; Q96KG7; -.
DR PaxDb; Q96KG7; -.
DR PeptideAtlas; Q96KG7; -.
DR PRIDE; Q96KG7; -.
DR ProteomicsDB; 77067; -. [Q96KG7-1]
DR ProteomicsDB; 77068; -. [Q96KG7-2]
DR Antibodypedia; 14004; 92 antibodies from 14 providers.
DR DNASU; 84466; -.
DR Ensembl; ENST00000274473.6; ENSP00000274473.6; ENSG00000145794.17. [Q96KG7-1]
DR Ensembl; ENST00000418761.6; ENSP00000416284.2; ENSG00000145794.17. [Q96KG7-2]
DR Ensembl; ENST00000503335.7; ENSP00000423354.2; ENSG00000145794.17. [Q96KG7-1]
DR Ensembl; ENST00000508365.5; ENSP00000423195.1; ENSG00000145794.17. [Q96KG7-2]
DR GeneID; 84466; -.
DR KEGG; hsa:84466; -.
DR MANE-Select; ENST00000503335.7; ENSP00000423354.2; NM_001256545.2; NP_001243474.1.
DR UCSC; uc003kuh.5; human. [Q96KG7-1]
DR CTD; 84466; -.
DR DisGeNET; 84466; -.
DR GeneCards; MEGF10; -.
DR HGNC; HGNC:29634; MEGF10.
DR HPA; ENSG00000145794; Tissue enriched (brain).
DR MalaCards; MEGF10; -.
DR MIM; 612453; gene.
DR MIM; 614399; phenotype.
DR neXtProt; NX_Q96KG7; -.
DR OpenTargets; ENSG00000145794; -.
DR Orphanet; 439212; Early-onset myopathy-areflexia-respiratory distress-dysphagia syndrome.
DR PharmGKB; PA144596410; -.
DR VEuPathDB; HostDB:ENSG00000145794; -.
DR eggNOG; KOG1218; Eukaryota.
DR GeneTree; ENSGT00940000157703; -.
DR HOGENOM; CLU_008281_1_0_1; -.
DR InParanoid; Q96KG7; -.
DR OMA; SSHCGCK; -.
DR OrthoDB; 561378at2759; -.
DR PhylomeDB; Q96KG7; -.
DR TreeFam; TF332598; -.
DR PathwayCommons; Q96KG7; -.
DR SignaLink; Q96KG7; -.
DR SIGNOR; Q96KG7; -.
DR BioGRID-ORCS; 84466; 15 hits in 1066 CRISPR screens.
DR ChiTaRS; MEGF10; human.
DR GeneWiki; MEGF10; -.
DR GenomeRNAi; 84466; -.
DR Pharos; Q96KG7; Tbio.
DR PRO; PR:Q96KG7; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q96KG7; protein.
DR Bgee; ENSG00000145794; Expressed in corpus callosum and 156 other tissues.
DR Genevisible; Q96KG7; HS.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0001891; C:phagocytic cup; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001849; F:complement component C1q complex binding; IDA:MGI.
DR GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
DR GO; GO:0005044; F:scavenger receptor activity; IDA:MGI.
DR GO; GO:0043277; P:apoptotic cell clearance; IBA:GO_Central.
DR GO; GO:1902742; P:apoptotic process involved in development; ISS:UniProtKB.
DR GO; GO:0043652; P:engulfment of apoptotic cell; ISS:UniProtKB.
DR GO; GO:0034109; P:homotypic cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0055001; P:muscle cell development; IMP:UniProtKB.
DR GO; GO:0033002; P:muscle cell proliferation; IMP:UniProtKB.
DR GO; GO:0048627; P:myoblast development; IEA:Ensembl.
DR GO; GO:0051451; P:myoblast migration; IMP:UniProtKB.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:2000288; P:positive regulation of myoblast proliferation; IMP:UniProtKB.
DR GO; GO:0043654; P:recognition of apoptotic cell; IEA:Ensembl.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0048641; P:regulation of skeletal muscle tissue development; IMP:UniProtKB.
DR GO; GO:0014719; P:skeletal muscle satellite cell activation; ISS:UniProtKB.
DR GO; GO:0014816; P:skeletal muscle satellite cell differentiation; IMP:UniProtKB.
DR GO; GO:0014841; P:skeletal muscle satellite cell proliferation; ISS:UniProtKB.
DR CDD; cd00055; EGF_Lam; 1.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR011489; EMI_domain.
DR InterPro; IPR002049; LE_dom.
DR Pfam; PF12661; hEGF; 6.
DR Pfam; PF00053; Laminin_EGF; 4.
DR SMART; SM00181; EGF; 17.
DR SMART; SM00180; EGF_Lam; 14.
DR PROSITE; PS00022; EGF_1; 17.
DR PROSITE; PS01186; EGF_2; 17.
DR PROSITE; PS50026; EGF_3; 15.
DR PROSITE; PS51041; EMI; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane; Cell projection;
KW Disease variant; Disulfide bond; EGF-like domain; Glycoprotein; Membrane;
KW Myogenesis; Phagocytosis; Phosphoprotein; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1140
FT /note="Multiple epidermal growth factor-like domains
FT protein 10"
FT /id="PRO_0000309732"
FT TOPO_DOM 26..857
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 858..878
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 879..1140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..107
FT /note="EMI"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00384"
FT DOMAIN 106..136
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 144..179
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 187..222
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 230..265
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 278..308
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 316..351
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 405..440
FT /note="EGF-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 453..483
FT /note="EGF-like 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 491..526
FT /note="EGF-like 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 539..569
FT /note="EGF-like 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 577..612
FT /note="EGF-like 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 665..700
FT /note="EGF-like 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 713..743
FT /note="EGF-like 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 751..786
FT /note="EGF-like 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 799..829
FT /note="EGF-like 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 1..857
FT /note="Necessary for interaction with AP2M1, self-assembly
FT and formation of the irregular, mosaic-like adhesion
FT pattern"
FT /evidence="ECO:0000269|PubMed:17643423"
FT REGION 945..1140
FT /note="Necessary for formation of large intracellular
FT vacuoles"
FT REGION 1111..1140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1118..1140
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1030
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:23954233"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..95
FT /evidence="ECO:0000255"
FT DISULFID 60..69
FT /evidence="ECO:0000255"
FT DISULFID 94..105
FT /evidence="ECO:0000255"
FT DISULFID 109..118
FT /evidence="ECO:0000250"
FT DISULFID 113..124
FT /evidence="ECO:0000250"
FT DISULFID 126..135
FT /evidence="ECO:0000250"
FT DISULFID 148..160
FT /evidence="ECO:0000250"
FT DISULFID 154..167
FT /evidence="ECO:0000250"
FT DISULFID 169..178
FT /evidence="ECO:0000250"
FT DISULFID 191..203
FT /evidence="ECO:0000250"
FT DISULFID 197..210
FT /evidence="ECO:0000250"
FT DISULFID 212..221
FT /evidence="ECO:0000250"
FT DISULFID 234..246
FT /evidence="ECO:0000250"
FT DISULFID 240..253
FT /evidence="ECO:0000250"
FT DISULFID 255..264
FT /evidence="ECO:0000250"
FT DISULFID 281..289
FT /evidence="ECO:0000250"
FT DISULFID 283..296
FT /evidence="ECO:0000250"
FT DISULFID 298..307
FT /evidence="ECO:0000250"
FT DISULFID 320..332
FT /evidence="ECO:0000250"
FT DISULFID 326..339
FT /evidence="ECO:0000250"
FT DISULFID 341..350
FT /evidence="ECO:0000250"
FT DISULFID 409..421
FT /evidence="ECO:0000250"
FT DISULFID 415..428
FT /evidence="ECO:0000250"
FT DISULFID 430..439
FT /evidence="ECO:0000250"
FT DISULFID 456..464
FT /evidence="ECO:0000250"
FT DISULFID 458..471
FT /evidence="ECO:0000250"
FT DISULFID 473..482
FT /evidence="ECO:0000250"
FT DISULFID 495..507
FT /evidence="ECO:0000250"
FT DISULFID 501..514
FT /evidence="ECO:0000250"
FT DISULFID 516..525
FT /evidence="ECO:0000250"
FT DISULFID 542..550
FT /evidence="ECO:0000250"
FT DISULFID 544..557
FT /evidence="ECO:0000250"
FT DISULFID 559..568
FT /evidence="ECO:0000250"
FT DISULFID 581..593
FT /evidence="ECO:0000250"
FT DISULFID 587..600
FT /evidence="ECO:0000250"
FT DISULFID 602..611
FT /evidence="ECO:0000250"
FT DISULFID 669..681
FT /evidence="ECO:0000250"
FT DISULFID 675..688
FT /evidence="ECO:0000250"
FT DISULFID 690..699
FT /evidence="ECO:0000250"
FT DISULFID 716..724
FT /evidence="ECO:0000250"
FT DISULFID 718..731
FT /evidence="ECO:0000250"
FT DISULFID 733..742
FT /evidence="ECO:0000250"
FT DISULFID 755..767
FT /evidence="ECO:0000250"
FT DISULFID 761..774
FT /evidence="ECO:0000250"
FT DISULFID 776..785
FT /evidence="ECO:0000250"
FT DISULFID 802..810
FT /evidence="ECO:0000250"
FT DISULFID 804..817
FT /evidence="ECO:0000250"
FT DISULFID 819..828
FT /evidence="ECO:0000250"
FT VAR_SEQ 566..567
FT /note="VH -> LF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029244"
FT VAR_SEQ 568..1140
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029245"
FT VARIANT 71
FT /note="R -> W (in EMARDD; unknown pathological
FT significance; dbSNP:rs387907074)"
FT /evidence="ECO:0000269|PubMed:22371254, ECO:0000269|Ref.14"
FT /id="VAR_067469"
FT VARIANT 206
FT /note="V -> I (in dbSNP:rs3812054)"
FT /id="VAR_036988"
FT VARIANT 326
FT /note="C -> R (in EMARDD; slightly decreased tyrosine
FT phosphorylation; slightly reduced apoptotic cell
FT engulfement by astrocytes; no effect on cell membrane
FT location; no effect on binding to C1q; no effect on
FT myoblasts migration and proliferation; no effect on
FT interaction with NOTCH1; dbSNP:rs387907073)"
FT /evidence="ECO:0000269|PubMed:22371254,
FT ECO:0000269|PubMed:23954233, ECO:0000269|PubMed:27170117,
FT ECO:0000269|PubMed:28498977, ECO:0000269|Ref.14"
FT /id="VAR_067470"
FT VARIANT 774
FT /note="C -> R (in EMARDD; also found in a patient with
FT MEGF10 myopathy; impairs tyrosine phosphorylation; no
FT effect on cell membrane location; impairs binding to C1q;
FT reduced apoptotic cell engulfement by astrocytes by 50%;
FT reduced myoblast migration and proliferation; decreased
FT interaction with NOTCH1; no effect on NOTCH1 nuclear
FT location; dbSNP:rs387907072)"
FT /evidence="ECO:0000269|PubMed:22101682,
FT ECO:0000269|PubMed:22371254, ECO:0000269|PubMed:23954233,
FT ECO:0000269|PubMed:27170117, ECO:0000269|PubMed:28498977,
FT ECO:0000269|Ref.14"
FT /id="VAR_067471"
FT VARIANT 897
FT /note="P -> L (in dbSNP:rs13183625)"
FT /id="VAR_046377"
FT VARIANT 1030
FT /note="Y -> C (probable disease-associated variant found in
FT a patient with MEGF10 myopathy; dbSNP:rs1433266858)"
FT /evidence="ECO:0000269|Ref.14"
FT /id="VAR_081905"
FT VARIANT 1072
FT /note="R -> K (in dbSNP:rs17164935)"
FT /id="VAR_036989"
FT MUTAGEN 927
FT /note="N->A: Does not interact with GULP1; when associated
FT with A-930."
FT /evidence="ECO:0000269|PubMed:17205124"
FT MUTAGEN 930
FT /note="Y->A: Does not interact with GULP1; when associated
FT with A-927."
FT /evidence="ECO:0000269|PubMed:17205124"
FT MUTAGEN 1030
FT /note="Y->D: Enhances cell proliferation."
FT /evidence="ECO:0000269|PubMed:23954233"
FT MUTAGEN 1030
FT /note="Y->F: Abolishes tyrosine phosphorylation. Unable to
FT enhance cell proliferation."
FT /evidence="ECO:0000269|PubMed:23954233"
FT CONFLICT 543
FT /note="D -> G (in Ref. 2; CAH18275)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1140 AA; 122205 MW; 45B2FA239423895A CRC64;
MVISLNSCLS FICLLLCHWI GTASPLNLED PNVCSHWESY SVTVQESYPH PFDQIYYTSC
TDILNWFKCT RHRVSYRTAY RHGEKTMYRR KSQCCPGFYE SGEMCVPHCA DKCVHGRCIA
PNTCQCEPGW GGTNCSSACD GDHWGPHCTS RCQCKNGALC NPITGACHCA AGFRGWRCED
RCEQGTYGND CHQRCQCQNG ATCDHVTGEC RCPPGYTGAF CEDLCPPGKH GPQCEQRCPC
QNGGVCHHVT GECSCPSGWM GTVCGQPCPE GRFGKNCSQE CQCHNGGTCD AATGQCHCSP
GYTGERCQDE CPVGTYGVLC AETCQCVNGG KCYHVSGACL CEAGFAGERC EARLCPEGLY
GIKCDKRCPC HLENTHSCHP MSGECACKPG WSGLYCNETC SPGFYGEACQ QICSCQNGAD
CDSVTGKCTC APGFKGIDCS TPCPLGTYGI NCSSRCGCKN DAVCSPVDGS CTCKAGWHGV
DCSIRCPSGT WGFGCNLTCQ CLNGGACNTL DGTCTCAPGW RGEKCELPCQ DGTYGLNCAE
RCDCSHADGC HPTTGHCRCL PGWSGVHCDS VCAEGRWGPN CSLPCYCKNG ASCSPDDGIC
ECAPGFRGTT CQRICSPGFY GHRCSQTCPQ CVHSSGPCHH ITGLCDCLPG FTGALCNEVC
PSGRFGKNCA GICTCTNNGT CNPIDRSCQC YPGWIGSDCS QPCPPAHWGP NCIHTCNCHN
GAFCSAYDGE CKCTPGWTGL YCTQRCPLGF YGKDCALICQ CQNGADCDHI SGQCTCRTGF
MGRHCEQKCP SGTYGYGCRQ ICDCLNNSTC DHITGTCYCS PGWKGARCDQ AGVIIVGNLN
SLSRTSTALP ADSYQIGAIA GIIILVLVVL FLLALFIIYR HKQKGKESSM PAVTYTPAMR
VVNADYTISG TLPHSNGGNA NSHYFTNPSY HTLTQCATSP HVNNRDRMTV TKSKNNQLFV
NLKNVNPGKR GPVGDCTGTL PADWKHGGYL NELGAFGLDR SYMGKSLKDL GKNSEYNSSN
CSLSSSENPY ATIKDPPVLI PKSSECGYVE MKSPARRDSP YAEINNSTSA NRNVYEVEPT
VSVVQGVFSN NGRLSQDPYD LPKNSHIPCH YDLLPVRDSS SSPKQEDSGG SSSNSSSSSE
