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Q96KG7 (MEG10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Multiple epidermal growth factor-like domains protein 10

Short name=Multiple EGF-like domains protein 10
Gene names
Name:MEGF10
Synonyms:KIAA1780
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1140 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Membrane receptor involved in phagocytosis by macrophages of apoptotic cells. Cooperates with ABCA1 within the process of engulfment. Promotes the formation of large intracellular vacuoles and may be responsible for the uptake of amyloid-beta peptides. May also function in the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion. Mosaics provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements. May play role in cell adhesion and motility. Is also an essential factor in the regulation of myogenesis. Controls the balance between skeletal muscle satellite cells proliferation and differentiation problably through regulation of the notch signaling pathway. Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

Homopolymer Probable. Interacts with GULP1 and ABCA1. Interacts with AP2M1. Does not interact with MEGF11. Ref.5 Ref.6 Ref.7

Subcellular location

Cell membrane; Single-pass type I membrane protein. Basolateral cell membrane; Single-pass type I membrane protein. Cell projectionphagocytic cup. Note: Enriched at the sites of contact with apoptotic thymocyte cells By similarity. Forms an irregular, mosaic-like adhesion pattern in region of the cell surface that becomes firmely fixed to the substrate. Expressed at the cell surface in clusters around cell corpses during engulfment. During the engulfment of apoptotic thymocytes, recruited at the bottom of the forming phagocytic cup. Colocalizes with ABCA1 in absence of any phagocytic challenge. Does not localize within lamellipodia. Does not localize with MEGF11. Ref.5 Ref.6

Domain

The EMI and EGF-like domains work in concert to promote self-assembly.

Post-translational modification

Phosphorylated on tyrosine residues. Ref.7

Ubiquitinated; mono- and polyubiquitinated forms are detected. Ref.7

Involvement in disease

Myopathy, early-onset, areflexia, respiratory distress, and dysphagia (EMARDD) [MIM:614399]: An autosomal recessive congenital myopathy characterized by onset at birth, or early in infancy, of respiratory distress caused by diaphragmatic weakness. Additional features are dysphagia resulting in poor feeding, failure to thrive, poor head control, facial weakness, cleft palate, contractures and scoliosis. Affected individuals become ventilator-dependent, and most require feeding by gastrostomy. The disorder results in severe muscle weakness and most patients never achieve walking. Death from respiratory failure in childhood occurs in about half of patients. Muscle biopsies from affected individuals show myopathic changes, replacement of myofibers with fatty tissue, small and incompletely fused muscle fibers, and variation in fiber size. Short regions of sarcomeric disorganization with few or no mitochondria (minicores) have been observed in some cases.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10

Sequence similarities

Belongs to the MEGF family.

Contains 15 EGF-like domains.

Contains 1 EMI domain.

Sequence caution

The sequence BAB47409.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processCell adhesion
Myogenesis
Phagocytosis
   Cellular componentCell membrane
Cell projection
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainEGF-like domain
Repeat
Signal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processhomotypic cell-cell adhesion

Inferred from direct assay PubMed 22407321. Source: UniProtKB

muscle cell development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

recognition of apoptotic cell

Inferred from electronic annotation. Source: Ensembl

regulation of muscle cell differentiation

Inferred from mutant phenotype Ref.9. Source: UniProtKB

regulation of skeletal muscle tissue development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

satellite cell activation

Inferred from sequence or structural similarity. Source: UniProtKB

satellite cell differentiation

Inferred from mutant phenotype Ref.9. Source: UniProtKB

satellite cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentbasolateral plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell projection

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

phagocytic cup

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96KG7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96KG7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     566-567: VH → LF
     568-1140: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 11401115Multiple epidermal growth factor-like domains protein 10
PRO_0000309732

Regions

Topological domain26 – 857832Extracellular Potential
Transmembrane858 – 87821Helical; Potential
Topological domain879 – 1140262Cytoplasmic Potential
Domain30 – 10778EMI
Domain106 – 13631EGF-like 1
Domain144 – 17936EGF-like 2
Domain187 – 22236EGF-like 3
Domain230 – 26536EGF-like 4
Domain278 – 30831EGF-like 5
Domain316 – 35136EGF-like 6
Domain405 – 44036EGF-like 7
Domain453 – 48331EGF-like 8
Domain491 – 52636EGF-like 9
Domain539 – 56931EGF-like 10
Domain577 – 61236EGF-like 11
Domain665 – 70036EGF-like 12
Domain713 – 74331EGF-like 13
Domain751 – 78636EGF-like 14
Domain799 – 82931EGF-like 15
Region1 – 857857Necessary for interaction with AP2M1, self-assembly and formation of the irregular, mosaic-like adhesion pattern
Region945 – 1140196Necessary for formation of large intracellular vacuoles
Compositional bias1119 – 113921Ser-rich

Amino acid modifications

Glycosylation1341N-linked (GlcNAc...) Potential
Glycosylation4961N-linked (GlcNAc...) Potential
Disulfide bond34 ↔ 95 Potential
Disulfide bond60 ↔ 69 Potential
Disulfide bond94 ↔ 105 Potential
Disulfide bond109 ↔ 118 By similarity
Disulfide bond113 ↔ 124 By similarity
Disulfide bond126 ↔ 135 By similarity
Disulfide bond148 ↔ 160 By similarity
Disulfide bond154 ↔ 167 By similarity
Disulfide bond169 ↔ 178 By similarity
Disulfide bond191 ↔ 203 By similarity
Disulfide bond197 ↔ 210 By similarity
Disulfide bond212 ↔ 221 By similarity
Disulfide bond234 ↔ 246 By similarity
Disulfide bond240 ↔ 253 By similarity
Disulfide bond255 ↔ 264 By similarity
Disulfide bond281 ↔ 289 By similarity
Disulfide bond283 ↔ 296 By similarity
Disulfide bond298 ↔ 307 By similarity
Disulfide bond320 ↔ 332 By similarity
Disulfide bond326 ↔ 339 By similarity
Disulfide bond341 ↔ 350 By similarity
Disulfide bond409 ↔ 421 By similarity
Disulfide bond415 ↔ 428 By similarity
Disulfide bond430 ↔ 439 By similarity
Disulfide bond456 ↔ 464 By similarity
Disulfide bond458 ↔ 471 By similarity
Disulfide bond473 ↔ 482 By similarity
Disulfide bond495 ↔ 507 By similarity
Disulfide bond501 ↔ 514 By similarity
Disulfide bond516 ↔ 525 By similarity
Disulfide bond542 ↔ 550 By similarity
Disulfide bond544 ↔ 557 By similarity
Disulfide bond559 ↔ 568 By similarity
Disulfide bond581 ↔ 593 By similarity
Disulfide bond587 ↔ 600 By similarity
Disulfide bond602 ↔ 611 By similarity
Disulfide bond669 ↔ 681 By similarity
Disulfide bond675 ↔ 688 By similarity
Disulfide bond690 ↔ 699 By similarity
Disulfide bond716 ↔ 724 By similarity
Disulfide bond718 ↔ 731 By similarity
Disulfide bond733 ↔ 742 By similarity
Disulfide bond755 ↔ 767 By similarity
Disulfide bond761 ↔ 774 By similarity
Disulfide bond776 ↔ 785 By similarity
Disulfide bond802 ↔ 810 By similarity
Disulfide bond804 ↔ 817 By similarity
Disulfide bond819 ↔ 828 By similarity

Natural variations

Alternative sequence566 – 5672VH → LF in isoform 2.
VSP_029244
Alternative sequence568 – 1140573Missing in isoform 2.
VSP_029245
Natural variant711R → W in a patient with EMARDD; unknown pathological significance. Ref.10
VAR_067469
Natural variant2061V → I.
Corresponds to variant rs3812054 [ dbSNP | Ensembl ].
VAR_036988
Natural variant3261C → R in EMARDD. Ref.10
VAR_067470
Natural variant7741C → R in EMARDD. Ref.9 Ref.10
VAR_067471
Natural variant8971P → L.
Corresponds to variant rs13183625 [ dbSNP | Ensembl ].
VAR_046377
Natural variant10721R → K.
Corresponds to variant rs17164935 [ dbSNP | Ensembl ].
VAR_036989

Experimental info

Mutagenesis9271N → A: Does not interact with GULP1; when associated with A-930. Ref.5
Mutagenesis9301Y → A: Does not interact with GULP1; when associated with A-927. Ref.5
Sequence conflict5431D → G in CAH18275. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 45B2FA239423895A

FASTA1,140122,205
        10         20         30         40         50         60 
MVISLNSCLS FICLLLCHWI GTASPLNLED PNVCSHWESY SVTVQESYPH PFDQIYYTSC 

        70         80         90        100        110        120 
TDILNWFKCT RHRVSYRTAY RHGEKTMYRR KSQCCPGFYE SGEMCVPHCA DKCVHGRCIA 

       130        140        150        160        170        180 
PNTCQCEPGW GGTNCSSACD GDHWGPHCTS RCQCKNGALC NPITGACHCA AGFRGWRCED 

       190        200        210        220        230        240 
RCEQGTYGND CHQRCQCQNG ATCDHVTGEC RCPPGYTGAF CEDLCPPGKH GPQCEQRCPC 

       250        260        270        280        290        300 
QNGGVCHHVT GECSCPSGWM GTVCGQPCPE GRFGKNCSQE CQCHNGGTCD AATGQCHCSP 

       310        320        330        340        350        360 
GYTGERCQDE CPVGTYGVLC AETCQCVNGG KCYHVSGACL CEAGFAGERC EARLCPEGLY 

       370        380        390        400        410        420 
GIKCDKRCPC HLENTHSCHP MSGECACKPG WSGLYCNETC SPGFYGEACQ QICSCQNGAD 

       430        440        450        460        470        480 
CDSVTGKCTC APGFKGIDCS TPCPLGTYGI NCSSRCGCKN DAVCSPVDGS CTCKAGWHGV 

       490        500        510        520        530        540 
DCSIRCPSGT WGFGCNLTCQ CLNGGACNTL DGTCTCAPGW RGEKCELPCQ DGTYGLNCAE 

       550        560        570        580        590        600 
RCDCSHADGC HPTTGHCRCL PGWSGVHCDS VCAEGRWGPN CSLPCYCKNG ASCSPDDGIC 

       610        620        630        640        650        660 
ECAPGFRGTT CQRICSPGFY GHRCSQTCPQ CVHSSGPCHH ITGLCDCLPG FTGALCNEVC 

       670        680        690        700        710        720 
PSGRFGKNCA GICTCTNNGT CNPIDRSCQC YPGWIGSDCS QPCPPAHWGP NCIHTCNCHN 

       730        740        750        760        770        780 
GAFCSAYDGE CKCTPGWTGL YCTQRCPLGF YGKDCALICQ CQNGADCDHI SGQCTCRTGF 

       790        800        810        820        830        840 
MGRHCEQKCP SGTYGYGCRQ ICDCLNNSTC DHITGTCYCS PGWKGARCDQ AGVIIVGNLN 

       850        860        870        880        890        900 
SLSRTSTALP ADSYQIGAIA GIIILVLVVL FLLALFIIYR HKQKGKESSM PAVTYTPAMR 

       910        920        930        940        950        960 
VVNADYTISG TLPHSNGGNA NSHYFTNPSY HTLTQCATSP HVNNRDRMTV TKSKNNQLFV 

       970        980        990       1000       1010       1020 
NLKNVNPGKR GPVGDCTGTL PADWKHGGYL NELGAFGLDR SYMGKSLKDL GKNSEYNSSN 

      1030       1040       1050       1060       1070       1080 
CSLSSSENPY ATIKDPPVLI PKSSECGYVE MKSPARRDSP YAEINNSTSA NRNVYEVEPT 

      1090       1100       1110       1120       1130       1140 
VSVVQGVFSN NGRLSQDPYD LPKNSHIPCH YDLLPVRDSS SSPKQEDSGG SSSNSSSSSE 

« Hide

Isoform 2 [UniParc].

Checksum: CF2FB8CDEB7CF627
Show »

FASTA56760,797

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.
DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Retina.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Muscle.
[5]"Cooperation between engulfment receptors: the case of ABCA1 and MEGF10."
Hamon Y., Trompier D., Ma Z., Venegas V., Pophillat M., Mignotte V., Zhou Z., Chimini G.
PLoS ONE 1:E120-E120(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GULP1 AND ABCA1, MUTAGENESIS OF ASN-927 AND TYR-930, SUBCELLULAR LOCATION.
[6]"The mammalian Ced-1 ortholog MEGF10/KIAA1780 displays a novel adhesion pattern."
Suzuki E., Nakayama M.
Exp. Cell Res. 313:2451-2464(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"MEGF10 is a mammalian ortholog of CED-1 that interacts with clathrin assembly protein complex 2 medium chain and induces large vacuole formation."
Suzuki E., Nakayama M.
Exp. Cell Res. 313:3729-3742(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH AP2M1 AND GULP1, PHOSPHORYLATION, UBIQUITINATION.
[8]"MEGF10 functions as a receptor for the uptake of amyloid-beta."
Singh T.D., Park S.Y., Bae J.S., Yun Y., Bae Y.C., Park R.W., Kim I.S.
FEBS Lett. 584:3936-3942(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ENDOCYTOSIS.
[9]"Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD)."
Logan C.V., Lucke B., Pottinger C., Abdelhamed Z.A., Parry D.A., Szymanska K., Diggle C.P., Riesen A., Morgan J.E., Markham G., Ellis I., Manzur A.Y., Markham A.F., Shires M., Helliwell T., Scoto M., Hubner C., Bonthron D.T. expand/collapse author list , Taylor G.R., Sheridan E., Muntoni F., Carr I.M., Schuelke M., Johnson C.A.
Nat. Genet. 43:1189-1192(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MYOGENESIS, VARIANT EMARDD ARG-774.
[10]"Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicores."
Boyden S.E., Mahoney L.J., Kawahara G., Myers J.A., Mitsuhashi S., Estrella E.A., Duncan A.R., Dey F., Dechene E.T., Blasko-Goehringer J.M., Bonnemann C.G., Darras B.T., Mendell J.R., Lidov H.G., Nishino I., Beggs A.H., Kunkel L.M., Kang P.B.
Neurogenetics 13:115-124(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EMARDD ARG-326 AND ARG-774, VARIANT TRP-71.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB058676 mRNA. Translation: BAB47409.2. Different initiation.
CR749437 mRNA. Translation: CAH18275.1.
CH471062 Genomic DNA. Translation: EAW62406.1.
BC020198 mRNA. Translation: AAH20198.1.
BC152478 mRNA. Translation: AAI52479.1.
RefSeqNP_001243474.1. NM_001256545.1.
NP_115822.1. NM_032446.2.
UniGeneHs.438709.

3D structure databases

ProteinModelPortalQ96KG7.
SMRQ96KG7. Positions 90-833.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124099. 5 interactions.
IntActQ96KG7. 24 interactions.
STRING9606.ENSP00000274473.

PTM databases

PhosphoSiteQ96KG7.

Polymorphism databases

DMDM74716908.

Proteomic databases

PaxDbQ96KG7.
PRIDEQ96KG7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000274473; ENSP00000274473; ENSG00000145794. [Q96KG7-1]
ENST00000418761; ENSP00000416284; ENSG00000145794. [Q96KG7-2]
ENST00000503335; ENSP00000423354; ENSG00000145794. [Q96KG7-1]
ENST00000508365; ENSP00000423195; ENSG00000145794. [Q96KG7-2]
GeneID84466.
KEGGhsa:84466.
UCSCuc003kuh.4. human. [Q96KG7-1]
uc010jdc.1. human. [Q96KG7-2]

Organism-specific databases

CTD84466.
GeneCardsGC05P126654.
HGNCHGNC:29634. MEGF10.
HPAHPA026876.
MIM612453. gene.
614399. phenotype.
neXtProtNX_Q96KG7.
Orphanet98920. Spinal muscular atrophy with respiratory distress.
PharmGKBPA144596410.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG12793.
HOGENOMHOG000294130.
HOVERGENHBG108333.
InParanoidQ96KG7.
OMAFGCNLTC.
OrthoDBEOG72C50D.
PhylomeDBQ96KG7.
TreeFamTF332598.

Gene expression databases

BgeeQ96KG7.
CleanExHS_MEGF10.
GenevestigatorQ96KG7.

Family and domain databases

InterProIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR002049. EGF_laminin.
IPR011489. EMI_domain.
[Graphical view]
PfamPF12661. hEGF. 3 hits.
PF00053. Laminin_EGF. 4 hits.
[Graphical view]
SMARTSM00181. EGF. 11 hits.
SM00180. EGF_Lam. 6 hits.
[Graphical view]
PROSITEPS00022. EGF_1. 17 hits.
PS01186. EGF_2. 17 hits.
PS50026. EGF_3. 15 hits.
PS51041. EMI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMEGF10.
GenomeRNAi84466.
NextBio74274.
PROQ96KG7.
SOURCESearch...

Entry information

Entry nameMEG10_HUMAN
AccessionPrimary (citable) accession number: Q96KG7
Secondary accession number(s): Q68DE5, Q8WUL3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM