ID MEGF6_HUMAN Reviewed; 1541 AA. AC O75095; Q4AC86; Q5VV39; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 28-JUL-2009, sequence version 4. DT 13-FEB-2019, entry version 146. DE RecName: Full=Multiple epidermal growth factor-like domains protein 6; DE Short=Multiple EGF-like domains protein 6; DE AltName: Full=Epidermal growth factor-like protein 3; DE Short=EGF-like protein 3; DE Flags: Precursor; GN Name=MEGF6; Synonyms=EGFL3, KIAA0815; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS GLY-131; RP LEU-916 AND ALA-1137. RC TISSUE=Brain, and Spleen; RX PubMed=9693030; DOI=10.1006/geno.1998.5341; RA Nakayama M., Nakajima D., Nagase T., Nomura N., Seki N., Ohara O.; RT "Identification of high-molecular-weight proteins with multiple EGF- RT like motifs by motif-trap screening."; RL Genomics 51:27-34(1998). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). CC -!- INTERACTION: CC O15265:ATXN7; NbExp=2; IntAct=EBI-947597, EBI-708350; CC O00555:CACNA1A; NbExp=2; IntAct=EBI-947597, EBI-766279; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75095-1; Sequence=Displayed; CC Name=2; CC IsoId=O75095-2; Sequence=VSP_037740, VSP_037741, VSP_037742, CC VSP_037743, VSP_037744; CC Note=No experimental confirmation available.; CC -!- SEQUENCE CAUTION: CC Sequence=BAA32467.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAE19678.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=BAE19678.1; Type=Frameshift; Positions=1522; 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; AB011539; BAA32467.2; ALT_INIT; mRNA. DR EMBL; AB231860; BAE19678.1; ALT_SEQ; mRNA. DR EMBL; AL512413; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513320; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS41237.1; -. [O75095-1] DR RefSeq; NP_001400.3; NM_001409.3. [O75095-1] DR UniGene; Hs.593645; -. DR ProteinModelPortal; O75095; -. DR SMR; O75095; -. DR BioGrid; 108273; 7. DR IntAct; O75095; 7. DR STRING; 9606.ENSP00000348982; -. DR iPTMnet; O75095; -. DR PhosphoSitePlus; O75095; -. DR BioMuta; MEGF6; -. DR jPOST; O75095; -. DR PaxDb; O75095; -. DR PeptideAtlas; O75095; -. DR PRIDE; O75095; -. DR ProteomicsDB; 49758; -. DR ProteomicsDB; 49759; -. [O75095-2] DR DNASU; 1953; -. DR Ensembl; ENST00000294599; ENSP00000294599; ENSG00000162591. [O75095-2] DR Ensembl; ENST00000356575; ENSP00000348982; ENSG00000162591. [O75095-1] DR GeneID; 1953; -. DR KEGG; hsa:1953; -. DR UCSC; uc001akk.4; human. [O75095-1] DR CTD; 1953; -. DR EuPathDB; HostDB:ENSG00000162591.15; -. DR GeneCards; MEGF6; -. DR H-InvDB; HIX0000066; -. DR HGNC; HGNC:3232; MEGF6. DR HPA; HPA052129; -. DR MIM; 604266; gene. DR neXtProt; NX_O75095; -. DR OpenTargets; ENSG00000162591; -. DR PharmGKB; PA27665; -. DR eggNOG; KOG1218; Eukaryota. DR eggNOG; ENOG410XQWV; LUCA. DR GeneTree; ENSGT00940000156971; -. DR HOGENOM; HOG000097840; -. DR HOVERGEN; HBG079790; -. DR InParanoid; O75095; -. DR OMA; SCKAGFR; -. DR OrthoDB; 25795at2759; -. DR PhylomeDB; O75095; -. DR TreeFam; TF332598; -. DR ChiTaRS; MEGF6; human. DR GenomeRNAi; 1953; -. DR PRO; PR:O75095; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000162591; Expressed in 127 organ(s), highest expression level in descending thoracic aorta. DR ExpressionAtlas; O75095; baseline and differential. DR Genevisible; O75095; HS. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR011489; EMI_domain. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR002049; Laminin_EGF. DR Pfam; PF07645; EGF_CA; 1. DR Pfam; PF12661; hEGF; 5. DR Pfam; PF00053; Laminin_EGF; 5. DR SMART; SM00181; EGF; 31. DR SMART; SM00179; EGF_CA; 8. DR SMART; SM00180; EGF_Lam; 22. DR SUPFAM; SSF57184; SSF57184; 3. DR PROSITE; PS00010; ASX_HYDROXYL; 4. DR PROSITE; PS00022; EGF_1; 23. DR PROSITE; PS01186; EGF_2; 24. DR PROSITE; PS50026; EGF_3; 23. DR PROSITE; PS01187; EGF_CA; 4. DR PROSITE; PS51041; EMI; 1. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Complete proteome; Disulfide bond; KW EGF-like domain; Glycoprotein; Polymorphism; Reference proteome; KW Repeat; Secreted; Signal. FT SIGNAL 1 30 {ECO:0000255}. FT CHAIN 31 1541 Multiple epidermal growth factor-like FT domains protein 6. FT /FTId=PRO_0000007524. FT DOMAIN 44 125 EMI. {ECO:0000255|PROSITE- FT ProRule:PRU00384}. FT DOMAIN 124 159 EGF-like 1. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 161 201 EGF-like 2; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 206 242 EGF-like 3. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 238 284 EGF-like 4. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 285 325 EGF-like 5; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 335 370 EGF-like 6. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 375 411 EGF-like 7. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 412 452 EGF-like 8; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 516 552 EGF-like 9. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 560 595 EGF-like 10. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 603 638 EGF-like 11. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 736 770 EGF-like 12. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 783 814 EGF-like 13. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 822 857 EGF-like 14. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 865 901 EGF-like 15. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 909 944 EGF-like 16. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 955 987 EGF-like 17. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 995 1030 EGF-like 18. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1038 1073 EGF-like 19. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1081 1116 EGF-like 20. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1124 1159 EGF-like 21. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1211 1246 EGF-like 22. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1254 1289 EGF-like 23. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1297 1332 EGF-like 24. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1345 1375 EGF-like 25. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1383 1418 EGF-like 26. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 1469 1504 EGF-like 27. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT CARBOHYD 252 252 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 739 739 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 48 111 {ECO:0000255}. FT DISULFID 77 83 {ECO:0000255}. FT DISULFID 110 123 {ECO:0000255}. FT DISULFID 128 139 {ECO:0000250}. FT DISULFID 133 147 {ECO:0000250}. FT DISULFID 149 158 {ECO:0000250}. FT DISULFID 165 176 {ECO:0000250}. FT DISULFID 172 185 {ECO:0000250}. FT DISULFID 187 200 {ECO:0000250}. FT DISULFID 242 255 {ECO:0000250}. FT DISULFID 248 268 {ECO:0000250}. FT DISULFID 270 283 {ECO:0000250}. FT DISULFID 289 300 {ECO:0000250}. FT DISULFID 296 309 {ECO:0000250}. FT DISULFID 311 324 {ECO:0000250}. FT DISULFID 416 427 {ECO:0000250}. FT DISULFID 423 436 {ECO:0000250}. FT DISULFID 438 451 {ECO:0000250}. FT DISULFID 520 533 {ECO:0000250}. FT DISULFID 527 540 {ECO:0000250}. FT DISULFID 542 551 {ECO:0000250}. FT DISULFID 564 576 {ECO:0000250}. FT DISULFID 570 583 {ECO:0000250}. FT DISULFID 585 594 {ECO:0000250}. FT DISULFID 607 619 {ECO:0000250}. FT DISULFID 613 626 {ECO:0000250}. FT DISULFID 628 637 {ECO:0000250}. FT DISULFID 740 751 {ECO:0000250}. FT DISULFID 744 758 {ECO:0000250}. FT DISULFID 760 769 {ECO:0000250}. FT DISULFID 786 795 {ECO:0000250}. FT DISULFID 789 802 {ECO:0000250}. FT DISULFID 804 813 {ECO:0000250}. FT DISULFID 826 838 {ECO:0000250}. FT DISULFID 832 845 {ECO:0000250}. FT DISULFID 847 856 {ECO:0000250}. FT DISULFID 869 882 {ECO:0000250}. FT DISULFID 873 889 {ECO:0000250}. FT DISULFID 891 900 {ECO:0000250}. FT DISULFID 913 925 {ECO:0000250}. FT DISULFID 919 932 {ECO:0000250}. FT DISULFID 934 943 {ECO:0000250}. FT DISULFID 999 1011 {ECO:0000250}. FT DISULFID 1005 1018 {ECO:0000250}. FT DISULFID 1020 1029 {ECO:0000250}. FT DISULFID 1042 1054 {ECO:0000250}. FT DISULFID 1048 1061 {ECO:0000250}. FT DISULFID 1063 1072 {ECO:0000250}. FT DISULFID 1085 1097 {ECO:0000250}. FT DISULFID 1091 1104 {ECO:0000250}. FT DISULFID 1106 1115 {ECO:0000250}. FT DISULFID 1128 1140 {ECO:0000250}. FT DISULFID 1134 1147 {ECO:0000250}. FT DISULFID 1149 1158 {ECO:0000250}. FT DISULFID 1215 1227 {ECO:0000250}. FT DISULFID 1221 1234 {ECO:0000250}. FT DISULFID 1236 1245 {ECO:0000250}. FT DISULFID 1258 1270 {ECO:0000250}. FT DISULFID 1264 1277 {ECO:0000250}. FT DISULFID 1279 1288 {ECO:0000250}. FT DISULFID 1301 1313 {ECO:0000250}. FT DISULFID 1307 1320 {ECO:0000250}. FT DISULFID 1322 1331 {ECO:0000250}. FT DISULFID 1348 1356 {ECO:0000250}. FT DISULFID 1350 1363 {ECO:0000250}. FT DISULFID 1365 1374 {ECO:0000250}. FT DISULFID 1387 1399 {ECO:0000250}. FT DISULFID 1393 1406 {ECO:0000250}. FT DISULFID 1408 1417 {ECO:0000250}. FT DISULFID 1473 1485 {ECO:0000250}. FT DISULFID 1479 1492 {ECO:0000250}. FT DISULFID 1494 1503 {ECO:0000250}. FT VAR_SEQ 1 159 Missing (in isoform 2). FT {ECO:0000303|PubMed:9693030}. FT /FTId=VSP_037740. FT VAR_SEQ 160 160 Y -> MGASRDRGLAALWCLGLLGGLARVAGTHYRYLWRGC FT YPCHLGQAGYPVSAGDQRP (in isoform 2). FT {ECO:0000303|PubMed:9693030}. FT /FTId=VSP_037741. FT VAR_SEQ 989 1075 TCPAHTYGHNCSQACACFNGASCDPVHGQCHCAPGWMGPSC FT LQACPAGLYGDNCRHSCLCQNGGTCDPVSGHCACPEGWAGL FT ACEKE -> K (in isoform 2). FT {ECO:0000303|PubMed:9693030}. FT /FTId=VSP_037742. FT VAR_SEQ 1161 1205 ACPPGSFGEDCAQMCQCPGENPACHPATGTCSCAAGYHGPS FT CQQR -> G (in isoform 2). FT {ECO:0000303|PubMed:9693030}. FT /FTId=VSP_037743. FT VAR_SEQ 1377 1454 PCPPGFHGAGCQGLCWCQHGAPCDPISGRCLCPAGFHGHFC FT ERGCEPGSFGEGCHQRCDCDGGAPCDPVTGLCLCPPG -> FT R (in isoform 2). FT {ECO:0000303|PubMed:9693030}. FT /FTId=VSP_037744. FT VARIANT 115 115 M -> T (in dbSNP:rs7513275). FT /FTId=VAR_059258. FT VARIANT 131 131 S -> G (in dbSNP:rs2794340). FT {ECO:0000269|PubMed:9693030}. FT /FTId=VAR_058361. FT VARIANT 313 313 A -> V (in dbSNP:rs11585362). FT /FTId=VAR_059259. FT VARIANT 587 587 P -> L (in dbSNP:rs947345). FT /FTId=VAR_061155. FT VARIANT 688 688 L -> P (in dbSNP:rs2821008). FT /FTId=VAR_059260. FT VARIANT 916 916 R -> L (in dbSNP:rs7553399). FT {ECO:0000269|PubMed:9693030}. FT /FTId=VAR_058362. FT VARIANT 1137 1137 G -> A (in dbSNP:rs4648506). FT {ECO:0000269|PubMed:9693030}. FT /FTId=VAR_058363. FT VARIANT 1287 1287 R -> H (in dbSNP:rs57804877). FT /FTId=VAR_061156. FT VARIANT 1536 1536 G -> S (in dbSNP:rs57484147). FT /FTId=VAR_061157. SQ SEQUENCE 1541 AA; 161185 MW; EF2A7CB65140A7BB CRC64; MSFLEEARAA GRAVVLALVL LLLPAVPVGA SVPPRPLLPL QPGMPHVCAE QELTLVGRRQ PCVQALSHTV PVWKAGCGWQ AWCVGHERRT VYYMGYRQVY TTEARTVLRC CRGWMQQPDE EGCLSAECSA SLCFHGGRCV PGSAQPCHCP PGFQGPRCQY DVDECRTHNG GCQHRCVNTP GSYLCECKPG FRLHTDSRTC LAINSCALGN GGCQHHCVQL TITRHRCQCR PGFQLQEDGR HCVRRSPCAN RNGSCMHRCQ VVRGLARCEC HVGYQLAADG KACEDVDECA AGLAQCAHGC LNTQGSFKCV CHAGYELGAD GRQCYRIEME IVNSCEANNG GCSHGCSHTS AGPLCTCPRG YELDTDQRTC IDVDDCADSP CCQQVCTNNP GGYECGCYAG YRLSADGCGC EDVDECASSR GGCEHHCTNL AGSFQCSCEA GYRLHEDRRG CSPLEEPMVD LDGELPFVRP LPHIAVLQDE LPQLFQDDDV GADEEEAELR GEHTLTEKFV CLDDSFGHDC SLTCDDCRNG GTCLLGLDGC DCPEGWTGLI CNETCPPDTF GKNCSFSCSC QNGGTCDSVT GACRCPPGVS GTNCEDGCPK GYYGKHCRKK CNCANRGRCH RLYGACLCDP GLYGRFCHLT CPPWAFGPGC SEECQCVQPH TQSCDKRDGS CSCKAGFRGE RCQAECELGY FGPGCWQACT CPVGVACDSV SGECGKRCPA GFQGEDCGQE CPVGTFGVNC SSSCSCGGAP CHGVTGQCRC PPGRTGEDCE ADCPEGRWGL GCQEICPACQ HAARCDPETG ACLCLPGFVG SRCQDVCPAG WYGPSCQTRC SCANDGHCHP ATGHCSCAPG WTGFSCQRAC DTGHWGPDCS HPCNCSAGHG SCDAISGLCL CEAGYVGPRC EQQCPQGHFG PGCEQRCQCQ HGAACDHVSG ACTCPAGWRG TFCEHACPAG FFGLDCRSAC NCTAGAACDA VNGSCLCPAG RRGPRCAETC PAHTYGHNCS QACACFNGAS CDPVHGQCHC APGWMGPSCL QACPAGLYGD NCRHSCLCQN GGTCDPVSGH CACPEGWAGL ACEKECLPRD VRAGCRHSGG CLNGGLCDPH TGRCLCPAGW TGDKCQSPCL RGWFGEACAQ RCSCPPGAAC HHVTGACRCP PGFTGSGCEQ ACPPGSFGED CAQMCQCPGE NPACHPATGT CSCAAGYHGP SCQQRCPPGR YGPGCEQLCG CLNGGSCDAA TGACRCPTGF LGTDCNLTCP QGRFGPNCTH VCGCGQGAAC DPVTGTCLCP PGRAGVRCER GCPQNRFGVG CEHTCSCRNG GLCHASNGSC SCGLGWTGRH CELACPPGRY GAACHLECSC HNNSTCEPAT GTCRCGPGFY GQACEHPCPP GFHGAGCQGL CWCQHGAPCD PISGRCLCPA GFHGHFCERG CEPGSFGEGC HQRCDCDGGA PCDPVTGLCL CPPGRSGATC NLDCRRGQFG PSCTLHCDCG GGADCDPVSG QCHCVDGYMG PTCREGGPLR LPENPSLAQG SAGTLPASSR PTSRSGGPAR H //