MEAK7_HUMAN
ID MEAK7_HUMAN Reviewed; 456 AA.
AC Q6P9B6; Q8IZ64; Q9HCG3; Q9NTE8;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=MTOR-associated protein MEAK7 {ECO:0000305};
DE Short=MEAK7 {ECO:0000305};
DE AltName: Full=MTOR associated protein, eak-7 homolog {ECO:0000312|HGNC:HGNC:29325};
DE AltName: Full=TBC/LysM-associated domain-containing protein 1;
DE AltName: Full=TLD domain-containing protein 1;
GN Name=MEAK7 {ECO:0000312|HGNC:HGNC:29325}; Synonyms=KIAA1609, TLDC1;
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], AND VARIANTS GLU-172; VAL-220 AND
RP ARG-267.
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS VAL-220 AND
RP ARG-267.
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], AND VARIANTS GLU-172; VAL-220 AND
RP ARG-267.
RC TISSUE=Kidney, and Placenta;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 343-456.
RC TISSUE=Mammary cancer;
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 [6]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [7]
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 [8]
RP MYRISTOYLATION AT GLY-2, AND SUBCELLULAR LOCATION.
RX PubMed=24223779; DOI=10.1371/journal.pone.0078235;
RA Moriya K., Nagatoshi K., Noriyasu Y., Okamura T., Takamitsu E., Suzuki T.,
RA Utsumi T.;
RT "Protein N-myristoylation plays a critical role in the endoplasmic
RT reticulum morphological change induced by overexpression of protein
RT Lunapark, an integral membrane protein of the endoplasmic reticulum.";
RL PLoS ONE 8:E78235-E78235(2013).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MTOR AND MLST8, INDUCTION
RP BY NUTRIENTS, AND MUTAGENESIS OF GLY-2.
RX PubMed=29750193; DOI=10.1126/sciadv.aao5838;
RA Nguyen J.T., Ray C., Fox A.L., Mendonca D.B., Kim J.K., Krebsbach P.H.;
RT "Mammalian EAK-7 activates alternative mTOR signaling to regulate cell
RT proliferation and migration.";
RL Sci. Adv. 4:EAAO5838-EAAO5838(2018).
CC -!- FUNCTION: Activates an alternative mTOR signaling through RPS6KB2
CC activation and EIF4EBP1 repression to regulate cell proliferation and
CC migration (PubMed:29750193). Recruits MTOR at the lysosome, essential
CC for MTOR signaling at the lysosome (PubMed:29750193).
CC {ECO:0000269|PubMed:29750193}.
CC -!- SUBUNIT: Interacts (via C-terminal domain) with MTOR and MLST8; the
CC interaction with MTOR increases upon nutrient stimulation.
CC {ECO:0000269|PubMed:29750193}.
CC -!- INTERACTION:
CC Q6P9B6; Q15645: TRIP13; NbExp=4; IntAct=EBI-746504, EBI-358993;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:24223779}. Cytoplasm
CC {ECO:0000269|PubMed:24223779}. Lysosome {ECO:0000269|PubMed:29750193}.
CC -!- INDUCTION: Addition of nutrients and insulin induces its expression (at
CC protein level). {ECO:0000269|PubMed:29750193}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13435.1; Type=Erroneous initiation; Note=Extended 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; AB046829; BAB13435.1; ALT_INIT; mRNA.
DR EMBL; AC022165; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471114; EAW95478.1; -; Genomic_DNA.
DR EMBL; BC023251; AAH23251.1; -; mRNA.
DR EMBL; BC060844; AAH60844.1; -; mRNA.
DR EMBL; AL137316; CAB70693.1; -; mRNA.
DR CCDS; CCDS32498.1; -.
DR PIR; T46288; T46288.
DR RefSeq; NP_065998.3; NM_020947.3.
DR RefSeq; XP_005256132.1; XM_005256075.2.
DR RefSeq; XP_006721303.1; XM_006721240.2.
DR RefSeq; XP_011521550.1; XM_011523248.2.
DR RefSeq; XP_011521551.1; XM_011523249.2.
DR RefSeq; XP_016878999.1; XM_017023510.1.
DR RefSeq; XP_016879000.1; XM_017023511.1.
DR AlphaFoldDB; Q6P9B6; -.
DR SMR; Q6P9B6; -.
DR BioGRID; 121731; 41.
DR ELM; Q6P9B6; -.
DR IntAct; Q6P9B6; 13.
DR MINT; Q6P9B6; -.
DR STRING; 9606.ENSP00000343635; -.
DR iPTMnet; Q6P9B6; -.
DR MetOSite; Q6P9B6; -.
DR PhosphoSitePlus; Q6P9B6; -.
DR SwissPalm; Q6P9B6; -.
DR BioMuta; TLDC1; -.
DR DMDM; 296434547; -.
DR EPD; Q6P9B6; -.
DR jPOST; Q6P9B6; -.
DR MassIVE; Q6P9B6; -.
DR MaxQB; Q6P9B6; -.
DR PaxDb; Q6P9B6; -.
DR PeptideAtlas; Q6P9B6; -.
DR PRIDE; Q6P9B6; -.
DR ProteomicsDB; 67035; -.
DR Antibodypedia; 48850; 224 antibodies from 18 providers.
DR DNASU; 57707; -.
DR Ensembl; ENST00000343629.11; ENSP00000343635.6; ENSG00000140950.16.
DR GeneID; 57707; -.
DR KEGG; hsa:57707; -.
DR MANE-Select; ENST00000343629.11; ENSP00000343635.6; NM_020947.4; NP_065998.3.
DR UCSC; uc002fib.4; human.
DR CTD; 57707; -.
DR DisGeNET; 57707; -.
DR GeneCards; MEAK7; -.
DR HGNC; HGNC:29325; MEAK7.
DR HPA; ENSG00000140950; Low tissue specificity.
DR MIM; 619331; gene.
DR neXtProt; NX_Q6P9B6; -.
DR OpenTargets; ENSG00000140950; -.
DR PharmGKB; PA144596416; -.
DR VEuPathDB; HostDB:ENSG00000140950; -.
DR eggNOG; KOG2557; Eukaryota.
DR GeneTree; ENSGT00940000158087; -.
DR HOGENOM; CLU_036763_2_0_1; -.
DR InParanoid; Q6P9B6; -.
DR OMA; VIEDWVF; -.
DR OrthoDB; 585082at2759; -.
DR PhylomeDB; Q6P9B6; -.
DR TreeFam; TF316541; -.
DR PathwayCommons; Q6P9B6; -.
DR SignaLink; Q6P9B6; -.
DR BioGRID-ORCS; 57707; 25 hits in 1082 CRISPR screens.
DR ChiTaRS; TLDC1; human.
DR GenomeRNAi; 57707; -.
DR Pharos; Q6P9B6; Tdark.
DR PRO; PR:Q6P9B6; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q6P9B6; protein.
DR Bgee; ENSG00000140950; Expressed in cervix squamous epithelium and 137 other tissues.
DR ExpressionAtlas; Q6P9B6; baseline and differential.
DR Genevisible; Q6P9B6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1903204; P:negative regulation of oxidative stress-induced neuron death; IEA:Ensembl.
DR GO; GO:0150032; P:positive regulation of protein localization to lysosome; IDA:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0043200; P:response to amino acid; IDA:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IDA:UniProtKB.
DR GO; GO:0031667; P:response to nutrient levels; IDA:UniProtKB.
DR GO; GO:0031929; P:TOR signaling; IMP:UniProtKB.
DR InterPro; IPR006571; TLDc_dom.
DR Pfam; PF07534; TLD; 1.
DR SMART; SM00584; TLDc; 1.
DR PROSITE; PS51886; TLDC; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Lipoprotein; Lysosome; Membrane; Myristate; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..456
FT /note="MTOR-associated protein MEAK7"
FT /id="PRO_0000313640"
FT DOMAIN 244..412
FT /note="TLDc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01234"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:20213681,
FT ECO:0000269|PubMed:24223779"
FT VARIANT 10
FT /note="R -> L (in dbSNP:rs8046813)"
FT /id="VAR_037675"
FT VARIANT 97
FT /note="H -> Q (in dbSNP:rs8055536)"
FT /id="VAR_037676"
FT VARIANT 172
FT /note="D -> E (in dbSNP:rs436278)"
FT /evidence="ECO:0000269|PubMed:10997877,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_037677"
FT VARIANT 220
FT /note="I -> V (in dbSNP:rs431818)"
FT /evidence="ECO:0000269|PubMed:10997877,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_037678"
FT VARIANT 233
FT /note="E -> D (in dbSNP:rs34244563)"
FT /id="VAR_037679"
FT VARIANT 267
FT /note="C -> R (in dbSNP:rs422145)"
FT /evidence="ECO:0000269|PubMed:10997877,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_037680"
FT VARIANT 443
FT /note="S -> L (in dbSNP:rs34628943)"
FT /id="VAR_037681"
FT MUTAGEN 2
FT /note="G->A: Abolishes lysosomal location."
FT /evidence="ECO:0000269|PubMed:29750193"
SQ SEQUENCE 456 AA; 50994 MW; 3237DF7BB9818667 CRC64;
MGNSRSRVGR SFCSQFLPEE QAEIDQLFDA LSSDKNSPNV SSKSFSLKAL QNHVGEALPP
EMVTRLYDGM RRVDLTGKAK GPSENVSQEQ FTASMSHLLK GNSEEKSLMI MKMISATEGP
VKAREVQKFT EDLVGSVVHV LSHRQELRGW TGKEAPGPNP RVQVLAAQLL SDMKLQDGKR
LLGPQWLDYD CDRAVIEDWV FRVPHVAIFL SVVICKGFLI LCSSLDLTTL VPERQVDQGR
GFESILDVLS VMYINAQLPR EQRHRWCLLF SSELHGHSFS QLCGHITHRG PCVAVLEDHD
KHVFGGFASC SWEVKPQFQG DNRCFLFSIC PSMAVYTHTG YNDHYMYLNH GQQTIPNGLG
MGGQHNYFGL WVDVDFGKGH SRAKPTCTTY NSPQLSAQEN FQFDKMEVWA VGDPSEEQLA
KGNKSILDAD PEAQALLEIS GHSRHSEGLR EVPDDE
