MIEAP_HUMAN
ID MIEAP_HUMAN Reviewed; 538 AA.
AC Q8TC71; B4E2R0; E5RLK1; Q8IY48; Q8N7D7;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Mitochondria-eating protein;
DE AltName: Full=Spermatogenesis-associated protein 18;
GN Name=SPATA18; Synonyms=MIEAP;
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), FUNCTION, SUBCELLULAR
RP LOCATION, AND INDUCTION.
RX PubMed=21264221; DOI=10.1371/journal.pone.0016054;
RA Miyamoto Y., Kitamura N., Nakamura Y., Futamura M., Miyamoto T.,
RA Yoshida M., Ono M., Ichinose S., Arakawa H.;
RT "Possible existence of lysosome-like organella within mitochondria and its
RT role in mitochondrial quality control.";
RL PLoS ONE 6:E16054-E16054(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 135-538 (ISOFORM 1), AND VARIANT PRO-227.
RC TISSUE=Testis, and Trachea;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-483.
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 [6]
RP INDUCTION.
RX PubMed=21300779; DOI=10.1128/mcb.01072-10;
RA Bornstein C., Brosh R., Molchadsky A., Madar S., Kogan-Sakin I.,
RA Goldstein I., Chakravarti D., Flores E.R., Goldfinger N., Sarig R.,
RA Rotter V.;
RT "SPATA18, a spermatogenesis-associated gene, is a novel transcriptional
RT target of p53 and p63.";
RL Mol. Cell. Biol. 31:1679-1689(2011).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BNIP3L.
RX PubMed=21264228; DOI=10.1371/journal.pone.0016060;
RA Kitamura N., Nakamura Y., Miyamoto Y., Miyamoto T., Kabu K., Yoshida M.,
RA Futamura M., Ichinose S., Arakawa H.;
RT "Mieap, a p53-inducible protein, controls mitochondrial quality by
RT repairing or eliminating unhealthy mitochondria.";
RL PLoS ONE 6:E16060-E16060(2011).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BNIP3 AND BNIP3L.
RX PubMed=22292033; DOI=10.1371/journal.pone.0030767;
RA Nakamura Y., Kitamura N., Shinogi D., Yoshida M., Goda O., Murai R.,
RA Kamino H., Arakawa H.;
RT "BNIP3 and NIX mediate Mieap-induced accumulation of lysosomal proteins
RT within mitochondria.";
RL PLoS ONE 7:E30767-E30767(2012).
CC -!- FUNCTION: Key regulator of mitochondrial quality that mediates the
CC repairing or degradation of unhealthy mitochondria in response to
CC mitochondrial damage. Mediator of mitochondrial protein catabolic
CC process (also named MALM) by mediating the degradation of damaged
CC proteins inside mitochondria by promoting the accumulation in the
CC mitochondrial matrix of hydrolases that are characteristic of the
CC lysosomal lumen. Also involved in mitochondrion degradation of damaged
CC mitochondria by promoting the formation of vacuole-like structures
CC (named MIV), which engulf and degrade unhealthy mitochondria by
CC accumulating lysosomes. The physical interaction of SPATA18/MIEAP,
CC BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the
CC opening of a pore in the mitochondrial double membrane in order to
CC mediate the translocation of lysosomal proteins from the cytoplasm to
CC the mitochondrial matrix. {ECO:0000269|PubMed:21264221,
CC ECO:0000269|PubMed:21264228, ECO:0000269|PubMed:22292033}.
CC -!- SUBUNIT: Interacts (via coiled-coil domains) with BNIP3L (via BH3
CC domain). Interacts (via coiled-coil domains) with BNIP3 (via BH3
CC domain). {ECO:0000269|PubMed:21264228, ECO:0000269|PubMed:22292033}.
CC -!- INTERACTION:
CC Q8TC71; Q13155: AIMP2; NbExp=3; IntAct=EBI-11334239, EBI-745226;
CC Q8TC71; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-11334239, EBI-3866279;
CC Q8TC71; Q68D86: CCDC102B; NbExp=3; IntAct=EBI-11334239, EBI-10171570;
CC Q8TC71; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-11334239, EBI-2349927;
CC Q8TC71; O95995: GAS8; NbExp=3; IntAct=EBI-11334239, EBI-1052570;
CC Q8TC71; Q08379: GOLGA2; NbExp=3; IntAct=EBI-11334239, EBI-618309;
CC Q8TC71; P49639: HOXA1; NbExp=3; IntAct=EBI-11334239, EBI-740785;
CC Q8TC71; Q5T3J3: LRIF1; NbExp=3; IntAct=EBI-11334239, EBI-473196;
CC Q8TC71; Q9Y6D9: MAD1L1; NbExp=3; IntAct=EBI-11334239, EBI-742610;
CC Q8TC71; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-11334239, EBI-14066006;
CC Q8TC71; Q8TC71: SPATA18; NbExp=3; IntAct=EBI-11334239, EBI-11334239;
CC Q8TC71; Q9Y6A5: TACC3; NbExp=3; IntAct=EBI-11334239, EBI-2554984;
CC Q8TC71; Q96PF1: TGM7; NbExp=3; IntAct=EBI-11334239, EBI-12029034;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21264228,
CC ECO:0000269|PubMed:22292033}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:21264228, ECO:0000269|PubMed:22292033}.
CC Note=Localizes to the cytoplasm under normal conditions
CC (PubMed:21264228). Relocalizes to mitochondrion outer membrane
CC following cellular stress. Colocalizes with BNIP3 and BNIP3L at the
CC mitochondrion outer membrane (PubMed:22292033).
CC {ECO:0000269|PubMed:21264228, ECO:0000269|PubMed:22292033}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha, Mieap-alpha;
CC IsoId=Q8TC71-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta, Mieap-beta;
CC IsoId=Q8TC71-2; Sequence=VSP_041048;
CC -!- INDUCTION: By p53/TP53 and p63/TP63. Directly activated by p53/TP53.
CC {ECO:0000269|PubMed:21264221, ECO:0000269|PubMed:21300779}.
CC -!- SIMILARITY: Belongs to the MIEAP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC05356.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB465501; BAJ53738.1; -; mRNA.
DR EMBL; AB465502; BAJ53739.1; -; mRNA.
DR EMBL; AK098625; BAC05356.1; ALT_INIT; mRNA.
DR EMBL; AK304386; BAG65222.1; -; mRNA.
DR EMBL; AC093858; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX05433.1; -; Genomic_DNA.
DR EMBL; BC025396; AAH25396.1; -; mRNA.
DR EMBL; BC037886; AAH37886.1; -; mRNA.
DR CCDS; CCDS3489.1; -. [Q8TC71-1]
DR CCDS; CCDS75124.1; -. [Q8TC71-2]
DR RefSeq; NP_001284537.1; NM_001297608.1. [Q8TC71-2]
DR RefSeq; NP_660306.1; NM_145263.3. [Q8TC71-1]
DR AlphaFoldDB; Q8TC71; -.
DR SMR; Q8TC71; -.
DR BioGRID; 126329; 22.
DR IntAct; Q8TC71; 16.
DR MINT; Q8TC71; -.
DR STRING; 9606.ENSP00000295213; -.
DR iPTMnet; Q8TC71; -.
DR PhosphoSitePlus; Q8TC71; -.
DR BioMuta; SPATA18; -.
DR DMDM; 74751399; -.
DR EPD; Q8TC71; -.
DR jPOST; Q8TC71; -.
DR MassIVE; Q8TC71; -.
DR PaxDb; Q8TC71; -.
DR PeptideAtlas; Q8TC71; -.
DR PRIDE; Q8TC71; -.
DR ProteomicsDB; 74095; -. [Q8TC71-1]
DR ProteomicsDB; 74096; -. [Q8TC71-2]
DR Antibodypedia; 49630; 121 antibodies from 24 providers.
DR DNASU; 132671; -.
DR Ensembl; ENST00000295213.9; ENSP00000295213.4; ENSG00000163071.11. [Q8TC71-1]
DR Ensembl; ENST00000419395.6; ENSP00000415309.2; ENSG00000163071.11. [Q8TC71-2]
DR GeneID; 132671; -.
DR KEGG; hsa:132671; -.
DR MANE-Select; ENST00000295213.9; ENSP00000295213.4; NM_145263.4; NP_660306.1.
DR UCSC; uc003gzl.4; human. [Q8TC71-1]
DR CTD; 132671; -.
DR DisGeNET; 132671; -.
DR GeneCards; SPATA18; -.
DR HGNC; HGNC:29579; SPATA18.
DR HPA; ENSG00000163071; Tissue enhanced (fallopian tube, testis).
DR MIM; 612814; gene.
DR neXtProt; NX_Q8TC71; -.
DR OpenTargets; ENSG00000163071; -.
DR PharmGKB; PA142670883; -.
DR VEuPathDB; HostDB:ENSG00000163071; -.
DR eggNOG; ENOG502QQMJ; Eukaryota.
DR GeneTree; ENSGT00390000013532; -.
DR HOGENOM; CLU_041752_0_0_1; -.
DR InParanoid; Q8TC71; -.
DR OMA; NDNKYRR; -.
DR PhylomeDB; Q8TC71; -.
DR TreeFam; TF328808; -.
DR PathwayCommons; Q8TC71; -.
DR SignaLink; Q8TC71; -.
DR BioGRID-ORCS; 132671; 10 hits in 1070 CRISPR screens.
DR ChiTaRS; SPATA18; human.
DR GenomeRNAi; 132671; -.
DR Pharos; Q8TC71; Tbio.
DR PRO; PR:Q8TC71; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8TC71; protein.
DR Bgee; ENSG00000163071; Expressed in sperm and 153 other tissues.
DR ExpressionAtlas; Q8TC71; baseline and differential.
DR Genevisible; Q8TC71; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0035694; P:mitochondrial protein catabolic process; IMP:UniProtKB.
DR GO; GO:0035695; P:mitophagy by induced vacuole formation; IMP:UniProtKB.
DR InterPro; IPR026169; MIEAP.
DR InterPro; IPR031981; MIEAP_C.
DR PANTHER; PTHR21771; PTHR21771; 1.
DR Pfam; PF16026; MIEAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..538
FT /note="Mitochondria-eating protein"
FT /id="PRO_0000254165"
FT REGION 97..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 247..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 118..187
FT /evidence="ECO:0000255"
FT COILED 219..256
FT /evidence="ECO:0000255"
FT COMPBIAS 102..120
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..213
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 248..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6AYL6"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6AYL6"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6AYL6"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6AYL6"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6AYL6"
FT VAR_SEQ 141..173
FT /note="DLVETEKNLEESKNRSAISLLAAEEEINQLKKQ -> E (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:21264221"
FT /id="VSP_041048"
FT VARIANT 227
FT /note="S -> P (in dbSNP:rs3860707)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_028828"
FT VARIANT 483
FT /note="K -> R (in dbSNP:rs11558773)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_028829"
FT CONFLICT 318
FT /note="Q -> E (in Ref. 5; AAH37886)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 538 AA; 61109 MW; 365754F577F8ED7F CRC64;
MAENLKRLVS NETLRTLQEK LDFWLKEYNT NTCDQNLNHC LELIEQVAKV QGQLFGILTA
AAQEGGRNDG VETIKSRLLP WLEASFTAAS LGKSVDSKVP SLQDTFDRER HKDPSPRDRD
MQQLDSNLNS TRSQCNQVQD DLVETEKNLE ESKNRSAISL LAAEEEINQL KKQLKSLQAQ
EDARHRNTDQ RSSENRRSEP WSLEERKREQ WNSLKQNADQ QDTEAMSDYK KQLRNLKEEI
AVLSAEKSAL QGRSSRSRSP SPAPRSRSCS RSRSASPSTA VKVRRPSPNR SKLSNVARKA
ALLSRFSDSY SQARLDAQCL LRRCIDKAET VQRIIYIATV EAFHVAKMAF RHFKIHVRKS
LTPSYVGSND FENAVLDYVI CHLDLYDSQS SVNDVIRAMN VNPKISFPPV VDFCLLSDFI
QEICCIAFAM QALEPPLDIA YGADGEVFND CKYRRSYDSD FTAPLVLYHV WPALMENDCV
IMKGEAVTRR GAFWNSVRSV SRCRSRSLSP ICPRSQIGLN TMSRSRSPSP IRCGLPRF
