ID   LPPRC_HUMAN             Reviewed;        1394 AA.
AC   P42704; A0PJE3; A8K1V1; Q53PC0; Q53QN7; Q6ZUD8; Q7Z7A6; Q96D84;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   24-JUL-2007, sequence version 3.
DT   27-MAR-2024, entry version 212.
DE   RecName: Full=Leucine-rich PPR motif-containing protein, mitochondrial;
DE   AltName: Full=130 kDa leucine-rich protein;
DE            Short=LRP 130;
DE   AltName: Full=GP130;
DE   Flags: Precursor;
GN   Name=LRPPRC; Synonyms=LRP130;
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], FUNCTION IN COX ASSEMBLY, TISSUE SPECIFICITY,
RP   AND SUBCELLULAR LOCATION.
RX   PubMed=15139850; DOI=10.1042/bj20040469;
RA   Xu F., Morin C., Mitchell G., Ackerley C., Robinson B.H.;
RT   "The role of the LRPPRC (leucine-rich pentatricopeptide repeat cassette)
RT   gene in cytochrome oxidase assembly: mutation causes lowered levels of COX
RT   (cytochrome c oxidase) I and COX III mRNA.";
RL   Biochem. J. 382:331-336(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Hippocampus, and Testis;
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 MRNA].
RC   TISSUE=Brain, Muscle, Placenta, and Testis;
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 [MRNA] OF 108-1394.
RC   TISSUE=Liver;
RX   PubMed=8012652; DOI=10.1007/bf02631402;
RA   Hou J., Wang F., McKeehan W.L.;
RT   "Molecular cloning and expression of the gene for a major leucine-rich
RT   protein from human hepatoblastoma cells (HepG2).";
RL   In Vitro Cell. Dev. Biol. Anim. 30A:111-114(1994).
RN   [6]
RP   PROTEIN SEQUENCE OF 156-170; 260-280; 304-314; 454-463; 530-541; 656-672;
RP   740-750; 764-772; 1050-1059; 1091-1098; 1177-1189 AND 1339-1347, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=B-cell lymphoma, and Colon carcinoma;
RA   Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E.;
RL   Submitted (JUL-2007) to UniProtKB.
RN   [7]
RP   FUNCTION IN MRNA EXPORT, IDENTIFICATION IN NMRNP COMPLEXES, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=11585913; DOI=10.1128/mcb.21.21.7307-7319.2001;
RA   Mili S., Shu H.J., Zhao Y., Pinol-Roma S.;
RT   "Distinct RNP complexes of shuttling hnRNP proteins with pre-mRNA and mRNA:
RT   candidate intermediates in formation and export of mRNA.";
RL   Mol. Cell. Biol. 21:7307-7319(2001).
RN   [8]
RP   TISSUE SPECIFICITY, AND INTERACTION WITH CECR2; HEBP2; MAP1S AND UXT.
RX   PubMed=11827465; DOI=10.1006/geno.2001.6679;
RA   Liu L., McKeehan W.L.;
RT   "Sequence analysis of LRPPRC and its SEC1 domain interaction partners
RT   suggests roles in cytoskeletal organization, vesicular trafficking,
RT   nucleocytosolic shuttling, and chromosome activity.";
RL   Genomics 79:124-136(2002).
RN   [9]
RP   RNA-BINDING, FUNCTION IN MRNA EXPORT, AND SUBCELLULAR LOCATION.
RX   PubMed=12832482; DOI=10.1128/mcb.23.14.4972-4982.2003;
RA   Mili S., Pinol-Roma S.;
RT   "LRP130, a pentatricopeptide motif protein with a noncanonical RNA-binding
RT   domain, is bound in vivo to mitochondrial and nuclear RNAs.";
RL   Mol. Cell. Biol. 23:4972-4982(2003).
RN   [10]
RP   FUNCTION IN MRNA EXPORT, AND SUBCELLULAR LOCATION.
RX   PubMed=15081402; DOI=10.1016/j.bbrc.2004.03.103;
RA   Tsuchiya N., Fukuda H., Nakashima K., Nagao M., Sugimura T., Nakagama H.;
RT   "LRP130, a single-stranded DNA/RNA-binding protein, localizes at the outer
RT   nuclear and endoplasmic reticulum membrane, and interacts with mRNA in
RT   vivo.";
RL   Biochem. Biophys. Res. Commun. 317:736-743(2004).
RN   [11]
RP   FUNCTION IN TRANSCRIPTION REGULATION, IDENTIFICATION BY MASS SPECTROMETRY,
RP   AND SUBCELLULAR LOCATION.
RX   PubMed=15272088; DOI=10.1093/nar/gkh722;
RA   Labialle S., Dayan G., Gayet L., Rigal D., Gambrelle J., Baggetto L.G.;
RT   "New invMED1 element cis-activates human multidrug-related MDR1 and MVP
RT   genes, involving the LRP130 protein.";
RL   Nucleic Acids Res. 32:3864-3876(2004).
RN   [12]
RP   INTERACTION WITH MAP1S.
RX   PubMed=15907802; DOI=10.1016/j.bbrc.2005.05.006;
RA   Liu L., Vo A., Liu G., McKeehan W.L.;
RT   "Putative tumor suppressor RASSF1 interactive protein and cell death
RT   inducer C19ORF5 is a DNA binding protein.";
RL   Biochem. Biophys. Res. Commun. 332:670-676(2005).
RN   [13]
RP   FUNCTION IN TRANSCRIPTION REGULATION, AND INTERACTION WITH PPARGC1A.
RX   PubMed=17050673; DOI=10.1101/gad.1483906;
RA   Cooper M.P., Qu L., Rohas L.M., Lin J., Yang W., Erdjument-Bromage H.,
RA   Tempst P., Spiegelman B.M.;
RT   "Defects in energy homeostasis in Leigh syndrome French Canadian variant
RT   through PGC-1alpha/LRP130 complex.";
RL   Genes Dev. 20:2996-3009(2006).
RN   [14]
RP   FUNCTION, INTERACTION WITH EIF4E, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP   TYR-441 AND TYR-583.
RX   PubMed=19262567; DOI=10.1038/emboj.2009.53;
RA   Topisirovic I., Siddiqui N., Lapointe V.L., Trost M., Thibault P.,
RA   Bangeranye C., Pinol-Roma S., Borden K.L.;
RT   "Molecular dissection of the eukaryotic initiation factor 4E (eIF4E)
RT   export-competent RNP.";
RL   EMBO J. 28:1087-1098(2009).
RN   [15]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-155; LYS-187; LYS-292; LYS-613;
RP   LYS-726 AND LYS-750, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [16]
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   [17]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1026; SER-1029; THR-1136 AND
RP   SER-1138, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [18]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [19]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [20]
RP   FUNCTION, AND INTERACTION WITH EIF4E; IPO8 AND XPO1.
RX   PubMed=28325843; DOI=10.1261/rna.060137.116;
RA   Volpon L., Culjkovic-Kraljacic B., Sohn H.S., Blanchet-Cohen A.,
RA   Osborne M.J., Borden K.L.B.;
RT   "A biochemical framework for eIF4E-dependent mRNA export and nuclear
RT   recycling of the export machinery.";
RL   RNA 23:927-937(2017).
RN   [21]
RP   VARIANT MC4DN5 VAL-354.
RX   PubMed=12529507; DOI=10.1073/pnas.242716699;
RA   Mootha V.K., Lepage P., Miller K., Bunkenborg J., Reich M., Hjerrild M.,
RA   Delmonte T., Villeneuve A., Sladek R., Xu F., Mitchell G.A., Morin C.,
RA   Mann M., Hudson T.J., Robinson B., Rioux J.D., Lander E.S.;
RT   "Identification of a gene causing human cytochrome c oxidase deficiency by
RT   integrative genomics.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:605-610(2003).
RN   [22]
RP   VARIANTS MC4DN5 VAL-866 DEL AND LYS-909 DEL.
RX   PubMed=26510951; DOI=10.1093/brain/awv291;
RA   Olahova M., Hardy S.A., Hall J., Yarham J.W., Haack T.B., Wilson W.C.,
RA   Alston C.L., He L., Aznauryan E., Brown R.M., Brown G.K., Morris A.A.,
RA   Mundy H., Broomfield A., Barbosa I.A., Simpson M.A., Deshpande C.,
RA   Moeslinger D., Koch J., Stettner G.M., Bonnen P.E., Prokisch H.,
RA   Lightowlers R.N., McFarland R., Chrzanowska-Lightowlers Z.M., Taylor R.W.;
RT   "LRPPRC mutations cause early-onset multisystem mitochondrial disease
RT   outside of the French-Canadian population.";
RL   Brain 138:3503-3519(2015).
CC   -!- FUNCTION: May play a role in RNA metabolism in both nuclei and
CC       mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs
CC       and is part of nmRNP complexes at late stages of mRNA maturation which
CC       are possibly associated with nuclear mRNA export. Positively modulates
CC       nuclear export of mRNAs containing the EIF4E sensitivity element (4ESE)
CC       by binding simultaneously to both EIF4E and the 4ESE and acting as a
CC       platform for assembly for the RNA export complex (PubMed:19262567,
CC       PubMed:28325843). Also binds to exportin XPO1/CRM1 to engage the
CC       nuclear pore and traffic the bound mRNAs to the cytoplasm
CC       (PubMed:28325843). May bind mature mRNA in the nucleus outer membrane.
CC       In mitochondria binds to poly(A) mRNA. Plays a role in translation or
CC       stability of mitochondrially encoded cytochrome c oxidase (COX)
CC       subunits. May be involved in transcription regulation. Cooperates with
CC       PPARGC1A to regulate certain mitochondrially encoded genes and
CC       gluconeogenic genes and may regulate docking of PPARGC1A to
CC       transcription factors. Seems to be involved in the transcription
CC       regulation of the multidrug-related genes MDR1 and MVP. Part of a
CC       nuclear factor that binds to the invMED1 element of MDR1 and MVP gene
CC       promoters. Binds single-stranded DNA (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:11585913, ECO:0000269|PubMed:12832482,
CC       ECO:0000269|PubMed:15081402, ECO:0000269|PubMed:15139850,
CC       ECO:0000269|PubMed:15272088, ECO:0000269|PubMed:17050673,
CC       ECO:0000269|PubMed:19262567, ECO:0000269|PubMed:28325843}.
CC   -!- SUBUNIT: Interacts with CECR2, HEBP2, MAP1S and UXT. Interacts with
CC       PPARGC1A. Interacts with FOXO1 (By similarity). Component of mRNP
CC       complexes associated with HNRPA1. Interacts (via N-terminus) with
CC       EIF4E; the interaction promotes association of EIF4E with 4ESE-
CC       containing mRNAs (PubMed:19262567, PubMed:28325843). Interacts with
CC       exportin XPO1/CRM1; interacts both alone and in complex with EIF4E and
CC       4ESE-containing mRNAs to form an EIF4E-dependent mRNA export complex
CC       (PubMed:28325843). Interacts with importin IPO8; the interaction occurs
CC       when LRPPRC is in its RNA-free form and returns LRPPRC to the nucleus
CC       for further export rounds (PubMed:28325843). {ECO:0000250,
CC       ECO:0000269|PubMed:11585913, ECO:0000269|PubMed:11827465,
CC       ECO:0000269|PubMed:15907802, ECO:0000269|PubMed:17050673,
CC       ECO:0000269|PubMed:19262567, ECO:0000269|PubMed:28325843}.
CC   -!- INTERACTION:
CC       P42704; P05067: APP; NbExp=8; IntAct=EBI-1050853, EBI-77613;
CC       P42704; P06730: EIF4E; NbExp=6; IntAct=EBI-1050853, EBI-73440;
CC       P42704; Q9UBK2: PPARGC1A; NbExp=2; IntAct=EBI-1050853, EBI-765486;
CC       P42704; Q9GZT3: SLIRP; NbExp=3; IntAct=EBI-1050853, EBI-1050793;
CC       P42704; P63104: YWHAZ; NbExp=2; IntAct=EBI-1050853, EBI-347088;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19262567}.
CC       Nucleus {ECO:0000269|PubMed:19262567}. Nucleus, nucleoplasm. Nucleus
CC       inner membrane. Nucleus outer membrane. Note=Seems to be predominantly
CC       mitochondrial.
CC   -!- TISSUE SPECIFICITY: Expressed ubiquitously. Expression is highest in
CC       heart, skeletal muscle, kidney and liver, intermediate in brain, non-
CC       mucosal colon, spleen and placenta, and lowest in small intestine,
CC       thymus, lung and peripheral blood leukocytes.
CC       {ECO:0000269|PubMed:11827465, ECO:0000269|PubMed:15139850}.
CC   -!- DISEASE: Mitochondrial complex IV deficiency, nuclear type 5 (MC4DN5)
CC       [MIM:220111]: An autosomal recessive, severe mitochondrial disease with
CC       multisystemic manifestations and early onset. Clinical features include
CC       delayed psychomotor development, impaired intellectual development with
CC       speech delay, mild dysmorphic facial features, hypotonia, ataxia, and
CC       seizures. Brain imaging shows bilaterally symmetrical necrotic lesions
CC       in subcortical brain regions. Mortality is high, due to episodes of
CC       severe metabolic acidosis and coma. {ECO:0000269|PubMed:12529507,
CC       ECO:0000269|PubMed:26510951}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA67549.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAA67549.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AY289212; AAP41922.1; -; mRNA.
DR   EMBL; AK125781; BAC86287.1; -; mRNA.
DR   EMBL; AK290016; BAF82705.1; -; mRNA.
DR   EMBL; AC108476; AAY24012.1; -; Genomic_DNA.
DR   EMBL; AC127379; AAY24043.1; -; Genomic_DNA.
DR   EMBL; BC010282; AAH10282.1; -; mRNA.
DR   EMBL; BC026034; AAH26034.1; -; mRNA.
DR   EMBL; BC050311; AAH50311.1; -; mRNA.
DR   EMBL; BC130285; AAI30286.1; -; mRNA.
DR   EMBL; M92439; AAA67549.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS33189.1; -.
DR   PIR; S27954; S27954.
DR   RefSeq; NP_573566.2; NM_133259.3.
DR   PDB; 8ANY; EM; 2.85 A; A5=1-1394.
DR   PDBsum; 8ANY; -.
DR   AlphaFoldDB; P42704; -.
DR   EMDB; EMD-15544; -.
DR   SMR; P42704; -.
DR   BioGRID; 115432; 815.
DR   CORUM; P42704; -.
DR   DIP; DIP-27543N; -.
DR   IntAct; P42704; 121.
DR   MINT; P42704; -.
DR   STRING; 9606.ENSP00000260665; -.
DR   ChEMBL; CHEMBL4295762; -.
DR   CarbonylDB; P42704; -.
DR   GlyGen; P42704; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P42704; -.
DR   MetOSite; P42704; -.
DR   PhosphoSitePlus; P42704; -.
DR   SwissPalm; P42704; -.
DR   BioMuta; LRPPRC; -.
DR   DMDM; 156632706; -.
DR   EPD; P42704; -.
DR   jPOST; P42704; -.
DR   MassIVE; P42704; -.
DR   MaxQB; P42704; -.
DR   PaxDb; 9606-ENSP00000260665; -.
DR   PeptideAtlas; P42704; -.
DR   ProteomicsDB; 55547; -.
DR   Pumba; P42704; -.
DR   Antibodypedia; 47400; 208 antibodies from 29 providers.
DR   DNASU; 10128; -.
DR   Ensembl; ENST00000260665.12; ENSP00000260665.7; ENSG00000138095.20.
DR   GeneID; 10128; -.
DR   KEGG; hsa:10128; -.
DR   MANE-Select; ENST00000260665.12; ENSP00000260665.7; NM_133259.4; NP_573566.2.
DR   UCSC; uc002rtr.3; human.
DR   AGR; HGNC:15714; -.
DR   CTD; 10128; -.
DR   DisGeNET; 10128; -.
DR   GeneCards; LRPPRC; -.
DR   HGNC; HGNC:15714; LRPPRC.
DR   HPA; ENSG00000138095; Low tissue specificity.
DR   MalaCards; LRPPRC; -.
DR   MIM; 220111; phenotype.
DR   MIM; 607544; gene.
DR   neXtProt; NX_P42704; -.
DR   OpenTargets; ENSG00000138095; -.
DR   Orphanet; 70472; Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type.
DR   PharmGKB; PA30459; -.
DR   VEuPathDB; HostDB:ENSG00000138095; -.
DR   eggNOG; KOG4318; Eukaryota.
DR   GeneTree; ENSGT00960000186682; -.
DR   HOGENOM; CLU_006166_0_0_1; -.
DR   InParanoid; P42704; -.
DR   OMA; ASKQIWD; -.
DR   OrthoDB; 5479341at2759; -.
DR   PhylomeDB; P42704; -.
DR   TreeFam; TF323626; -.
DR   PathwayCommons; P42704; -.
DR   Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-HSA-611105; Respiratory electron transport.
DR   Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR   Reactome; R-HSA-9836573; Mitochondrial RNA degradation.
DR   SignaLink; P42704; -.
DR   BioGRID-ORCS; 10128; 434 hits in 1169 CRISPR screens.
DR   ChiTaRS; LRPPRC; human.
DR   GeneWiki; LRPPRC; -.
DR   GenomeRNAi; 10128; -.
DR   Pharos; P42704; Tbio.
DR   PRO; PR:P42704; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P42704; Protein.
DR   Bgee; ENSG00000138095; Expressed in skeletal muscle tissue of rectus abdominis and 220 other cell types or tissues.
DR   ExpressionAtlas; P42704; baseline and differential.
DR   GO; GO:0000794; C:condensed nuclear chromosome; IDA:HGNC-UCL.
DR   GO; GO:0005856; C:cytoskeleton; IDA:HGNC-UCL.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005640; C:nuclear outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:HGNC-UCL.
DR   GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR   GO; GO:0048487; F:beta-tubulin binding; IDA:HGNC-UCL.
DR   GO; GO:0008017; F:microtubule binding; TAS:HGNC-UCL.
DR   GO; GO:0003730; F:mRNA 3'-UTR binding; IBA:GO_Central.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0003697; F:single-stranded DNA binding; IEA:Ensembl.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0000957; P:mitochondrial RNA catabolic process; IEA:Ensembl.
DR   GO; GO:0047497; P:mitochondrion transport along microtubule; TAS:HGNC-UCL.
DR   GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR   GO; GO:0000961; P:negative regulation of mitochondrial RNA catabolic process; IEA:Ensembl.
DR   GO; GO:0070129; P:regulation of mitochondrial translation; IBA:GO_Central.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 4.
DR   InterPro; IPR033490; LRP130.
DR   InterPro; IPR002885; Pentatricopeptide_rpt.
DR   InterPro; IPR033443; PPR_long.
DR   InterPro; IPR011990; TPR-like_helical_dom_sf.
DR   NCBIfam; TIGR00756; PPR; 1.
DR   PANTHER; PTHR46669; LEUCINE-RICH PPR MOTIF-CONTAINING PROTEIN, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR46669:SF1; LEUCINE-RICH PPR MOTIF-CONTAINING PROTEIN, MITOCHONDRIAL; 1.
DR   Pfam; PF01535; PPR; 3.
DR   Pfam; PF13812; PPR_3; 1.
DR   Pfam; PF17177; PPR_long; 1.
DR   PROSITE; PS51375; PPR; 11.
DR   Genevisible; P42704; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Direct protein sequencing; Disease variant;
KW   DNA-binding; Leigh syndrome; Membrane; Mitochondrion; mRNA transport;
KW   Nucleus; Phosphoprotein; Primary mitochondrial disease; Reference proteome;
KW   Repeat; RNA-binding; Transcription; Transcription regulation;
KW   Transit peptide; Transport.
FT   TRANSIT         1..59
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           60..1394
FT                   /note="Leucine-rich PPR motif-containing protein,
FT                   mitochondrial"
FT                   /id="PRO_0000084467"
FT   REPEAT          126..160
FT                   /note="PPR 1"
FT   REPEAT          161..195
FT                   /note="PPR 2"
FT   REPEAT          196..230
FT                   /note="PPR 3"
FT   REPEAT          231..265
FT                   /note="PPR 4"
FT   REPEAT          266..300
FT                   /note="PPR 5"
FT   REPEAT          301..335
FT                   /note="PPR 6"
FT   REPEAT          403..437
FT                   /note="PPR 7"
FT   REPEAT          438..472
FT                   /note="PPR 8"
FT   REPEAT          678..709
FT                   /note="PPR 9"
FT   REPEAT          710..746
FT                   /note="PPR 10"
FT   REPEAT          747..784
FT                   /note="PPR 11"
FT   REPEAT          785..820
FT                   /note="PPR 12"
FT   REPEAT          821..856
FT                   /note="PPR 13"
FT   REPEAT          954..988
FT                   /note="PPR 14"
FT   REPEAT          1031..1065
FT                   /note="PPR 15"
FT   REPEAT          1066..1102
FT                   /note="PPR 16"
FT   REPEAT          1103..1137
FT                   /note="PPR 17"
FT   REPEAT          1138..1175
FT                   /note="PPR 18"
FT   REPEAT          1176..1210
FT                   /note="PPR 19"
FT   REPEAT          1317..1351
FT                   /note="PPR 20"
FT   REGION          1121..1394
FT                   /note="RNA-binding"
FT   MOD_RES         155
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         187
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         226
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PB66"
FT   MOD_RES         292
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         463
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PB66"
FT   MOD_RES         613
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         726
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         750
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         1026
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1027
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5SGE0"
FT   MOD_RES         1029
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1136
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1138
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         354
FT                   /note="A -> V (in MC4DN5; dbSNP:rs119466000)"
FT                   /evidence="ECO:0000269|PubMed:12529507"
FT                   /id="VAR_018656"
FT   VARIANT         478
FT                   /note="T -> A (in dbSNP:rs35035668)"
FT                   /id="VAR_052935"
FT   VARIANT         866
FT                   /note="Missing (in MC4DN5; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:26510951"
FT                   /id="VAR_075428"
FT   VARIANT         909
FT                   /note="Missing (in MC4DN5; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:26510951"
FT                   /id="VAR_075429"
FT   MUTAGEN         441
FT                   /note="Y->A: Reduces binding to EIF4E."
FT                   /evidence="ECO:0000269|PubMed:19262567"
FT   MUTAGEN         583
FT                   /note="Y->A: Reduces binding to EIF4E."
FT                   /evidence="ECO:0000269|PubMed:19262567"
FT   CONFLICT        54
FT                   /note="S -> G (in Ref. 2; BAF82705)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        296
FT                   /note="S -> F (in Ref. 5; AAA67549)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        528..531
FT                   /note="LKSN -> YFPI (in Ref. 4; AAH26034)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        556
FT                   /note="L -> V (in Ref. 5; AAA67549)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        583
FT                   /note="Y -> N (in Ref. 5; AAA67549)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        648
FT                   /note="S -> R (in Ref. 5; AAA67549)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        676
FT                   /note="Q -> R (in Ref. 2; BAC86287)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        702
FT                   /note="K -> R (in Ref. 2; BAC86287)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        750..752
FT                   /note="KYV -> NYL (in Ref. 5; AAA67549)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        769
FT                   /note="N -> K (in Ref. 5; AAA67549)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1192
FT                   /note="N -> D (in Ref. 2; BAC86287)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1394 AA;  157905 MW;  61AB0C8BF8A972E6 CRC64;
     MAALLRSARW LLRAGAAPRL PLSLRLLPGG PGRLHAASYL PAARAGPVAG GLLSPARLYA
     IAAKEKDIQE ESTFSSRKIS NQFDWALMRL DLSVRRTGRI PKKLLQKVFN DTCRSGGLGG
     SHALLLLRSC GSLLPELKLE ERTEFAHRIW DTLQKLGAVY DVSHYNALLK VYLQNEYKFS
     PTDFLAKMEE ANIQPNRVTY QRLIASYCNV GDIEGASKIL GFMKTKDLPV TEAVFSALVT
     GHARAGDMEN AENILTVMRD AGIEPGPDTY LALLNAYAEK GDIDHVKQTL EKVEKSELHL
     MDRDLLQIIF SFSKAGYPQY VSEILEKVTC ERRYIPDAMN LILLLVTEKL EDVALQILLA
     CPVSKEDGPS VFGSFFLQHC VTMNTPVEKL TDYCKKLKEV QMHSFPLQFT LHCALLANKT
     DLAKALMKAV KEEGFPIRPH YFWPLLVGRR KEKNVQGIIE ILKGMQELGV HPDQETYTDY
     VIPCFDSVNS ARAILQENGC LSDSDMFSQA GLRSEAANGN LDFVLSFLKS NTLPISLQSI
     RSSLLLGFRR SMNINLWSEI TELLYKDGRY CQEPRGPTEA VGYFLYNLID SMSDSEVQAK
     EEHLRQYFHQ LEKMNVKIPE NIYRGIRNLL ESYHVPELIK DAHLLVESKN LDFQKTVQLT
     SSELESTLET LKAENQPIRD VLKQLILVLC SEENMQKALE LKAKYESDMV TGGYAALINL
     CCRHDKVEDA LNLKEEFDRL DSSAVLDTGK YVGLVRVLAK HGKLQDAINI LKEMKEKDVL
     IKDTTALSFF HMLNGAALRG EIETVKQLHE AIVTLGLAEP STNISFPLVT VHLEKGDLST
     ALEVAIDCYE KYKVLPRIHD VLCKLVEKGE TDLIQKAMDF VSQEQGEMVM LYDLFFAFLQ
     TGNYKEAKKI IETPGIRARS ARLQWFCDRC VANNQVETLE KLVELTQKLF ECDRDQMYYN
     LLKLYKINGD WQRADAVWNK IQEENVIPRE KTLRLLAEIL REGNQEVPFD VPELWYEDEK
     HSLNSSSAST TEPDFQKDIL IACRLNQKKG AYDIFLNAKE QNIVFNAETY SNLIKLLMSE
     DYFTQAMEVK AFAETHIKGF TLNDAANSRL IITQVRRDYL KEAVTTLKTV LDQQQTPSRL
     AVTRVIQALA MKGDVENIEV VQKMLNGLED SIGLSKMVFI NNIALAQIKN NNIDAAIENI
     ENMLTSENKV IEPQYFGLAY LFRKVIEEQL EPAVEKISIM AERLANQFAI YKPVTDFFLQ
     LVDAGKVDDA RALLQRCGAI AEQTPILLLF LLRNSRKQGK ASTVKSVLEL IPELNEKEEA
     YNSLMKSYVS EKDVTSAKAL YEHLTAKNTK LDDLFLKRYA SLLKYAGEPV PFIEPPESFE
     FYAQQLRKLR ENSS
//