LYRM4_HUMAN
ID LYRM4_HUMAN Reviewed; 91 AA.
AC Q9HD34; A8K543; Q5XKP1;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=LYR motif-containing protein 4;
GN Name=LYRM4; Synonyms=C6orf149, ISD11; ORFNames=CGI-203;
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].
RX PubMed=11342225; DOI=10.1016/s0167-4781(00)00295-5;
RA Lai C.-H., Chiu J.-Y., Lin W.-C.;
RT "Identification of the human crooked neck gene by comparative gene
RT identification.";
RL Biochim. Biophys. Acta 1517:449-454(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Niu H.R., Ma K.T., Zhang N.H.;
RT "A gene cloned by one-hybrid system.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-11.
RC TISSUE=Pancreas;
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 PROTEIN SEQUENCE OF 45-58, FUNCTION, INTERACTION WITH FXN, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17331979; DOI=10.1093/hmg/ddm038;
RA Shan Y., Napoli E., Cortopassi G.;
RT "Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and
RT multiple mitochondrial chaperones.";
RL Hum. Mol. Genet. 16:929-941(2007).
RN [7]
RP INTERACTION WITH NFS1.
RX PubMed=18650437; DOI=10.1074/jbc.m804064200;
RA Marelja Z., Stoecklein W., Nimtz M., Leimkuehler S.;
RT "A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor
RT for MOCS3, a protein involved in molybdenum cofactor biosynthesis.";
RL J. Biol. Chem. 283:25178-25185(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NFS1.
RX PubMed=19454487; DOI=10.1093/hmg/ddp239;
RA Shi Y., Ghosh M.C., Tong W.H., Rouault T.A.;
RT "Human ISD11 is essential for both iron-sulfur cluster assembly and
RT maintenance of normal cellular iron homeostasis.";
RL Hum. Mol. Genet. 18:3014-3025(2009).
RN [9]
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 [10]
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 [11]
RP VARIANT COXPD19 LEU-68, AND CHARACTERIZATION OF VARIANT COXPD19 LEU-68.
RX PubMed=23814038; DOI=10.1093/hmg/ddt295;
RA Lim S.C., Friemel M., Marum J.E., Tucker E.J., Bruno D.L., Riley L.G.,
RA Christodoulou J., Kirk E.P., Boneh A., DeGennaro C.M., Springer M.,
RA Mootha V.K., Rouault T.A., Leimkuhler S., Thorburn D.R., Compton A.G.;
RT "Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11,
RT cause deficiency of multiple respiratory chain complexes.";
RL Hum. Mol. Genet. 22:4460-4473(2013).
CC -!- FUNCTION: Required for nuclear and mitochondrial iron-sulfur protein
CC biosynthesis. {ECO:0000269|PubMed:17331979,
CC ECO:0000269|PubMed:19454487}.
CC -!- PATHWAY: Cofactor biosynthesis; iron-sulfur cluster biosynthesis.
CC -!- SUBUNIT: Interacts with FXN. Interaction is increased by nickel.
CC Interaction is inhibited by calcium, magnesium, manganese, copper,
CC cobalt, zinc, and iron. Forms a complex with the cytosolic/nuclear form
CC of NFS1. The complex increased the stability of NFS1.
CC {ECO:0000269|PubMed:17331979, ECO:0000269|PubMed:18650437,
CC ECO:0000269|PubMed:19454487}.
CC -!- INTERACTION:
CC Q9HD34; Q9Y697: NFS1; NbExp=8; IntAct=EBI-3920810, EBI-1751791;
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Nucleus.
CC -!- TISSUE SPECIFICITY: Reduced mRNA levels in Friedreich ataxia patients.
CC {ECO:0000269|PubMed:17331979}.
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 19 (COXPD19)
CC [MIM:615595]: A mitochondrial disorder characterized by respiratory
CC distress, hypotonia, and severe lactic acidosis in the newborn period.
CC Other features include gastroesophageal reflux and elevated liver
CC enzymes with normal synthetic function. {ECO:0000269|PubMed:23814038}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Reduction of LYRM4 levels by siRNA increases the total
CC iron content, and reduces cytosolic and mitochondrial aconitase
CC activities and NFS1 protein levels.
CC -!- SIMILARITY: Belongs to the complex I LYR family. {ECO:0000305}.
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DR EMBL; AF285118; AAG01155.1; -; mRNA.
DR EMBL; AF170070; AAF25797.1; -; mRNA.
DR EMBL; AK291158; BAF83847.1; -; mRNA.
DR EMBL; AL035653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121978; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162381; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009552; AAH09552.1; -; mRNA.
DR CCDS; CCDS4493.1; -.
DR RefSeq; NP_001158313.1; NM_001164841.2.
DR RefSeq; NP_065141.3; NM_020408.5.
DR PDB; 5USR; X-ray; 3.09 A; B/D/F/H=1-91.
DR PDB; 5WGB; X-ray; 2.75 A; B=1-91.
DR PDB; 5WKP; X-ray; 3.15 A; B/F=1-91.
DR PDB; 5WLW; X-ray; 3.32 A; B/F=1-91.
DR PDB; 6NZU; EM; 3.20 A; B/F=1-91.
DR PDB; 6ODD; X-ray; 2.00 A; B=5-78.
DR PDB; 6UXE; X-ray; 1.57 A; B=1-91.
DR PDB; 6W1D; X-ray; 1.79 A; B=1-91.
DR PDB; 6WI2; X-ray; 1.95 A; B=1-91.
DR PDB; 6WIH; X-ray; 1.90 A; B=1-91.
DR PDB; 7RTK; X-ray; 2.50 A; B=1-91.
DR PDBsum; 5USR; -.
DR PDBsum; 5WGB; -.
DR PDBsum; 5WKP; -.
DR PDBsum; 5WLW; -.
DR PDBsum; 6NZU; -.
DR PDBsum; 6ODD; -.
DR PDBsum; 6UXE; -.
DR PDBsum; 6W1D; -.
DR PDBsum; 6WI2; -.
DR PDBsum; 6WIH; -.
DR PDBsum; 7RTK; -.
DR AlphaFoldDB; Q9HD34; -.
DR SASBDB; Q9HD34; -.
DR SMR; Q9HD34; -.
DR BioGRID; 121391; 65.
DR ComplexPortal; CPX-5641; Mitochondrial NIAUFX iron-sulfur cluster assembly complex.
DR CORUM; Q9HD34; -.
DR IntAct; Q9HD34; 31.
DR STRING; 9606.ENSP00000420026; -.
DR iPTMnet; Q9HD34; -.
DR PhosphoSitePlus; Q9HD34; -.
DR BioMuta; LYRM4; -.
DR DMDM; 46576652; -.
DR EPD; Q9HD34; -.
DR jPOST; Q9HD34; -.
DR MassIVE; Q9HD34; -.
DR MaxQB; Q9HD34; -.
DR PaxDb; Q9HD34; -.
DR PeptideAtlas; Q9HD34; -.
DR PRIDE; Q9HD34; -.
DR ProteomicsDB; 81823; -.
DR TopDownProteomics; Q9HD34; -.
DR Antibodypedia; 24549; 93 antibodies from 16 providers.
DR DNASU; 57128; -.
DR Ensembl; ENST00000330636.9; ENSP00000418787.1; ENSG00000214113.11.
DR GeneID; 57128; -.
DR KEGG; hsa:57128; -.
DR MANE-Select; ENST00000330636.9; ENSP00000418787.1; NM_020408.6; NP_065141.3.
DR UCSC; uc003mwp.5; human.
DR CTD; 57128; -.
DR DisGeNET; 57128; -.
DR GeneCards; LYRM4; -.
DR HGNC; HGNC:21365; LYRM4.
DR HPA; ENSG00000214113; Low tissue specificity.
DR MalaCards; LYRM4; -.
DR MIM; 613311; gene.
DR MIM; 615595; phenotype.
DR neXtProt; NX_Q9HD34; -.
DR OpenTargets; ENSG00000214113; -.
DR Orphanet; 397593; Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency.
DR PharmGKB; PA162394762; -.
DR VEuPathDB; HostDB:ENSG00000214113; -.
DR eggNOG; KOG3801; Eukaryota.
DR GeneTree; ENSGT00940000157289; -.
DR InParanoid; Q9HD34; -.
DR OMA; AYNYRMY; -.
DR OrthoDB; 1561410at2759; -.
DR PhylomeDB; Q9HD34; -.
DR PathwayCommons; Q9HD34; -.
DR Reactome; R-HSA-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR SignaLink; Q9HD34; -.
DR SIGNOR; Q9HD34; -.
DR UniPathway; UPA00266; -.
DR BioGRID-ORCS; 57128; 678 hits in 1095 CRISPR screens.
DR ChiTaRS; LYRM4; human.
DR GenomeRNAi; 57128; -.
DR Pharos; Q9HD34; Tbio.
DR PRO; PR:Q9HD34; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9HD34; protein.
DR Bgee; ENSG00000214113; Expressed in cartilage tissue and 189 other tissues.
DR ExpressionAtlas; Q9HD34; baseline and differential.
DR Genevisible; Q9HD34; HS.
DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; IC:ComplexPortal.
DR GO; GO:1990221; C:L-cysteine desulfurase complex; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IBA:GO_Central.
DR CDD; cd20264; Complex1_LYR_LYRM4; 1.
DR InterPro; IPR008011; Complex1_LYR_dom.
DR InterPro; IPR045297; Complex1_LYR_LYRM4.
DR Pfam; PF05347; Complex1_LYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disease variant; Mitochondrion;
KW Nucleus; Primary mitochondrial disease; Reference proteome.
FT CHAIN 1..91
FT /note="LYR motif-containing protein 4"
FT /id="PRO_0000174308"
FT MOD_RES 47
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K215"
FT VARIANT 11
FT /note="S -> A (in dbSNP:rs2224391)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_024551"
FT VARIANT 68
FT /note="R -> L (in COXPD19; can form a normal complex with
FT NFS1 but the desulfurase enzymatic activity of this complex
FT is severely decreased compared to control;
FT dbSNP:rs587777218)"
FT /evidence="ECO:0000269|PubMed:23814038"
FT /id="VAR_070943"
FT HELIX 5..20
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 26..42
FT /evidence="ECO:0007829|PDB:6UXE"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 49..75
FT /evidence="ECO:0007829|PDB:6UXE"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:6UXE"
SQ SEQUENCE 91 AA; 10758 MW; F0C5919CA701F3F3 CRC64;
MAASSRAQVL SLYRAMLRES KRFSAYNYRT YAVRRIRDAF RENKNVKDPV EIQTLVNKAK
RDLGVIRRQV HIGQLYSTDK LIIENRDMPR T
