NUBPL_HUMAN
ID NUBPL_HUMAN Reviewed; 319 AA.
AC Q8TB37; B4DHZ1; Q86TZ4; Q9H9M2;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Iron-sulfur protein NUBPL;
DE AltName: Full=IND1 homolog;
DE AltName: Full=Nucleotide-binding protein-like;
DE AltName: Full=huInd1;
DE Flags: Precursor;
GN Name=NUBPL; Synonyms=C14orf127;
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] (ISOFORM 2).
RC TISSUE=Neuroblastoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma, 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].
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] OF 8-319 (ISOFORM 1), AND VARIANT
RP THR-198.
RC TISSUE=Prostatic adenocarcinoma;
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 FUNCTION, IRON-SULFUR CLUSTER-BINDING, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF CYS-244 AND CYS-247.
RX PubMed=19752196; DOI=10.1128/mcb.00817-09;
RA Sheftel A.D., Stehling O., Pierik A.J., Netz D.J., Kerscher S.,
RA Elsasser H.P., Wittig I., Balk J., Brandt U., Lill R.;
RT "Human ind1, an iron-sulfur cluster assembly factor for respiratory complex
RT I.";
RL Mol. Cell. Biol. 29:6059-6073(2009).
RN [6]
RP INVOLVEMENT IN MC1DN21, AND VARIANT ARG-56.
RX PubMed=20818383; DOI=10.1038/ng.659;
RA Calvo S.E., Tucker E.J., Compton A.G., Kirby D.M., Crawford G., Burtt N.P.,
RA Rivas M., Guiducci C., Bruno D.L., Goldberger O.A., Redman M.C.,
RA Wiltshire E., Wilson C.J., Altshuler D., Gabriel S.B., Daly M.J.,
RA Thorburn D.R., Mootha V.K.;
RT "High-throughput, pooled sequencing identifies mutations in NUBPL and
RT FOXRED1 in human complex I deficiency.";
RL Nat. Genet. 42:851-858(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 CHARACTERIZATION OF VARIANT ARG-56.
RX PubMed=22072591; DOI=10.1002/humu.21654;
RA Tucker E.J., Mimaki M., Compton A.G., McKenzie M., Ryan M.T.,
RA Thorburn D.R.;
RT "Next generation sequencing in molecular diagnosis: NUBPL mutations
RT highlight the challenges of variant detection and interpretation.";
RL Hum. Mutat. 33:411-418(2012).
RN [9]
RP VARIANTS MC1DN21 TYR-105 AND PHE-193, AND VARIANT ARG-56.
RX PubMed=23553477; DOI=10.1212/wnl.0b013e31828f1914;
RA Kevelam S.H., Rodenburg R.J., Wolf N.I., Ferreira P., Lunsing R.J.,
RA Nijtmans L.G., Mitchell A., Arroyo H.A., Rating D., Vanderver A.,
RA van Berkel C.G., Abbink T.E., Heutink P., van der Knaap M.S.;
RT "NUBPL mutations in patients with complex I deficiency and a distinct MRI
RT pattern.";
RL Neurology 80:1577-1583(2013).
CC -!- FUNCTION: Required for the assembly of the mitochondrial membrane
CC respiratory chain NADH dehydrogenase (Complex I). May deliver of one or
CC more Fe-S clusters to complex I subunits.
CC {ECO:0000269|PubMed:19752196}.
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Note=Binds 1 [4Fe-4S] cluster.;
CC -!- INTERACTION:
CC Q8TB37; Q8N371-3: KDM8; NbExp=3; IntAct=EBI-12852610, EBI-12161375;
CC Q8TB37; Q9Y5Y2: NUBP2; NbExp=6; IntAct=EBI-12852610, EBI-1048886;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19752196}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TB37-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TB37-2; Sequence=VSP_020985, VSP_008797;
CC -!- TISSUE SPECIFICITY: Highest expression in liver and kidney. expressed
CC at significant levels in small intestine and brain (at protein level).
CC {ECO:0000269|PubMed:19752196}.
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 21 (MC1DN21)
CC [MIM:618242]: A form of mitochondrial complex I deficiency, the most
CC common biochemical signature of mitochondrial disorders, a group of
CC highly heterogeneous conditions characterized by defective oxidative
CC phosphorylation, which collectively affects 1 in 5-10000 live births.
CC Clinical disorders have variable severity, ranging from lethal neonatal
CC disease to adult-onset neurodegenerative disorders. Phenotypes include
CC macrocephaly with progressive leukodystrophy, non-specific
CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh
CC syndrome, Leber hereditary optic neuropathy, and some forms of
CC Parkinson disease. MC1DN21 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:20818383,
CC ECO:0000269|PubMed:23553477}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to exon skipping. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the Mrp/NBP35 ATP-binding proteins family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH24919.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14203.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD62349.1; 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; BX248028; CAD62349.1; ALT_INIT; mRNA.
DR EMBL; AK022722; BAB14203.1; ALT_INIT; mRNA.
DR EMBL; AK295326; BAG58303.1; -; mRNA.
DR EMBL; AK316445; BAH14816.1; -; mRNA.
DR EMBL; CH471078; EAW65942.1; -; Genomic_DNA.
DR EMBL; BC024919; AAH24919.1; ALT_INIT; mRNA.
DR CCDS; CCDS41940.1; -. [Q8TB37-1]
DR RefSeq; NP_001188502.1; NM_001201573.1.
DR RefSeq; NP_079428.2; NM_025152.2. [Q8TB37-1]
DR AlphaFoldDB; Q8TB37; -.
DR SMR; Q8TB37; -.
DR BioGRID; 123190; 80.
DR IntAct; Q8TB37; 11.
DR STRING; 9606.ENSP00000281081; -.
DR iPTMnet; Q8TB37; -.
DR PhosphoSitePlus; Q8TB37; -.
DR BioMuta; NUBPL; -.
DR DMDM; 116242683; -.
DR EPD; Q8TB37; -.
DR jPOST; Q8TB37; -.
DR MassIVE; Q8TB37; -.
DR MaxQB; Q8TB37; -.
DR PaxDb; Q8TB37; -.
DR PeptideAtlas; Q8TB37; -.
DR PRIDE; Q8TB37; -.
DR ProteomicsDB; 73958; -. [Q8TB37-1]
DR ProteomicsDB; 73959; -. [Q8TB37-2]
DR Antibodypedia; 23093; 264 antibodies from 23 providers.
DR DNASU; 80224; -.
DR Ensembl; ENST00000281081.12; ENSP00000281081.7; ENSG00000151413.17. [Q8TB37-1]
DR Ensembl; ENST00000547839.5; ENSP00000449918.1; ENSG00000151413.17. [Q8TB37-2]
DR GeneID; 80224; -.
DR KEGG; hsa:80224; -.
DR MANE-Select; ENST00000281081.12; ENSP00000281081.7; NM_025152.3; NP_079428.2.
DR UCSC; uc059apb.1; human. [Q8TB37-1]
DR CTD; 80224; -.
DR DisGeNET; 80224; -.
DR GeneCards; NUBPL; -.
DR HGNC; HGNC:20278; NUBPL.
DR HPA; ENSG00000151413; Low tissue specificity.
DR MalaCards; NUBPL; -.
DR MIM; 613621; gene.
DR MIM; 618242; phenotype.
DR neXtProt; NX_Q8TB37; -.
DR OpenTargets; ENSG00000151413; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR PharmGKB; PA134907818; -.
DR VEuPathDB; HostDB:ENSG00000151413; -.
DR eggNOG; KOG3022; Eukaryota.
DR GeneTree; ENSGT00950000183193; -.
DR HOGENOM; CLU_024839_0_2_1; -.
DR InParanoid; Q8TB37; -.
DR OMA; NMAYFTP; -.
DR PhylomeDB; Q8TB37; -.
DR TreeFam; TF323196; -.
DR PathwayCommons; Q8TB37; -.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; Q8TB37; -.
DR BioGRID-ORCS; 80224; 111 hits in 1082 CRISPR screens.
DR ChiTaRS; NUBPL; human.
DR GenomeRNAi; 80224; -.
DR Pharos; Q8TB37; Tbio.
DR PRO; PR:Q8TB37; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8TB37; protein.
DR Bgee; ENSG00000151413; Expressed in calcaneal tendon and 187 other tissues.
DR ExpressionAtlas; Q8TB37; baseline and differential.
DR Genevisible; Q8TB37; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0140663; F:ATP-dependent FeS chaperone activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IBA:GO_Central.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_02040; Mrp_NBP35; 1.
DR InterPro; IPR019591; Mrp/NBP35_ATP-bd.
DR InterPro; IPR000808; Mrp_CS.
DR InterPro; IPR044304; NUBPL-like.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR033756; YlxH/NBP35.
DR PANTHER; PTHR42961; PTHR42961; 1.
DR Pfam; PF10609; ParA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS01215; MRP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Disease variant; Iron; Iron-sulfur;
KW Metal-binding; Mitochondrion; Nucleotide-binding;
KW Primary mitochondrial disease; Reference proteome; Transit peptide.
FT TRANSIT 1..38
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 39..319
FT /note="Iron-sulfur protein NUBPL"
FT /id="PRO_0000184950"
FT BINDING 75..82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT VAR_SEQ 173
FT /note="D -> L (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_020985"
FT VAR_SEQ 174..319
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_008797"
FT VARIANT 56
FT /note="G -> R (rare variant found in a patient with
FT mitochondrial complex I deficiency; unknown pathological
FT significance; found in association with a nucleotide
FT transition causing exon skipping; does not affect protein
FT stability, processing and import in the mitochondrion; can
FT restore complex I activity when overexpressed in patient
FT fibroblasts; dbSNP:rs200401432)"
FT /evidence="ECO:0000269|PubMed:20818383,
FT ECO:0000269|PubMed:22072591, ECO:0000269|PubMed:23553477"
FT /id="VAR_064570"
FT VARIANT 105
FT /note="D -> Y (in MC1DN21; dbSNP:rs397515440)"
FT /evidence="ECO:0000269|PubMed:23553477"
FT /id="VAR_069767"
FT VARIANT 193
FT /note="L -> F (in MC1DN21; dbSNP:rs552722349)"
FT /evidence="ECO:0000269|PubMed:23553477"
FT /id="VAR_069768"
FT VARIANT 198
FT /note="N -> T (in dbSNP:rs11558436)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027895"
FT MUTAGEN 244
FT /note="C->A: Defect in complex I assembly; when associated
FT with A-247."
FT /evidence="ECO:0000269|PubMed:19752196"
FT MUTAGEN 247
FT /note="C->A: Defect in complex I assembly; when associated
FT with A-244."
FT /evidence="ECO:0000269|PubMed:19752196"
SQ SEQUENCE 319 AA; 34083 MW; 7A497482A4D449A4 CRC64;
MGIWQRLLLF GGVSLRAGGG ATAPLGGSRA MVCGRQLSGA GSETLKQRRT QIMSRGLPKQ
KPIEGVKQVI VVASGKGGVG KSTTAVNLAL ALAANDSSKA IGLLDVDVYG PSVPKMMNLK
GNPELSQSNL MRPLLNYGIA CMSMGFLVEE SEPVVWRGLM VMSAIEKLLR QVDWGQLDYL
VVDMPPGTGD VQLSVSQNIP ITGAVIVSTP QDIALMDAHK GAEMFRRVHV PVLGLVQNMS
VFQCPKCKHK THIFGADGAR KLAQTLGLEV LGDIPLHLNI REASDTGQPI VFSQPESDEA
KAYLRIAVEV VRRLPSPSE
