TIM50_HUMAN
ID TIM50_HUMAN Reviewed; 353 AA.
AC Q3ZCQ8; Q330K1; Q6QA00; Q96FJ5; Q96GY2; Q9H370;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Mitochondrial import inner membrane translocase subunit TIM50;
DE Flags: Precursor;
GN Name=TIMM50; Synonyms=TIM50; ORFNames=PRO1512;
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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND INTERACTION WITH TIMM23.
RX PubMed=15044455; DOI=10.1074/jbc.m402049200;
RA Guo Y., Cheong N., Zhang Z., De Rose R., Deng Y., Farber S.A.,
RA Fernandes-Alnemri T., Alnemri E.S.;
RT "Tim50, a component of the mitochondrial translocator, regulates
RT mitochondrial integrity and cell death.";
RL J. Biol. Chem. 279:24813-24825(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Zheng H., Xie Y., Mao Y.;
RT "Cloning of a novel splice variant of TIM50L.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND PARTIAL
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, Eye, and 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-353.
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Bi J., Zhou G., Dong C., Zai Y., Xu W.,
RA Gao F., Liu M., He F.;
RT "Functional prediction of the coding sequences of 75 new genes deduced by
RT analysis of cDNA clones from human fetal liver.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 98-113; 275-284; 285-295 AND 335-345, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 98-113, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORM 2), RNA-BINDING
RP (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), TISSUE SPECIFICITY, AND
RP INTERACTION WITH COIL.
RX PubMed=16008839; DOI=10.1186/1471-2121-6-29;
RA Xu H., Somers Z.B., Robinson M.L. II, Hebert M.D.;
RT "Tim50a, a nuclear isoform of the mitochondrial Tim50, interacts with
RT proteins involved in snRNP biogenesis.";
RL BMC Cell Biol. 6:29-29(2005).
RN [10]
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 [11]
RP INTERACTION WITH DNAJC15.
RX PubMed=23263864; DOI=10.1093/hmg/dds541;
RA Schusdziarra C., Blamowska M., Azem A., Hell K.;
RT "Methylation-controlled J-protein MCJ acts in the import of proteins into
RT human mitochondria.";
RL Hum. Mol. Genet. 22:1348-1357(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45 AND SER-341, AND
RP 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 [13]
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 [14]
RP INVOLVEMENT IN MGCA9, AND VARIANTS MGCA9 TRP-114 AND MET-149.
RX PubMed=27573165; DOI=10.1111/cge.12855;
RG NISC Intramural Sequencing;
RA Shahrour M.A., Staretz-Chacham O., Dayan D., Stephen J., Weech A.,
RA Damseh N., Pri Chen H., Edvardson S., Mazaheri S., Saada A.,
RA Hershkovitz E., Shaag A., Huizing M., Abu-Libdeh B., Gahl W.A., Azem A.,
RA Anikster Y., Vilboux T., Elpeleg O., Malicdan M.C.;
RT "Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and
RT variable complex V deficiency associated with TIMM50 mutations.";
RL Clin. Genet. 91:690-696(2017).
CC -!- FUNCTION: Essential component of the TIM23 complex, a complex that
CC mediates the translocation of transit peptide-containing proteins
CC across the mitochondrial inner membrane. Has some phosphatase activity
CC in vitro; however such activity may not be relevant in vivo.
CC {ECO:0000269|PubMed:15044455}.
CC -!- FUNCTION: [Isoform 2]: May participate in the release of snRNPs and SMN
CC from the Cajal body. {ECO:0000269|PubMed:16008839}.
CC -!- SUBUNIT: Component of the TIM23 complex at least composed of TIMM23,
CC TIMM17 (TIMM17A or TIMM17B) and TIMM50; within this complex, directly
CC interacts with TIMM23 (PubMed:15044455). The complex interacts with the
CC TIMM44 component of the PAM complex and with DNAJC15 (PubMed:23263864).
CC {ECO:0000269|PubMed:15044455, ECO:0000269|PubMed:23263864}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with COIL and snRNPs (PubMed:16008839).
CC {ECO:0000269|PubMed:16008839}.
CC -!- INTERACTION:
CC Q3ZCQ8; P10398: ARAF; NbExp=4; IntAct=EBI-355175, EBI-365961;
CC Q3ZCQ8; P04049: RAF1; NbExp=6; IntAct=EBI-355175, EBI-365996;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:15044455}; Single-pass membrane protein
CC {ECO:0000269|PubMed:15044455}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus speckle
CC {ECO:0000269|PubMed:16008839}. Note=Nuclear and enriched in speckles
CC with snRNPs. {ECO:0000269|PubMed:16008839}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3ZCQ8-1; Sequence=Displayed;
CC Name=2; Synonyms=Tim50a;
CC IsoId=Q3ZCQ8-2; Sequence=VSP_016389;
CC Name=3;
CC IsoId=Q3ZCQ8-3; Sequence=VSP_047682, VSP_047683;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in
CC brain, kidney and liver (at protein level).
CC {ECO:0000269|PubMed:15044455, ECO:0000269|PubMed:16008839}.
CC -!- DOMAIN: The FCP1 homology domain does not contain the canonical D-x-D-
CC x-[TV] active site, suggesting that it probably does not display
CC phosphatase activity in vivo.
CC -!- DISEASE: 3-methylglutaconic aciduria 9 (MGCA9) [MIM:617698]: An
CC autosomal recessive disease characterized by early-onset seizures,
CC severely delayed psychomotor development and intellectual disability.
CC Patients have hypotonia or spasticity, and laboratory investigations
CC show increased serum lactate and 3-methylglutaconic aciduria.
CC {ECO:0000269|PubMed:27573165}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TIM50 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG35534.1; Type=Miscellaneous discrepancy; Note=Chimera.; 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; AY551341; AAT01208.1; -; mRNA.
DR EMBL; AY444561; AAS68537.1; -; mRNA.
DR EMBL; AC011500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009072; AAH09072.1; -; mRNA.
DR EMBL; BC010736; AAH10736.1; -; mRNA.
DR EMBL; BC050082; AAH50082.1; -; mRNA.
DR EMBL; BC121146; AAI21147.1; -; mRNA.
DR EMBL; AF130109; AAG35534.1; ALT_SEQ; mRNA.
DR CCDS; CCDS33023.1; -. [Q3ZCQ8-1]
DR RefSeq; NP_001001563.1; NM_001001563.3. [Q3ZCQ8-1]
DR RefSeq; NP_001316488.1; NM_001329559.1. [Q3ZCQ8-3]
DR AlphaFoldDB; Q3ZCQ8; -.
DR SMR; Q3ZCQ8; -.
DR BioGRID; 124961; 225.
DR ComplexPortal; CPX-6129; TIM23 mitochondrial inner membrane pre-sequence translocase complex, TIM17A variant.
DR ComplexPortal; CPX-6130; TIM23 mitochondrial inner membrane pre-sequence translocase complex, TIM17B variant.
DR CORUM; Q3ZCQ8; -.
DR DIP; DIP-34058N; -.
DR IntAct; Q3ZCQ8; 106.
DR MINT; Q3ZCQ8; -.
DR STRING; 9606.ENSP00000445806; -.
DR ChEMBL; CHEMBL4295842; -.
DR DEPOD; TIMM50; -.
DR iPTMnet; Q3ZCQ8; -.
DR PhosphoSitePlus; Q3ZCQ8; -.
DR SwissPalm; Q3ZCQ8; -.
DR BioMuta; TIMM50; -.
DR DMDM; 83305924; -.
DR EPD; Q3ZCQ8; -.
DR jPOST; Q3ZCQ8; -.
DR MassIVE; Q3ZCQ8; -.
DR MaxQB; Q3ZCQ8; -.
DR PaxDb; Q3ZCQ8; -.
DR PeptideAtlas; Q3ZCQ8; -.
DR PRIDE; Q3ZCQ8; -.
DR ProteomicsDB; 61635; -.
DR ProteomicsDB; 61909; -. [Q3ZCQ8-1]
DR ProteomicsDB; 61910; -. [Q3ZCQ8-2]
DR TopDownProteomics; Q3ZCQ8-1; -. [Q3ZCQ8-1]
DR TopDownProteomics; Q3ZCQ8-2; -. [Q3ZCQ8-2]
DR Antibodypedia; 30377; 187 antibodies from 32 providers.
DR DNASU; 92609; -.
DR Ensembl; ENST00000544017.5; ENSP00000445806.2; ENSG00000105197.11. [Q3ZCQ8-2]
DR Ensembl; ENST00000607714.6; ENSP00000475531.1; ENSG00000105197.11. [Q3ZCQ8-1]
DR GeneID; 92609; -.
DR KEGG; hsa:92609; -.
DR MANE-Select; ENST00000607714.6; ENSP00000475531.1; NM_001001563.5; NP_001001563.2.
DR UCSC; uc002olu.1; human. [Q3ZCQ8-1]
DR CTD; 92609; -.
DR DisGeNET; 92609; -.
DR GeneCards; TIMM50; -.
DR HGNC; HGNC:23656; TIMM50.
DR HPA; ENSG00000105197; Low tissue specificity.
DR MalaCards; TIMM50; -.
DR MIM; 607381; gene.
DR MIM; 617698; phenotype.
DR neXtProt; NX_Q3ZCQ8; -.
DR OpenTargets; ENSG00000105197; -.
DR Orphanet; 505216; 3-methylglutaconic aciduria type 9.
DR PharmGKB; PA134902846; -.
DR VEuPathDB; HostDB:ENSG00000105197; -.
DR eggNOG; KOG2832; Eukaryota.
DR GeneTree; ENSGT01040000240503; -.
DR HOGENOM; CLU_048293_1_1_1; -.
DR InParanoid; Q3ZCQ8; -.
DR PhylomeDB; Q3ZCQ8; -.
DR TreeFam; TF106198; -.
DR PathwayCommons; Q3ZCQ8; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR SignaLink; Q3ZCQ8; -.
DR SIGNOR; Q3ZCQ8; -.
DR BioGRID-ORCS; 92609; 106 hits in 1094 CRISPR screens.
DR ChiTaRS; TIMM50; human.
DR GeneWiki; TIMM50; -.
DR GenomeRNAi; 92609; -.
DR Pharos; Q3ZCQ8; Tbio.
DR PRO; PR:Q3ZCQ8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q3ZCQ8; protein.
DR Bgee; ENSG00000105197; Expressed in left testis and 173 other tissues.
DR ExpressionAtlas; Q3ZCQ8; baseline and differential.
DR Genevisible; Q3ZCQ8; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005744; C:TIM23 mitochondrial import inner membrane translocase complex; IPI:UniProtKB.
DR GO; GO:0005134; F:interleukin-2 receptor binding; IDA:MGI.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:MGI.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006886; P:intracellular protein transport; IC:ComplexPortal.
DR GO; GO:0007006; P:mitochondrial membrane organization; IMP:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0030150; P:protein import into mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:MGI.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR004274; FCP1_dom.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR027111; Tim50.
DR PANTHER; PTHR12210:SF3; PTHR12210:SF3; 1.
DR Pfam; PF03031; NIF; 1.
DR SMART; SM00577; CPDc; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR PROSITE; PS50969; FCP1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disease variant; Epilepsy;
KW Intellectual disability; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; RNA-binding; Transit peptide; Translocation;
KW Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..44
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 45..353
FT /note="Mitochondrial import inner membrane translocase
FT subunit TIM50"
FT /id="PRO_0000043115"
FT TOPO_DOM 45..65
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 66..86
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 87..353
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT DOMAIN 143..286
FT /note="FCP1 homology"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00336"
FT REGION 25..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..11
FT /note="MAASAAVFSRL -> MVPRFLMSSTM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_047682"
FT VAR_SEQ 1
FT /note="M -> MASALSLGNKCDPFLRCVLCRGGGALQGPRGRGPDDFESQLSPPGSA
FT RRLVRSKRACGNPPDAFGLSRASVHPPLPRVSIGCSSGPGRAKRERVGGAAWRQRKM
FT (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_016389"
FT VAR_SEQ 12..124
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_047683"
FT VARIANT 114
FT /note="R -> W (in MGCA9; unknown pathological significance;
FT dbSNP:rs1300848445)"
FT /evidence="ECO:0000269|PubMed:27573165"
FT /id="VAR_078568"
FT VARIANT 149
FT /note="T -> M (in MGCA9; unknown pathological significance;
FT dbSNP:rs1244226820)"
FT /evidence="ECO:0000269|PubMed:27573165"
FT /id="VAR_078569"
SQ SEQUENCE 353 AA; 39646 MW; 524EB9989BBF6988 CRC64;
MAASAAVFSR LRSGLRLGSR GLCTRLATPP RRAPDQAAEI GSRGSTKAQG PQQQPGSEGP
SYAKKVALWL AGLLGAGGTV SVVYIFGNNP VDENGAKIPD EFDNDPILVQ QLRRTYKYFK
DYRQMIIEPT SPCLLPDPLQ EPYYQPPYTL VLELTGVLLH PEWSLATGWR FKKRPGIETL
FQQLAPLYEI VIFTSETGMT AFPLIDSVDP HGFISYRLFR DATRYMDGHH VKDISCLNRD
PARVVVVDCK KEAFRLQPYN GVALRPWDGN SDDRVLLDLS AFLKTIALNG VEDVRTVLEH
YALEDDPLAA FKQRQSRLEQ EEQQRLAELS KSNKQNLFLG SLTSRLWPRS KQP
