TIM44_MOUSE
ID TIM44_MOUSE Reviewed; 452 AA.
AC O35857; Q2NLC5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Mitochondrial import inner membrane translocase subunit TIM44;
DE Flags: Precursor;
GN Name=Timm44; Synonyms=Mimt44, Tim44;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RC STRAIN=CD-1; TISSUE=Kidney;
RX PubMed=9419343; DOI=10.1073/pnas.95.1.144;
RA Wada J., Kanwar Y.S.;
RT "Characterization of mammalian translocase of inner mitochondrial membrane
RT (Tim44) isolated from diabetic newborn mouse kidney.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:144-149(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary tumor;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-177 AND LYS-217, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP FUNCTION, INTERACTION WITH TIMM23; SLC25A4 AND SLC25A5, AND MUTAGENESIS OF
RP LYS-282.
RX PubMed=31618756; DOI=10.1038/s41586-019-1667-4;
RA Hoshino A., Wang W.J., Wada S., McDermott-Roe C., Evans C.S., Gosis B.,
RA Morley M.P., Rathi K.S., Li J., Li K., Yang S., McManus M.J., Bowman C.,
RA Potluri P., Levin M., Damrauer S., Wallace D.C., Holzbaur E.L.F., Arany Z.;
RT "The ADP/ATP translocase drives mitophagy independent of nucleotide
RT exchange.";
RL Nature 575:375-379(2019).
CC -!- FUNCTION: Essential component of the PAM complex, a complex required
CC for the translocation of transit peptide-containing proteins from the
CC inner membrane into the mitochondrial matrix in an ATP-dependent manner
CC (PubMed:31618756). Recruits mitochondrial HSP70 to drive protein
CC translocation into the matrix using ATP as an energy source (By
CC similarity). {ECO:0000250|UniProtKB:Q01852,
CC ECO:0000269|PubMed:31618756}.
CC -!- SUBUNIT: Probable component of the PAM complex at least composed of a
CC mitochondrial HSP70 protein, GRPEL1 or GRPEL2, TIMM44, TIMM16/PAM16 and
CC TIMM14/DNAJC19 (By similarity). The complex interacts with the TIMM23
CC component of the TIM23 complex (PubMed:31618756). Interacts with
CC SLC25A4/ANT1 and SLC25A5/ANT2; leading to inhibit the presequence
CC translocase TIMM23, thereby promoting stabilization of PINK1
CC (PubMed:31618756). {ECO:0000250|UniProtKB:Q01852,
CC ECO:0000269|PubMed:31618756}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:9419343}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9419343}; Matrix side {ECO:0000269|PubMed:9419343}.
CC -!- SIMILARITY: Belongs to the Tim44 family. {ECO:0000305}.
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DR EMBL; U69898; AAB97624.1; -; mRNA.
DR EMBL; CH466566; EDL21992.1; -; Genomic_DNA.
DR EMBL; BC110677; AAI10678.1; -; mRNA.
DR EMBL; BC117523; AAI17524.1; -; mRNA.
DR EMBL; BC117524; AAI17525.1; -; mRNA.
DR CCDS; CCDS22083.1; -.
DR RefSeq; NP_035722.2; NM_011592.2.
DR AlphaFoldDB; O35857; -.
DR SMR; O35857; -.
DR BioGRID; 204201; 40.
DR IntAct; O35857; 2.
DR MINT; O35857; -.
DR STRING; 10090.ENSMUSP00000003029; -.
DR iPTMnet; O35857; -.
DR PhosphoSitePlus; O35857; -.
DR SwissPalm; O35857; -.
DR REPRODUCTION-2DPAGE; O35857; -.
DR EPD; O35857; -.
DR jPOST; O35857; -.
DR MaxQB; O35857; -.
DR PaxDb; O35857; -.
DR PeptideAtlas; O35857; -.
DR PRIDE; O35857; -.
DR ProteomicsDB; 259508; -.
DR Antibodypedia; 24720; 62 antibodies from 21 providers.
DR DNASU; 21856; -.
DR Ensembl; ENSMUST00000003029; ENSMUSP00000003029; ENSMUSG00000002949.
DR GeneID; 21856; -.
DR KEGG; mmu:21856; -.
DR UCSC; uc009ktq.2; mouse.
DR CTD; 10469; -.
DR MGI; MGI:1343262; Timm44.
DR VEuPathDB; HostDB:ENSMUSG00000002949; -.
DR eggNOG; KOG2580; Eukaryota.
DR GeneTree; ENSGT00390000000051; -.
DR HOGENOM; CLU_020932_1_1_1; -.
DR InParanoid; O35857; -.
DR OMA; PVFVVTC; -.
DR OrthoDB; 1041560at2759; -.
DR PhylomeDB; O35857; -.
DR TreeFam; TF106197; -.
DR BioGRID-ORCS; 21856; 27 hits in 72 CRISPR screens.
DR ChiTaRS; Timm44; mouse.
DR PRO; PR:O35857; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; O35857; protein.
DR Bgee; ENSMUSG00000002949; Expressed in ciliary body and 259 other tissues.
DR Genevisible; O35857; MM.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; ISO:MGI.
DR GO; GO:0030150; P:protein import into mitochondrial matrix; IBA:GO_Central.
DR InterPro; IPR032710; NTF2-like_dom_sf.
DR InterPro; IPR017303; Tim44.
DR InterPro; IPR039544; Tim44-like.
DR InterPro; IPR007379; Tim44-like_dom.
DR PANTHER; PTHR10721; PTHR10721; 1.
DR Pfam; PF04280; Tim44; 1.
DR PIRSF; PIRSF037871; TIM44; 1.
DR SMART; SM00978; Tim44; 1.
DR SUPFAM; SSF54427; SSF54427; 1.
DR TIGRFAMs; TIGR00984; 3a0801s03tim44; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Nucleotide-binding; Phosphoprotein; Protein transport; Reference proteome;
KW Transit peptide; Translocation; Transport.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..452
FT /note="Mitochondrial import inner membrane translocase
FT subunit TIM44"
FT /id="PRO_0000034315"
FT BINDING 166..173
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 128
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43615"
FT MOD_RES 177
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43615"
FT MOD_RES 217
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MUTAGEN 282
FT /note="K->D: Abolished interaction with SLC25A4/ANT1."
FT /evidence="ECO:0000269|PubMed:31618756"
FT CONFLICT 5
FT /note="A -> R (in Ref. 1; AAB97624)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 452 AA; 51091 MW; DC3E5F4E43972D2F CRC64;
MAAAALRGGW CRCPRRCLGS GIQFLSSHNL PHGSSYQISR PGRELTLTKS YSSGSRKGFL
SGLLDNIKQE LAKNKEMKES IKKFRDEAKK LEESDALQEA RRKYKSIESE TVRTSEAIKK
KLGELTGTVK ESLDEVSKSD LGRKIKEGVE EAARTAKQSA ESVSKSGEKL GKTAAFKAIS
QGVESVKKEL DESVLGQTGP YRRPERLRKR TEFAGAKFKE SKVFEANEEA LGVVLHKDSK
WYQQWKDFKD NNVVFNRFFE MKMKYDESDN VLIRASRALT DKVTDLLGGL FSKTEMSEVL
TEILRVDPTF DKDHFLHQCE TDIIPNILEA MISGELDILK DWCYEATYSQ LAHPIQQAKA
LGFQFHSRIL DISNVDLAMG KMMEQGPVLI VTFQAQVVMV IKNSKGEVYD GDPDKVQRML
YVWALCRDQE ELNPYAAWRL LDISASSTEQ IL
