ID TIM44_HUMAN Reviewed; 452 AA. AC O43615; A8K0R9; D6W664; Q8N193; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 08-NOV-2002, sequence version 2. DT 27-MAR-2024, entry version 197. DE RecName: Full=Mitochondrial import inner membrane translocase subunit TIM44; DE Flags: Precursor; GN Name=TIMM44; Synonyms=MIMT44, TIM44; 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], AND SUBCELLULAR LOCATION. RC TISSUE=Skeletal muscle; RX PubMed=10339406; DOI=10.1006/jmbi.1999.2751; RA Bauer M.F., Gempel K., Reichert A.S., Rappold G.A., Lichtner P., RA Gerbitz K.-D., Neupert W., Brunner M., Hofmann S.; RT "Genetic and structural characterization of the human mitochondrial inner RT membrane translocase."; RL J. Mol. Biol. 289:69-82(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Amygdala; 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]. RC TISSUE=Brain; 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 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 [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-128 AND SER-180, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [8] 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 [9] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 266-452. RX PubMed=18084070; DOI=10.1107/s0907444907051463; RA Handa N., Kishishita S., Morita S., Akasaka R., Jin Z., Chrzas J., Chen L., RA Liu Z.J., Wang B.C., Sugano S., Tanaka A., Terada T., Shirouzu M., RA Yokoyama S.; RT "Structure of the human Tim44 C-terminal domain in complex with RT pentaethylene glycol: ligand-bound form."; RL Acta Crystallogr. D 63:1225-1234(2007). 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 (By similarity). Recruits mitochondrial HSP70 to drive protein CC translocation into the matrix using ATP as an energy source (By CC similarity). {ECO:0000250|UniProtKB:O35857, CC ECO:0000250|UniProtKB:Q01852}. 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. Interacts with SLC25A4/ANT1 and CC SLC25A5/ANT2; leading to inhibit the presequence translocase TIMM23, CC thereby promoting stabilization of PINK1 (By similarity). CC {ECO:0000250|UniProtKB:O35857, ECO:0000250|UniProtKB:Q01852}. CC -!- INTERACTION: CC O43615; P10398: ARAF; NbExp=3; IntAct=EBI-861737, EBI-365961; CC O43615; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-861737, EBI-10961624; CC O43615; Q96DZ9: CMTM5; NbExp=3; IntAct=EBI-861737, EBI-2548702; CC O43615; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-861737, EBI-11522780; CC O43615; Q01658: DR1; NbExp=3; IntAct=EBI-861737, EBI-750300; CC O43615; Q00403: GTF2B; NbExp=3; IntAct=EBI-861737, EBI-389564; CC O43615; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-861737, EBI-1054873; CC O43615; O95562: SFT2D2; NbExp=3; IntAct=EBI-861737, EBI-4402330; CC O43615; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-861737, EBI-7353612; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:10339406}; Peripheral membrane protein CC {ECO:0000269|PubMed:10339406}; Matrix side CC {ECO:0000269|PubMed:10339406}. Mitochondrion matrix CC {ECO:0000269|PubMed:10339406}. CC -!- SIMILARITY: Belongs to the Tim44 family. {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; AF041254; AAB97740.1; -; mRNA. DR EMBL; AK289634; BAF82323.1; -; mRNA. DR EMBL; CH471139; EAW68954.1; -; Genomic_DNA. DR EMBL; CH471139; EAW68955.1; -; Genomic_DNA. DR EMBL; BC033628; AAH33628.1; -; mRNA. DR CCDS; CCDS12192.1; -. DR RefSeq; NP_006342.2; NM_006351.3. DR PDB; 2CW9; X-ray; 1.90 A; A=266-452. DR PDBsum; 2CW9; -. DR AlphaFoldDB; O43615; -. DR SMR; O43615; -. DR BioGRID; 115732; 235. 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; O43615; -. DR IntAct; O43615; 74. DR MINT; O43615; -. DR STRING; 9606.ENSP00000270538; -. DR GlyGen; O43615; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; O43615; -. DR MetOSite; O43615; -. DR PhosphoSitePlus; O43615; -. DR SwissPalm; O43615; -. DR BioMuta; TIMM44; -. DR EPD; O43615; -. DR jPOST; O43615; -. DR MassIVE; O43615; -. DR MaxQB; O43615; -. DR PaxDb; 9606-ENSP00000270538; -. DR PeptideAtlas; O43615; -. DR ProteomicsDB; 49083; -. DR Pumba; O43615; -. DR Antibodypedia; 24720; 76 antibodies from 22 providers. DR DNASU; 10469; -. DR Ensembl; ENST00000270538.8; ENSP00000270538.2; ENSG00000104980.8. DR GeneID; 10469; -. DR KEGG; hsa:10469; -. DR MANE-Select; ENST00000270538.8; ENSP00000270538.2; NM_006351.4; NP_006342.2. DR UCSC; uc002miz.4; human. DR AGR; HGNC:17316; -. DR CTD; 10469; -. DR DisGeNET; 10469; -. DR GeneCards; TIMM44; -. DR HGNC; HGNC:17316; TIMM44. DR HPA; ENSG00000104980; Low tissue specificity. DR MIM; 605058; gene. DR neXtProt; NX_O43615; -. DR OpenTargets; ENSG00000104980; -. DR PharmGKB; PA38229; -. DR VEuPathDB; HostDB:ENSG00000104980; -. DR eggNOG; KOG2580; Eukaryota. DR GeneTree; ENSGT00390000000051; -. DR HOGENOM; CLU_020932_1_1_1; -. DR InParanoid; O43615; -. DR OMA; IGKGASW; -. DR OrthoDB; 2873015at2759; -. DR PhylomeDB; O43615; -. DR TreeFam; TF106197; -. DR PathwayCommons; O43615; -. DR Reactome; R-HSA-1268020; Mitochondrial protein import. DR SignaLink; O43615; -. DR SIGNOR; O43615; -. DR BioGRID-ORCS; 10469; 689 hits in 1155 CRISPR screens. DR ChiTaRS; TIMM44; human. DR EvolutionaryTrace; O43615; -. DR GeneWiki; TIMM44; -. DR GenomeRNAi; 10469; -. DR Pharos; O43615; Tbio. DR PRO; PR:O43615; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O43615; Protein. DR Bgee; ENSG00000104980; Expressed in apex of heart and 180 other cell types or tissues. DR ExpressionAtlas; O43615; baseline and differential. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:BHF-UCL. DR GO; GO:0005759; C:mitochondrial matrix; IDA:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005744; C:TIM23 mitochondrial import inner membrane translocase complex; NAS:ComplexPortal. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0051087; F:protein-folding chaperone binding; IBA:GO_Central. DR GO; GO:0006886; P:intracellular protein transport; NAS:ComplexPortal. DR GO; GO:0030150; P:protein import into mitochondrial matrix; IBA:GO_Central. DR GO; GO:0006626; P:protein targeting to mitochondrion; TAS:ProtInc. DR Gene3D; 3.10.450.240; -; 1. DR InterPro; IPR032710; NTF2-like_dom_sf. DR InterPro; IPR017303; Tim44. DR InterPro; IPR039544; Tim44-like. DR InterPro; IPR007379; Tim44-like_dom. DR NCBIfam; TIGR00984; 3a0801s03tim44; 1. DR PANTHER; PTHR10721; MITOCHONDRIAL IMPORT INNER MEMBRANE TRANSLOCASE SUBUNIT TIM44; 1. DR PANTHER; PTHR10721:SF1; MITOCHONDRIAL IMPORT INNER MEMBRANE TRANSLOCASE SUBUNIT TIM44; 1. DR Pfam; PF04280; Tim44; 1. DR PIRSF; PIRSF037871; TIM44; 1. DR SMART; SM00978; Tim44; 1. DR SUPFAM; SSF54427; NTF2-like; 1. DR Genevisible; O43615; HS. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Nucleotide-binding; Phosphoprotein; KW Protein transport; Reference proteome; Transit peptide; Translocation; KW 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_0000034314" 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:0007744|PubMed:23186163" FT MOD_RES 180 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 217 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:O35857" FT CONFLICT 189 FT /note="E -> A (in Ref. 1; AAB97740)" FT /evidence="ECO:0000305" FT CONFLICT 226 FT /note="P -> A (in Ref. 1; AAB97740)" FT /evidence="ECO:0000305" FT HELIX 271..286 FT /evidence="ECO:0007829|PDB:2CW9" FT HELIX 292..306 FT /evidence="ECO:0007829|PDB:2CW9" FT HELIX 312..321 FT /evidence="ECO:0007829|PDB:2CW9" FT HELIX 323..333 FT /evidence="ECO:0007829|PDB:2CW9" FT HELIX 336..342 FT /evidence="ECO:0007829|PDB:2CW9" FT HELIX 345..360 FT /evidence="ECO:0007829|PDB:2CW9" FT STRAND 368..383 FT /evidence="ECO:0007829|PDB:2CW9" FT STRAND 386..398 FT /evidence="ECO:0007829|PDB:2CW9" FT STRAND 400..402 FT /evidence="ECO:0007829|PDB:2CW9" FT STRAND 408..411 FT /evidence="ECO:0007829|PDB:2CW9" FT STRAND 417..427 FT /evidence="ECO:0007829|PDB:2CW9" FT HELIX 434..436 FT /evidence="ECO:0007829|PDB:2CW9" FT STRAND 438..447 FT /evidence="ECO:0007829|PDB:2CW9" SQ SEQUENCE 452 AA; 51356 MW; 15BECF875611BE96 CRC64; MAAAALRSGW CRCPRRCLGS GIQFLSSHNL PHGSTYQMRR PGGELPLSKS YSSGNRKGFL SGLLDNVKQE LAKNKEMKES IKKFRDEARR LEESDVLQEA RRKYKTIESE TVRTSEVLRK KLGELTGTVK ESLHEVSKSD LGRKIKEGVE EAAKTAKQSA ESVSKGGEKL GRTAAFRALS QGVESVKKEI DDSVLGQTGP YRRPQRLRKR TEFAGDKFKE EKVFEPNEEA LGVVLHKDSK WYQQWKDFKE NNVVFNRFFE MKMKYDESDN AFIRASRALT DKVTDLLGGL FSKTEMSEVL TEILRVDPAF DKDRFLKQCE NDIIPNVLEA MISGELDILK DWCYEATYSQ LAHPIQQAKA LGLQFHSRIL DIDNVDLAMG KMMEQGPVLI ITFQAQLVMV VRNPKGEVVE GDPDKVLRML YVWALCRDQD ELNPYAAWRL LDISASSTEQ IL //