TIM44_HUMAN
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 03-AUG-2022, entry version 188.
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}.
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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; 199.
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; 56.
DR MINT; O43615; -.
DR STRING; 9606.ENSP00000270538; -.
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; O43615; -.
DR PeptideAtlas; O43615; -.
DR PRIDE; O43615; -.
DR ProteomicsDB; 49083; -.
DR Antibodypedia; 24720; 62 antibodies from 21 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 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; PVFVVTC; -.
DR OrthoDB; 1041560at2759; -.
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; 658 hits in 1076 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 178 other tissues.
DR ExpressionAtlas; O43615; baseline and differential.
DR Genevisible; O43615; HS.
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; IC:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051087; F:chaperone binding; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IC: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 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 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
