TIM16_HUMAN
ID TIM16_HUMAN Reviewed; 125 AA.
AC Q9Y3D7; Q6I9Z3; Q9H5X3;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Mitochondrial import inner membrane translocase subunit TIM16;
DE AltName: Full=Mitochondria-associated granulocyte macrophage CSF-signaling molecule;
DE AltName: Full=Presequence translocated-associated motor subunit PAM16;
GN Name=PAM16; Synonyms=MAGMAS, TIM16, TIMM16; ORFNames=CGI-136;
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], SUBCELLULAR LOCATION, AND VARIANT LYS-114.
RC TISSUE=Peripheral blood;
RX PubMed=11750097; DOI=10.1016/s0301-472x(01)00749-4;
RA Jubinsky P.T., Messer A., Bender J., Morris R.E., Ciraolo G.M., Witte D.P.,
RA Hawley R.G., Short M.K.;
RT "Identification and characterization of Magmas, a novel mitochondria-
RT associated protein involved in granulocyte-macrophage colony-stimulating
RT factor signal transduction.";
RL Exp. Hematol. 29:1392-1402(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=15704001; DOI=10.1007/s10735-004-3840-8;
RA Jubinsky P.T., Short M.K., Mutema G., Morris R.E., Ciraolo G.M., Li M.;
RT "Magmas expression in neoplastic human prostate.";
RL J. Mol. Histol. 36:69-75(2005).
RN [7]
RP FUNCTION, INTERACTION WITH DNAJC19, ASSOCIATION WITH THE TIM23 COMPLEX,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ILE-62; 85-ASP--SER-87; PHE-92;
RP TYR-93 AND LEU-94.
RX PubMed=20053669; DOI=10.1093/hmg/ddq002;
RA Sinha D., Joshi N., Chittoor B., Samji P., D'Silva P.;
RT "Role of Magmas in protein transport and human mitochondria biogenesis.";
RL Hum. Mol. Genet. 19:1248-1262(2010).
RN [8]
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 [9]
RP INVOLVEMENT IN SMDMDM, AND VARIANT SMDMDM ASP-76.
RX PubMed=24786642; DOI=10.1371/journal.pgen.1004311;
RA Mehawej C., Delahodde A., Legeai-Mallet L., Delague V., Kaci N.,
RA Desvignes J.P., Kibar Z., Capo-Chichi J.M., Chouery E., Munnich A.,
RA Cormier-Daire V., Megarbane A.;
RT "The impairment of MAGMAS function in human is responsible for a severe
RT skeletal dysplasia.";
RL PLoS Genet. 10:E1004311-E1004311(2014).
CC -!- FUNCTION: Regulates ATP-dependent protein translocation into the
CC mitochondrial matrix. Inhibits DNAJC19 stimulation of HSPA9/Mortalin
CC ATPase activity. {ECO:0000269|PubMed:20053669}.
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). Interacts with DNAJC19. Directly
CC interacts with DNAJC15; this interaction counteracts DNAJC15-dependent
CC stimulation of HSPA9 ATPase activity. Associates with the TIM23
CC complex. Associates with the TIM23 complex (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q9CQV1,
CC ECO:0000269|PubMed:20053669, ECO:0000269|PubMed:23263864}.
CC -!- INTERACTION:
CC Q9Y3D7; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-721147, EBI-714543;
CC Q9Y3D7; Q9Y5T4: DNAJC15; NbExp=4; IntAct=EBI-721147, EBI-10329228;
CC Q9Y3D7; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-721147, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:11750097, ECO:0000269|PubMed:20053669}; Peripheral
CC membrane protein {ECO:0000269|PubMed:11750097,
CC ECO:0000269|PubMed:20053669}; Matrix side {ECO:0000269|PubMed:11750097,
CC ECO:0000269|PubMed:20053669}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:15704001}.
CC -!- INDUCTION: By CSF2/GM-CSF.
CC -!- DOMAIN: The J-like region, although related to the J domain does not
CC have co-chaperone activity. {ECO:0000250}.
CC -!- DISEASE: Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type
CC (SMDMDM) [MIM:613320]: An autosomal recessive disease characterized by
CC pre- and postnatal short stature, developmental delay, dysmorphic
CC facial appearance, narrow chest, prominent abdomen, platyspondyly, and
CC short limbs. {ECO:0000269|PubMed:24786642}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TIM16/PAM16 family. {ECO:0000305}.
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DR EMBL; AF349455; AAL57767.1; -; mRNA.
DR EMBL; AF151894; AAD34131.1; -; mRNA.
DR EMBL; AK026514; BAB15494.1; -; mRNA.
DR EMBL; CR457362; CAG33643.1; -; mRNA.
DR EMBL; BC005024; AAH05024.1; -; mRNA.
DR CCDS; CCDS10512.1; -.
DR RefSeq; NP_057153.8; NM_016069.9.
DR AlphaFoldDB; Q9Y3D7; -.
DR SMR; Q9Y3D7; -.
DR BioGRID; 119231; 114.
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 IntAct; Q9Y3D7; 21.
DR MINT; Q9Y3D7; -.
DR STRING; 9606.ENSP00000315693; -.
DR iPTMnet; Q9Y3D7; -.
DR PhosphoSitePlus; Q9Y3D7; -.
DR BioMuta; PAM16; -.
DR DMDM; 23503082; -.
DR EPD; Q9Y3D7; -.
DR jPOST; Q9Y3D7; -.
DR MassIVE; Q9Y3D7; -.
DR MaxQB; Q9Y3D7; -.
DR PaxDb; Q9Y3D7; -.
DR PeptideAtlas; Q9Y3D7; -.
DR PRIDE; Q9Y3D7; -.
DR ProteomicsDB; 86023; -.
DR TopDownProteomics; Q9Y3D7; -.
DR Antibodypedia; 56377; 94 antibodies from 16 providers.
DR DNASU; 51025; -.
DR Ensembl; ENST00000318059.8; ENSP00000315693.3; ENSG00000217930.8.
DR Ensembl; ENST00000576217.1; ENSP00000461047.1; ENSG00000217930.8.
DR Ensembl; ENST00000616009.2; ENSP00000484240.1; ENSG00000282228.1.
DR Ensembl; ENST00000634045.1; ENSP00000487678.1; ENSG00000282228.1.
DR GeneID; 51025; -.
DR KEGG; hsa:51025; -.
DR MANE-Select; ENST00000318059.8; ENSP00000315693.3; NM_016069.11; NP_057153.8.
DR UCSC; uc002cwd.4; human.
DR CTD; 51025; -.
DR DisGeNET; 51025; -.
DR GeneCards; PAM16; -.
DR HGNC; HGNC:29679; PAM16.
DR HPA; ENSG00000217930; Tissue enhanced (skeletal).
DR MalaCards; PAM16; -.
DR MIM; 613320; phenotype.
DR MIM; 614336; gene.
DR neXtProt; NX_Q9Y3D7; -.
DR OpenTargets; ENSG00000217930; -.
DR Orphanet; 401979; Autosomal recessive spondylometaphyseal dysplasia, Megarbane type.
DR VEuPathDB; HostDB:ENSG00000217930; -.
DR eggNOG; KOG3442; Eukaryota.
DR GeneTree; ENSGT00390000012037; -.
DR HOGENOM; CLU_101461_3_0_1; -.
DR InParanoid; Q9Y3D7; -.
DR OMA; AKYLIQI; -.
DR PhylomeDB; Q9Y3D7; -.
DR TreeFam; TF315134; -.
DR PathwayCommons; Q9Y3D7; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR SignaLink; Q9Y3D7; -.
DR SIGNOR; Q9Y3D7; -.
DR BioGRID-ORCS; 51025; 758 hits in 1038 CRISPR screens.
DR GenomeRNAi; 51025; -.
DR Pharos; Q9Y3D7; Tbio.
DR PRO; PR:Q9Y3D7; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9Y3D7; protein.
DR Bgee; ENSG00000217930; Expressed in gastrocnemius and 93 other tissues.
DR ExpressionAtlas; Q9Y3D7; baseline and differential.
DR Genevisible; Q9Y3D7; HS.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; IDA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IC:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:GO_Central.
DR GO; GO:0001405; C:PAM complex, Tim23 associated import motor; IGI:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:GO_Central.
DR GO; GO:0005744; C:TIM23 mitochondrial import inner membrane translocase complex; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IC:ComplexPortal.
DR GO; GO:0032780; P:negative regulation of ATP-dependent activity; IDA:GO_Central.
DR GO; GO:0001503; P:ossification; IMP:UniProtKB.
DR GO; GO:0030150; P:protein import into mitochondrial matrix; IGI:GO_Central.
DR Gene3D; 1.10.287.110; -; 1.
DR InterPro; IPR036869; J_dom_sf.
DR InterPro; IPR005341; Tim16.
DR PANTHER; PTHR12388; PTHR12388; 1.
PE 1: Evidence at protein level;
KW Disease variant; Dwarfism; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Translocation; Transport.
FT CHAIN 1..125
FT /note="Mitochondrial import inner membrane translocase
FT subunit TIM16"
FT /id="PRO_0000214078"
FT REGION 58..110
FT /note="J-like"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CQV1"
FT VARIANT 76
FT /note="N -> D (in SMDMDM; dbSNP:rs786203989)"
FT /evidence="ECO:0000269|PubMed:24786642"
FT /id="VAR_073419"
FT VARIANT 114
FT /note="Q -> K (in dbSNP:rs11989)"
FT /evidence="ECO:0000269|PubMed:11750097"
FT /id="VAR_013764"
FT MUTAGEN 62
FT /note="I->A,Q,W: Substantial loss of protein translocation
FT into mitochondria in a heterologous system."
FT /evidence="ECO:0000269|PubMed:20053669"
FT MUTAGEN 85..87
FT /note="DKS->HPD: No effect on protein translocation into
FT mitochondria in a heterologous system."
FT /evidence="ECO:0000269|PubMed:20053669"
FT MUTAGEN 92
FT /note="F->G: Partial loss of protein translocation into
FT mitochondria in a heterologous system. Substantial loss of
FT protein translocation into mitochondria in a heterologous
FT system; when associated with G-93. Partial loss of DNAJC19-
FT binding. Loss of DNAJC19-binding; when associated with G-
FT 93. Partial loss of inhibition of DNAJC19 stimulation of
FT HSPA9 ATPase activity. Complete loss of inhibition of
FT DNAJC19 stimulation of HSPA9 ATPase activity; when
FT associated with G-93."
FT /evidence="ECO:0000269|PubMed:20053669"
FT MUTAGEN 93
FT /note="Y->G: Partial loss of protein translocation into
FT mitochondria in a heterologous system. Substantial loss of
FT protein translocation into mitochondria in a heterologous
FT system; when associated with G-92. Loss of DNAJC19-binding;
FT when associated with G-92. Complete loss of inhibition of
FT DNAJC19 stimulation of HSPA9 ATPase activity; when
FT associated with G-92."
FT /evidence="ECO:0000269|PubMed:20053669"
FT MUTAGEN 94
FT /note="L->A: No effect on protein translocation into
FT mitochondria in a heterologous system."
FT /evidence="ECO:0000269|PubMed:20053669"
FT MUTAGEN 94
FT /note="L->Q: Substantial loss of protein translocation into
FT mitochondria in a heterologous system. Substantial loss of
FT DNAJC19-binding. Partial loss of inhibition of DNAJC19
FT stimulation of HSPA9 ATPase activity."
FT /evidence="ECO:0000269|PubMed:20053669"
FT CONFLICT 120
FT /note="G -> W (in Ref. 2; AAD34131)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 125 AA; 13825 MW; 5E7877B30CC89C61 CRC64;
MAKYLAQIIV MGVQVVGRAF ARALRQEFAA SRAAADARGR AGHRSAAASN LSGLSLQEAQ
QILNVSKLSP EEVQKNYEHL FKVNDKSVGG SFYLQSKVVR AKERLDEELK IQAQEDREKG
QMPHT
