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 24-JAN-2024, entry version 184. 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}. 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; 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; 120. 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; 9606-ENSP00000315693; -. DR PeptideAtlas; Q9Y3D7; -. DR ProteomicsDB; 86023; -. DR Pumba; Q9Y3D7; -. DR TopDownProteomics; Q9Y3D7; -. DR Antibodypedia; 56377; 124 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 AGR; HGNC:29679; -. 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 OrthoDB; 5474889at2759; -. 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; 767 hits in 1107 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 95 other cell types or tissues. DR ExpressionAtlas; Q9Y3D7; baseline and differential. DR Genevisible; Q9Y3D7; HS. DR GO; GO:0005743; C:mitochondrial inner membrane; NAS: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; NAS: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; DnaJ domain; 1. DR InterPro; IPR036869; J_dom_sf. DR InterPro; IPR005341; Tim16. DR PANTHER; PTHR12388; MITOCHONDRIA ASSOCIATED GRANULOCYTE MACROPHAGE CSF SIGNALING MOLECULE; 1. DR PANTHER; PTHR12388:SF0; MITOCHONDRIAL IMPORT INNER MEMBRANE TRANSLOCASE SUBUNIT TIM16; 1. DR Pfam; PF03656; Pam16; 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 //