ID FIS1_HUMAN Reviewed; 152 AA. AC Q9Y3D6; Q9BTP3; DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 19-JUL-2003, sequence version 2. DT 09-JUL-2014, entry version 127. DE RecName: Full=Mitochondrial fission 1 protein; DE AltName: Full=FIS1 homolog; DE Short=hFis1; DE AltName: Full=Tetratricopeptide repeat protein 11; DE Short=TPR repeat protein 11; GN Name=FIS1; Synonyms=TTC11; ORFNames=CGI-135; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 1-16, ACETYLATION AT MET-1, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (JUN-2005) to UniProtKB. RN [5] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12783892; DOI=10.1074/jbc.M303758200; RA James D.I., Parone P.A., Mattenberger Y., Martinou J.-C.; RT "hFis1, a novel component of the mammalian mitochondrial fission RT machinery."; RL J. Biol. Chem. 278:36373-36379(2003). RN [6] RP FUNCTION, AND INTERACTION WITH DNM1L. RX PubMed=12861026; DOI=10.1128/MCB.23.15.5409-5420.2003; RA Yoon Y., Krueger E.W., Oswald B.J., McNiven M.A.; RT "The mitochondrial protein hFis1 regulates mitochondrial fission in RT mammalian cells through an interaction with the dynamin-like protein RT DLP1."; RL Mol. Cell. Biol. 23:5409-5420(2003). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS OF LYS-149 RP AND LYS-151. RX PubMed=14996942; DOI=10.1242/jcs.01058; RA Stojanovski D., Koutsopoulos O.S., Okamoto K., Ryan M.T.; RT "Levels of human Fis1 at the mitochondrial outer membrane regulate RT mitochondrial morphology."; RL J. Cell Sci. 117:1201-1210(2004). RN [8] RP FUNCTION, INTERACTION WITH DNM1L, AND MUTAGENESIS OF LEU-14; LEU-42; RP LEU-58; LEU-77; LEU-91 AND LEU-110. RX PubMed=16118244; DOI=10.1242/jcs.02537; RA Yu T., Fox R.J., Burwell L.S., Yoon Y.; RT "Regulation of mitochondrial fission and apoptosis by the RT mitochondrial outer membrane protein hFis1."; RL J. Cell Sci. 118:4141-4151(2005). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16107562; DOI=10.1091/mbc.E05-02-0159; RA Koch A., Yoon Y., Bonekamp N.A., McNiven M.A., Schrader M.; RT "A role for Fis1 in both mitochondrial and peroxisomal fission in RT mammalian cells."; RL Mol. Biol. Cell 16:5077-5086(2005). RN [10] RP UBIQUITINATION BY MARCH5, AND INTERACTION WITH MARCH5. RX PubMed=16874301; DOI=10.1038/sj.emboj.7601249; RA Yonashiro R., Ishido S., Kyo S., Fukuda T., Goto E., Matsuki Y., RA Ohmura-Hoshino M., Sada K., Hotta H., Yamamura H., Inatome R., RA Yanagi S.; RT "A novel mitochondrial ubiquitin ligase plays a critical role in RT mitochondrial dynamics."; RL EMBO J. 25:3618-3626(2006). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] 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., RA Buerckstuemmer T., 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 [13] RP INTERACTION WITH MIEF1. RX PubMed=21701560; DOI=10.1038/emboj.2011.198; RA Zhao J., Liu T., Jin S., Wang X., Qu M., Uhlen P., Tomilin N., RA Shupliakov O., Lendahl U., Nister M.; RT "Human MIEF1 recruits Drp1 to mitochondrial outer membranes and RT promotes mitochondrial fusion rather than fission."; RL EMBO J. 30:2762-2778(2011). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=23921378; DOI=10.1074/jbc.M113.479873; RA Palmer C.S., Elgass K.D., Parton R.G., Osellame L.D., Stojanovski D., RA Ryan M.T.; RT "MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 RT recruitment and are specific for mitochondrial fission."; RL J. Biol. Chem. 288:27584-27593(2013). RN [15] RP FUNCTION. RX PubMed=23283981; DOI=10.1091/mbc.E12-10-0721; RA Loson O.C., Song Z., Chen H., Chan D.C.; RT "Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial RT fission."; RL Mol. Biol. Cell 24:659-667(2013). RN [16] RP FUNCTION. RX PubMed=23530241; DOI=10.1073/pnas.1300855110; RA Koirala S., Guo Q., Kalia R., Bui H.T., Eckert D.M., Frost A., RA Shaw J.M.; RT "Interchangeable adaptors regulate mitochondrial dynamin assembly for RT membrane scission."; RL Proc. Natl. Acad. Sci. U.S.A. 110:E1342-E1351(2013). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-123. RX PubMed=14705031; DOI=10.1002/prot.10524; RA Dohm J.A., Lee S.J., Hardwick J.M., Hill R.B., Gittis A.G.; RT "Cytosolic domain of the human mitochondrial fission protein fis1 RT adopts a TPR fold."; RL Proteins 54:153-156(2004). RN [18] RP STRUCTURE BY NMR, AND SUBCELLULAR LOCATION. RX PubMed=14623186; DOI=10.1016/j.jmb.2003.09.064; RA Suzuki M., Jeong S.-Y., Karbowski M., Youle R.J., Tjandra N.; RT "The solution structure of human mitochondria fission protein Fis1 RT reveals a novel TPR-like helix bundle."; RL J. Mol. Biol. 334:445-458(2003). CC -!- FUNCTION: Involved in the fragmentation of the mitochondrial CC network and its perinuclear clustering. Plays a minor role in the CC recruitment and association of the fission mediator dynamin- CC related protein 1 (DNM1L) to the mitochondrial surface and CC mitochondrial fission. Can induce cytochrome c release from the CC mitochondrion to the cytosol, ultimately leading to apoptosis. CC Also mediates peroxisomal fission. CC -!- SUBUNIT: Interacts with DNM1L/DLP1 through the TPR region. CC Interacts with MARCH5. Interacts with MIEF1. CC -!- INTERACTION: CC P51572:BCAP31; NbExp=8; IntAct=EBI-3385283, EBI-77683; CC Q9NQG6:MIEF1; NbExp=4; IntAct=EBI-3385283, EBI-740987; CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass CC membrane protein. Peroxisome membrane; Single-pass membrane CC protein. CC -!- DOMAIN: The C-terminus is required for mitochondrial or CC peroxisomal localization, while the N-terminus is necessary for CC mitochondrial or peroxisomal fission, localization and regulation CC of the interaction with DNM1L. CC -!- PTM: Ubiquitinated by MARCH5. CC -!- SIMILARITY: Belongs to the FIS1 family. CC -!- SIMILARITY: Contains 1 TPR repeat. 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; AF151893; AAD34130.1; -; mRNA. DR EMBL; AC006329; AAP22366.1; -; Genomic_DNA. DR EMBL; BC003540; AAH03540.1; -; mRNA. DR EMBL; BC009428; AAH09428.1; -; mRNA. DR CCDS; CCDS43626.1; -. DR RefSeq; NP_057152.2; NM_016068.2. DR UniGene; Hs.423968; -. DR PDB; 1NZN; X-ray; 2.00 A; A=1-123. DR PDB; 1PC2; NMR; -; A=1-145. DR PDBsum; 1NZN; -. DR PDBsum; 1PC2; -. DR DisProt; DP00457; -. DR ProteinModelPortal; Q9Y3D6; -. DR SMR; Q9Y3D6; 1-145. DR BioGrid; 119230; 23. DR IntAct; Q9Y3D6; 9. DR MINT; MINT-2844167; -. DR STRING; 9606.ENSP00000223136; -. DR PhosphoSite; Q9Y3D6; -. DR DMDM; 33112470; -. DR UCD-2DPAGE; Q9Y3D6; -. DR MaxQB; Q9Y3D6; -. DR PaxDb; Q9Y3D6; -. DR PeptideAtlas; Q9Y3D6; -. DR PRIDE; Q9Y3D6; -. DR DNASU; 51024; -. DR Ensembl; ENST00000223136; ENSP00000223136; ENSG00000214253. DR GeneID; 51024; -. DR KEGG; hsa:51024; -. DR UCSC; uc003uyj.4; human. DR CTD; 51024; -. DR GeneCards; GC07M100882; -. DR HGNC; HGNC:21689; FIS1. DR HPA; HPA017430; -. DR MIM; 609003; gene. DR neXtProt; NX_Q9Y3D6; -. DR PharmGKB; PA134984211; -. DR eggNOG; NOG235677; -. DR HOGENOM; HOG000165386; -. DR HOVERGEN; HBG081530; -. DR InParanoid; Q9Y3D6; -. DR KO; K17969; -. DR OMA; EIFRTSP; -. DR PhylomeDB; Q9Y3D6; -. DR TreeFam; TF315180; -. DR ChiTaRS; FIS1; human. DR EvolutionaryTrace; Q9Y3D6; -. DR GeneWiki; FIS1; -. DR GenomeRNAi; 51024; -. DR NextBio; 53558; -. DR PRO; PR:Q9Y3D6; -. DR ArrayExpress; Q9Y3D6; -. DR Bgee; Q9Y3D6; -. DR CleanEx; HS_FIS1; -. DR Genevestigator; Q9Y3D6; -. DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:UniProtKB. DR GO; GO:0005779; C:integral component of peroxisomal membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB. DR GO; GO:0043234; C:protein complex; IDA:UniProtKB. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0005102; F:receptor binding; IPI:UniProtKB. DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IMP:UniProtKB. DR GO; GO:0000266; P:mitochondrial fission; IDA:UniProtKB. DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0008053; P:mitochondrial fusion; IMP:UniProtKB. DR GO; GO:0000422; P:mitochondrion degradation; IDA:UniProtKB. DR GO; GO:0070584; P:mitochondrion morphogenesis; IMP:UniProtKB. DR GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; IMP:UniProtKB. DR GO; GO:0016559; P:peroxisome fission; IDA:UniProtKB. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:UniProtKB. DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; IMP:UniProtKB. DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IDA:UniProtKB. DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IDA:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IMP:UniProtKB. DR GO; GO:0006626; P:protein targeting to mitochondrion; IMP:UniProtKB. DR GO; GO:0010821; P:regulation of mitochondrion organization; IMP:UniProtKB. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:UniProtKB. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR016543; Fis1. DR InterPro; IPR028061; Fis1_TPR_C. DR InterPro; IPR028058; Fis1_TPR_N. DR InterPro; IPR011990; TPR-like_helical. DR PANTHER; PTHR13247; PTHR13247; 1. DR Pfam; PF14853; Fis1_TPR_C; 1. DR Pfam; PF14852; Fis1_TPR_N; 1. DR PIRSF; PIRSF008835; TPR_repeat_11_Fis1; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Apoptosis; Complete proteome; KW Direct protein sequencing; Membrane; Mitochondrion; KW Mitochondrion outer membrane; Peroxisome; Reference proteome; KW TPR repeat; Transmembrane; Transmembrane helix; Ubl conjugation. FT CHAIN 1 152 Mitochondrial fission 1 protein. FT /FTId=PRO_0000106393. FT TOPO_DOM 1 122 Cytoplasmic (Potential). FT TRANSMEM 123 143 Helical; (Potential). FT TOPO_DOM 144 152 Mitochondrial intermembrane (Potential). FT REPEAT 71 104 TPR. FT MOD_RES 1 1 N-acetylmethionine. FT MUTAGEN 14 14 L->P: Approximately 40% of cells display FT fragmented mitochondria. FT MUTAGEN 42 42 L->P: Less than 15% of cells display FT fragmented mitochondria. FT MUTAGEN 58 58 L->P: Less than 15% of cells display FT fragmented mitochondria. FT MUTAGEN 77 77 L->P: Less than 15% of cells display FT fragmented mitochondria. Shows greatly FT reduced binding to DNM1L. FT MUTAGEN 91 91 L->P: Less than 15% of cells display FT fragmented mitochondria. Shows greatly FT reduced binding to DNM1L. FT MUTAGEN 110 110 L->P: Approximately 40% of cells display FT fragmented mitochondria. No change in FT binding to DNM1L. FT MUTAGEN 149 149 K->A: Protein localizes to both FT mitochondrion and endoplasmic reticulum. FT Protein localizes to endoplasmic FT reticulum only; when associated with A- FT 151. FT MUTAGEN 151 151 K->A: Protein localizes to both FT mitochondrion and endoplasmic reticulum. FT Protein localizes to endoplasmic FT reticulum only; when associated with A- FT 149. FT CONFLICT 45 46 SK -> TR (in Ref. 1; AAD34130). FT HELIX 1 27 FT HELIX 32 42 FT STRAND 45 47 FT HELIX 48 61 FT TURN 62 64 FT HELIX 67 83 FT HELIX 87 100 FT HELIX 105 120 FT STRAND 129 133 FT STRAND 142 144 SQ SEQUENCE 152 AA; 16938 MW; 6E76EC02B3731A9B CRC64; MEAVLNELVS VEDLLKFEKK FQSEKAAGSV SKSTQFEYAW CLVRSKYNDD IRKGIVLLEE LLPKGSKEEQ RDYVFYLAVG NYRLKEYEKA LKYVRGLLQT EPQNNQAKEL ERLIDKAMKK DGLVGMAIVG GMALGVAGLA GLIGLAVSKS KS //