Full text data of FIS1
FIS1
(TTC11)
[Confidence: high (present in two of the MS resources)]
Mitochondrial fission 1 protein (FIS1 homolog; hFis1; Tetratricopeptide repeat protein 11; TPR repeat protein 11)
Mitochondrial fission 1 protein (FIS1 homolog; hFis1; Tetratricopeptide repeat protein 11; TPR repeat protein 11)
hRBCD
IPI00007052
IPI00007052 TPR repeat containing protein TPR repeat containing protein membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a integral membrane protein n/a found at its expected molecular weight found at molecular weight
IPI00007052 TPR repeat containing protein TPR repeat containing protein membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a integral membrane protein n/a found at its expected molecular weight found at molecular weight
UniProt
Q9Y3D6
ID FIS1_HUMAN Reviewed; 152 AA.
AC Q9Y3D6; Q9BTP3;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 19-JUL-2003, sequence version 2.
DT 22-JAN-2014, entry version 121.
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 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 MASS SPECTROMETRY.
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.
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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 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 IntAct; Q9Y3D6; 9.
DR MINT; MINT-2844167; -.
DR STRING; 9606.ENSP00000223136; -.
DR PhosphoSite; Q9Y3D6; -.
DR DMDM; 33112470; -.
DR UCD-2DPAGE; 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 OMA; EIFRTSP; -.
DR PhylomeDB; Q9Y3D6; -.
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 to mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005779; C:integral to peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IMP: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: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.
DR PROSITE; PS50005; TPR; FALSE_NEG.
DR PROSITE; PS50293; TPR_REGION; FALSE_NEG.
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
//
ID FIS1_HUMAN Reviewed; 152 AA.
AC Q9Y3D6; Q9BTP3;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 19-JUL-2003, sequence version 2.
DT 22-JAN-2014, entry version 121.
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 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 MASS SPECTROMETRY.
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.
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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 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 IntAct; Q9Y3D6; 9.
DR MINT; MINT-2844167; -.
DR STRING; 9606.ENSP00000223136; -.
DR PhosphoSite; Q9Y3D6; -.
DR DMDM; 33112470; -.
DR UCD-2DPAGE; 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 OMA; EIFRTSP; -.
DR PhylomeDB; Q9Y3D6; -.
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 to mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005779; C:integral to peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IMP: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: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.
DR PROSITE; PS50005; TPR; FALSE_NEG.
DR PROSITE; PS50293; TPR_REGION; FALSE_NEG.
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
//
MIM
609003
*RECORD*
*FIELD* NO
609003
*FIELD* TI
*609003 TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 11; TTC11
;;FIS1, S. CEREVISIAE, HOMOLOG OF
read more*FIELD* TX
DESCRIPTION
The balance between fission and fusion regulates the morphology of
mitochondria. TTC11 is a component of a mitochondrial complex that
promotes mitochondrial fission (James et al., 2003).
CLONING
By searching for sequences similar to yeast Fis1, followed by PCR of a
liver cDNA library, James et al. (2003) cloned FIS1. The deduced
152-amino acid protein contains a central leucine zipper, a coiled-coil
region, and a C-terminal transmembrane domain. It also contains a region
showing high interspecies homology and a putative tetratricopeptide
repeat. Immunocytochemical analysis of HeLa cells detected endogenous
FIS1 expression in mitochondria. Protease treatment indicated that FIS1
is expressed at the outer mitochondrial membrane. Transfection of a
C-terminal truncated FIS1 resulted in cytoplasmic expression, indicating
that the C terminus is required for mitochondrial localization.
Yoon et al. (2003) cloned human FIS1 by PCR. The deduced 152-amino acid
protein has a calculated molecular mass of 17 kD.
GENE FUNCTION
By overexpression of FIS1 in various cell types, James et al. (2003)
found that FIS1 localizes to the outer mitochondrial membrane and
induces mitochondrial fission. Fission was inhibited by a
dominant-negative mutant of DRP1 (DNM1L; 603850). Fragmentation of the
tubular mitochondrial network by FIS1 was followed by the release of
cytochrome c and ultimately apoptosis. BCLXL (600039) blocked cytochrome
c release and apoptosis, but failed to prevent mitochondrial
fragmentation. James et al. (2003) concluded that FIS1 is part of the
mammalian fission machinery and that the regulation of mitochondrial
fission may be involved in apoptosis.
By differential tagging and deletion analysis, Yoon et al. (2003)
demonstrated that the C terminus of human FIS1 was essential for
mitochondrial localization, and that the cytosolic N terminus was
necessary for mitochondrial fission. Increased FIS1 expression promoted
mitochondrial fission and the accumulation of fragmented mitochondria.
Conversely, cells microinjected with anti-FIS1 antibodies or treated
with antisense FIS1 oligonucleotides developed elongated and collapsed
mitochondria. Furthermore, FRET and coimmunoprecipitation studies
demonstrated that human FIS1 interacted with rat Dnm1l, suggesting that
FIS1 participates in mitochondrial fission by recruiting DNM1L from the
cytosol. Yoon et al. (2003) concluded that FIS1 is a limiting factor in
mitochondrial fission and that the number of FIS1 molecules on the
mitochondrial surface determines fission frequency.
Frieden et al. (2004) found that the dramatic mitochondrial
fragmentation induced by FIS1 overexpression had no effect on the
mitochondrial transmembrane potential, pH, or the ability to take up
Ca(2+) released from intracellular stores upon agonist stimulation.
Malena et al. (2009) tested the hypothesis that altering the balance
between mitochondrial fusion and fission could influence the segregation
of mutant and wildtype mtDNA variants, because it would modify the
number of organelles per cell. Human cells heteroplasmic for the
pathologic 3243A-G (MTTL1; 590050.0001) mitochondrial DNA mutation were
transfected with constructs designed to silence DRP1 or human FIS1,
whose gene products are required for mitochondrial fission. DRP1 and
human FIS1 gene silencing were both associated with increased levels of
mutant mitochondrial DNA. The authors concluded that the extent of the
mitochondrial reticular network appears to be an important factor in
determining mutant load.
BIOCHEMICAL FEATURES
Dohm et al. (2004) determined the crystal structure of the cytosolic
domain of human FIS1 to 2.0-angstrom resolution. They found that FIS1
adopts a tetratricopeptide fold suitable for protein binding
interactions, and that the open structure has a concave binding surface
that can accommodate a helix. Helix alpha-1 of FIS1 may also act as a
molecular switch to promote either the monomeric or dimeric FIS1
conformation, modulating the accessibility of different binding
surfaces. The structure allows FIS1 to be free in solution, or to act as
a scaffold for protein interactions. Dohm et al. (2004) hypothesized
that FIS1 may be a target for signals mediating apoptosis as well as
fission.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the TTC11
gene to chromosome 7 (Genbank GENBANK WI-11506).
*FIELD* RF
1. Dohm, J. A.; Lee, S. J.; Hardwick, J. M.; Hill, R. B.; Gittis,
A. G.: Cytosolic domain of the human mitochondrial fission protein
Fis1 adopts a TPR fold. Proteins 54: 153-156, 2004.
2. Frieden, M.; James, D.; Castelbou, C.; Danckaert, A.; Martinou,
J.-C.; Demaurex, N.: Ca(2+) homeostasis during mitochondrial fragmentation
and perinuclear clustering induced by hFis1. J. Biol. Chem. 279:
22704-22714, 2004.
3. James, D. I.; Parone, P. A.; Mattenberger, Y.; Martinou, J.-C.
: hFis1, a novel component of the mammalian mitochondrial fission
machinery. J. Biol. Chem. 278: 36373-36379, 2003. Note: Erratum:
J. Biol. Chem. 279: 36166 only, 2004.
4. Malena, A.; Loro, E.; Di Re, M.; Holt, I. J.; Vergani, L.: Inhibition
of mitochondrial fission favours mutant over wild-type mitochondrial
DNA. Hum. Molec. Genet. 18: 3407-3416, 2009.
5. Yoon, Y.; Krueger, E. W.; Oswald, B. J.; McNiven, M. A.: The mitochondrial
protein hFis1 regulates mitochondrial fission in mammalian cells through
an interaction with the dynamin-like protein DLP1. Molec. Cell. Biol. 23:
5409-5420, 2003.
*FIELD* CN
George E. Tiller - updated: 7/7/2010
*FIELD* CD
Patricia A. Hartz: 10/28/2004
*FIELD* ED
mgross: 02/26/2013
alopez: 11/26/2012
alopez: 7/20/2010
terry: 7/7/2010
mgross: 1/22/2010
alopez: 10/28/2004
*RECORD*
*FIELD* NO
609003
*FIELD* TI
*609003 TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 11; TTC11
;;FIS1, S. CEREVISIAE, HOMOLOG OF
read more*FIELD* TX
DESCRIPTION
The balance between fission and fusion regulates the morphology of
mitochondria. TTC11 is a component of a mitochondrial complex that
promotes mitochondrial fission (James et al., 2003).
CLONING
By searching for sequences similar to yeast Fis1, followed by PCR of a
liver cDNA library, James et al. (2003) cloned FIS1. The deduced
152-amino acid protein contains a central leucine zipper, a coiled-coil
region, and a C-terminal transmembrane domain. It also contains a region
showing high interspecies homology and a putative tetratricopeptide
repeat. Immunocytochemical analysis of HeLa cells detected endogenous
FIS1 expression in mitochondria. Protease treatment indicated that FIS1
is expressed at the outer mitochondrial membrane. Transfection of a
C-terminal truncated FIS1 resulted in cytoplasmic expression, indicating
that the C terminus is required for mitochondrial localization.
Yoon et al. (2003) cloned human FIS1 by PCR. The deduced 152-amino acid
protein has a calculated molecular mass of 17 kD.
GENE FUNCTION
By overexpression of FIS1 in various cell types, James et al. (2003)
found that FIS1 localizes to the outer mitochondrial membrane and
induces mitochondrial fission. Fission was inhibited by a
dominant-negative mutant of DRP1 (DNM1L; 603850). Fragmentation of the
tubular mitochondrial network by FIS1 was followed by the release of
cytochrome c and ultimately apoptosis. BCLXL (600039) blocked cytochrome
c release and apoptosis, but failed to prevent mitochondrial
fragmentation. James et al. (2003) concluded that FIS1 is part of the
mammalian fission machinery and that the regulation of mitochondrial
fission may be involved in apoptosis.
By differential tagging and deletion analysis, Yoon et al. (2003)
demonstrated that the C terminus of human FIS1 was essential for
mitochondrial localization, and that the cytosolic N terminus was
necessary for mitochondrial fission. Increased FIS1 expression promoted
mitochondrial fission and the accumulation of fragmented mitochondria.
Conversely, cells microinjected with anti-FIS1 antibodies or treated
with antisense FIS1 oligonucleotides developed elongated and collapsed
mitochondria. Furthermore, FRET and coimmunoprecipitation studies
demonstrated that human FIS1 interacted with rat Dnm1l, suggesting that
FIS1 participates in mitochondrial fission by recruiting DNM1L from the
cytosol. Yoon et al. (2003) concluded that FIS1 is a limiting factor in
mitochondrial fission and that the number of FIS1 molecules on the
mitochondrial surface determines fission frequency.
Frieden et al. (2004) found that the dramatic mitochondrial
fragmentation induced by FIS1 overexpression had no effect on the
mitochondrial transmembrane potential, pH, or the ability to take up
Ca(2+) released from intracellular stores upon agonist stimulation.
Malena et al. (2009) tested the hypothesis that altering the balance
between mitochondrial fusion and fission could influence the segregation
of mutant and wildtype mtDNA variants, because it would modify the
number of organelles per cell. Human cells heteroplasmic for the
pathologic 3243A-G (MTTL1; 590050.0001) mitochondrial DNA mutation were
transfected with constructs designed to silence DRP1 or human FIS1,
whose gene products are required for mitochondrial fission. DRP1 and
human FIS1 gene silencing were both associated with increased levels of
mutant mitochondrial DNA. The authors concluded that the extent of the
mitochondrial reticular network appears to be an important factor in
determining mutant load.
BIOCHEMICAL FEATURES
Dohm et al. (2004) determined the crystal structure of the cytosolic
domain of human FIS1 to 2.0-angstrom resolution. They found that FIS1
adopts a tetratricopeptide fold suitable for protein binding
interactions, and that the open structure has a concave binding surface
that can accommodate a helix. Helix alpha-1 of FIS1 may also act as a
molecular switch to promote either the monomeric or dimeric FIS1
conformation, modulating the accessibility of different binding
surfaces. The structure allows FIS1 to be free in solution, or to act as
a scaffold for protein interactions. Dohm et al. (2004) hypothesized
that FIS1 may be a target for signals mediating apoptosis as well as
fission.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the TTC11
gene to chromosome 7 (Genbank GENBANK WI-11506).
*FIELD* RF
1. Dohm, J. A.; Lee, S. J.; Hardwick, J. M.; Hill, R. B.; Gittis,
A. G.: Cytosolic domain of the human mitochondrial fission protein
Fis1 adopts a TPR fold. Proteins 54: 153-156, 2004.
2. Frieden, M.; James, D.; Castelbou, C.; Danckaert, A.; Martinou,
J.-C.; Demaurex, N.: Ca(2+) homeostasis during mitochondrial fragmentation
and perinuclear clustering induced by hFis1. J. Biol. Chem. 279:
22704-22714, 2004.
3. James, D. I.; Parone, P. A.; Mattenberger, Y.; Martinou, J.-C.
: hFis1, a novel component of the mammalian mitochondrial fission
machinery. J. Biol. Chem. 278: 36373-36379, 2003. Note: Erratum:
J. Biol. Chem. 279: 36166 only, 2004.
4. Malena, A.; Loro, E.; Di Re, M.; Holt, I. J.; Vergani, L.: Inhibition
of mitochondrial fission favours mutant over wild-type mitochondrial
DNA. Hum. Molec. Genet. 18: 3407-3416, 2009.
5. Yoon, Y.; Krueger, E. W.; Oswald, B. J.; McNiven, M. A.: The mitochondrial
protein hFis1 regulates mitochondrial fission in mammalian cells through
an interaction with the dynamin-like protein DLP1. Molec. Cell. Biol. 23:
5409-5420, 2003.
*FIELD* CN
George E. Tiller - updated: 7/7/2010
*FIELD* CD
Patricia A. Hartz: 10/28/2004
*FIELD* ED
mgross: 02/26/2013
alopez: 11/26/2012
alopez: 7/20/2010
terry: 7/7/2010
mgross: 1/22/2010
alopez: 10/28/2004