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Q9Y3D6 (FIS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitochondrial fission 1 protein
Alternative name(s):
FIS1 homolog
Short name=hFis1
Tetratricopeptide repeat protein 11
Short name=TPR repeat protein 11
Gene names
Name:FIS1
Synonyms:TTC11
ORF Names:CGI-135
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length152 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the fragmentation of the mitochondrial network and its perinuclear clustering. Plays a minor role in the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface and mitochondrial fission. Can induce cytochrome c release from the mitochondrion to the cytosol, ultimately leading to apoptosis. Also mediates peroxisomal fission. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.15 Ref.16

Subunit structure

Interacts with DNM1L/DLP1 through the TPR region. Interacts with MARCH5. Interacts with MIEF1. Ref.6 Ref.8 Ref.10 Ref.13

Subcellular location

Mitochondrion outer membrane; Single-pass membrane protein. Peroxisome membrane; Single-pass membrane protein Ref.5 Ref.7 Ref.9 Ref.14 Ref.18.

Domain

The C-terminus is required for mitochondrial or peroxisomal localization, while the N-terminus is necessary for mitochondrial or peroxisomal fission, localization and regulation of the interaction with DNM1L.

Post-translational modification

Ubiquitinated by MARCH5. Ref.10

Sequence similarities

Belongs to the FIS1 family.

Contains 1 TPR repeat.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentMembrane
Mitochondrion
Mitochondrion outer membrane
Peroxisome
   DomainTPR repeat
Transmembrane
Transmembrane helix
   PTMAcetylation
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium-mediated signaling using intracellular calcium source

Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB

mitochondrial fission

Inferred from direct assay Ref.8PubMed 18845145. Source: UniProtKB

mitochondrial fragmentation involved in apoptotic process

Inferred from direct assay Ref.8PubMed 17545159. Source: UniProtKB

mitochondrial fusion

Inferred from mutant phenotype Ref.14. Source: UniProtKB

mitochondrion degradation

Inferred from direct assay PubMed 18515060. Source: UniProtKB

mitochondrion morphogenesis

Inferred from mutant phenotype PubMed 18845145. Source: UniProtKB

negative regulation of endoplasmic reticulum calcium ion concentration

Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB

peroxisome fission

Inferred from direct assay Ref.9PubMed 17408615. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB

positive regulation of mitochondrial calcium ion concentration

Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB

positive regulation of mitochondrial fission

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of protein targeting to membrane

Inferred from direct assay Ref.15. Source: UniProtKB

protein homooligomerization

Inferred from mutant phenotype PubMed 18845145. Source: UniProtKB

protein targeting to mitochondrion

Inferred from mutant phenotype PubMed 18845145. Source: UniProtKB

regulation of mitochondrion organization

Inferred from mutant phenotype PubMed 18353969PubMed 21149567. Source: UniProtKB

release of cytochrome c from mitochondria

Inferred from mutant phenotype PubMed 19864424. Source: UniProtKB

   Cellular_componentintegral component of mitochondrial outer membrane

Inferred from direct assay Ref.7. Source: UniProtKB

integral component of peroxisomal membrane

Inferred from direct assay Ref.9PubMed 17408615. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 17408615PubMed 17545159PubMed 18782765PubMed 19864424PubMed 20451243PubMed 21183955. Source: UniProtKB

peroxisome

Inferred from direct assay PubMed 18782765PubMed 20451243Ref.14. Source: UniProtKB

protein complex

Inferred from direct assay PubMed 17408615PubMed 20826455. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.6Ref.10PubMed 17408615PubMed 18782765PubMed 20826455PubMed 21149567Ref.13. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 20178365. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BCAP31P515728EBI-3385283,EBI-77683
MIEF1Q9NQG64EBI-3385283,EBI-740987

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 152152Mitochondrial fission 1 protein
PRO_0000106393

Regions

Topological domain1 – 122122Cytoplasmic Potential
Transmembrane123 – 14321Helical; Potential
Topological domain144 – 1529Mitochondrial intermembrane Potential
Repeat71 – 10434TPR

Amino acid modifications

Modified residue11N-acetylmethionine Ref.4 Ref.11

Experimental info

Mutagenesis141L → P: Approximately 40% of cells display fragmented mitochondria. Ref.8
Mutagenesis421L → P: Less than 15% of cells display fragmented mitochondria. Ref.8
Mutagenesis581L → P: Less than 15% of cells display fragmented mitochondria. Ref.8
Mutagenesis771L → P: Less than 15% of cells display fragmented mitochondria. Shows greatly reduced binding to DNM1L. Ref.8
Mutagenesis911L → P: Less than 15% of cells display fragmented mitochondria. Shows greatly reduced binding to DNM1L. Ref.8
Mutagenesis1101L → P: Approximately 40% of cells display fragmented mitochondria. No change in binding to DNM1L. Ref.8
Mutagenesis1491K → A: Protein localizes to both mitochondrion and endoplasmic reticulum. Protein localizes to endoplasmic reticulum only; when associated with A-151. Ref.7
Mutagenesis1511K → A: Protein localizes to both mitochondrion and endoplasmic reticulum. Protein localizes to endoplasmic reticulum only; when associated with A-149. Ref.7
Sequence conflict45 – 462SK → TR in AAD34130. Ref.1

Secondary structure

.................. 152
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Y3D6 [UniParc].

Last modified July 19, 2003. Version 2.
Checksum: 6E76EC02B3731A9B

FASTA15216,938
        10         20         30         40         50         60 
MEAVLNELVS VEDLLKFEKK FQSEKAAGSV SKSTQFEYAW CLVRSKYNDD IRKGIVLLEE 

        70         80         90        100        110        120 
LLPKGSKEEQ RDYVFYLAVG NYRLKEYEKA LKYVRGLLQT EPQNNQAKEL ERLIDKAMKK 

       130        140        150 
DGLVGMAIVG GMALGVAGLA GLIGLAVSKS KS 

« Hide

References

« Hide 'large scale' references
[1]"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics."
Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.
Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[4]Bienvenut W.V.
Submitted (JUN-2005) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-16, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: B-cell lymphoma.
[5]"hFis1, a novel component of the mammalian mitochondrial fission machinery."
James D.I., Parone P.A., Mattenberger Y., Martinou J.-C.
J. Biol. Chem. 278:36373-36379(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]"The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1."
Yoon Y., Krueger E.W., Oswald B.J., McNiven M.A.
Mol. Cell. Biol. 23:5409-5420(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DNM1L.
[7]"Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology."
Stojanovski D., Koutsopoulos O.S., Okamoto K., Ryan M.T.
J. Cell Sci. 117:1201-1210(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF LYS-149 AND LYS-151.
[8]"Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1."
Yu T., Fox R.J., Burwell L.S., Yoon Y.
J. Cell Sci. 118:4141-4151(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DNM1L, MUTAGENESIS OF LEU-14; LEU-42; LEU-58; LEU-77; LEU-91 AND LEU-110.
[9]"A role for Fis1 in both mitochondrial and peroxisomal fission in mammalian cells."
Koch A., Yoon Y., Bonekamp N.A., McNiven M.A., Schrader M.
Mol. Biol. Cell 16:5077-5086(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]"A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics."
Yonashiro R., Ishido S., Kyo S., Fukuda T., Goto E., Matsuki Y., Ohmura-Hoshino M., Sada K., Hotta H., Yamamura H., Inatome R., Yanagi S.
EMBO J. 25:3618-3626(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY MARCH5, INTERACTION WITH MARCH5.
[11]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission."
Zhao J., Liu T., Jin S., Wang X., Qu M., Uhlen P., Tomilin N., Shupliakov O., Lendahl U., Nister M.
EMBO J. 30:2762-2778(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MIEF1.
[14]"MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission."
Palmer C.S., Elgass K.D., Parton R.G., Osellame L.D., Stojanovski D., Ryan M.T.
J. Biol. Chem. 288:27584-27593(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[15]"Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission."
Loson O.C., Song Z., Chen H., Chan D.C.
Mol. Biol. Cell 24:659-667(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission."
Koirala S., Guo Q., Kalia R., Bui H.T., Eckert D.M., Frost A., Shaw J.M.
Proc. Natl. Acad. Sci. U.S.A. 110:E1342-E1351(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"Cytosolic domain of the human mitochondrial fission protein fis1 adopts a TPR fold."
Dohm J.A., Lee S.J., Hardwick J.M., Hill R.B., Gittis A.G.
Proteins 54:153-156(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-123.
[18]"The solution structure of human mitochondria fission protein Fis1 reveals a novel TPR-like helix bundle."
Suzuki M., Jeong S.-Y., Karbowski M., Youle R.J., Tjandra N.
J. Mol. Biol. 334:445-458(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF151893 mRNA. Translation: AAD34130.1.
AC006329 Genomic DNA. Translation: AAP22366.1.
BC003540 mRNA. Translation: AAH03540.1.
BC009428 mRNA. Translation: AAH09428.1.
CCDSCCDS43626.1.
RefSeqNP_057152.2. NM_016068.2.
UniGeneHs.423968.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NZNX-ray2.00A1-123[»]
1PC2NMR-A1-145[»]
DisProtDP00457.
ProteinModelPortalQ9Y3D6.
SMRQ9Y3D6. Positions 1-145.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119230. 23 interactions.
IntActQ9Y3D6. 9 interactions.
MINTMINT-2844167.
STRING9606.ENSP00000223136.

PTM databases

PhosphoSiteQ9Y3D6.

Polymorphism databases

DMDM33112470.

2D gel databases

UCD-2DPAGEQ9Y3D6.

Proteomic databases

MaxQBQ9Y3D6.
PaxDbQ9Y3D6.
PeptideAtlasQ9Y3D6.
PRIDEQ9Y3D6.

Protocols and materials databases

DNASU51024.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000223136; ENSP00000223136; ENSG00000214253.
GeneID51024.
KEGGhsa:51024.
UCSCuc003uyj.4. human.

Organism-specific databases

CTD51024.
GeneCardsGC07M100882.
HGNCHGNC:21689. FIS1.
HPAHPA017430.
MIM609003. gene.
neXtProtNX_Q9Y3D6.
PharmGKBPA134984211.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG235677.
HOGENOMHOG000165386.
HOVERGENHBG081530.
InParanoidQ9Y3D6.
KOK17969.
OMAEIFRTSP.
PhylomeDBQ9Y3D6.
TreeFamTF315180.

Gene expression databases

ArrayExpressQ9Y3D6.
BgeeQ9Y3D6.
CleanExHS_FIS1.
GenevestigatorQ9Y3D6.

Family and domain databases

Gene3D1.25.40.10. 1 hit.
InterProIPR016543. Fis1.
IPR028061. Fis1_TPR_C.
IPR028058. Fis1_TPR_N.
IPR011990. TPR-like_helical.
[Graphical view]
PANTHERPTHR13247. PTHR13247. 1 hit.
PfamPF14853. Fis1_TPR_C. 1 hit.
PF14852. Fis1_TPR_N. 1 hit.
[Graphical view]
PIRSFPIRSF008835. TPR_repeat_11_Fis1. 1 hit.
ProtoNetSearch...

Other

ChiTaRSFIS1. human.
EvolutionaryTraceQ9Y3D6.
GeneWikiFIS1.
GenomeRNAi51024.
NextBio53558.
PROQ9Y3D6.
SOURCESearch...

Entry information

Entry nameFIS1_HUMAN
AccessionPrimary (citable) accession number: Q9Y3D6
Secondary accession number(s): Q9BTP3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2003
Last sequence update: July 19, 2003
Last modified: July 9, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM