Q9Y3D6 (FIS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	152 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Promotes the fragmentation of the mitochondrial network and its perinuclear clustering. 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
Subunit structure	Interacts with DNM1L/DLP1 through the TPR region. Interacts with MARCH5. Interacts with MID51. Ref.6 Ref.8 Ref.10 Ref.12
Subcellular location	Mitochondrion outer membrane; Single-pass membrane protein. Peroxisome membrane; Single-pass membrane protein Ref.5 Ref.7 Ref.9 Ref.14.
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 process	Apoptosis
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane Peroxisome
Domain	TPR repeat Transmembrane Transmembrane helix
PTM	Acetylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	calcium-mediated signaling using intracellular calcium source Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB elevation of cytosolic calcium ion concentration Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB elevation of mitochondrial calcium ion concentration Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB mitochondrial fragmentation involved in apoptotic process Inferred from direct assay PubMed 17545159. Source: UniProtKB mitochondrion degradation Inferred from direct assay PubMed 18515060. Source: UniProtKB mitochondrion morphogenesis Inferred from mutant phenotype PubMed 18845145. 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 intrinsic apoptotic signaling pathway Inferred from mutant phenotype PubMed 21183955. Source: UniProtKB protein homooligomerization Inferred from mutant phenotype PubMed 18845145. Source: UniProtKB protein targeting to mitochondrion Inferred from mutant phenotype PubMed 18845145. Source: UniProtKB reduction of endoplasmic reticulum calcium ion concentration Inferred from mutant phenotype PubMed 21183955. 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_component	integral to mitochondrial outer membrane Inferred from direct assay Ref.7. Source: UniProtKB integral to peroxisomal membrane Inferred from direct assay Ref.9PubMed 17408615. Source: UniProtKB protein complex Inferred from direct assay PubMed 17408615PubMed 20826455. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCAP31	P51572	8	EBI-3385283,EBI-77683

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 152

152

Mitochondrial fission 1 protein

PRO_0000106393

Regions

Topological domain

1 – 122

122

Cytoplasmic Potential

Transmembrane

123 – 143

21

Helical; Potential

Topological domain

144 – 152

9

Mitochondrial intermembrane Potential

Repeat

71 – 104

34

TPR

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.4

Experimental info

Mutagenesis

14

1

L → P: Approximately 40% of cells display fragmented mitochondria. Ref.8

Mutagenesis

42

1

L → P: Less than 15% of cells display fragmented mitochondria. Ref.8

Mutagenesis

58

1

L → P: Less than 15% of cells display fragmented mitochondria. Ref.8

Mutagenesis

77

1

L → P: Less than 15% of cells display fragmented mitochondria. Shows greatly reduced binding to DNM1L. Ref.8

Mutagenesis

91

1

L → P: Less than 15% of cells display fragmented mitochondria. Shows greatly reduced binding to DNM1L. Ref.8

Mutagenesis

110

1

L → P: Approximately 40% of cells display fragmented mitochondria. No change in binding to DNM1L. Ref.8

Mutagenesis

149

1

K → A: Protein localizes to both mitochondrion and endoplasmic reticulum. Protein localizes to endoplasmic reticulum only; when associated with A-151. Ref.7

Mutagenesis

151

1

K → A: Protein localizes to both mitochondrion and endoplasmic reticulum. Protein localizes to endoplasmic reticulum only; when associated with A-149. Ref.7

Sequence conflict

45 – 46

2

SK → TR in AAD34130. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

152

Helix Strand Turn

Details...

Helix

1 – 27

27

Helix

32 – 42

11

Beta strand

45 – 47

3

Helix

48 – 61

14

Turn

62 – 64

3

Helix

67 – 83

17

Helix

87 – 100

14

Helix

105 – 120

16

Beta strand

129 – 133

5

Beta strand

142 – 144

3

Sequences

	Sequence		Length	Mass (Da)
	Q9Y3D6 [UniParc]. Last modified July 19, 2003. Version 2. Checksum: 6E76EC02B3731A9B	FASTA	152	16,938
	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

References

	« Hide 'large scale' referencesShow '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. , 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, 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]	"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].
[12]	"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 MID51.
[13]	"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.
[14]	"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.

IPI

IPI00007052.

RefSeq

NP_057152.2. NM_016068.2.

UniGene

Hs.423968.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NZN	X-ray	2.00	A	1-123	[»]
1PC2	NMR	-	A	1-145	[»]

DisProt

DP00457.

ProteinModelPortal

Q9Y3D6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y3D6. 4 interactions.

MINT

MINT-2844167.

STRING

9606.ENSP00000223136.

PTM databases

PhosphoSite

Q9Y3D6.

Polymorphism databases

DMDM

33112470.

2D gel databases

UCD-2DPAGE

Q9Y3D6.

Proteomic databases

PaxDb

Q9Y3D6.

PeptideAtlas

Q9Y3D6.

PRIDE

Q9Y3D6.

Protocols and materials databases

DNASU

51024.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000223136; ENSP00000223136; ENSG00000214253.

GeneID

51024.

KEGG

hsa:51024.

UCSC

uc003uyj.4. human.

Organism-specific databases

CTD

51024.

GeneCards

GC07M100882.

HGNC

HGNC:21689. FIS1.

HPA

HPA017430.

MIM

609003. gene.

neXtProt

NX_Q9Y3D6.

PharmGKB

PA134984211.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG235677.

HOGENOM

HOG000165386.

HOVERGEN

HBG081530.

InParanoid

Q9Y3D6.

OMA

DKALKKD.

OrthoDB

EOG4XSKRC.

PhylomeDB

Q9Y3D6.

Gene expression databases

ArrayExpress

Q9Y3D6.

Bgee

Q9Y3D6.

CleanEx

HS_FIS1.

Genevestigator

Q9Y3D6.

GermOnline

ENSG00000106404. Homo sapiens.

Family and domain databases

Gene3D

1.25.40.10. 1 hit.

InterPro

IPR016543. Tetratricopeptide_rpt_11_Fis1.
IPR011990. TPR-like_helical.
[Graphical view]

PANTHER

PTHR13247. PTHR13247. 1 hit.

PIRSF

PIRSF008835. TPR_repeat_11_Fis1. 1 hit.

PROSITE

PS50005. TPR. False negative.
PS50293. TPR_REGION. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

FIS1. human.

EvolutionaryTrace

Q9Y3D6.

GenomeRNAi

51024.

NextBio

53558.

SOURCE

Search...

Entry information

Entry name

FIS1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.