Full text data of IMMT
IMMT
(HMP, MINOS2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Mitochondrial inner membrane protein (Cell proliferation-inducing gene 4/52 protein; Mitofilin; p87/89)
Mitochondrial inner membrane protein (Cell proliferation-inducing gene 4/52 protein; Mitofilin; p87/89)
Comments
Isoform Q16891-3 was detected.
Isoform Q16891-3 was detected.
UniProt
Q16891
ID IMMT_HUMAN Reviewed; 758 AA.
AC Q16891; B1H0U5; B2R5N6; Q14539; Q15092; Q68D41; Q69HW5; Q6IBL0;
read moreAC Q7Z3X1; Q8TAJ5; Q9P0V2;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Mitochondrial inner membrane protein;
DE AltName: Full=Cell proliferation-inducing gene 4/52 protein;
DE AltName: Full=Mitofilin;
DE AltName: Full=p87/89;
GN Name=IMMT; Synonyms=HMP, MINOS2; ORFNames=PIG4, PIG52;
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 [MRNA] (ISOFORM 1).
RX PubMed=8039717; DOI=10.1016/0378-1119(94)90394-8;
RA Icho T., Ikeda T., Matsumoto Y., Hanaoka F., Kaji K., Tsuchida N.;
RT "A novel human gene that is preferentially transcribed in heart
RT muscle.";
RL Gene 144:301-306(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-124.
RX PubMed=9168817; DOI=10.1006/excr.1997.3539;
RA Gieffers C., Korioth F., Heimann P., Ungermann C., Frey J.;
RT "Mitofilin is a transmembrane protein of the inner mitochondrial
RT membrane expressed as two isoforms.";
RL Exp. Cell Res. 232:395-399(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RA Kim J.W., Kim H.K., Shin S.M.;
RT "Identification of a human cell proliferation gene.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 159-758 (ISOFORM 3), AND VARIANT
RP SER-124.
RC TISSUE=Colon endothelium, and Fetal liver;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix, and Muscle;
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 [8]
RP PROTEIN SEQUENCE OF 85-101; 103-119; 123-130; 171-195; 223-229;
RP 258-269; 287-297; 316-343; 345-366; 386-395; 428-436; 500-525;
RP 548-564; 582-600; 624-632; 645-652 AND 720-726, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (APR-2005) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 144-758 (ISOFORM 1).
RC TISSUE=Mammary carcinoma;
RA Weidenmueller U., Tur M.K., Tawadros S., Engert A., Barth S.;
RT "Detection of membrane-associated proteins using serum of mice
RT immunized with membrane fractions of breast carcinoma cells.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP PROTEIN SEQUENCE OF 354-366; 372-385; 517-525; 527-545; 548-564 AND
RP 601-623, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-211; LYS-222 AND LYS-451,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(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 CHCHD3 AND OPA1.
RX PubMed=21081504; DOI=10.1074/jbc.M110.171975;
RA Darshi M., Mendiola V.L., Mackey M.R., Murphy A.N., Koller A.,
RA Perkins G.A., Ellisman M.H., Taylor S.S.;
RT "ChChd3, an inner mitochondrial membrane protein, is essential for
RT maintaining crista integrity and mitochondrial function.";
RL J. Biol. Chem. 286:2918-2932(2011).
RN [14]
RP IDENTIFICATION IN THE MINOS/MITOS COMPLEX.
RX PubMed=22114354; DOI=10.1091/mbc.E11-09-0774;
RA Alkhaja A.K., Jans D.C., Nikolov M., Vukotic M., Lytovchenko O.,
RA Ludewig F., Schliebs W., Riedel D., Urlaub H., Jakobs S., Deckers M.;
RT "MINOS1 is a conserved component of mitofilin complexes and required
RT for mitochondrial function and cristae organization.";
RL Mol. Biol. Cell 23:247-257(2012).
RN [15]
RP INTERACTION WITH CHCHD6.
RX PubMed=22228767; DOI=10.1074/jbc.M111.277103;
RA An J., Shi J., He Q., Lui K., Liu Y., Huang Y., Sheikh M.S.;
RT "CHCM1/CHCHD6, a novel mitochondrial protein linked to regulation of
RT mitofilin and mitochondrial cristae morphology.";
RL J. Biol. Chem. 287:7411-7426(2012).
CC -!- SUBUNIT: Interacts with OPA1, preferentially with the soluble OPA1
CC form. Component of the MINOS/MitOS complex, that includes IMMT,
CC HSPA9 and CHCHD3 and associates with mitochondrial outer membrane
CC proteins SAMM50, MTX1 and MTX2. Interacts with CHCHD6; the
CC interaction is direct.
CC -!- INTERACTION:
CC O60341:KDM1A; NbExp=2; IntAct=EBI-473801, EBI-710124;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q16891-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16891-2; Sequence=VSP_013220;
CC Name=3;
CC IsoId=Q16891-3; Sequence=VSP_013221;
CC Name=4;
CC IsoId=Q16891-4; Sequence=VSP_047362;
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH18389.1; Type=Erroneous termination; Positions=759; Note=Translated as stop;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D21091; BAA04653.1; -; mRNA.
DR EMBL; D21092; BAA04654.1; -; mRNA.
DR EMBL; D21093; BAA04655.1; -; mRNA.
DR EMBL; D21094; BAA04656.1; -; mRNA.
DR EMBL; L42572; AAA85336.1; -; mRNA.
DR EMBL; CR456793; CAG33074.1; -; mRNA.
DR EMBL; AK312251; BAG35183.1; -; mRNA.
DR EMBL; AY232292; AAP69987.1; -; mRNA.
DR EMBL; AY921637; AAX10024.1; -; mRNA.
DR EMBL; BX537369; CAD97612.1; -; mRNA.
DR EMBL; CR749590; CAH18389.1; ALT_TERM; mRNA.
DR EMBL; BC002412; AAH02412.1; -; mRNA.
DR EMBL; BC027458; AAH27458.1; -; mRNA.
DR EMBL; AF148646; AAF73126.1; -; mRNA.
DR RefSeq; NP_001093639.1; NM_001100169.1.
DR RefSeq; NP_001093640.1; NM_001100170.1.
DR RefSeq; NP_006830.2; NM_006839.2.
DR RefSeq; XP_005264170.1; XM_005264113.1.
DR UniGene; Hs.148559; -.
DR ProteinModelPortal; Q16891; -.
DR DIP; DIP-32517N; -.
DR IntAct; Q16891; 69.
DR MINT; MINT-1034498; -.
DR PhosphoSite; Q16891; -.
DR DMDM; 29427676; -.
DR REPRODUCTION-2DPAGE; IPI00554469; -.
DR REPRODUCTION-2DPAGE; Q16891; -.
DR PaxDb; Q16891; -.
DR PRIDE; Q16891; -.
DR DNASU; 10989; -.
DR Ensembl; ENST00000410111; ENSP00000387262; ENSG00000132305.
DR Ensembl; ENST00000442664; ENSP00000407788; ENSG00000132305.
DR Ensembl; ENST00000449247; ENSP00000396899; ENSG00000132305.
DR GeneID; 10989; -.
DR KEGG; hsa:10989; -.
DR UCSC; uc002sqy.4; human.
DR CTD; 10989; -.
DR GeneCards; GC02M086282; -.
DR HGNC; HGNC:6047; IMMT.
DR HPA; CAB022439; -.
DR MIM; 600378; gene.
DR neXtProt; NX_Q16891; -.
DR PharmGKB; PA29858; -.
DR eggNOG; NOG307662; -.
DR HOVERGEN; HBG039233; -.
DR InParanoid; Q16891; -.
DR OMA; QKQKGDT; -.
DR ChiTaRS; IMMT; human.
DR GeneWiki; IMMT; -.
DR GenomeRNAi; 10989; -.
DR NextBio; 41751; -.
DR PRO; PR:Q16891; -.
DR ArrayExpress; Q16891; -.
DR Bgee; Q16891; -.
DR Genevestigator; Q16891; -.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR InterPro; IPR019133; Mt-IM_prot_Mitofilin.
DR Pfam; PF09731; Mitofilin; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Polymorphism; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 758 Mitochondrial inner membrane protein.
FT /FTId=PRO_0000084184.
FT TOPO_DOM 1 45 Mitochondrial matrix (Potential).
FT TRANSMEM 46 64 Helical; (Potential).
FT TOPO_DOM 65 758 Mitochondrial intermembrane (Potential).
FT MOD_RES 211 211 N6-acetyllysine.
FT MOD_RES 222 222 N6-acetyllysine.
FT MOD_RES 451 451 N6-acetyllysine.
FT VAR_SEQ 142 152 Missing (in isoform 2).
FT /FTId=VSP_013220.
FT VAR_SEQ 187 219 EEASSSSIRERPPEEVAARLAQQEKQEQVKIES -> A
FT (in isoform 3).
FT /FTId=VSP_013221.
FT VAR_SEQ 188 188 Missing (in isoform 4).
FT /FTId=VSP_047362.
FT VARIANT 124 124 P -> S (in dbSNP:rs6750289).
FT /FTId=VAR_021530.
FT VARIANT 294 294 A -> V (in dbSNP:rs35233009).
FT /FTId=VAR_051068.
FT CONFLICT 144 151 EAAQIISA -> ARAPASLT (in Ref. 9;
FT AAF73126).
FT CONFLICT 151 151 A -> S (in Ref. 3; CAG33074).
FT CONFLICT 154 154 D -> E (in Ref. 4; BAG35183).
FT CONFLICT 173 173 H -> Y (in Ref. 9; AAF73126).
FT CONFLICT 312 312 A -> T (in Ref. 9; AAF73126).
FT CONFLICT 325 325 T -> S (in Ref. 9; AAF73126).
FT CONFLICT 388 393 SVSDLA -> T (in Ref. 9; AAF73126).
FT CONFLICT 432 432 L -> S (in Ref. 6; CAH18389).
FT CONFLICT 449 449 V -> A (in Ref. 6; CAH18389).
FT CONFLICT 731 731 T -> A (in Ref. 6; CAH18389).
FT CONFLICT 758 758 E -> D (in Ref. 3; CAG33074).
SQ SEQUENCE 758 AA; 83678 MW; 357F25DCABB02E50 CRC64;
MLRACQLSGV TAAAQSCLCG KFVLRPLRPC RRYSTSGSSG LTTGKIAGAG LLFVGGGIGG
TILYAKWDSH FRESVEKTIP YSDKLFEMVL GPAAYNVPLP KKSIQSGPLK ISSVSEVMKE
SKQPASQLQK QKGDTPASAT APTEAAQIIS AAGDTLSVPA PAVQPEESLK TDHPEIGEGK
PTPALSEEAS SSSIRERPPE EVAARLAQQE KQEQVKIESL AKSLEDALRQ TASVTLQAIA
AQNAAVQAVN AHSNILKAAM DNSEIAGEKK SAQWRTVEGA LKERRKAVDE AADALLKAKE
ELEKMKSVIE NAKKKEVAGA KPHITAAEGK LHNMIVDLDN VVKKVQAAQS EAKVVSQYHE
LVVQARDDFK RELDSITPEV LPGWKGMSVS DLADKLSTDD LNSLIAHAHR RIDQLNRELA
EQKATEKQHI TLALEKQKLE EKRAFDSAVA KALEHHRSEI QAEQDRKIEE VRDAMENEMR
TQLRRQAAAH TDHLRDVLRV QEQELKSEFE QNLSEKLSEQ ELQFRRLSQE QVDNFTLDIN
TAYARLRGIE QAVQSHAVAE EEARKAHQLW LSVEALKYSM KTSSAETPTI PLGSAVEAIK
ANCSDNEFTQ ALTAAIPPES LTRGVYSEET LRARFYAVQK LARRVAMIDE TRNSLYQYFL
SYLQSLLLFP PQQLKPPPEL CPEDINTFKL LSYASYCIEH GDLELAAKFV NQLKGESRRV
AQDWLKEARM TLETKQIVEI LTAYASAVGI GTTQVQPE
//
ID IMMT_HUMAN Reviewed; 758 AA.
AC Q16891; B1H0U5; B2R5N6; Q14539; Q15092; Q68D41; Q69HW5; Q6IBL0;
read moreAC Q7Z3X1; Q8TAJ5; Q9P0V2;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Mitochondrial inner membrane protein;
DE AltName: Full=Cell proliferation-inducing gene 4/52 protein;
DE AltName: Full=Mitofilin;
DE AltName: Full=p87/89;
GN Name=IMMT; Synonyms=HMP, MINOS2; ORFNames=PIG4, PIG52;
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 [MRNA] (ISOFORM 1).
RX PubMed=8039717; DOI=10.1016/0378-1119(94)90394-8;
RA Icho T., Ikeda T., Matsumoto Y., Hanaoka F., Kaji K., Tsuchida N.;
RT "A novel human gene that is preferentially transcribed in heart
RT muscle.";
RL Gene 144:301-306(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-124.
RX PubMed=9168817; DOI=10.1006/excr.1997.3539;
RA Gieffers C., Korioth F., Heimann P., Ungermann C., Frey J.;
RT "Mitofilin is a transmembrane protein of the inner mitochondrial
RT membrane expressed as two isoforms.";
RL Exp. Cell Res. 232:395-399(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RA Kim J.W., Kim H.K., Shin S.M.;
RT "Identification of a human cell proliferation gene.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 159-758 (ISOFORM 3), AND VARIANT
RP SER-124.
RC TISSUE=Colon endothelium, and Fetal liver;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix, and Muscle;
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 [8]
RP PROTEIN SEQUENCE OF 85-101; 103-119; 123-130; 171-195; 223-229;
RP 258-269; 287-297; 316-343; 345-366; 386-395; 428-436; 500-525;
RP 548-564; 582-600; 624-632; 645-652 AND 720-726, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (APR-2005) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 144-758 (ISOFORM 1).
RC TISSUE=Mammary carcinoma;
RA Weidenmueller U., Tur M.K., Tawadros S., Engert A., Barth S.;
RT "Detection of membrane-associated proteins using serum of mice
RT immunized with membrane fractions of breast carcinoma cells.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP PROTEIN SEQUENCE OF 354-366; 372-385; 517-525; 527-545; 548-564 AND
RP 601-623, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-211; LYS-222 AND LYS-451,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(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 CHCHD3 AND OPA1.
RX PubMed=21081504; DOI=10.1074/jbc.M110.171975;
RA Darshi M., Mendiola V.L., Mackey M.R., Murphy A.N., Koller A.,
RA Perkins G.A., Ellisman M.H., Taylor S.S.;
RT "ChChd3, an inner mitochondrial membrane protein, is essential for
RT maintaining crista integrity and mitochondrial function.";
RL J. Biol. Chem. 286:2918-2932(2011).
RN [14]
RP IDENTIFICATION IN THE MINOS/MITOS COMPLEX.
RX PubMed=22114354; DOI=10.1091/mbc.E11-09-0774;
RA Alkhaja A.K., Jans D.C., Nikolov M., Vukotic M., Lytovchenko O.,
RA Ludewig F., Schliebs W., Riedel D., Urlaub H., Jakobs S., Deckers M.;
RT "MINOS1 is a conserved component of mitofilin complexes and required
RT for mitochondrial function and cristae organization.";
RL Mol. Biol. Cell 23:247-257(2012).
RN [15]
RP INTERACTION WITH CHCHD6.
RX PubMed=22228767; DOI=10.1074/jbc.M111.277103;
RA An J., Shi J., He Q., Lui K., Liu Y., Huang Y., Sheikh M.S.;
RT "CHCM1/CHCHD6, a novel mitochondrial protein linked to regulation of
RT mitofilin and mitochondrial cristae morphology.";
RL J. Biol. Chem. 287:7411-7426(2012).
CC -!- SUBUNIT: Interacts with OPA1, preferentially with the soluble OPA1
CC form. Component of the MINOS/MitOS complex, that includes IMMT,
CC HSPA9 and CHCHD3 and associates with mitochondrial outer membrane
CC proteins SAMM50, MTX1 and MTX2. Interacts with CHCHD6; the
CC interaction is direct.
CC -!- INTERACTION:
CC O60341:KDM1A; NbExp=2; IntAct=EBI-473801, EBI-710124;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q16891-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16891-2; Sequence=VSP_013220;
CC Name=3;
CC IsoId=Q16891-3; Sequence=VSP_013221;
CC Name=4;
CC IsoId=Q16891-4; Sequence=VSP_047362;
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH18389.1; Type=Erroneous termination; Positions=759; Note=Translated as stop;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D21091; BAA04653.1; -; mRNA.
DR EMBL; D21092; BAA04654.1; -; mRNA.
DR EMBL; D21093; BAA04655.1; -; mRNA.
DR EMBL; D21094; BAA04656.1; -; mRNA.
DR EMBL; L42572; AAA85336.1; -; mRNA.
DR EMBL; CR456793; CAG33074.1; -; mRNA.
DR EMBL; AK312251; BAG35183.1; -; mRNA.
DR EMBL; AY232292; AAP69987.1; -; mRNA.
DR EMBL; AY921637; AAX10024.1; -; mRNA.
DR EMBL; BX537369; CAD97612.1; -; mRNA.
DR EMBL; CR749590; CAH18389.1; ALT_TERM; mRNA.
DR EMBL; BC002412; AAH02412.1; -; mRNA.
DR EMBL; BC027458; AAH27458.1; -; mRNA.
DR EMBL; AF148646; AAF73126.1; -; mRNA.
DR RefSeq; NP_001093639.1; NM_001100169.1.
DR RefSeq; NP_001093640.1; NM_001100170.1.
DR RefSeq; NP_006830.2; NM_006839.2.
DR RefSeq; XP_005264170.1; XM_005264113.1.
DR UniGene; Hs.148559; -.
DR ProteinModelPortal; Q16891; -.
DR DIP; DIP-32517N; -.
DR IntAct; Q16891; 69.
DR MINT; MINT-1034498; -.
DR PhosphoSite; Q16891; -.
DR DMDM; 29427676; -.
DR REPRODUCTION-2DPAGE; IPI00554469; -.
DR REPRODUCTION-2DPAGE; Q16891; -.
DR PaxDb; Q16891; -.
DR PRIDE; Q16891; -.
DR DNASU; 10989; -.
DR Ensembl; ENST00000410111; ENSP00000387262; ENSG00000132305.
DR Ensembl; ENST00000442664; ENSP00000407788; ENSG00000132305.
DR Ensembl; ENST00000449247; ENSP00000396899; ENSG00000132305.
DR GeneID; 10989; -.
DR KEGG; hsa:10989; -.
DR UCSC; uc002sqy.4; human.
DR CTD; 10989; -.
DR GeneCards; GC02M086282; -.
DR HGNC; HGNC:6047; IMMT.
DR HPA; CAB022439; -.
DR MIM; 600378; gene.
DR neXtProt; NX_Q16891; -.
DR PharmGKB; PA29858; -.
DR eggNOG; NOG307662; -.
DR HOVERGEN; HBG039233; -.
DR InParanoid; Q16891; -.
DR OMA; QKQKGDT; -.
DR ChiTaRS; IMMT; human.
DR GeneWiki; IMMT; -.
DR GenomeRNAi; 10989; -.
DR NextBio; 41751; -.
DR PRO; PR:Q16891; -.
DR ArrayExpress; Q16891; -.
DR Bgee; Q16891; -.
DR Genevestigator; Q16891; -.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR InterPro; IPR019133; Mt-IM_prot_Mitofilin.
DR Pfam; PF09731; Mitofilin; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Polymorphism; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 758 Mitochondrial inner membrane protein.
FT /FTId=PRO_0000084184.
FT TOPO_DOM 1 45 Mitochondrial matrix (Potential).
FT TRANSMEM 46 64 Helical; (Potential).
FT TOPO_DOM 65 758 Mitochondrial intermembrane (Potential).
FT MOD_RES 211 211 N6-acetyllysine.
FT MOD_RES 222 222 N6-acetyllysine.
FT MOD_RES 451 451 N6-acetyllysine.
FT VAR_SEQ 142 152 Missing (in isoform 2).
FT /FTId=VSP_013220.
FT VAR_SEQ 187 219 EEASSSSIRERPPEEVAARLAQQEKQEQVKIES -> A
FT (in isoform 3).
FT /FTId=VSP_013221.
FT VAR_SEQ 188 188 Missing (in isoform 4).
FT /FTId=VSP_047362.
FT VARIANT 124 124 P -> S (in dbSNP:rs6750289).
FT /FTId=VAR_021530.
FT VARIANT 294 294 A -> V (in dbSNP:rs35233009).
FT /FTId=VAR_051068.
FT CONFLICT 144 151 EAAQIISA -> ARAPASLT (in Ref. 9;
FT AAF73126).
FT CONFLICT 151 151 A -> S (in Ref. 3; CAG33074).
FT CONFLICT 154 154 D -> E (in Ref. 4; BAG35183).
FT CONFLICT 173 173 H -> Y (in Ref. 9; AAF73126).
FT CONFLICT 312 312 A -> T (in Ref. 9; AAF73126).
FT CONFLICT 325 325 T -> S (in Ref. 9; AAF73126).
FT CONFLICT 388 393 SVSDLA -> T (in Ref. 9; AAF73126).
FT CONFLICT 432 432 L -> S (in Ref. 6; CAH18389).
FT CONFLICT 449 449 V -> A (in Ref. 6; CAH18389).
FT CONFLICT 731 731 T -> A (in Ref. 6; CAH18389).
FT CONFLICT 758 758 E -> D (in Ref. 3; CAG33074).
SQ SEQUENCE 758 AA; 83678 MW; 357F25DCABB02E50 CRC64;
MLRACQLSGV TAAAQSCLCG KFVLRPLRPC RRYSTSGSSG LTTGKIAGAG LLFVGGGIGG
TILYAKWDSH FRESVEKTIP YSDKLFEMVL GPAAYNVPLP KKSIQSGPLK ISSVSEVMKE
SKQPASQLQK QKGDTPASAT APTEAAQIIS AAGDTLSVPA PAVQPEESLK TDHPEIGEGK
PTPALSEEAS SSSIRERPPE EVAARLAQQE KQEQVKIESL AKSLEDALRQ TASVTLQAIA
AQNAAVQAVN AHSNILKAAM DNSEIAGEKK SAQWRTVEGA LKERRKAVDE AADALLKAKE
ELEKMKSVIE NAKKKEVAGA KPHITAAEGK LHNMIVDLDN VVKKVQAAQS EAKVVSQYHE
LVVQARDDFK RELDSITPEV LPGWKGMSVS DLADKLSTDD LNSLIAHAHR RIDQLNRELA
EQKATEKQHI TLALEKQKLE EKRAFDSAVA KALEHHRSEI QAEQDRKIEE VRDAMENEMR
TQLRRQAAAH TDHLRDVLRV QEQELKSEFE QNLSEKLSEQ ELQFRRLSQE QVDNFTLDIN
TAYARLRGIE QAVQSHAVAE EEARKAHQLW LSVEALKYSM KTSSAETPTI PLGSAVEAIK
ANCSDNEFTQ ALTAAIPPES LTRGVYSEET LRARFYAVQK LARRVAMIDE TRNSLYQYFL
SYLQSLLLFP PQQLKPPPEL CPEDINTFKL LSYASYCIEH GDLELAAKFV NQLKGESRRV
AQDWLKEARM TLETKQIVEI LTAYASAVGI GTTQVQPE
//
MIM
600378
*RECORD*
*FIELD* NO
600378
*FIELD* TI
*600378 INNER MEMBRANE PROTEIN, MITOCHONDRIAL; IMMT
;;MITOFILIN;;
HEART MUSCLE PROTEIN; HMP
read more*FIELD* TX
DESCRIPTION
Mitochondria are the center of cellular energy production, and cristae
of the inner mitochondrial membrane undergo morphologic changes in
response to metabolic state. Mitofilin is a protein of the inner
mitochondrial membrane that regulates mitochondrial cristae morphology
(John et al., 2005).
CLONING
The heart muscle protein gene is expressed predominantly in the heart
and is proposed to be an ATP-driven motor protein that interacts with
cytoskeletal components. Icho et al. (1994) cloned a full-length 2.7-kb
cDNA coding for a 758-amino acid protein. The protein has a possible
ATP-binding domain at the N terminus and a long alpha-helical domain
that could form a coiled-coil structure. Proteins with similar
structures include myosin II (see 160730), an actin-based motor protein,
and kinesin (see 602809), a microtubule-based motor protein.
By screening an osteoblast cDNA library and PCR of total RNA isolated
from MG63 human osteosarcoma cells, Gieffers et al. (1997) cloned 2
splice variants of mitofilin. The variants differ in the presence or
absence of 33 bp in the coding region, and the deduced proteins contain
758 or 747 amino acids. Both proteins contain a cleavable 34-amino acid
N-terminal mitochondrial targeting signal, followed by a transmembrane
domain and a large C-terminal domain. The shorter protein lacks 11 amino
acids following the transmembrane domain. Gieffers et al. (1997)
determined that mitofilin is anchored to the inner mitochondrial
membrane, with the short N terminus facing the mitochondrial matrix and
the large C-terminal domain extending into the mitochondrial
intermembrane space. Human osteoblast cells subjected to 2-dimensional
Western blot analysis expressed mitofilin isoforms at apparent molecular
masses of 88 and 90 kD.
John et al. (2005) stated that mouse and human mitofilin have 3
centrally located coiled-coil domains that are predicted to be involved
in protein-protein interactions. Immunohistochemical analysis of
transfected COS-7 cells and immunoelectron microscopy of embryonic mouse
heart detected mitofilin localized to the base of cristae membranes or
the inner boundary membrane.
GENE FUNCTION
By density gradient centrifugation of mouse liver mitochondria, John et
al. (2005) detected mitofilin in a homotypic protein complex of about
1.2 MD. Knockdown of HeLa cell mitofilin via small interfering RNA
(siRNA) disorganized mitochondrial inner membranes. Inner membranes
failed to form tubular or vesicular cristae, but appeared as concentric
stacks of membrane sheets that fused intermittently in a membranous
network. Mitochondrial fission and fusion appeared normal. Electron
microscopic tomography estimated a substantial increase in
inner-to-outer membrane ratio, with no cristae junctions. Mitochondria
subsequently showed increased reactive oxygen species, membrane
potential, and metabolic flux, although oxidative phosphorylation was
not increased. Cell proliferation slowed and was followed by apoptosis.
Overexpression of mitofilin in HeLa cells had no effect on membrane
architecture, apoptosis, or cell proliferation. John et al. (2005)
concluded that mitofilin is indispensable for intramitochondrial
morphology.
Using a monoclonal antibody directed against mitofilin, followed by
SDS-PAGE and mass spectrometry, Xie et al. (2007) identified a protein
complex in human heart mitochondria that, in addition to mitofilin,
included SAMM50 (612058), metaxin-1 (MTX1; 600605), metaxin-2 (MTX2;
608555), CHCHD3 (613748), CHCHD6 (615634), and DNAJC11 (614827).
Using yeast mutants, von der Malsburg et al. (2011) identified Fcj1, the
yeast ortholog of mitofilin, as a constituent of an inner mitochondrial
membrane protein complex required to keep cristae membranes connected to
the inner boundary membrane. In addition, Fcj1 was coupled to outer
mitochondrial membranes and promoted mitochondrial protein import.
By mutation analysis, An et al. (2012) found that the C-terminal
coiled-coil helix-coiled-coil helix (CHCH) domain of CHCM1 (CHCHD6) was
required for interaction of CHCM1 with mitofilin. Knockdown of CHCM1
reduced the protein content of mitofilin and altered the morphology of
mitochondrial cristae in a manner that was similar to, but distinct
from, that observed following knockdown of mitofilin. Like depletion of
mitofilin, depletion of CHCM1 reduced cell growth and induced
mitochondrial dysfunction, with decreases in oxygen consumption and ATP
synthesis. Knockdown of mitofilin reduced CHCM1 protein levels,
suggesting that the 2 proteins stabilize one another. An et al. (2012)
concluded that CHCM1 and mitofilin act together to regulate
mitochondrial cristae morphology.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the IMMT
gene to chromosome 2p11.2 (TMAP G62066).
*FIELD* RF
1. An, J.; Shi, J.; He, Q.; Lui, K.; Liu, Y.; Huang, Y.; Sheikh, M.
S.: CHCM1/CHCHD6, novel mitochondrial protein linked to regulation
of mitofilin and mitochondrial cristae morphology. J. Biol. Chem. 287:
7411-7426, 2012.
2. Gieffers, C.; Korioth, F.; Heimann, P.; Ungermann, C.; Frey, J.
: Mitofilin is a transmembrane protein of the inner mitochondrial
membrane expressed as two isoforms. Exp. Cell. Res. 232: 395-399,
1997.
3. Icho, T.; Ikeda, T.; Matsumoto, Y.; Hanaoka, F.; Kaji, K.; Tsuchida,
N.: A novel human gene that is preferentially transcribed in heart
muscle. Gene 144: 301-306, 1994.
4. John, G. B.; Shang, Y.; Li, L.; Renken, C.; Mannella, C. A.; Selker,
J. M. L.; Rangell, L.; Bennett, M. J.; Zha, J.: The mitochondrial
inner membrane protein mitofilin controls cristae morphology. Molec.
Biol. Cell 16: 1543-1554, 2005.
5. von der Malsburg, K.; Muller, J. M.; Bohnert, M.; Oeljeklaus, S.;
Kwiatkowska, P.; Becker, T.; Loniewska-Lwowska, A.; Wiese, S.; Rao,
S.; Milenkovic, D.; Hutu, D. P.; Zerbes, R. M; and 12 others: Dual
role of mitofilin in mitochondrial membrane organization and protein
biogenesis. Dev. Cell 21: 694-707, 2011.
6. Xie, J.; Marusich, M. F.; Souda, P.; Whitelegge, J.; Capaldi, R.
A.: The mitochondrial inner membrane protein mitofilin exists as
a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix
domain-containing protein 3 and 6 and DnaJC11. FEBS Lett. 581: 3542-3549,
2007.
*FIELD* CN
Patricia A. Hartz - updated: 02/12/2014
*FIELD* CD
Victor A. McKusick: 2/8/1995
*FIELD* ED
mgross: 02/12/2014
mcolton: 2/7/2014
mgross: 2/20/2009
alopez: 4/4/2000
alopez: 3/31/2000
carol: 3/30/2000
carol: 2/8/1995
*RECORD*
*FIELD* NO
600378
*FIELD* TI
*600378 INNER MEMBRANE PROTEIN, MITOCHONDRIAL; IMMT
;;MITOFILIN;;
HEART MUSCLE PROTEIN; HMP
read more*FIELD* TX
DESCRIPTION
Mitochondria are the center of cellular energy production, and cristae
of the inner mitochondrial membrane undergo morphologic changes in
response to metabolic state. Mitofilin is a protein of the inner
mitochondrial membrane that regulates mitochondrial cristae morphology
(John et al., 2005).
CLONING
The heart muscle protein gene is expressed predominantly in the heart
and is proposed to be an ATP-driven motor protein that interacts with
cytoskeletal components. Icho et al. (1994) cloned a full-length 2.7-kb
cDNA coding for a 758-amino acid protein. The protein has a possible
ATP-binding domain at the N terminus and a long alpha-helical domain
that could form a coiled-coil structure. Proteins with similar
structures include myosin II (see 160730), an actin-based motor protein,
and kinesin (see 602809), a microtubule-based motor protein.
By screening an osteoblast cDNA library and PCR of total RNA isolated
from MG63 human osteosarcoma cells, Gieffers et al. (1997) cloned 2
splice variants of mitofilin. The variants differ in the presence or
absence of 33 bp in the coding region, and the deduced proteins contain
758 or 747 amino acids. Both proteins contain a cleavable 34-amino acid
N-terminal mitochondrial targeting signal, followed by a transmembrane
domain and a large C-terminal domain. The shorter protein lacks 11 amino
acids following the transmembrane domain. Gieffers et al. (1997)
determined that mitofilin is anchored to the inner mitochondrial
membrane, with the short N terminus facing the mitochondrial matrix and
the large C-terminal domain extending into the mitochondrial
intermembrane space. Human osteoblast cells subjected to 2-dimensional
Western blot analysis expressed mitofilin isoforms at apparent molecular
masses of 88 and 90 kD.
John et al. (2005) stated that mouse and human mitofilin have 3
centrally located coiled-coil domains that are predicted to be involved
in protein-protein interactions. Immunohistochemical analysis of
transfected COS-7 cells and immunoelectron microscopy of embryonic mouse
heart detected mitofilin localized to the base of cristae membranes or
the inner boundary membrane.
GENE FUNCTION
By density gradient centrifugation of mouse liver mitochondria, John et
al. (2005) detected mitofilin in a homotypic protein complex of about
1.2 MD. Knockdown of HeLa cell mitofilin via small interfering RNA
(siRNA) disorganized mitochondrial inner membranes. Inner membranes
failed to form tubular or vesicular cristae, but appeared as concentric
stacks of membrane sheets that fused intermittently in a membranous
network. Mitochondrial fission and fusion appeared normal. Electron
microscopic tomography estimated a substantial increase in
inner-to-outer membrane ratio, with no cristae junctions. Mitochondria
subsequently showed increased reactive oxygen species, membrane
potential, and metabolic flux, although oxidative phosphorylation was
not increased. Cell proliferation slowed and was followed by apoptosis.
Overexpression of mitofilin in HeLa cells had no effect on membrane
architecture, apoptosis, or cell proliferation. John et al. (2005)
concluded that mitofilin is indispensable for intramitochondrial
morphology.
Using a monoclonal antibody directed against mitofilin, followed by
SDS-PAGE and mass spectrometry, Xie et al. (2007) identified a protein
complex in human heart mitochondria that, in addition to mitofilin,
included SAMM50 (612058), metaxin-1 (MTX1; 600605), metaxin-2 (MTX2;
608555), CHCHD3 (613748), CHCHD6 (615634), and DNAJC11 (614827).
Using yeast mutants, von der Malsburg et al. (2011) identified Fcj1, the
yeast ortholog of mitofilin, as a constituent of an inner mitochondrial
membrane protein complex required to keep cristae membranes connected to
the inner boundary membrane. In addition, Fcj1 was coupled to outer
mitochondrial membranes and promoted mitochondrial protein import.
By mutation analysis, An et al. (2012) found that the C-terminal
coiled-coil helix-coiled-coil helix (CHCH) domain of CHCM1 (CHCHD6) was
required for interaction of CHCM1 with mitofilin. Knockdown of CHCM1
reduced the protein content of mitofilin and altered the morphology of
mitochondrial cristae in a manner that was similar to, but distinct
from, that observed following knockdown of mitofilin. Like depletion of
mitofilin, depletion of CHCM1 reduced cell growth and induced
mitochondrial dysfunction, with decreases in oxygen consumption and ATP
synthesis. Knockdown of mitofilin reduced CHCM1 protein levels,
suggesting that the 2 proteins stabilize one another. An et al. (2012)
concluded that CHCM1 and mitofilin act together to regulate
mitochondrial cristae morphology.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the IMMT
gene to chromosome 2p11.2 (TMAP G62066).
*FIELD* RF
1. An, J.; Shi, J.; He, Q.; Lui, K.; Liu, Y.; Huang, Y.; Sheikh, M.
S.: CHCM1/CHCHD6, novel mitochondrial protein linked to regulation
of mitofilin and mitochondrial cristae morphology. J. Biol. Chem. 287:
7411-7426, 2012.
2. Gieffers, C.; Korioth, F.; Heimann, P.; Ungermann, C.; Frey, J.
: Mitofilin is a transmembrane protein of the inner mitochondrial
membrane expressed as two isoforms. Exp. Cell. Res. 232: 395-399,
1997.
3. Icho, T.; Ikeda, T.; Matsumoto, Y.; Hanaoka, F.; Kaji, K.; Tsuchida,
N.: A novel human gene that is preferentially transcribed in heart
muscle. Gene 144: 301-306, 1994.
4. John, G. B.; Shang, Y.; Li, L.; Renken, C.; Mannella, C. A.; Selker,
J. M. L.; Rangell, L.; Bennett, M. J.; Zha, J.: The mitochondrial
inner membrane protein mitofilin controls cristae morphology. Molec.
Biol. Cell 16: 1543-1554, 2005.
5. von der Malsburg, K.; Muller, J. M.; Bohnert, M.; Oeljeklaus, S.;
Kwiatkowska, P.; Becker, T.; Loniewska-Lwowska, A.; Wiese, S.; Rao,
S.; Milenkovic, D.; Hutu, D. P.; Zerbes, R. M; and 12 others: Dual
role of mitofilin in mitochondrial membrane organization and protein
biogenesis. Dev. Cell 21: 694-707, 2011.
6. Xie, J.; Marusich, M. F.; Souda, P.; Whitelegge, J.; Capaldi, R.
A.: The mitochondrial inner membrane protein mitofilin exists as
a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix
domain-containing protein 3 and 6 and DnaJC11. FEBS Lett. 581: 3542-3549,
2007.
*FIELD* CN
Patricia A. Hartz - updated: 02/12/2014
*FIELD* CD
Victor A. McKusick: 2/8/1995
*FIELD* ED
mgross: 02/12/2014
mcolton: 2/7/2014
mgross: 2/20/2009
alopez: 4/4/2000
alopez: 3/31/2000
carol: 3/30/2000
carol: 2/8/1995