MIC26_HUMAN
ID MIC26_HUMAN Reviewed; 198 AA.
AC Q9BUR5; B2R4K9; Q9H3J9;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=MICOS complex subunit MIC26 {ECO:0000303|PubMed:25764979};
DE AltName: Full=Apolipoprotein O;
DE AltName: Full=MICOS complex subunit MIC23 {ECO:0000303|PubMed:25781180};
DE AltName: Full=Protein FAM121B;
DE Flags: Precursor;
GN Name=APOO;
GN Synonyms=FAM121B, MIC23 {ECO:0000303|PubMed:25781180},
GN MIC26 {ECO:0000303|PubMed:25764979}; ORFNames=My025, UNQ1866/PRO4302;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RA Mao Y.M., Xie Y., Zheng Z.H.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, Skin, and Urinary bladder;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND COVALENT LINKAGE
RP WITH CHONDROITIN SULFATE.
RX PubMed=16956892; DOI=10.1074/jbc.m510861200;
RA Lamant M., Smih F., Harmancey R., Philip-Couderc P., Pathak A.,
RA Roncalli J., Galinier M., Collet X., Massabuau P., Senard J.-M., Rouet P.;
RT "ApoO, a novel apolipoprotein, is an original glycoprotein up-regulated by
RT diabetes in human heart.";
RL J. Biol. Chem. 281:36289-36302(2006).
RN [7]
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., Buerckstuemmer T.,
RA 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 [8]
RP FUNCTION.
RX PubMed=24743151; DOI=10.1172/jci74668;
RA Turkieh A., Caubere C., Barutaut M., Desmoulin F., Harmancey R.,
RA Galinier M., Berry M., Dambrin C., Polidori C., Casteilla L., Koukoui F.,
RA Rouet P., Smih F.;
RT "Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart.";
RL J. Clin. Invest. 124:2277-2286(2014).
RN [9]
RP FUNCTION, NOMENCLATURE, IDENTIFICATION IN THE MICOS COMPLEX, SUBCELLULAR
RP LOCATION, GLYCOSYLATION, AND INTERACTION WITH MICOS10; APOOL AND IMMT.
RX PubMed=25764979; DOI=10.1016/j.bbamcr.2015.03.004;
RA Koob S., Barrera M., Anand R., Reichert A.S.;
RT "The non-glycosylated isoform of MIC26 is a constituent of the mammalian
RT MICOS complex and promotes formation of crista junctions.";
RL Biochim. Biophys. Acta 1853:1551-1563(2015).
RN [10]
RP IDENTIFICATION IN THE MICOS COMPLEX.
RX PubMed=25997101; DOI=10.7554/elife.06265;
RA Guarani V., McNeill E.M., Paulo J.A., Huttlin E.L., Froehlich F.,
RA Gygi S.P., Van Vactor D., Harper J.W.;
RT "QIL1 is a novel mitochondrial protein required for MICOS complex stability
RT and cristae morphology.";
RL Elife 4:0-0(2015).
RN [11]
RP IDENTIFICATION IN THE MICOS COMPLEX, NOMENCLATURE, INTERACTION WITH IMMT,
RP AND SUBCELLULAR LOCATION.
RX PubMed=25781180; DOI=10.1371/journal.pone.0120213;
RA Ott C., Dorsch E., Fraunholz M., Straub S., Kozjak-Pavlovic V.;
RT "Detailed analysis of the human mitochondrial contact site complex indicate
RT a hierarchy of subunits.";
RL PLoS ONE 10:E0120213-E0120213(2015).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Component of the MICOS complex, a large protein complex of
CC the mitochondrial inner membrane that plays crucial roles in the
CC maintenance of crista junctions, inner membrane architecture, and
CC formation of contact sites to the outer membrane. Plays a crucial role
CC in crista junction formation and mitochondrial function
CC (PubMed:25764979). Can promote cardiac lipotoxicity by enhancing
CC mitochondrial respiration and fatty acid metabolism in cardiac
CC myoblasts (PubMed:24743151). Promotes cholesterol efflux from
CC macrophage cells. Detected in HDL, LDL and VLDL. Secreted by a
CC microsomal triglyceride transfer protein (MTTP)-dependent mechanism,
CC probably as a VLDL-associated protein that is subsequently transferred
CC to HDL (PubMed:16956892). {ECO:0000269|PubMed:16956892,
CC ECO:0000269|PubMed:24743151, ECO:0000269|PubMed:25764979}.
CC -!- SUBUNIT: Component of the mitochondrial contact site and cristae
CC organizing system (MICOS) complex, composed of at least MICOS10/MIC10,
CC CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26
CC and MICOS13/MIC13. This complex was also known under the names MINOS or
CC MitOS complex. he MICOS complex associates with mitochondrial outer
CC membrane proteins SAMM50, MTX1 and MTX2 (together described as
CC components of the mitochondrial outer membrane sorting assembly
CC machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane
CC protein TMEM11 and with HSPA9 (PubMed:25764979, PubMed:25781180,
CC PubMed:25997101). The MICOS and SAM complexes together with DNAJC11 are
CC part of a large protein complex spanning both membranes termed the
CC mitochondrial intermembrane space bridging (MIB) complex. Interacts
CC with IMMT/MIC60 (PubMed:25764979, PubMed:25781180). Interacts with
CC MICOS10/MIC10 and APOOL/MIC27 (PubMed:25764979).
CC {ECO:0000269|PubMed:25764979, ECO:0000269|PubMed:25781180,
CC ECO:0000269|PubMed:25997101, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:25764979}; Single-pass membrane protein
CC {ECO:0000255}. Secreted {ECO:0000269|PubMed:16956892,
CC ECO:0000269|PubMed:25764979}. Mitochondrion
CC {ECO:0000269|PubMed:25781180}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:25764979}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:25764979}. Note=Exists in three distinct forms: a
CC glycosylated and secreted form, an ER/Golgi-resident form and a non-
CC glycosylated mitochondrial form. {ECO:0000269|PubMed:25764979}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BUR5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BUR5-2; Sequence=VSP_023333;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined. Up-regulated in
CC diabetic heart. {ECO:0000269|PubMed:16956892}.
CC -!- PTM: O-glycosylation; glycosaminoglycan of chondroitin-sulfate type.
CC {ECO:0000269|PubMed:16956892, ECO:0000269|PubMed:25764979}.
CC -!- SIMILARITY: Belongs to the apolipoprotein O/MICOS complex subunit Mic27
CC family. {ECO:0000305}.
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DR EMBL; AF061264; AAG43139.1; -; mRNA.
DR EMBL; AY359114; AAQ89472.1; -; mRNA.
DR EMBL; AK311865; BAG34806.1; -; mRNA.
DR EMBL; CH471074; EAW99002.1; -; Genomic_DNA.
DR EMBL; BC002333; AAH02333.1; -; mRNA.
DR EMBL; BC010102; AAH10102.1; -; mRNA.
DR EMBL; BC016814; AAH16814.1; -; mRNA.
DR CCDS; CCDS14208.1; -. [Q9BUR5-1]
DR RefSeq; NP_077027.1; NM_024122.4. [Q9BUR5-1]
DR RefSeq; XP_016885326.1; XM_017029837.1. [Q9BUR5-1]
DR AlphaFoldDB; Q9BUR5; -.
DR BioGRID; 122556; 135.
DR ComplexPortal; CPX-6141; MICOS mitochondrial contact site and cristae organizing system complex.
DR CORUM; Q9BUR5; -.
DR IntAct; Q9BUR5; 7.
DR MINT; Q9BUR5; -.
DR STRING; 9606.ENSP00000368528; -.
DR TCDB; 8.A.156.3.1; the micos complex (micos-c) family.
DR CarbonylDB; Q9BUR5; -.
DR GlyGen; Q9BUR5; 1 site.
DR iPTMnet; Q9BUR5; -.
DR PhosphoSitePlus; Q9BUR5; -.
DR SwissPalm; Q9BUR5; -.
DR BioMuta; APOO; -.
DR DMDM; 74733244; -.
DR EPD; Q9BUR5; -.
DR jPOST; Q9BUR5; -.
DR MassIVE; Q9BUR5; -.
DR MaxQB; Q9BUR5; -.
DR PaxDb; Q9BUR5; -.
DR PeptideAtlas; Q9BUR5; -.
DR PRIDE; Q9BUR5; -.
DR ProteomicsDB; 79123; -. [Q9BUR5-1]
DR ProteomicsDB; 79124; -. [Q9BUR5-2]
DR TopDownProteomics; Q9BUR5-1; -. [Q9BUR5-1]
DR TopDownProteomics; Q9BUR5-2; -. [Q9BUR5-2]
DR Antibodypedia; 564; 181 antibodies from 27 providers.
DR DNASU; 79135; -.
DR Ensembl; ENST00000379226.9; ENSP00000368528.4; ENSG00000184831.14. [Q9BUR5-1]
DR GeneID; 79135; -.
DR KEGG; hsa:79135; -.
DR MANE-Select; ENST00000379226.9; ENSP00000368528.4; NM_024122.5; NP_077027.1.
DR UCSC; uc004dax.4; human. [Q9BUR5-1]
DR CTD; 79135; -.
DR DisGeNET; 79135; -.
DR GeneCards; APOO; -.
DR HGNC; HGNC:28727; APOO.
DR HPA; ENSG00000184831; Low tissue specificity.
DR MalaCards; APOO; -.
DR MIM; 300753; gene.
DR neXtProt; NX_Q9BUR5; -.
DR OpenTargets; ENSG00000184831; -.
DR PharmGKB; PA162376709; -.
DR VEuPathDB; HostDB:ENSG00000184831; -.
DR eggNOG; KOG4798; Eukaryota.
DR GeneTree; ENSGT00530000063666; -.
DR InParanoid; Q9BUR5; -.
DR OMA; YTSWCQD; -.
DR PhylomeDB; Q9BUR5; -.
DR TreeFam; TF315313; -.
DR PathwayCommons; Q9BUR5; -.
DR Reactome; R-HSA-8949613; Cristae formation.
DR SignaLink; Q9BUR5; -.
DR BioGRID-ORCS; 79135; 9 hits in 703 CRISPR screens.
DR ChiTaRS; APOO; human.
DR GeneWiki; Apolipoprotein_O; -.
DR GenomeRNAi; 79135; -.
DR Pharos; Q9BUR5; Tbio.
DR PRO; PR:Q9BUR5; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9BUR5; protein.
DR Bgee; ENSG00000184831; Expressed in decidua and 187 other tissues.
DR ExpressionAtlas; Q9BUR5; baseline and differential.
DR Genevisible; Q9BUR5; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:BHF-UCL.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0034364; C:high-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0034362; C:low-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0140275; C:MIB complex; HDA:UniProtKB.
DR GO; GO:0061617; C:MICOS complex; IDA:UniProtKB.
DR GO; GO:0044284; C:mitochondrial crista junction; IC:ComplexPortal.
DR GO; GO:0005743; C:mitochondrial inner membrane; IC:ComplexPortal.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0001401; C:SAM complex; HDA:UniProtKB.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0042407; P:cristae formation; IMP:UniProtKB.
DR GO; GO:0007007; P:inner mitochondrial membrane organization; IC:UniProtKB.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR InterPro; IPR019166; MIC26/MIC27.
DR InterPro; IPR033182; MIC26/MIC27_animal.
DR PANTHER; PTHR14564; PTHR14564; 1.
DR Pfam; PF09769; ApoO; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW HDL; LDL; Lipid transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Proteoglycan; Reference proteome; Secreted;
KW Signal; Transmembrane; Transmembrane helix; Transport; VLDL.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..198
FT /note="MICOS complex subunit MIC26"
FT /id="PRO_0000254646"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 162
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 80..109
FT /note="ETYSQTKPKMQSLVQWGLDSYDYLQNAPPG -> TAMTISKMHLLD (in
FT isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_023333"
SQ SEQUENCE 198 AA; 22285 MW; BEC99607F54E98E2 CRC64;
MFKVIQRSVG PASLSLLTFK VYAAPKKDSP PKNSVKVDEL SLYSVPEGQS KYVEEARSQL
EESISQLRHY CEPYTTWCQE TYSQTKPKMQ SLVQWGLDSY DYLQNAPPGF FPRLGVIGFA
GLIGLLLARG SKIKKLVYPP GFMGLAASLY YPQQAIVFAQ VSGERLYDWG LRGYIVIEDL
WKENFQKPGN VKNSPGTK
