S2546_HUMAN
ID S2546_HUMAN Reviewed; 418 AA.
AC Q96AG3; A8K2F2; B3KRE6; B4DTA3; D3DSZ6; D6R9W7; Q04197;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Mitochondrial outer membrane protein SLC25A46 {ECO:0000305};
DE AltName: Full=Solute carrier family 25 member 46;
GN Name=SLC25A46 {ECO:0000312|HGNC:HGNC:25198}; Synonyms=TB1;
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 [MRNA] (ISOFORM 1).
RX PubMed=1651562; DOI=10.1126/science.1651562;
RA Kinzler K.W., Nilbert M.C., Su L.-K., Vogelstein B., Bryan T.M., Levy D.B.,
RA Smith K.J., Preisinger A.C., Hedge P., McKechnie D., Finniear R.,
RA Markham A., Groffen J., Boguski M.S., Altschul S.F., Horii A.K., Ando H.,
RA Miyoshi Y., Miki Y., Nishisho I., Nakamura Y.;
RT "Identification of FAP locus genes from chromosome 5q21.";
RL Science 253:661-665(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain, Placenta, and Thalamus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 IDENTIFICATION.
RX PubMed=16949250; DOI=10.1016/j.ygeno.2006.06.016;
RA Haitina T., Lindblom J., Renstroem T., Fredriksson R.;
RT "Fourteen novel human members of mitochondrial solute carrier family 25
RT (SLC25) widely expressed in the central nervous system.";
RL Genomics 88:779-790(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-45, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-45, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IMMT, INVOLVEMENT IN
RP HMSN6B, AND VARIANTS HMSN6B ASP-249; LEU-333; ASP-335 AND CYS-340.
RX PubMed=26168012; DOI=10.1038/ng.3354;
RA Abrams A.J., Hufnagel R.B., Rebelo A., Zanna C., Patel N., Gonzalez M.A.,
RA Campeanu I.J., Griffin L.B., Groenewald S., Strickland A.V., Tao F.,
RA Speziani F., Abreu L., Schuele R., Caporali L., La Morgia C., Maresca A.,
RA Liguori R., Lodi R., Ahmed Z.M., Sund K.L., Wang X., Krueger L.A., Peng Y.,
RA Prada C.E., Prows C.A., Schorry E.K., Antonellis A., Zimmerman H.H.,
RA Abdul-Rahman O.A., Yang Y., Downes S.M., Prince J., Fontanesi F.,
RA Barrientos A., Nemeth A.H., Carelli V., Huang T., Zuchner S., Dallman J.E.;
RT "Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic
RT atrophy spectrum disorder.";
RL Nat. Genet. 47:926-932(2015).
RN [13]
RP INVOLVEMENT IN PCH1E, VARIANT PCH1E PRO-341, CHARACTERIZATION OF VARIANT
RP PCH1E PRO-341, CHARACTERIZATION OF VARIANTS HMSN6B ASP-249; LEU-333;
RP ASP-335; CYS-340, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27543974; DOI=10.1093/brain/aww212;
RA Wan J., Steffen J., Yourshaw M., Mamsa H., Andersen E.,
RA Rudnik-Schoeneborn S., Pope K., Howell K.B., McLean C.A., Kornberg A.J.,
RA Joseph J., Lockhart P.J., Zerres K., Ryan M.M., Nelson S.F., Koehler C.M.,
RA Jen J.C.;
RT "Loss of function of SLC25A46 causes lethal congenital pontocerebellar
RT hypoplasia.";
RL Brain 139:2877-2890(2016).
RN [14]
RP VARIANT PCH1E ILE-142, CHARACTERIZATION OF VARIANT PCH1E ILE-142, FUNCTION,
RP INTERACTION WITH THE EMC AND MICOS COMPLEXES, AND SUBCELLULAR LOCATION.
RX PubMed=27390132; DOI=10.15252/emmm.201506159;
RA Janer A., Prudent J., Paupe V., Fahiminiya S., Majewski J., Sgarioto N.,
RA Des Rosiers C., Forest A., Lin Z.Y., Gingras A.C., Mitchell G.,
RA McBride H.M., Shoubridge E.A.;
RT "SLC25A46 is required for mitochondrial lipid homeostasis and cristae
RT maintenance and is responsible for Leigh syndrome.";
RL EMBO Mol. Med. 8:1019-1038(2016).
RN [15]
RP VARIANT HMSN6B ARG-138.
RX PubMed=27430653; DOI=10.1002/mds.26716;
RA Charlesworth G., Balint B., Mencacci N.E., Carr L., Wood N.W., Bhatia K.P.;
RT "SLC25A46 mutations underlie progressive myoclonic ataxia with optic
RT atrophy and neuropathy.";
RL Mov. Disord. 31:1249-1251(2016).
RN [16]
RP VARIANT PCH1E 231-ARG--ILE-418 DEL.
RX PubMed=28637197; DOI=10.1093/brain/awx147;
RA van Dijk T., Rudnik-Schoeneborn S., Senderek J., Hajmousa G., Mei H.,
RA Dusl M., Aronica E., Barth P., Baas F.;
RT "Pontocerebellar hypoplasia with spinal muscular atrophy (PCH1):
RT identification of SLC25A46 mutations in the original Dutch PCH1 family.";
RL Brain 140:e46-e46(2017).
RN [17]
RP VARIANTS PCH1E 14-TYR--ILE-418 DEL AND 246-ARG--ILE-418 DEL.
RX PubMed=28653766; DOI=10.1111/cge.13084;
RA Braunisch M.C., Gallwitz H., Abicht A., Diebold I., Holinski-Feder E.,
RA Van Maldergem L., Lammens M., Kovacs-Nagy R., Alhaddad B., Strom T.M.,
RA Meitinger T., Senderek J., Rudnik-Schoeneborn S., Haack T.B.;
RT "Extension of the phenotype of biallelic loss-of-function mutations in
RT SLC25A46 to the severe form of pontocerebellar hypoplasia type I.";
RL Clin. Genet. 93:255-265(2018).
CC -!- FUNCTION: Transmembrane protein of the mitochondrial outer membrane
CC that controls mitochondrial organization (PubMed:26168012,
CC PubMed:27543974, PubMed:27390132). May regulate the assembly of the
CC MICOS (mitochondrial contact site and cristae organizing system)
CC complex which is essential to the biogenesis and dynamics of
CC mitochondrial cristae, the inwards folds of the inner mitochondrial
CC membrane (PubMed:27390132). Through its interaction with the EMC
CC (endoplasmic reticulum membrane protein complex), could regulate
CC mitochondrial lipid homeostasis and thereby mitochondrial fission
CC (PubMed:27390132). {ECO:0000269|PubMed:26168012,
CC ECO:0000269|PubMed:27390132, ECO:0000269|PubMed:27543974}.
CC -!- SUBUNIT: Associates with the mitochondrial contact site and cristae
CC organizing system (MICOS) complex (PubMed:26168012, PubMed:27390132).
CC May associate with the endoplasmic reticulum membrane protein complex
CC (EMC) (PubMed:27390132). {ECO:0000269|PubMed:26168012,
CC ECO:0000269|PubMed:27390132}.
CC -!- INTERACTION:
CC Q96AG3; Q13520: AQP6; NbExp=3; IntAct=EBI-10281975, EBI-13059134;
CC Q96AG3; Q13643: FHL3; NbExp=6; IntAct=EBI-10281975, EBI-741101;
CC Q96AG3; Q8IVP5: FUNDC1; NbExp=3; IntAct=EBI-10281975, EBI-3059266;
CC Q96AG3; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-10281975, EBI-1052304;
CC Q96AG3; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-10281975, EBI-18053395;
CC Q96AG3; O95214: LEPROTL1; NbExp=3; IntAct=EBI-10281975, EBI-750776;
CC Q96AG3; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-10281975, EBI-373355;
CC Q96AG3; Q2M2E3: ODF4; NbExp=3; IntAct=EBI-10281975, EBI-12382569;
CC Q96AG3; Q9BRK0: REEP2; NbExp=3; IntAct=EBI-10281975, EBI-11337973;
CC Q96AG3; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-10281975, EBI-7545592;
CC Q96AG3; Q14973: SLC10A1; NbExp=3; IntAct=EBI-10281975, EBI-3923031;
CC Q96AG3; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-10281975, EBI-18159983;
CC Q96AG3; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-10281975, EBI-3907610;
CC Q96AG3; Q9UHI5: SLC7A8; NbExp=3; IntAct=EBI-10281975, EBI-13292283;
CC Q96AG3; Q3ZAQ7: VMA21; NbExp=3; IntAct=EBI-10281975, EBI-1055364;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:26168012, ECO:0000269|PubMed:27390132,
CC ECO:0000269|PubMed:27543974}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96AG3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96AG3-2; Sequence=VSP_056112;
CC Name=3;
CC IsoId=Q96AG3-3; Sequence=VSP_056351;
CC -!- DISEASE: Neuropathy, hereditary motor and sensory, 6B, with optic
CC atrophy (HMSN6B) [MIM:616505]: An autosomal recessive neurologic
CC disorder characterized by early-onset optic atrophy, progressive visual
CC loss, and peripheral sensorimotor neuropathy manifesting as axonal
CC Charcot-Marie-Tooth disease, with variable age at onset and severity.
CC Charcot-Marie-Tooth disease is a disorder of the peripheral nervous
CC system, characterized by progressive weakness and atrophy, initially of
CC the peroneal muscles and later of the distal muscles of the arms. It is
CC classified in two main groups on the basis of electrophysiologic
CC properties and histopathology: primary peripheral demyelinating
CC neuropathies and primary peripheral axonal neuropathies. Peripheral
CC axonal neuropathies are characterized by signs of axonal regeneration
CC in the absence of obvious myelin alterations, and normal or slightly
CC reduced nerve conduction velocities. {ECO:0000269|PubMed:26168012,
CC ECO:0000269|PubMed:27430653, ECO:0000269|PubMed:27543974}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Pontocerebellar hypoplasia 1E (PCH1E) [MIM:619303]: A form of
CC pontocerebellar hypoplasia, a disorder characterized by structural
CC defects of the pons and cerebellum, evident upon brain imaging. PCH1E
CC is an autosomal recessive form characterized by severe hypotonia and
CC respiratory insufficiency apparent soon after birth. Additional
CC features may include optic atrophy, peripheral neuropathy, dysmorphic
CC features, congenital contracture or foot deformities, and seizures.
CC Death occurs in the first days or weeks of life. Postmortem brain
CC imaging show pontocerebellar atrophy and loss of anterior motor neurons
CC in the spinal cord. {ECO:0000269|PubMed:27390132,
CC ECO:0000269|PubMed:27543974, ECO:0000269|PubMed:28637197,
CC ECO:0000269|PubMed:28653766}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA03587.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M74089; AAA03587.1; ALT_INIT; mRNA.
DR EMBL; AK091427; BAG52358.1; -; mRNA.
DR EMBL; AK290217; BAF82906.1; -; mRNA.
DR EMBL; AK300123; BAG61915.1; -; mRNA.
DR EMBL; AC008650; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471086; EAW49040.1; -; Genomic_DNA.
DR EMBL; CH471086; EAW49041.1; -; Genomic_DNA.
DR EMBL; BC017169; AAH17169.1; -; mRNA.
DR CCDS; CCDS4100.1; -. [Q96AG3-1]
DR CCDS; CCDS78045.1; -. [Q96AG3-3]
DR RefSeq; NP_001290178.1; NM_001303249.2. [Q96AG3-3]
DR RefSeq; NP_001290179.1; NM_001303250.2.
DR RefSeq; NP_620128.1; NM_138773.3. [Q96AG3-1]
DR AlphaFoldDB; Q96AG3; -.
DR BioGRID; 124798; 266.
DR IntAct; Q96AG3; 33.
DR STRING; 9606.ENSP00000348211; -.
DR TCDB; 2.A.29.30.1; the mitochondrial carrier (mc) family.
DR iPTMnet; Q96AG3; -.
DR PhosphoSitePlus; Q96AG3; -.
DR BioMuta; SLC25A46; -.
DR DMDM; 74751740; -.
DR EPD; Q96AG3; -.
DR jPOST; Q96AG3; -.
DR MassIVE; Q96AG3; -.
DR MaxQB; Q96AG3; -.
DR PaxDb; Q96AG3; -.
DR PeptideAtlas; Q96AG3; -.
DR PRIDE; Q96AG3; -.
DR ProteomicsDB; 3595; -.
DR ProteomicsDB; 5092; -.
DR ProteomicsDB; 75961; -. [Q96AG3-1]
DR Antibodypedia; 13498; 120 antibodies from 23 providers.
DR DNASU; 91137; -.
DR Ensembl; ENST00000355943.8; ENSP00000348211.3; ENSG00000164209.17. [Q96AG3-1]
DR Ensembl; ENST00000447245.6; ENSP00000399717.2; ENSG00000164209.17. [Q96AG3-3]
DR Ensembl; ENST00000504098.1; ENSP00000425708.1; ENSG00000164209.17. [Q96AG3-2]
DR GeneID; 91137; -.
DR KEGG; hsa:91137; -.
DR MANE-Select; ENST00000355943.8; ENSP00000348211.3; NM_138773.4; NP_620128.1.
DR UCSC; uc003koz.5; human. [Q96AG3-1]
DR CTD; 91137; -.
DR DisGeNET; 91137; -.
DR GeneCards; SLC25A46; -.
DR HGNC; HGNC:25198; SLC25A46.
DR HPA; ENSG00000164209; Low tissue specificity.
DR MalaCards; SLC25A46; -.
DR MIM; 610826; gene.
DR MIM; 616505; phenotype.
DR MIM; 619303; phenotype.
DR neXtProt; NX_Q96AG3; -.
DR OpenTargets; ENSG00000164209; -.
DR Orphanet; 90120; Hereditary motor and sensory neuropathy type 6.
DR Orphanet; 2254; Pontocerebellar hypoplasia type 1.
DR PharmGKB; PA162403737; -.
DR VEuPathDB; HostDB:ENSG00000164209; -.
DR eggNOG; KOG2954; Eukaryota.
DR GeneTree; ENSGT00390000015874; -.
DR HOGENOM; CLU_047010_0_0_1; -.
DR InParanoid; Q96AG3; -.
DR OMA; HKWNLKQ; -.
DR OrthoDB; 937901at2759; -.
DR PhylomeDB; Q96AG3; -.
DR TreeFam; TF313365; -.
DR PathwayCommons; Q96AG3; -.
DR SignaLink; Q96AG3; -.
DR BioGRID-ORCS; 91137; 27 hits in 1080 CRISPR screens.
DR ChiTaRS; SLC25A46; human.
DR GenomeRNAi; 91137; -.
DR Pharos; Q96AG3; Tbio.
DR PRO; PR:Q96AG3; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q96AG3; protein.
DR Bgee; ENSG00000164209; Expressed in secondary oocyte and 208 other tissues.
DR ExpressionAtlas; Q96AG3; baseline and differential.
DR Genevisible; Q96AG3; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; IEA:Ensembl.
DR GO; GO:0061564; P:axon development; IBA:GO_Central.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IEA:Ensembl.
DR GO; GO:0042407; P:cristae formation; IMP:UniProtKB.
DR GO; GO:0016358; P:dendrite development; IEA:Ensembl.
DR GO; GO:0031987; P:locomotion involved in locomotory behavior; IEA:Ensembl.
DR GO; GO:0000266; P:mitochondrial fission; IDA:UniProtKB.
DR GO; GO:0090149; P:mitochondrial membrane fission; IEA:InterPro.
DR GO; GO:0006839; P:mitochondrial transport; IEA:Ensembl.
DR GO; GO:0022011; P:myelination in peripheral nervous system; IEA:Ensembl.
DR GO; GO:0021554; P:optic nerve development; IEA:Ensembl.
DR GO; GO:0048936; P:peripheral nervous system neuron axonogenesis; IEA:Ensembl.
DR GO; GO:0055091; P:phospholipid homeostasis; IMP:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IMP:UniProtKB.
DR GO; GO:0008535; P:respiratory chain complex IV assembly; IMP:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; IEA:Ensembl.
DR Gene3D; 1.50.40.10; -; 2.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR InterPro; IPR039158; SLC25A46.
DR PANTHER; PTHR21252; PTHR21252; 1.
DR Pfam; PF00153; Mito_carr; 1.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Charcot-Marie-Tooth disease; Disease variant;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Neurodegeneration;
KW Neuropathy; Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..418
FT /note="Mitochondrial outer membrane protein SLC25A46"
FT /id="PRO_0000291828"
FT TRANSMEM 103..123
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 258..278
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 314..334
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 96..187
FT /note="Solcar 1"
FT REPEAT 311..413
FT /note="Solcar 2"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 44..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..93
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CQS4"
FT MOD_RES 45
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..146
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056112"
FT VAR_SEQ 225..305
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056351"
FT VARIANT 14..418
FT /note="Missing (in PCH1E)"
FT /evidence="ECO:0000269|PubMed:28653766"
FT /id="VAR_085718"
FT VARIANT 138
FT /note="L -> R (in HMSN6B; unknown pathological
FT significance; dbSNP:rs1057519295)"
FT /evidence="ECO:0000269|PubMed:27430653"
FT /id="VAR_085719"
FT VARIANT 142
FT /note="T -> I (in PCH1E; loss of protein expression;
FT dbSNP:rs1057519296)"
FT /evidence="ECO:0000269|PubMed:27390132"
FT /id="VAR_085720"
FT VARIANT 231..418
FT /note="Missing (in PCH1E)"
FT /evidence="ECO:0000269|PubMed:28637197"
FT /id="VAR_085721"
FT VARIANT 246..418
FT /note="Missing (in PCH1E)"
FT /evidence="ECO:0000269|PubMed:28653766"
FT /id="VAR_085722"
FT VARIANT 249
FT /note="G -> D (in HMSN6B; unknown pathological
FT significance; no effect on protein abundance;
FT dbSNP:rs200725073)"
FT /evidence="ECO:0000269|PubMed:26168012,
FT ECO:0000269|PubMed:27543974"
FT /id="VAR_075818"
FT VARIANT 333
FT /note="P -> L (in HMSN6B; decreased protein abundance;
FT dbSNP:rs1057518750)"
FT /evidence="ECO:0000269|PubMed:26168012,
FT ECO:0000269|PubMed:27543974"
FT /id="VAR_075819"
FT VARIANT 335
FT /note="E -> D (in HMSN6B; unknown pathological
FT significance; slightly decreased protein abundance;
FT dbSNP:rs1057518748)"
FT /evidence="ECO:0000269|PubMed:26168012,
FT ECO:0000269|PubMed:27543974"
FT /id="VAR_075820"
FT VARIANT 340
FT /note="R -> C (in HMSN6B; slightly decreased protein
FT abundance; dbSNP:rs746681765)"
FT /evidence="ECO:0000269|PubMed:26168012,
FT ECO:0000269|PubMed:27543974"
FT /id="VAR_075821"
FT VARIANT 341
FT /note="L -> P (in PCH1E; decreased protein abundance; loss
FT of function in mitochondrial fission; no effect on
FT localization to the mitochondrial outer membrane;
FT dbSNP:rs1057519294)"
FT /evidence="ECO:0000269|PubMed:27543974"
FT /id="VAR_085723"
SQ SEQUENCE 418 AA; 46174 MW; 97341574207816AB CRC64;
MHPRRPDGFD GLGYRGGARD EQGFGGAFPA RSFSTGSDLG HWVTTPPDIP GSRNLHWGEK
SPPYGVPTTS TPYEGPTEEP FSSGGGGSVQ GQSSEQLNRF AGFGIGLASL FTENVLAHPC
IVLRRQCQVN YHAQHYHLTP FTVINIMYSF NKTQGPRALW KGMGSTFIVQ GVTLGAEGII
SEFTPLPREV LHKWSPKQIG EHLLLKSLTY VVAMPFYSAS LIETVQSEII RDNTGILECV
KEGIGRVIGM GVPHSKRLLP LLSLIFPTVL HGVLHYIISS VIQKFVLLIL KRKTYNSHLA
ESTSPVQSML DAYFPELIAN FAASLCSDVI LYPLETVLHR LHIQGTRTII DNTDLGYEVL
PINTQYEGMR DCINTIRQEE GVFGFYKGFG AVIIQYTLHA AVLQITKIIY STLLQNNI
