SAMC_HUMAN
ID SAMC_HUMAN Reviewed; 274 AA.
AC Q70HW3; A8K758; B3KRZ7; F8WAB8; Q7Z786; Q96E68;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=S-adenosylmethionine mitochondrial carrier protein;
DE AltName: Full=Mitochondrial S-adenosylmethionine transporter;
DE AltName: Full=Solute carrier family 25 member 26;
GN Name=SLC25A26; Synonyms=SAMC;
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), FUNCTION, ACTIVITY REGULATION,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT ASN-41.
RX PubMed=14674884; DOI=10.1042/bj20031664;
RA Agrimi G., Di Noia M.A., Marobbio C.M.T., Fiermonte G., Lasorsa F.M.,
RA Palmieri F.;
RT "Identification of the human mitochondrial S-adenosylmethionine
RT transporter: bacterial expression, reconstitution, functional
RT characterization and tissue distribution.";
RL Biochem. J. 379:183-190(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP ASN-41 AND MET-208.
RC TISSUE=Placenta, and Skeletal muscle;
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], AND VARIANTS ASN-41 AND
RP MET-208.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Ovary, and Placenta;
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, INVOLVEMENT IN COXPD28, VARIANTS COXPD28 VAL-102; GLY-148 AND
RP LEU-199, AND CHARACTERIZATION OF VARIANTS COXPD28 VAL-102; GLY-148 AND
RP LEU-199.
RX PubMed=26522469; DOI=10.1016/j.ajhg.2015.09.013;
RA Kishita Y., Pajak A., Bolar N.A., Marobbio C.M., Maffezzini C.,
RA Miniero D.V., Monne M., Kohda M., Stranneheim H., Murayama K., Naess K.,
RA Lesko N., Bruhn H., Mourier A., Wibom R., Nennesmo I., Jespers A.,
RA Govaert P., Ohtake A., Van Laer L., Loeys B.L., Freyer C., Palmieri F.,
RA Wredenberg A., Okazaki Y., Wedell A.;
RT "Intra-mitochondrial methylation deficiency due to mutations in SLC25A26.";
RL Am. J. Hum. Genet. 97:761-768(2015).
CC -!- FUNCTION: Mitochondrial solute carriers shuttle metabolites,
CC nucleotides, and cofactors through the mitochondrial inner membrane.
CC Specifically mediates the transport of S-adenosylmethionine (SAM) into
CC the mitochondria. {ECO:0000269|PubMed:14674884,
CC ECO:0000269|PubMed:26522469}.
CC -!- ACTIVITY REGULATION: Strongly inhibited by tannic acid and Bromocresol
CC Purple. {ECO:0000269|PubMed:14674884}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:14674884}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:14674884}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q70HW3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q70HW3-2; Sequence=VSP_031062;
CC Name=3;
CC IsoId=Q70HW3-3; Sequence=VSP_031062, VSP_031063, VSP_031064;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in testis, with
CC moderate expression in brain, heart, kidney, lung, skeletal muscle,
CC pancreas, small intestine and liver, and low expression in spleen.
CC {ECO:0000269|PubMed:14674884}.
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 28 (COXPD28)
CC [MIM:616794]: An autosomal recessive mitochondrial disorder
CC characterized by decreased activities of respiratory chain enzymes, and
CC variable clinical manifestations. Clinical features include episodic
CC metabolic decompensation beginning in infancy, mild muscle weakness,
CC cardiorespiratory insufficiency, developmental delay, or even death.
CC {ECO:0000269|PubMed:26522469}. 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}.
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DR EMBL; AJ580932; CAE45652.1; -; mRNA.
DR EMBL; AK092495; BAG52559.1; -; mRNA.
DR EMBL; AK096876; BAG53388.1; -; mRNA.
DR EMBL; AK291873; BAF84562.1; -; mRNA.
DR EMBL; AC145425; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC170165; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092034; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC170801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC235952; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AEKP01024816; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65449.1; -; Genomic_DNA.
DR EMBL; CH471055; EAW65451.1; -; Genomic_DNA.
DR EMBL; BC003399; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC012852; AAH12852.2; -; mRNA.
DR CCDS; CCDS2905.2; -. [Q70HW3-1]
DR CCDS; CCDS54604.1; -. [Q70HW3-2]
DR RefSeq; NP_001158268.1; NM_001164796.1. [Q70HW3-2]
DR RefSeq; NP_775742.4; NM_173471.3. [Q70HW3-1]
DR RefSeq; XP_011531629.1; XM_011533327.2. [Q70HW3-2]
DR AlphaFoldDB; Q70HW3; -.
DR SMR; Q70HW3; -.
DR BioGRID; 125423; 6.
DR IntAct; Q70HW3; 1.
DR STRING; 9606.ENSP00000346955; -.
DR TCDB; 2.A.29.18.3; the mitochondrial carrier (mc) family.
DR iPTMnet; Q70HW3; -.
DR PhosphoSitePlus; Q70HW3; -.
DR BioMuta; SLC25A26; -.
DR DMDM; 74749739; -.
DR EPD; Q70HW3; -.
DR jPOST; Q70HW3; -.
DR MassIVE; Q70HW3; -.
DR MaxQB; Q70HW3; -.
DR PaxDb; Q70HW3; -.
DR PeptideAtlas; Q70HW3; -.
DR PRIDE; Q70HW3; -.
DR ProteomicsDB; 30470; -.
DR ProteomicsDB; 68552; -. [Q70HW3-1]
DR ProteomicsDB; 68553; -. [Q70HW3-2]
DR ProteomicsDB; 68554; -. [Q70HW3-3]
DR Antibodypedia; 15419; 111 antibodies from 19 providers.
DR DNASU; 115286; -.
DR Ensembl; ENST00000336733.10; ENSP00000336801.5; ENSG00000144741.19. [Q70HW3-2]
DR Ensembl; ENST00000354883.11; ENSP00000346955.6; ENSG00000144741.19. [Q70HW3-1]
DR Ensembl; ENST00000632575.1; ENSP00000488865.1; ENSG00000282739.1. [Q70HW3-2]
DR Ensembl; ENST00000633701.1; ENSP00000488659.1; ENSG00000282739.1. [Q70HW3-1]
DR Ensembl; ENST00000676754.1; ENSP00000504323.1; ENSG00000144741.19. [Q70HW3-1]
DR Ensembl; ENST00000686511.1; ENSP00000509933.1; ENSG00000144741.19. [Q70HW3-2]
DR Ensembl; ENST00000691461.1; ENSP00000510022.1; ENSG00000144741.19. [Q70HW3-2]
DR GeneID; 115286; -.
DR KEGG; hsa:115286; -.
DR MANE-Select; ENST00000354883.11; ENSP00000346955.6; NM_001379210.1; NP_001366139.1.
DR UCSC; uc011bfq.2; human.
DR UCSC; uc011bfs.3; human. [Q70HW3-1]
DR CTD; 115286; -.
DR DisGeNET; 115286; -.
DR GeneCards; SLC25A26; -.
DR HGNC; HGNC:20661; SLC25A26.
DR HPA; ENSG00000144741; Low tissue specificity.
DR MalaCards; SLC25A26; -.
DR MIM; 611037; gene.
DR MIM; 616794; phenotype.
DR neXtProt; NX_Q70HW3; -.
DR OpenTargets; ENSG00000144741; -.
DR Orphanet; 466784; Neonatal severe cardiopulmonary failure due to mitochondrial methylation defect.
DR PharmGKB; PA134987831; -.
DR VEuPathDB; HostDB:ENSG00000144741; -.
DR eggNOG; KOG0768; Eukaryota.
DR GeneTree; ENSGT00550000074950; -.
DR InParanoid; Q70HW3; -.
DR OMA; PRVGWIS; -.
DR PhylomeDB; Q70HW3; -.
DR TreeFam; TF313186; -.
DR PathwayCommons; Q70HW3; -.
DR Reactome; R-HSA-425393; Transport of inorganic cations/anions and amino acids/oligopeptides.
DR SignaLink; Q70HW3; -.
DR BioGRID-ORCS; 115286; 344 hits in 1096 CRISPR screens.
DR ChiTaRS; SLC25A26; human.
DR GenomeRNAi; 115286; -.
DR Pharos; Q70HW3; Tbio.
DR PRO; PR:Q70HW3; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q70HW3; protein.
DR Bgee; ENSG00000144741; Expressed in gastrocnemius and 98 other tissues.
DR ExpressionAtlas; Q70HW3; baseline and differential.
DR Genevisible; Q70HW3; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0000095; F:S-adenosyl-L-methionine transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0015805; P:S-adenosyl-L-methionine transport; IMP:UniProtKB.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 3.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..274
FT /note="S-adenosylmethionine mitochondrial carrier protein"
FT /id="PRO_0000317587"
FT TRANSMEM 5..25
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..69
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 4..77
FT /note="Solcar 1"
FT REPEAT 86..168
FT /note="Solcar 2"
FT REPEAT 177..265
FT /note="Solcar 3"
FT VAR_SEQ 1..88
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_031062"
FT VAR_SEQ 152..154
FT /note="IPF -> EED (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031063"
FT VAR_SEQ 155..274
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031064"
FT VARIANT 41
FT /note="S -> N (in dbSNP:rs146159281)"
FT /evidence="ECO:0000269|PubMed:14674884,
FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.3"
FT /id="VAR_080244"
FT VARIANT 102
FT /note="A -> V (in COXPD28; severe abrogation of S-
FT adenosylmethionine transport; dbSNP:rs869025314)"
FT /evidence="ECO:0000269|PubMed:26522469"
FT /id="VAR_076305"
FT VARIANT 148
FT /note="V -> G (in COXPD28; severe abrogation of S-
FT adenosylmethionine transport; dbSNP:rs869025313)"
FT /evidence="ECO:0000269|PubMed:26522469"
FT /id="VAR_076306"
FT VARIANT 199
FT /note="P -> L (in COXPD28; severe abrogation of S-
FT adenosylmethionine transport; dbSNP:rs869025315)"
FT /evidence="ECO:0000269|PubMed:26522469"
FT /id="VAR_076307"
FT VARIANT 208
FT /note="T -> M (in dbSNP:rs13874)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.3"
FT /id="VAR_058973"
FT CONFLICT 208
FT /note="T -> A (in Ref. 2; BAF84562)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 274 AA; 29354 MW; 97315DE9CC68D19D CRC64;
MDRPGFVAAL VAGGVAGVSV DLILFPLDTI KTRLQSPQGF SKAGGFHGIY AGVPSAAIGS
FPNAAAFFIT YEYVKWFLHA DSSSYLTPMK HMLAASAGEV VACLIRVPSE VVKQRAQVSA
STRTFQIFSN ILYEEGIQGL YRGYKSTVLR EIPFSLVQFP LWESLKALWS WRQDHVVDSW
QSAVCGAFAG GFAAAVTTPL DVAKTRITLA KAGSSTADGN VLSVLHGVWR SQGLAGLFAG
VFPRMAAISL GGFIFLGAYD RTHSLLLEVG RKSP
