S2538_HUMAN
ID S2538_HUMAN Reviewed; 304 AA.
AC Q96DW6; A1LP07; Q9NWX2;
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 glycine transporter {ECO:0000255|HAMAP-Rule:MF_03064};
DE AltName: Full=Appoptosin {ECO:0000303|PubMed:23115192};
DE AltName: Full=Mitochondrial glycine transporter GlyC {ECO:0000303|PubMed:27476175};
DE AltName: Full=Solute carrier family 25 member 38 {ECO:0000255|HAMAP-Rule:MF_03064};
GN Name=SLC25A38 {ECO:0000312|HGNC:HGNC:26054};
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].
RC TISSUE=Carcinoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
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 [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].
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 VARIANTS SIDBA2 GLU-130; HIS-134; PRO-187 AND HIS-209, FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=19412178; DOI=10.1038/ng.359;
RA Guernsey D.L., Jiang H., Campagna D.R., Evans S.C., Ferguson M.,
RA Kellogg M.D., Lachance M., Matsuoka M., Nightingale M., Rideout A.,
RA Saint-Amant L., Schmidt P.J., Orr A., Bottomley S.S., Fleming M.D.,
RA Ludman M., Dyack S., Fernandez C.V., Samuels M.E.;
RT "Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic
RT autosomal recessive congenital sideroblastic anemia.";
RL Nat. Genet. 41:651-653(2009).
RN [8]
RP INDUCTION.
RX PubMed=23115192; DOI=10.1523/jneurosci.3668-12.2012;
RA Zhang H., Zhang Y.W., Chen Y., Huang X., Zhou F., Wang W., Xian B.,
RA Zhang X., Masliah E., Chen Q., Han J.D., Bu G., Reed J.C., Liao F.F.,
RA Chen Y.G., Xu H.;
RT "Appoptosin is a novel pro-apoptotic protein and mediates cell death in
RT neurodegeneration.";
RL J. Neurosci. 32:15565-15576(2012).
RN [9]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=27476175; DOI=10.1074/jbc.m116.736876;
RA Lunetti P., Damiano F., De Benedetto G., Siculella L., Pennetta A.,
RA Muto L., Paradies E., Marobbio C.M., Dolce V., Capobianco L.;
RT "Characterization of human and yeast mitochondrial glycine carriers with
RT implications for heme biosynthesis and anemia.";
RL J. Biol. Chem. 291:19746-19759(2016).
CC -!- FUNCTION: Mitochondrial glycine transporter that imports glycine into
CC the mitochondrial matrix. Plays an important role in providing glycine
CC for the first enzymatic step in heme biosynthesis, the condensation of
CC glycine with succinyl-CoA to produce 5-aminolevulinate (ALA) in the
CC mitochondrial matrix. Required during erythropoiesis.
CC {ECO:0000255|HAMAP-Rule:MF_03064, ECO:0000269|PubMed:19412178,
CC ECO:0000269|PubMed:27476175}.
CC -!- FUNCTION: Plays a role as pro-apoptotic protein that induces caspase-
CC dependent apoptosis. {ECO:0000250|UniProtKB:Q91XD8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine(in) = glycine(out); Xref=Rhea:RHEA:70715,
CC ChEBI:CHEBI:57305; Evidence={ECO:0000269|PubMed:27476175};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_03064}; Multi-pass membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_03064}.
CC -!- TISSUE SPECIFICITY: Preferentially expressed in erythroid cells.
CC {ECO:0000269|PubMed:19412178}.
CC -!- INDUCTION: Up-regulated in the brains of patients with Alzheimer's
CC disease. {ECO:0000269|PubMed:23115192}.
CC -!- DISEASE: Anemia, sideroblastic, 2, pyridoxine-refractory (SIDBA2)
CC [MIM:205950]: A form of sideroblastic anemia not responsive to
CC pyridoxine. Sideroblastic anemia is characterized by anemia of varying
CC severity, hypochromic peripheral erythrocytes, systemic iron overload
CC secondary to chronic ineffective erythropoiesis, and the presence of
CC bone marrow ringed sideroblasts. Sideroblasts are characterized by
CC iron-loaded mitochondria clustered around the nucleus.
CC {ECO:0000269|PubMed:19412178}. 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 SLC25A38 subfamily. {ECO:0000255|HAMAP-Rule:MF_03064}.
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DR EMBL; AK000558; BAA91253.1; -; mRNA.
DR EMBL; CR457242; CAG33523.1; -; mRNA.
DR EMBL; BC013194; AAH13194.1; -; mRNA.
DR EMBL; AC099332; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104850; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64580.1; -; Genomic_DNA.
DR EMBL; CH471055; EAW64581.1; -; Genomic_DNA.
DR CCDS; CCDS2685.1; -.
DR RefSeq; NP_060345.2; NM_017875.2.
DR AlphaFoldDB; Q96DW6; -.
DR SMR; Q96DW6; -.
DR BioGRID; 120313; 5.
DR IntAct; Q96DW6; 4.
DR STRING; 9606.ENSP00000273158; -.
DR TCDB; 2.A.29.5.6; the mitochondrial carrier (mc) family.
DR iPTMnet; Q96DW6; -.
DR PhosphoSitePlus; Q96DW6; -.
DR BioMuta; SLC25A38; -.
DR DMDM; 74751821; -.
DR EPD; Q96DW6; -.
DR jPOST; Q96DW6; -.
DR MassIVE; Q96DW6; -.
DR MaxQB; Q96DW6; -.
DR PaxDb; Q96DW6; -.
DR PeptideAtlas; Q96DW6; -.
DR PRIDE; Q96DW6; -.
DR ProteomicsDB; 76331; -.
DR Antibodypedia; 12178; 128 antibodies from 26 providers.
DR DNASU; 54977; -.
DR Ensembl; ENST00000650617.1; ENSP00000497532.1; ENSG00000144659.13.
DR GeneID; 54977; -.
DR KEGG; hsa:54977; -.
DR MANE-Select; ENST00000650617.1; ENSP00000497532.1; NM_017875.4; NP_060345.2.
DR UCSC; uc003cjo.3; human.
DR CTD; 54977; -.
DR DisGeNET; 54977; -.
DR GeneCards; SLC25A38; -.
DR HGNC; HGNC:26054; SLC25A38.
DR HPA; ENSG00000144659; Low tissue specificity.
DR MalaCards; SLC25A38; -.
DR MIM; 205950; phenotype.
DR MIM; 610819; gene.
DR neXtProt; NX_Q96DW6; -.
DR OpenTargets; ENSG00000144659; -.
DR Orphanet; 260305; Autosomal recessive sideroblastic anemia.
DR PharmGKB; PA162403607; -.
DR VEuPathDB; HostDB:ENSG00000144659; -.
DR eggNOG; KOG0766; Eukaryota.
DR GeneTree; ENSGT00550000075117; -.
DR HOGENOM; CLU_015166_0_3_1; -.
DR InParanoid; Q96DW6; -.
DR OMA; IRDAPYA; -.
DR OrthoDB; 1531343at2759; -.
DR PhylomeDB; Q96DW6; -.
DR TreeFam; TF332793; -.
DR PathwayCommons; Q96DW6; -.
DR SignaLink; Q96DW6; -.
DR BioGRID-ORCS; 54977; 174 hits in 1045 CRISPR screens.
DR ChiTaRS; SLC25A38; human.
DR GenomeRNAi; 54977; -.
DR Pharos; Q96DW6; Tbio.
DR PRO; PR:Q96DW6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q96DW6; protein.
DR Bgee; ENSG00000144659; Expressed in body of pancreas and 182 other tissues.
DR ExpressionAtlas; Q96DW6; baseline and differential.
DR Genevisible; Q96DW6; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:1904983; P:glycine import into mitochondrion; IMP:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; TAS:UniProtKB.
DR Gene3D; 1.50.40.10; -; 2.
DR HAMAP; MF_03064; SLC25A38; 1.
DR InterPro; IPR030847; Hem25/SLC25A38.
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 Disease variant; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..304
FT /note="Mitochondrial glycine transporter"
FT /id="PRO_0000291802"
FT TRANSMEM 31..56
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 89..115
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 127..152
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 180..203
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 219..245
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT TRANSMEM 274..292
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT REPEAT 25..114
FT /note="Solcar 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT REPEAT 121..205
FT /note="Solcar 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT REPEAT 215..299
FT /note="Solcar 3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03064"
FT VARIANT 66
FT /note="R -> G (in dbSNP:rs34127778)"
FT /id="VAR_032862"
FT VARIANT 130
FT /note="G -> E (in SIDBA2; dbSNP:rs762562272)"
FT /evidence="ECO:0000269|PubMed:19412178"
FT /id="VAR_058093"
FT VARIANT 134
FT /note="R -> H (in SIDBA2)"
FT /evidence="ECO:0000269|PubMed:19412178"
FT /id="VAR_058094"
FT VARIANT 187
FT /note="R -> P (in SIDBA2; dbSNP:rs121918331)"
FT /evidence="ECO:0000269|PubMed:19412178"
FT /id="VAR_058095"
FT VARIANT 209
FT /note="D -> H (in SIDBA2; dbSNP:rs146864395)"
FT /evidence="ECO:0000269|PubMed:19412178"
FT /id="VAR_058096"
FT CONFLICT 239
FT /note="D -> G (in Ref. 1; BAA91253)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 304 AA; 33566 MW; 026B8121C40F8FF0 CRC64;
MIQNSRPSLL QPQDVGDTVE TLMLHPVIKA FLCGSISGTC STLLFQPLDL LKTRLQTLQP
SDHGSRRVGM LAVLLKVVRT ESLLGLWKGM SPSIVRCVPG VGIYFGTLYS LKQYFLRGHP
PTALESVMLG VGSRSVAGVC MSPITVIKTR YESGKYGYES IYAALRSIYH SEGHRGLFSG
LTATLLRDAP FSGIYLMFYN QTKNIVPHDQ VDATLIPITN FSCGIFAGIL ASLVTQPADV
IKTHMQLYPL KFQWIGQAVT LIFKDYGLRG FFQGGIPRAL RRTLMAAMAW TVYEEMMAKM
GLKS
