ID S2538_HUMAN Reviewed; 304 AA. AC Q96DW6; Q9NWX2; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 26-FEB-2020, entry version 140. DE RecName: Full=Mitochondrial glycine transporter {ECO:0000255|HAMAP-Rule:MF_03064}; 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:0000255|HAMAP-Rule:MF_03064}; 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 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 [4] 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 [5] 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 [6] RP FUNCTION. 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 -!- 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 -!- 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 mutations 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK000558; BAA91253.1; -; mRNA. DR EMBL; CR457242; CAG33523.1; -; mRNA. DR EMBL; BC013194; AAH13194.1; -; mRNA. DR CCDS; CCDS2685.1; -. DR RefSeq; NP_060345.2; NM_017875.2. 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 DNASU; 54977; -. DR Ensembl; ENST00000650617; ENSP00000497532; ENSG00000144659. DR GeneID; 54977; -. DR KEGG; hsa:54977; -. DR UCSC; uc003cjo.3; human. DR CTD; 54977; -. DR DisGeNET; 54977; -. DR GeneCards; SLC25A38; -. DR HGNC; HGNC:26054; SLC25A38. DR HPA; HPA041027; -. 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 eggNOG; KOG0766; Eukaryota. DR eggNOG; ENOG410XRMK; LUCA. DR GeneTree; ENSGT00550000075117; -. DR HOGENOM; CLU_015166_0_3_1; -. DR InParanoid; Q96DW6; -. DR KO; K15118; -. DR OMA; KVRYESN; -. DR OrthoDB; 1531343at2759; -. DR PhylomeDB; Q96DW6; -. DR TreeFam; TF332793; -. 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 211 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; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0015187; F:glycine transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB. DR GO; GO:1904983; P:glycine import into mitochondrion; IBA:GO_Central. 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 mutation; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Polymorphism; Reference proteome; Repeat; Transmembrane; KW 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 //