ID   SFXN2_HUMAN             Reviewed;         322 AA.
AC   Q96NB2; Q5JSM6;
DT   27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   27-MAR-2002, sequence version 2.
DT   27-MAR-2024, entry version 161.
DE   RecName: Full=Sideroflexin-2 {ECO:0000303|Ref.2};
GN   Name=SFXN2 {ECO:0000303|Ref.2, ECO:0000312|HGNC:HGNC:16086};
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], AND TISSUE SPECIFICITY.
RX   PubMed=12670026; DOI=10.1023/a:1022026001114;
RA   Ye X., Xu J., Cheng C., Yin G., Zeng L., Ji C., Gu S., Xie Y., Mao Y.;
RT   "Isolation and characterization of a novel human putative anemia-related
RT   gene homologous to mouse sideroflexin.";
RL   Biochem. Genet. 41:119-125(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton 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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Muscle;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-204.
RC   TISSUE=Neuroblastoma;
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   [5]
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   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [7]
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).
RN   [8]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=30442778; DOI=10.1126/science.aat9528;
RA   Kory N., Wyant G.A., Prakash G., Uit de Bos J., Bottanelli F., Pacold M.E.,
RA   Chan S.H., Lewis C.A., Wang T., Keys H.R., Guo Y.E., Sabatini D.M.;
RT   "SFXN1 is a mitochondrial serine transporter required for one-carbon
RT   metabolism.";
RL   Science 362:0-0(2018).
RN   [9]
RP   SUBCELLULAR LOCATION, AND FUNCTION.
RX   PubMed=30570704; DOI=10.1007/s12576-018-0652-2;
RA   Mon E.E., Wei F.Y., Ahmad R.N.R., Yamamoto T., Moroishi T., Tomizawa K.;
RT   "Regulation of mitochondrial iron homeostasis by sideroflexin 2.";
RL   J. Physiol. Sci. 69:359-373(2019).
CC   -!- FUNCTION: Mitochondrial amino-acid transporter that mediates transport
CC       of serine into mitochondria (PubMed:30442778). Involved in
CC       mitochondrial iron homeostasis by regulating heme biosynthesis
CC       (PubMed:30570704). {ECO:0000269|PubMed:30442778,
CC       ECO:0000269|PubMed:30570704}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-serine(in) = L-serine(out); Xref=Rhea:RHEA:35031,
CC         ChEBI:CHEBI:33384; Evidence={ECO:0000305|PubMed:30442778};
CC   -!- INTERACTION:
CC       Q96NB2; Q13520: AQP6; NbExp=3; IntAct=EBI-6381136, EBI-13059134;
CC       Q96NB2; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-6381136, EBI-18053395;
CC       Q96NB2; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-6381136, EBI-716063;
CC       Q96NB2; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-6381136, EBI-7545592;
CC       Q96NB2; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-6381136, EBI-8638294;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000269|PubMed:30442778}; Multi-pass membrane protein
CC       {ECO:0000255}. Mitochondrion outer membrane
CC       {ECO:0000269|PubMed:30570704}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Widely expressed, highest levels in kidney, liver,
CC       and pancreas. {ECO:0000269|PubMed:12670026}.
CC   -!- SIMILARITY: Belongs to the sideroflexin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB70993.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF462052; AAM09645.1; -; mRNA.
DR   EMBL; CH471066; EAW49675.1; -; Genomic_DNA.
DR   EMBL; CH471066; EAW49677.1; -; Genomic_DNA.
DR   EMBL; BC022091; AAH22091.1; -; mRNA.
DR   EMBL; AK055711; BAB70993.1; ALT_INIT; mRNA.
DR   CCDS; CCDS7539.1; -.
DR   RefSeq; NP_849189.1; NM_178858.4.
DR   RefSeq; XP_011537564.1; XM_011539262.2.
DR   RefSeq; XP_016871152.1; XM_017015663.1.
DR   AlphaFoldDB; Q96NB2; -.
DR   BioGRID; 125630; 115.
DR   IntAct; Q96NB2; 13.
DR   STRING; 9606.ENSP00000358909; -.
DR   TCDB; 2.A.54.1.8; the sideroflexin (sfxn) family (formerly the mitochondrial tricarboxylate carrier (mtc) family).
DR   iPTMnet; Q96NB2; -.
DR   PhosphoSitePlus; Q96NB2; -.
DR   SwissPalm; Q96NB2; -.
DR   BioMuta; SFXN2; -.
DR   EPD; Q96NB2; -.
DR   jPOST; Q96NB2; -.
DR   MassIVE; Q96NB2; -.
DR   MaxQB; Q96NB2; -.
DR   PaxDb; 9606-ENSP00000358909; -.
DR   PeptideAtlas; Q96NB2; -.
DR   ProteomicsDB; 77498; -.
DR   Pumba; Q96NB2; -.
DR   Antibodypedia; 18077; 98 antibodies from 18 providers.
DR   DNASU; 118980; -.
DR   Ensembl; ENST00000369893.10; ENSP00000358909.4; ENSG00000156398.13.
DR   GeneID; 118980; -.
DR   KEGG; hsa:118980; -.
DR   MANE-Select; ENST00000369893.10; ENSP00000358909.4; NM_178858.6; NP_849189.1.
DR   UCSC; uc001kwb.3; human.
DR   AGR; HGNC:16086; -.
DR   CTD; 118980; -.
DR   DisGeNET; 118980; -.
DR   GeneCards; SFXN2; -.
DR   HGNC; HGNC:16086; SFXN2.
DR   HPA; ENSG00000156398; Tissue enhanced (kidney, parathyroid gland).
DR   MIM; 615570; gene.
DR   neXtProt; NX_Q96NB2; -.
DR   OpenTargets; ENSG00000156398; -.
DR   PharmGKB; PA38091; -.
DR   VEuPathDB; HostDB:ENSG00000156398; -.
DR   eggNOG; KOG3767; Eukaryota.
DR   GeneTree; ENSGT01030000234641; -.
DR   HOGENOM; CLU_039425_1_0_1; -.
DR   InParanoid; Q96NB2; -.
DR   OMA; LEKYAWM; -.
DR   OrthoDB; 48449at2759; -.
DR   PhylomeDB; Q96NB2; -.
DR   TreeFam; TF313205; -.
DR   PathwayCommons; Q96NB2; -.
DR   SignaLink; Q96NB2; -.
DR   BioGRID-ORCS; 118980; 11 hits in 1160 CRISPR screens.
DR   ChiTaRS; SFXN2; human.
DR   GenomeRNAi; 118980; -.
DR   Pharos; Q96NB2; Tdark.
DR   PRO; PR:Q96NB2; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q96NB2; Protein.
DR   Bgee; ENSG00000156398; Expressed in kidney epithelium and 171 other cell types or tissues.
DR   ExpressionAtlas; Q96NB2; baseline and differential.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0015075; F:monoatomic ion transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:1990542; P:mitochondrial transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0140300; P:serine import into mitochondrion; IBA:GO_Central.
DR   InterPro; IPR004686; Mtc.
DR   NCBIfam; TIGR00798; mtc; 1.
DR   PANTHER; PTHR11153; SIDEROFLEXIN; 1.
DR   PANTHER; PTHR11153:SF14; SIDEROFLEXIN-2; 1.
DR   Pfam; PF03820; SFXNs; 1.
DR   Genevisible; Q96NB2; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Amino-acid transport; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Mitochondrion outer membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..322
FT                   /note="Sideroflexin-2"
FT                   /id="PRO_0000177035"
FT   TRANSMEM        100..122
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        142..164
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        174..192
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        228..250
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        265..287
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CONFLICT        145..204
FT                   /note="QMALSYFTATTTAVATAVGMNMLTKKAPPLVGRWVPFAAVAAANCVNIPMMR
FT                   QQELIKGI -> KRRPWWAAGCPLPLWLRLTVSISP (in Ref. 4; BAB70993)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   322 AA;  36232 MW;  329D577B2583DF31 CRC64;
     MEADLSGFNI DAPRWDQRTF LGRVKHFLNI TDPRTVFVSE RELDWAKVMV EKSRMGVVPP
     GTQVEQLLYA KKLYDSAFHP DTGEKMNVIG RMSFQLPGGM IITGFMLQFY RTMPAVIFWQ
     WVNQSFNALV NYTNRNAASP TSVRQMALSY FTATTTAVAT AVGMNMLTKK APPLVGRWVP
     FAAVAAANCV NIPMMRQQEL IKGICVKDRN ENEIGHSRRA AAIGITQVVI SRITMSAPGM
     ILLPVIMERL EKLHFMQKVK VLHAPLQVML SGCFLIFMVP VACGLFPQKC ELPVSYLEPK
     LQDTIKAKYG ELEPYVYFNK GL
//