SFXN2_HUMAN
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 03-AUG-2022, entry version 152.
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; 109.
DR IntAct; Q96NB2; 12.
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 BioMuta; SFXN2; -.
DR EPD; Q96NB2; -.
DR jPOST; Q96NB2; -.
DR MassIVE; Q96NB2; -.
DR MaxQB; Q96NB2; -.
DR PaxDb; Q96NB2; -.
DR PeptideAtlas; Q96NB2; -.
DR PRIDE; Q96NB2; -.
DR ProteomicsDB; 77498; -.
DR Antibodypedia; 18077; 81 antibodies from 17 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 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; RIVMCAP; -.
DR OrthoDB; 881974at2759; -.
DR PhylomeDB; Q96NB2; -.
DR TreeFam; TF313205; -.
DR PathwayCommons; Q96NB2; -.
DR SignaLink; Q96NB2; -.
DR BioGRID-ORCS; 118980; 9 hits in 1081 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 169 other tissues.
DR ExpressionAtlas; Q96NB2; baseline and differential.
DR Genevisible; Q96NB2; HS.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0022889; F:serine transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
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 PANTHER; PTHR11153; PTHR11153; 1.
DR Pfam; PF03820; SFXNs; 1.
DR TIGRFAMs; TIGR00798; mtc; 1.
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
