SFXN4_HUMAN
ID SFXN4_HUMAN Reviewed; 337 AA.
AC Q6P4A7; Q6WSU4; Q86TD9;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Sideroflexin-4 {ECO:0000303|PubMed:15489334};
DE AltName: Full=Breast cancer resistance marker 1 {ECO:0000303|Ref.1};
GN Name=SFXN4 {ECO:0000303|PubMed:15489334, ECO:0000312|HGNC:HGNC:16088};
GN Synonyms=BCRM1 {ECO:0000303|Ref.1};
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 3).
RC TISSUE=Mammary tumor;
RA Auclair D., Gong Y., Dai M., Kraeft S.-K., Chen L.B.;
RT "BCRM-1, a novel tumor marker for refractory cancers.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=14756423; DOI=10.1080/10425170310001605491;
RA Zheng H., Ji C., Zou X., Wu M., Jin Z., Yin G., Li J., Feng C., Cheng H.,
RA Gu S., Xie Y., Mao Y.;
RT "Molecular cloning and characterization of a novel human putative
RT transmembrane protein homologous to mouse sideroflexin associated with
RT sideroblastic anemia.";
RL DNA Seq. 14:369-373(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [9]
RP INVOLVEMENT IN COXPD18, AND SUBCELLULAR LOCATION.
RX PubMed=24119684; DOI=10.1016/j.ajhg.2013.09.011;
RA Hildick-Smith G.J., Cooney J.D., Garone C., Kremer L.S., Haack T.B.,
RA Thon J.N., Miyata N., Lieber D.S., Calvo S.E., Akman H.O., Yien Y.Y.,
RA Huston N.C., Branco D.S., Shah D.I., Freedman M.L., Koehler C.M.,
RA Italiano J.E. Jr., Merkenschlager A., Beblo S., Strom T.M., Meitinger T.,
RA Freisinger P., Donati M.A., Prokisch H., Mootha V.K., DiMauro S., Paw B.H.;
RT "Macrocytic anemia and mitochondriopathy resulting from a defect in
RT sideroflexin 4.";
RL Am. J. Hum. Genet. 93:906-914(2013).
RN [10]
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 [11]
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).
CC -!- FUNCTION: Mitochondrial amino-acid transporter (By similarity). Does
CC not act as a serine transporter: not able to mediate transport of
CC serine into mitochondria (PubMed:30442778).
CC {ECO:0000250|UniProtKB:Q9H9B4, ECO:0000269|PubMed:30442778}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:24119684, ECO:0000305|PubMed:30442778}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6P4A7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P4A7-2; Sequence=VSP_014609, VSP_014610;
CC Name=3;
CC IsoId=Q6P4A7-3; Sequence=VSP_014608;
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 18 (COXPD18)
CC [MIM:615578]: An autosomal recessive disorder of mitochondrial
CC dysfunction characterized by intrauterine growth retardation,
CC hypotonia, visual impairment, speech delay, and lactic acidosis
CC associated with decreased mitochondrial respiratory chain activity.
CC Affected patients may also show hematologic abnormalities, mainly
CC macrocytic anemia. {ECO:0000269|PubMed:24119684}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sideroflexin family. {ECO:0000305}.
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DR EMBL; AF336980; AAP23066.1; -; mRNA.
DR EMBL; AY269785; AAP97074.1; -; mRNA.
DR EMBL; AL355598; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355861; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063562; AAH63562.1; -; mRNA.
DR CCDS; CCDS7610.1; -. [Q6P4A7-1]
DR RefSeq; NP_998814.1; NM_213649.1. [Q6P4A7-1]
DR RefSeq; XP_005269583.1; XM_005269526.2. [Q6P4A7-3]
DR RefSeq; XP_005269584.1; XM_005269527.1. [Q6P4A7-3]
DR RefSeq; XP_011537584.1; XM_011539282.2. [Q6P4A7-3]
DR AlphaFoldDB; Q6P4A7; -.
DR BioGRID; 125645; 95.
DR IntAct; Q6P4A7; 22.
DR STRING; 9606.ENSP00000347924; -.
DR TCDB; 2.A.54.1.3; the sideroflexin (sfxn) family (formerly the mitochondrial tricarboxylate carrier (mtc) family.
DR iPTMnet; Q6P4A7; -.
DR PhosphoSitePlus; Q6P4A7; -.
DR BioMuta; SFXN4; -.
DR DMDM; 71153761; -.
DR EPD; Q6P4A7; -.
DR jPOST; Q6P4A7; -.
DR MassIVE; Q6P4A7; -.
DR MaxQB; Q6P4A7; -.
DR PaxDb; Q6P4A7; -.
DR PeptideAtlas; Q6P4A7; -.
DR PRIDE; Q6P4A7; -.
DR ProteomicsDB; 66955; -. [Q6P4A7-1]
DR ProteomicsDB; 66956; -. [Q6P4A7-2]
DR ProteomicsDB; 66957; -. [Q6P4A7-3]
DR Antibodypedia; 18795; 126 antibodies from 21 providers.
DR DNASU; 119559; -.
DR Ensembl; ENST00000355697.7; ENSP00000347924.2; ENSG00000183605.17. [Q6P4A7-1]
DR GeneID; 119559; -.
DR KEGG; hsa:119559; -.
DR MANE-Select; ENST00000355697.7; ENSP00000347924.2; NM_213649.2; NP_998814.1.
DR UCSC; uc001leb.4; human. [Q6P4A7-1]
DR CTD; 119559; -.
DR DisGeNET; 119559; -.
DR GeneCards; SFXN4; -.
DR HGNC; HGNC:16088; SFXN4.
DR HPA; ENSG00000183605; Low tissue specificity.
DR MalaCards; SFXN4; -.
DR MIM; 615564; gene.
DR MIM; 615578; phenotype.
DR neXtProt; NX_Q6P4A7; -.
DR OpenTargets; ENSG00000183605; -.
DR Orphanet; 391348; Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome.
DR PharmGKB; PA38093; -.
DR VEuPathDB; HostDB:ENSG00000183605; -.
DR eggNOG; KOG3767; Eukaryota.
DR GeneTree; ENSGT01030000234641; -.
DR HOGENOM; CLU_039425_3_0_1; -.
DR InParanoid; Q6P4A7; -.
DR OMA; SYTTCAG; -.
DR OrthoDB; 881974at2759; -.
DR PhylomeDB; Q6P4A7; -.
DR TreeFam; TF313205; -.
DR PathwayCommons; Q6P4A7; -.
DR SignaLink; Q6P4A7; -.
DR BioGRID-ORCS; 119559; 18 hits in 1079 CRISPR screens.
DR ChiTaRS; SFXN4; human.
DR GenomeRNAi; 119559; -.
DR Pharos; Q6P4A7; Tbio.
DR PRO; PR:Q6P4A7; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q6P4A7; protein.
DR Bgee; ENSG00000183605; Expressed in apex of heart and 181 other tissues.
DR ExpressionAtlas; Q6P4A7; baseline and differential.
DR Genevisible; Q6P4A7; HS.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0015075; F:ion transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0006865; P:amino acid transport; IEA:UniProtKB-KW.
DR GO; GO:1990542; P:mitochondrial transmembrane transport; IBA:GO_Central.
DR InterPro; IPR004686; Mtc.
DR InterPro; IPR028825; SFXN4.
DR PANTHER; PTHR11153; PTHR11153; 1.
DR PANTHER; PTHR11153:SF3; PTHR11153:SF3; 1.
DR Pfam; PF03820; SFXNs; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Amino-acid transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..337
FT /note="Sideroflexin-4"
FT /id="PRO_0000177041"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 197
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..116
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_014608"
FT VAR_SEQ 85..93
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14756423"
FT /id="VSP_014609"
FT VAR_SEQ 313..337
FT /note="IQYCSLEEKIQSPTEETEIFYHRGV -> VT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14756423"
FT /id="VSP_014610"
SQ SEQUENCE 337 AA; 37998 MW; 77A08F150D241277 CRC64;
MSLEQEEETQ PGRLLGRRDA VPAFIEPNVR FWITERQSFI RRFLQWTELL DPTNVFISVE
SIENSRQLLC TNEDVSSPAS ADQRIQEAWK RSLATVHPDS SNLIPKLFRP AAFLPFMAPT
VFLSMTPLKG IKSVILPQVF LCAYMAAFNS INGNRSYTCK PLERSLLMAG AVASSTFLGV
IPQFVQMKYG LTGPWIKRLL PVIFLVQASG MNVYMSRSLE SIKGIAVMDK EGNVLGHSRI
AGTKAVRETL ASRIVLFGTS ALIPEVFTYF FKRTQYFRKN PGSLWILKLS CTVLAMGLMV
PFSFSIFPQI GQIQYCSLEE KIQSPTEETE IFYHRGV
