ID   MFRN1_HUMAN             Reviewed;         338 AA.
AC   Q9NYZ2; A2RU93; Q53FT7; Q69YJ8; Q969S1; Q9P0J2;
DT   16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   20-MAY-2008, sequence version 2.
DT   24-JAN-2024, entry version 165.
DE   RecName: Full=Mitoferrin-1;
DE   AltName: Full=Mitochondrial iron transporter 1;
DE   AltName: Full=Mitochondrial solute carrier protein;
DE   AltName: Full=Solute carrier family 25 member 37;
GN   Name=SLC25A37; Synonyms=MFRN, MSCP; ORFNames=HT015;
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 2).
RA   Li Q., Eckenrode S., Ruan Q., Wang C., Shi J., McIndoe R.A., She J.;
RT   "Molecular cloning of a novel mictochondria solute carrier protein (MSCP)
RT   gene from mouse and human and its down-regulation in mouse spleen during
RT   the maturation of the immune system.";
RL   Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC   TISSUE=Adrenal gland;
RX   PubMed=10931946; DOI=10.1073/pnas.160270997;
RA   Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA   Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA   Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA   Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA   Chen M.-D., Chen J.-L.;
RT   "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT   and full-length cDNA cloning.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Hypothalamus;
RA   Song H., Gao G., Peng Y., Ren S., Chen Z., Han Z.;
RT   "A novel gene expressed in human hypothalamus.";
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-96.
RC   TISSUE=Pancreas;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, and Uterus;
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-338 (ISOFORM 2).
RC   TISSUE=Lymph node;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [8]
RP   FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF ASP-226.
RX   PubMed=35513392; DOI=10.1038/s41467-022-30126-9;
RA   Shi X., Reinstadler B., Shah H., To T.L., Byrne K., Summer L., Calvo S.E.,
RA   Goldberger O., Doench J.G., Mootha V.K., Shen H.;
RT   "Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial
RT   glutathione transport linking iron homeostasis to OXPHOS.";
RL   Nat. Commun. 13:2483-2483(2022).
CC   -!- FUNCTION: Mitochondrial iron transporter that specifically mediates
CC       iron uptake in developing erythroid cells, thereby playing an essential
CC       role in heme biosynthesis. {ECO:0000269|PubMed:35513392}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Fe(2+)(in) = Fe(2+)(out); Xref=Rhea:RHEA:28486,
CC         ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:35513392};
CC   -!- SUBUNIT: Interacts with ACB10; this interaction stabilizes SLC25A37 and
CC       enhances the function of SLC25A37 to import mitochondrial iron during
CC       erythroid differentiation. {ECO:0000250|UniProtKB:Q920G8}.
CC   -!- INTERACTION:
CC       Q9NYZ2; Q9UL41: PNMA3; NbExp=3; IntAct=EBI-13074156, EBI-11278955;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:Q287T7}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9NYZ2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NYZ2-2; Sequence=VSP_018402, VSP_018403;
CC       Name=4;
CC         IsoId=Q9NYZ2-4; Sequence=VSP_018400;
CC   -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF64141.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=CAH10415.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR   EMBL; AY032628; AAK38154.1; -; mRNA.
DR   EMBL; AF155660; AAF67479.1; -; mRNA.
DR   EMBL; AF223466; AAF64141.1; ALT_FRAME; mRNA.
DR   EMBL; AK223194; BAD96914.1; -; mRNA.
DR   EMBL; CH471080; EAW63617.1; -; Genomic_DNA.
DR   EMBL; BC132799; AAI32800.1; -; mRNA.
DR   EMBL; BC132801; AAI32802.1; -; mRNA.
DR   EMBL; BC015013; AAH15013.1; -; mRNA.
DR   EMBL; AL833186; CAH10415.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS47828.1; -. [Q9NYZ2-1]
DR   RefSeq; NP_001304741.1; NM_001317812.1. [Q9NYZ2-4]
DR   RefSeq; NP_001304742.1; NM_001317813.1.
DR   RefSeq; NP_001304743.1; NM_001317814.1.
DR   RefSeq; NP_057696.2; NM_016612.3. [Q9NYZ2-1]
DR   RefSeq; XP_011542856.1; XM_011544554.2.
DR   AlphaFoldDB; Q9NYZ2; -.
DR   SMR; Q9NYZ2; -.
DR   BioGRID; 119463; 7.
DR   IntAct; Q9NYZ2; 1.
DR   STRING; 9606.ENSP00000429200; -.
DR   TCDB; 2.A.29.5.7; the mitochondrial carrier (mc) family.
DR   iPTMnet; Q9NYZ2; -.
DR   PhosphoSitePlus; Q9NYZ2; -.
DR   BioMuta; SLC25A37; -.
DR   DMDM; 189047115; -.
DR   EPD; Q9NYZ2; -.
DR   jPOST; Q9NYZ2; -.
DR   MassIVE; Q9NYZ2; -.
DR   MaxQB; Q9NYZ2; -.
DR   PaxDb; 9606-ENSP00000429200; -.
DR   PeptideAtlas; Q9NYZ2; -.
DR   ProteomicsDB; 83303; -. [Q9NYZ2-1]
DR   ProteomicsDB; 83304; -. [Q9NYZ2-2]
DR   ProteomicsDB; 83305; -. [Q9NYZ2-4]
DR   Pumba; Q9NYZ2; -.
DR   Antibodypedia; 42015; 180 antibodies from 19 providers.
DR   DNASU; 51312; -.
DR   Ensembl; ENST00000290075.10; ENSP00000290075.6; ENSG00000147454.14. [Q9NYZ2-2]
DR   Ensembl; ENST00000519973.6; ENSP00000429200.1; ENSG00000147454.14. [Q9NYZ2-1]
DR   GeneID; 51312; -.
DR   KEGG; hsa:51312; -.
DR   MANE-Select; ENST00000519973.6; ENSP00000429200.1; NM_016612.4; NP_057696.2.
DR   UCSC; uc003xds.4; human. [Q9NYZ2-1]
DR   AGR; HGNC:29786; -.
DR   CTD; 51312; -.
DR   DisGeNET; 51312; -.
DR   GeneCards; SLC25A37; -.
DR   HGNC; HGNC:29786; SLC25A37.
DR   HPA; ENSG00000147454; Tissue enhanced (bone).
DR   MIM; 610387; gene.
DR   neXtProt; NX_Q9NYZ2; -.
DR   OpenTargets; ENSG00000147454; -.
DR   PharmGKB; PA142670909; -.
DR   VEuPathDB; HostDB:ENSG00000147454; -.
DR   eggNOG; KOG0760; Eukaryota.
DR   GeneTree; ENSGT00940000158607; -.
DR   HOGENOM; CLU_015166_3_1_1; -.
DR   InParanoid; Q9NYZ2; -.
DR   OMA; MYNSQHQ; -.
DR   OrthoDB; 5481380at2759; -.
DR   PhylomeDB; Q9NYZ2; -.
DR   TreeFam; TF314118; -.
DR   PathwayCommons; Q9NYZ2; -.
DR   Reactome; R-HSA-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR   SignaLink; Q9NYZ2; -.
DR   BioGRID-ORCS; 51312; 30 hits in 1172 CRISPR screens.
DR   ChiTaRS; SLC25A37; human.
DR   GeneWiki; SLC25A37; -.
DR   GenomeRNAi; 51312; -.
DR   Pharos; Q9NYZ2; Tbio.
DR   PRO; PR:Q9NYZ2; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q9NYZ2; Protein.
DR   Bgee; ENSG00000147454; Expressed in trabecular bone tissue and 191 other cell types or tissues.
DR   ExpressionAtlas; Q9NYZ2; baseline and differential.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031966; C:mitochondrial membrane; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0015093; F:ferrous iron transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0048250; P:iron import into the mitochondrion; IMP:UniProtKB.
DR   GO; GO:0046985; P:positive regulation of hemoglobin biosynthetic process; ISS:UniProtKB.
DR   Gene3D; 1.50.40.10; Mitochondrial carrier domain; 2.
DR   InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR   InterPro; IPR023395; Mt_carrier_dom_sf.
DR   PANTHER; PTHR45758:SF4; MITOFERRIN-1; 1.
DR   PANTHER; PTHR45758; MITOFERRIN-1-RELATED; 1.
DR   Pfam; PF00153; Mito_carr; 3.
DR   SUPFAM; SSF103506; Mitochondrial carrier; 1.
DR   PROSITE; PS50920; SOLCAR; 3.
DR   Genevisible; Q9NYZ2; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Ion transport; Iron; Iron transport; Membrane;
KW   Mitochondrion; Mitochondrion inner membrane; Reference proteome; Repeat;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..338
FT                   /note="Mitoferrin-1"
FT                   /id="PRO_0000235251"
FT   TRANSMEM        45..64
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        106..125
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        143..162
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        200..219
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        234..253
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        301..320
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   REPEAT          43..131
FT                   /note="Solcar 1"
FT   REPEAT          141..225
FT                   /note="Solcar 2"
FT   REPEAT          232..326
FT                   /note="Solcar 3"
FT   REGION          1..42
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        16..30
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..151
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:10931946"
FT                   /id="VSP_018400"
FT   VAR_SEQ         149..155
FT                   /note="AGSMATL -> LKAFVWS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17974005, ECO:0000303|Ref.1,
FT                   ECO:0000303|Ref.4"
FT                   /id="VSP_018402"
FT   VAR_SEQ         156..338
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17974005, ECO:0000303|Ref.1,
FT                   ECO:0000303|Ref.4"
FT                   /id="VSP_018403"
FT   VARIANT         87
FT                   /note="I -> V (in dbSNP:rs2942194)"
FT                   /id="VAR_043144"
FT   VARIANT         96
FT                   /note="R -> Q (in dbSNP:rs3736032)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_043145"
SQ   SEQUENCE   338 AA;  37323 MW;  14576DF1F1854FAA CRC64;
     MELRSGSVGS QAVARRMDGD SRDGGGGKDA TGSEDYENLP TSASVSTHMT AGAMAGILEH
     SVMYPVDSVK TRMQSLSPDP KAQYTSIYGA LKKIMRTEGF WRPLRGVNVM IMGAGPAHAM
     YFACYENMKR TLNDVFHHQG NSHLANGIAG SMATLLHDAV MNPAEVVKQR LQMYNSQHRS
     AISCIRTVWR TEGLGAFYRS YTTQLTMNIP FQSIHFITYE FLQEQVNPHR TYNPQSHIIS
     GGLAGALAAA ATTPLDVCKT LLNTQENVAL SLANISGRLS GMANAFRTVY QLNGLAGYFK
     GIQARVIYQM PSTAISWSVY EFFKYFLTKR QLENRAPY
//