ID   FRRS1_HUMAN             Reviewed;         592 AA.
AC   Q6ZNA5; A6NLN7;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   15-JAN-2008, sequence version 2.
DT   24-JAN-2024, entry version 138.
DE   RecName: Full=Ferric-chelate reductase 1;
DE            EC=1.-.-.-;
DE   AltName: Full=Stromal cell-derived receptor 2;
DE            Short=SDR-2;
GN   Name=FRRS1; Synonyms=SDFR2, SDR2;
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] (ISOFORM 2).
RC   TISSUE=Teratocarcinoma;
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 GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
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   [4]
RP   IDENTIFICATION.
RX   PubMed=16169296; DOI=10.1016/j.bbapap.2005.08.015;
RA   Tsubaki M., Takeuchi F., Nakanishi N.;
RT   "Cytochrome b561 protein family: expanding roles and versatile
RT   transmembrane electron transfer abilities as predicted by a new
RT   classification system and protein sequence motif analyses.";
RL   Biochim. Biophys. Acta 1753:174-190(2005).
CC   -!- FUNCTION: Ferric-chelate reductases reduce Fe(3+) to Fe(2+) before its
CC       transport from the endosome to the cytoplasm.
CC       {ECO:0000250|UniProtKB:Q8K385}.
CC   -!- COFACTOR:
CC       Name=heme b; Xref=ChEBI:CHEBI:60344;
CC         Evidence={ECO:0000250|UniProtKB:Q53TN4};
CC       Note=Binds 2 heme b groups non-covalently.
CC       {ECO:0000250|UniProtKB:Q53TN4};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6ZNA5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6ZNA5-2; Sequence=VSP_030400;
CC   -!- SIMILARITY: Belongs to the FRRS1 family. {ECO:0000305}.
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DR   EMBL; AK131302; BAD18470.1; -; mRNA.
DR   EMBL; AL451051; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471097; EAW72988.1; -; Genomic_DNA.
DR   CCDS; CCDS30780.1; -. [Q6ZNA5-2]
DR   CCDS; CCDS91007.1; -. [Q6ZNA5-1]
DR   RefSeq; NP_001013682.2; NM_001013660.2. [Q6ZNA5-2]
DR   RefSeq; XP_005270918.1; XM_005270861.3.
DR   RefSeq; XP_011539753.1; XM_011541451.2. [Q6ZNA5-1]
DR   RefSeq; XP_016856760.1; XM_017001271.1. [Q6ZNA5-1]
DR   AlphaFoldDB; Q6ZNA5; -.
DR   BioGRID; 133787; 3.
DR   STRING; 9606.ENSP00000287474; -.
DR   GlyCosmos; Q6ZNA5; 4 sites, 1 glycan.
DR   GlyGen; Q6ZNA5; 6 sites, 3 O-linked glycans (3 sites).
DR   iPTMnet; Q6ZNA5; -.
DR   PhosphoSitePlus; Q6ZNA5; -.
DR   BioMuta; FRRS1; -.
DR   DMDM; 166198896; -.
DR   EPD; Q6ZNA5; -.
DR   jPOST; Q6ZNA5; -.
DR   MassIVE; Q6ZNA5; -.
DR   MaxQB; Q6ZNA5; -.
DR   PaxDb; 9606-ENSP00000287474; -.
DR   PeptideAtlas; Q6ZNA5; -.
DR   ProteomicsDB; 68005; -. [Q6ZNA5-1]
DR   ProteomicsDB; 68006; -. [Q6ZNA5-2]
DR   Pumba; Q6ZNA5; -.
DR   Antibodypedia; 19970; 24 antibodies from 8 providers.
DR   DNASU; 391059; -.
DR   Ensembl; ENST00000287474.9; ENSP00000287474.4; ENSG00000156869.14. [Q6ZNA5-2]
DR   Ensembl; ENST00000646001.2; ENSP00000496583.2; ENSG00000156869.14. [Q6ZNA5-1]
DR   GeneID; 391059; -.
DR   KEGG; hsa:391059; -.
DR   MANE-Select; ENST00000646001.2; ENSP00000496583.2; NM_001361041.2; NP_001347970.1.
DR   UCSC; uc001dsh.1; human. [Q6ZNA5-1]
DR   AGR; HGNC:27622; -.
DR   CTD; 391059; -.
DR   GeneCards; FRRS1; -.
DR   HGNC; HGNC:27622; FRRS1.
DR   HPA; ENSG00000156869; Tissue enhanced (liver).
DR   MIM; 611578; gene.
DR   neXtProt; NX_Q6ZNA5; -.
DR   OpenTargets; ENSG00000156869; -.
DR   PharmGKB; PA142670941; -.
DR   VEuPathDB; HostDB:ENSG00000156869; -.
DR   eggNOG; KOG4293; Eukaryota.
DR   GeneTree; ENSGT00940000157704; -.
DR   HOGENOM; CLU_028305_0_0_1; -.
DR   InParanoid; Q6ZNA5; -.
DR   OMA; CEDVQGY; -.
DR   OrthoDB; 3027001at2759; -.
DR   PhylomeDB; Q6ZNA5; -.
DR   TreeFam; TF316169; -.
DR   PathwayCommons; Q6ZNA5; -.
DR   BioGRID-ORCS; 391059; 15 hits in 1159 CRISPR screens.
DR   ChiTaRS; FRRS1; human.
DR   GenomeRNAi; 391059; -.
DR   Pharos; Q6ZNA5; Tdark.
DR   PRO; PR:Q6ZNA5; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q6ZNA5; Protein.
DR   Bgee; ENSG00000156869; Expressed in buccal mucosa cell and 145 other cell types or tissues.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016722; F:oxidoreductase activity, acting on metal ions; ISS:HGNC.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; ISS:ARUK-UCL.
DR   CDD; cd08760; Cyt_b561_FRRS1_like; 1.
DR   CDD; cd09628; DOMON_SDR_2_like; 1.
DR   CDD; cd08544; Reeler; 1.
DR   Gene3D; 1.20.120.1770; -; 1.
DR   Gene3D; 2.60.40.4060; Reeler domain; 1.
DR   InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM.
DR   InterPro; IPR005018; DOMON_domain.
DR   InterPro; IPR002861; Reeler_dom.
DR   InterPro; IPR042307; Reeler_sf.
DR   PANTHER; PTHR45828; CYTOCHROME B561/FERRIC REDUCTASE TRANSMEMBRANE; 1.
DR   PANTHER; PTHR45828:SF3; FERRIC-CHELATE REDUCTASE 1; 1.
DR   Pfam; PF03351; DOMON; 1.
DR   Pfam; PF02014; Reeler; 1.
DR   SMART; SM00665; B561; 1.
DR   SMART; SM00664; DoH; 1.
DR   PROSITE; PS50939; CYTOCHROME_B561; 1.
DR   PROSITE; PS50836; DOMON; 1.
DR   PROSITE; PS51019; REELIN; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Electron transport; Glycoprotein; Heme; Iron;
KW   Membrane; Metal-binding; Oxidoreductase; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..592
FT                   /note="Ferric-chelate reductase 1"
FT                   /id="PRO_0000314843"
FT   TRANSMEM        2..22
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        372..392
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        415..435
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        446..466
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        491..511
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        515..535
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        569..589
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          13..179
FT                   /note="Reelin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00363"
FT   DOMAIN          216..331
FT                   /note="DOMON"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00246"
FT   DOMAIN          335..534
FT                   /note="Cytochrome b561"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00242"
FT   BINDING         373
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_label="1"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT   BINDING         414
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_label="2"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT   BINDING         446
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_label="1"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT   BINDING         482
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_label="2"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:Q53TN4"
FT   CARBOHYD        138
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        308
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        321
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         533..592
FT                   /note="VHAYRLSRKVEILDDDRIQILQSFTAVETEGHAFKKAVLAIYVCGNVTFLII
FT                   FLSAINHL -> LKYWMMTEFRSFSHLLQWKQRVMLLKRQCWQFMSVGMLLFSSYFYLQ
FT                   STIYEQAKTLAFAGQVIIIIKPKKLEACPDCLEHICEFSLGRLGSCL (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_030400"
FT   CONFLICT        179
FT                   /note="P -> L (in Ref. 1; BAD18470)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   592 AA;  66114 MW;  21EC19981C4AA95D CRC64;
     MAVSGFTLGT CILLLHISYV ANYPNGKVTQ SCHGMIPEHG HSPQSVPVHD IYVSQMTFRP
     GDQIEVTLSG HPFKGFLLEA RNAEDLNGPP IGSFTLIDSE VSQLLTCEDI QGSAVSHRSA
     SKKTEIKVYW NAPSSAPNHT QFLVTVVEKY KIYWVKIPGP IISQPNAFPF TTPKATVVPL
     PTLPPVSHLT KPFSASDCGN KKFCIRSPLN CDPEKEASCV FLSFTRDDQS VMVEMSGPSK
     GYLSFALSHD QWMGDDDAYL CIHEDQTVYI QPSHLTGRSH PVMDSRDTLE DMAWRLADGV
     MQCSFRRNIT LPGVKNRFDL NTSYYIFLAD GAANDGRIYK HSQQPLITYE KYDVTDSPKN
     IGGSHSVLLL KVHGALMFVA WMTTVSIGVL VARFFKPVWS KAFLLGEAAW FQVHRMLMFT
     TTVLTCIAFV MPFIYRGGWS RHAGYHPYLG CIVMTLAVLQ PLLAVFRPPL HDPRRQMFNW
     THWSMGTAAR IIAVAAMFLG MDLPGLNLPD SWKTYAMTGF VAWHVGTEVV LEVHAYRLSR
     KVEILDDDRI QILQSFTAVE TEGHAFKKAV LAIYVCGNVT FLIIFLSAIN HL
//