FRRS1_HUMAN
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 03-AUG-2022, entry version 130.
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 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; 1.
DR STRING; 9606.ENSP00000287474; -.
DR GlyGen; Q6ZNA5; 4 sites, 1 O-linked glycan (1 site).
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; Q6ZNA5; -.
DR PeptideAtlas; Q6ZNA5; -.
DR PRIDE; Q6ZNA5; -.
DR ProteomicsDB; 68005; -. [Q6ZNA5-1]
DR ProteomicsDB; 68006; -. [Q6ZNA5-2]
DR Antibodypedia; 19970; 14 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 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; 599276at2759; -.
DR PhylomeDB; Q6ZNA5; -.
DR TreeFam; TF316169; -.
DR PathwayCommons; Q6ZNA5; -.
DR BioGRID-ORCS; 391059; 15 hits in 1079 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 143 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
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:cellular iron ion homeostasis; ISS:ARUK-UCL.
DR CDD; cd08544; Reeler; 1.
DR Gene3D; 2.60.40.4060; -; 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 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
