S22AH_HUMAN
ID S22AH_HUMAN Reviewed; 538 AA.
AC Q8WUG5; A4UA13; A8MUT0; Q2TAB0; Q5BKY8; Q86U04; Q9H1D3; Q9NQD5;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Solute carrier family 22 member 17;
DE AltName: Full=24p3 receptor;
DE Short=24p3R;
DE AltName: Full=Brain-type organic cation transporter;
DE AltName: Full=Lipocalin-2 receptor;
DE AltName: Full=Neutrophil gelatinase-associated lipocalin receptor;
DE Short=NgalR;
GN Name=SLC22A17; Synonyms=BOCT, BOIT;
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), AND SUBCELLULAR LOCATION.
RX PubMed=17253959; DOI=10.1042/bj20060836;
RA Fang W.K., Xu L.Y., Lu X.F., Liao L.D., Cai W.J., Shen Z.Y., Li E.M.;
RT "A novel alternative spliced variant of neutrophil gelatinase-associated
RT lipocalin receptor in oesophageal carcinoma cells.";
RL Biochem. J. 403:297-303(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Neuroblastoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 72-538 (ISOFORM 2).
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 124-538 (ISOFORM 2).
RC TISSUE=Brain;
RA Bruess M., Hayer M., Boenisch H.;
RT "Cloning, functional expression and gene structure of a human brain organic
RT cation transporter.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INDUCTION.
RX PubMed=16377569; DOI=10.1016/j.cell.2005.10.027;
RA Devireddy L.R., Gazin C., Zhu X., Green M.R.;
RT "A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis
RT and iron uptake.";
RL Cell 123:1293-1305(2005).
RN [7]
RP INDUCTION.
RX PubMed=19229297; DOI=10.1038/emboj.2009.35;
RA Sheng Z., Wang S.Z., Green M.R.;
RT "Transcription and signalling pathways involved in BCR-ABL-mediated
RT misregulation of 24p3 and 24p3R.";
RL EMBO J. 28:866-876(2009).
CC -!- FUNCTION: Cell surface receptor for LCN2 (24p3) that plays a key role
CC in iron homeostasis and transport. Able to bind iron-bound LCN2 (holo-
CC 24p3), followed by internalization of holo-24p3 and release of iron,
CC thereby increasing intracellular iron concentration and leading to
CC inhibition of apoptosis. Also binds iron-free LCN2 (apo-24p3), followed
CC by internalization of apo-24p3 and its association with an
CC intracellular siderophore, leading to iron chelation and iron transfer
CC to the extracellular medium, thereby reducing intracellular iron
CC concentration and resulting in apoptosis (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q8WUG5; P07237: P4HB; NbExp=3; IntAct=EBI-11722858, EBI-395883;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17253959};
CC Multi-pass membrane protein {ECO:0000269|PubMed:17253959}. Vacuole
CC membrane {ECO:0000269|PubMed:17253959}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:17253959}. Note=Upon LCN2-binding, it is
CC internalized.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=NgalR-1;
CC IsoId=Q8WUG5-1; Sequence=Displayed;
CC Name=2; Synonyms=NgalR-2;
CC IsoId=Q8WUG5-2; Sequence=VSP_003774;
CC Name=3; Synonyms=NgalR-3;
CC IsoId=Q8WUG5-3; Sequence=VSP_039782, VSP_039783;
CC -!- TISSUE SPECIFICITY: Expressed in brain.
CC -!- INDUCTION: Expression is activated by RUNX3. Repressed by the
CC oncoprotein BCR-ABL; BCR-ABL misregulates expression by inducing a
CC switch in binding from RUNX3 to RUNX1, a repressor of 24p3R expression,
CC through a Ras signaling pathway. {ECO:0000269|PubMed:16377569,
CC ECO:0000269|PubMed:19229297}.
CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAC01119.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAC17762.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; DQ658848; ABG45942.1; -; mRNA.
DR EMBL; BX161416; CAD61891.1; -; mRNA.
DR EMBL; AL049829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020565; AAH20565.1; -; mRNA.
DR EMBL; BC090870; AAH90870.1; -; mRNA.
DR EMBL; BC111015; AAI11016.1; -; mRNA.
DR EMBL; AJ243122; CAC17762.1; ALT_INIT; Genomic_DNA.
DR EMBL; AJ243653; CAC01119.1; ALT_INIT; mRNA.
DR RefSeq; NP_001275979.1; NM_001289050.1.
DR RefSeq; NP_057693.3; NM_016609.4. [Q8WUG5-2]
DR RefSeq; NP_065105.2; NM_020372.3. [Q8WUG5-1]
DR RefSeq; XP_005267804.1; XM_005267747.4. [Q8WUG5-1]
DR RefSeq; XP_016876850.1; XM_017021361.1. [Q8WUG5-1]
DR RefSeq; XP_016876851.1; XM_017021362.1. [Q8WUG5-2]
DR AlphaFoldDB; Q8WUG5; -.
DR SMR; Q8WUG5; -.
DR BioGRID; 119461; 7.
DR IntAct; Q8WUG5; 6.
DR MINT; Q8WUG5; -.
DR STRING; 9606.ENSP00000380437; -.
DR TCDB; 2.A.1.19.8; the major facilitator superfamily (mfs).
DR GlyGen; Q8WUG5; 2 sites.
DR iPTMnet; Q8WUG5; -.
DR PhosphoSitePlus; Q8WUG5; -.
DR BioMuta; SLC22A17; -.
DR DMDM; 27805426; -.
DR EPD; Q8WUG5; -.
DR jPOST; Q8WUG5; -.
DR MassIVE; Q8WUG5; -.
DR PaxDb; Q8WUG5; -.
DR PeptideAtlas; Q8WUG5; -.
DR PRIDE; Q8WUG5; -.
DR ProteomicsDB; 74671; -. [Q8WUG5-1]
DR ProteomicsDB; 74672; -. [Q8WUG5-2]
DR ProteomicsDB; 74673; -. [Q8WUG5-3]
DR Antibodypedia; 111; 237 antibodies from 33 providers.
DR DNASU; 51310; -.
DR Ensembl; ENST00000397267.6; ENSP00000380437.2; ENSG00000092096.19.
DR GeneID; 51310; -.
DR KEGG; hsa:51310; -.
DR UCSC; uc001wjl.5; human. [Q8WUG5-1]
DR CTD; 51310; -.
DR DisGeNET; 51310; -.
DR GeneCards; SLC22A17; -.
DR HGNC; HGNC:23095; SLC22A17.
DR HPA; ENSG00000092096; Group enriched (brain, choroid plexus, pituitary gland).
DR MIM; 611461; gene.
DR neXtProt; NX_Q8WUG5; -.
DR PharmGKB; PA134879149; -.
DR VEuPathDB; HostDB:ENSG00000092096; -.
DR eggNOG; KOG0255; Eukaryota.
DR HOGENOM; CLU_001265_33_6_1; -.
DR InParanoid; Q8WUG5; -.
DR OMA; HHVIYSS; -.
DR OrthoDB; 1032137at2759; -.
DR PhylomeDB; Q8WUG5; -.
DR TreeFam; TF335753; -.
DR PathwayCommons; Q8WUG5; -.
DR Reactome; R-HSA-917937; Iron uptake and transport.
DR SignaLink; Q8WUG5; -.
DR BioGRID-ORCS; 51310; 33 hits in 1067 CRISPR screens.
DR ChiTaRS; SLC22A17; human.
DR GenomeRNAi; 51310; -.
DR Pharos; Q8WUG5; Tbio.
DR PRO; PR:Q8WUG5; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8WUG5; protein.
DR Bgee; ENSG00000092096; Expressed in right hemisphere of cerebellum and 131 other tissues.
DR ExpressionAtlas; Q8WUG5; baseline and differential.
DR Genevisible; Q8WUG5; HS.
DR GO; GO:0031301; C:integral component of organelle membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0006879; P:cellular iron ion homeostasis; TAS:Reactome.
DR GO; GO:0015891; P:siderophore transport; ISS:UniProtKB.
DR DisProt; DP01769; -.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR005828; MFS_sugar_transport-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR005829; Sugar_transporter_CS.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
DR PROSITE; PS00216; SUGAR_TRANSPORT_1; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Ion transport; Iron;
KW Iron transport; Membrane; Receptor; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Vacuole.
FT CHAIN 1..538
FT /note="Solute carrier family 22 member 17"
FT /id="PRO_0000220507"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 129..149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 366..386
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 473..493
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 176..207
FT /note="RLELCDPTQRLRVALAGELVGVGGHFLFLGLA -> PNDHRSLHPLPVLWLA
FT WFVPGVRTVADSEAAD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17253959"
FT /id="VSP_039782"
FT VAR_SEQ 208..538
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17253959"
FT /id="VSP_039783"
FT VAR_SEQ 388..406
FT /note="CEHPIFPTVWAQQGNPNRD -> Y (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2,
FT ECO:0000303|Ref.5"
FT /id="VSP_003774"
FT CONFLICT 103
FT /note="E -> G (in Ref. 1; ABG45942)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="R -> G (in Ref. 1; ABG45942)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="F -> S (in Ref. 4; CAC01119)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 538 AA; 57686 MW; B332F4ED80BF2387 CRC64;
MASDPIFTLA PPLHCHYGAF PPNASGWEQP PNASGVSVAS AALAASAASR VATSTDPSCS
GFAPPDFNHC LKDWDYNGLP VLTTNAIGQW DLVCDLGWQV ILEQILFILG FASGYLFLGY
PADRFGRRGI VLLTLGLVGP CGVGGAAAGS STGVMALRFL LGFLLAGVDL GVYLMRLELC
DPTQRLRVAL AGELVGVGGH FLFLGLALVS KDWRFLQRMI TAPCILFLFY GWPGLFLESA
RWLIVKRQIE EAQSVLRILA ERNRPHGQML GEEAQEALQD LENTCPLPAT SSFSFASLLN
YRNIWKNLLI LGFTNFIAHA IRHCYQPVGG GGSPSDFYLC SLLASGTAAL ACVFLGVTVD
RFGRRGILLL SMTLTGIASL VLLGLWDCEH PIFPTVWAQQ GNPNRDLNEA AITTFSVLGL
FSSQAAAILS TLLAAEVIPT TVRGRGLGLI MALGALGGLS GPAQRLHMGH GAFLQHVVLA
ACALLCILSI MLLPETKRKL LPEVLRDGEL CRRPSLLRQP PPTRCDHVPL LATPNPAL
