S39A5_HUMAN
ID S39A5_HUMAN Reviewed; 540 AA.
AC Q6ZMH5; B2R808; Q8N6Y3;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Zinc transporter ZIP5;
DE AltName: Full=Solute carrier family 39 member 5;
DE AltName: Full=Zrt- and Irt-like protein 5;
DE Short=ZIP-5;
DE Flags: Precursor;
GN Name=SLC39A5; Synonyms=ZIP5;
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].
RC TISSUE=Colon, and Kidney;
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 MRNA].
RC TISSUE=Pancreas;
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=15322118; DOI=10.1074/jbc.m408361200;
RA Wang F., Kim B.-E., Petris M.J., Eide D.J.;
RT "The mammalian Zip5 protein is a zinc transporter that localizes to the
RT basolateral surface of polarized cells.";
RL J. Biol. Chem. 279:51433-51441(2004).
RN [4]
RP FUNCTION, VARIANT MYP24 THR-304, AND CHARACTERIZATION OF VARIANT MYP24
RP THR-304.
RX PubMed=24891338; DOI=10.1136/jmedgenet-2014-102351;
RA Guo H., Jin X., Zhu T., Wang T., Tong P., Tian L., Peng Y., Sun L., Wan A.,
RA Chen J., Liu Y., Li Y., Tian Q., Xia L., Zhang L., Pan Y., Lu L., Liu Q.,
RA Shen L., Li Y., Xiong W., Li J., Tang B., Feng Y., Zhang X., Zhang Z.,
RA Pan Q., Hu Z., Xia K.;
RT "SLC39A5 mutations interfering with the BMP/TGF-beta pathway in non-
RT syndromic high myopia.";
RL J. Med. Genet. 51:518-525(2014).
RN [5]
RP METHYLATION AT HIS-375, AND MUTAGENESIS OF HIS-373; HIS-375 AND HIS-377.
RX PubMed=33563959; DOI=10.1038/s41467-020-20670-7;
RA Davydova E., Shimazu T., Schuhmacher M.K., Jakobsson M.E.,
RA Willemen H.L.D.M., Liu T., Moen A., Ho A.Y.Y., Malecki J., Schroer L.,
RA Pinto R., Suzuki T., Groensberg I.A., Sohtome Y., Akakabe M., Weirich S.,
RA Kikuchi M., Olsen J.V., Dohmae N., Umehara T., Sodeoka M., Siino V.,
RA McDonough M.A., Eijkelkamp N., Schofield C.J., Jeltsch A., Shinkai Y.,
RA Falnes P.O.;
RT "The methyltransferase METTL9 mediates pervasive 1-methylhistidine
RT modification in mammalian proteomes.";
RL Nat. Commun. 12:891-891(2021).
RN [6]
RP VARIANT MYP24 ALA-413.
RX PubMed=25525168; DOI=10.1167/iovs.14-14850;
RA Jiang D., Li J., Xiao X., Li S., Jia X., Sun W., Guo X., Zhang Q.;
RT "Detection of mutations in LRPAP1, CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2
RT in 298 families with early-onset high myopia by exome sequencing.";
RL Invest. Ophthalmol. Vis. Sci. 56:339-345(2015).
CC -!- FUNCTION: May play a role in polarized cells by carrying out serosal-
CC to-mucosal zinc transport (By similarity). Seems to play a central role
CC in controlling organismal zinc status (By similarity). Could regulate
CC the BMP/TGF-beta (bone morphogenetic protein/transforming growth
CC factor-beta) signaling pathway and modulates extracellular matrix (ECM)
CC proteins of the sclera (PubMed:24891338). Plays a role in eye
CC development (PubMed:24891338). {ECO:0000250|UniProtKB:Q9D856,
CC ECO:0000269|PubMed:24891338}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q9D856}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9D856}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney, pancreas, small
CC intestine, colon, spleen, fetal liver and fetal kidney.
CC {ECO:0000269|PubMed:15322118}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q9D856}.
CC -!- PTM: Methylated at His-375 by METTL9. {ECO:0000269|PubMed:33563959}.
CC -!- DISEASE: Myopia 24, autosomal dominant (MYP24) [MIM:615946]: A
CC refractive error of the eye, in which parallel rays from a distant
CC object come to focus in front of the retina, vision being better for
CC near objects than for far. {ECO:0000269|PubMed:24891338,
CC ECO:0000269|PubMed:25525168}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-2 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH27884.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG36005.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK172768; BAD18751.1; -; mRNA.
DR EMBL; AK313188; BAG36005.1; ALT_INIT; mRNA.
DR EMBL; BC027884; AAH27884.1; ALT_INIT; mRNA.
DR CCDS; CCDS8912.2; -.
DR RefSeq; NP_001128667.1; NM_001135195.1.
DR RefSeq; NP_775867.2; NM_173596.2.
DR RefSeq; XP_005268860.1; XM_005268803.1.
DR RefSeq; XP_011536500.1; XM_011538198.1.
DR RefSeq; XP_011536501.1; XM_011538199.1.
DR RefSeq; XP_011536502.1; XM_011538200.1.
DR RefSeq; XP_011536503.1; XM_011538201.1.
DR AlphaFoldDB; Q6ZMH5; -.
DR SMR; Q6ZMH5; -.
DR BioGRID; 129541; 51.
DR IntAct; Q6ZMH5; 46.
DR STRING; 9606.ENSP00000266980; -.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR TCDB; 2.A.5.4.10; the zinc (zn(2+))-iron (fe(2+)) permease (zip) family.
DR GlyGen; Q6ZMH5; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q6ZMH5; -.
DR PhosphoSitePlus; Q6ZMH5; -.
DR BioMuta; SLC39A5; -.
DR DMDM; 332278218; -.
DR jPOST; Q6ZMH5; -.
DR MassIVE; Q6ZMH5; -.
DR MaxQB; Q6ZMH5; -.
DR PaxDb; Q6ZMH5; -.
DR PeptideAtlas; Q6ZMH5; -.
DR PRIDE; Q6ZMH5; -.
DR ProteomicsDB; 67869; -.
DR TopDownProteomics; Q6ZMH5; -.
DR Antibodypedia; 15788; 99 antibodies from 27 providers.
DR DNASU; 283375; -.
DR Ensembl; ENST00000266980.8; ENSP00000266980.4; ENSG00000139540.12.
DR Ensembl; ENST00000454355.7; ENSP00000405360.2; ENSG00000139540.12.
DR GeneID; 283375; -.
DR KEGG; hsa:283375; -.
DR MANE-Select; ENST00000454355.7; ENSP00000405360.2; NM_173596.3; NP_775867.2.
DR UCSC; uc010sqj.3; human.
DR CTD; 283375; -.
DR DisGeNET; 283375; -.
DR GeneCards; SLC39A5; -.
DR HGNC; HGNC:20502; SLC39A5.
DR HPA; ENSG00000139540; Group enriched (intestine, kidney, liver, pancreas).
DR MalaCards; SLC39A5; -.
DR MIM; 608730; gene.
DR MIM; 615946; phenotype.
DR neXtProt; NX_Q6ZMH5; -.
DR OpenTargets; ENSG00000139540; -.
DR PharmGKB; PA134872687; -.
DR VEuPathDB; HostDB:ENSG00000139540; -.
DR eggNOG; KOG2693; Eukaryota.
DR GeneTree; ENSGT00940000161155; -.
DR HOGENOM; CLU_015114_13_2_1; -.
DR InParanoid; Q6ZMH5; -.
DR OMA; YMNIVSS; -.
DR OrthoDB; 657777at2759; -.
DR PhylomeDB; Q6ZMH5; -.
DR TreeFam; TF318470; -.
DR PathwayCommons; Q6ZMH5; -.
DR Reactome; R-HSA-442380; Zinc influx into cells by the SLC39 gene family.
DR SignaLink; Q6ZMH5; -.
DR BioGRID-ORCS; 283375; 147 hits in 1064 CRISPR screens.
DR GenomeRNAi; 283375; -.
DR Pharos; Q6ZMH5; Tbio.
DR PRO; PR:Q6ZMH5; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q6ZMH5; protein.
DR Bgee; ENSG00000139540; Expressed in body of pancreas and 127 other tissues.
DR ExpressionAtlas; Q6ZMH5; baseline and differential.
DR Genevisible; Q6ZMH5; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0034224; P:cellular response to zinc ion starvation; IEA:Ensembl.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IBA:GO_Central.
DR GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR GO; GO:0070315; P:G1 to G0 transition involved in cell differentiation; ISS:CAFA.
DR GO; GO:0061351; P:neural precursor cell proliferation; ISS:UniProtKB.
DR GO; GO:0048026; P:positive regulation of mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0071578; P:zinc ion import across plasma membrane; IBA:GO_Central.
DR InterPro; IPR003689; ZIP.
DR Pfam; PF02535; Zip; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Glycoprotein; Ion transport; Membrane;
KW Methylation; Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport; Zinc; Zinc transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..540
FT /note="Zinc transporter ZIP5"
FT /id="PRO_0000045795"
FT TOPO_DOM 21..212
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..244
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..287
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 445..465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 466..470
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 471..491
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 492..508
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 509..529
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 530..540
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT REGION 78..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D856"
FT MOD_RES 375
FT /note="Pros-methylhistidine"
FT /evidence="ECO:0000269|PubMed:33563959"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 304
FT /note="M -> T (in MYP24; affects the BMP/TGF-beta pathway
FT by suppressing expression of SMAD1; loss of function
FT mutation; dbSNP:rs587777625)"
FT /evidence="ECO:0000269|PubMed:24891338"
FT /id="VAR_071911"
FT VARIANT 413
FT /note="G -> A (in MYP24; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:25525168"
FT /id="VAR_074009"
FT MUTAGEN 373
FT /note="H->A: Reduced histidine methylation by METTL9."
FT /evidence="ECO:0000269|PubMed:33563959"
FT MUTAGEN 375
FT /note="H->A: Abolished histidine methylation by METTL9."
FT /evidence="ECO:0000269|PubMed:33563959"
FT MUTAGEN 377
FT /note="H->A: Does not affect histidine methylation by
FT METTL9."
FT /evidence="ECO:0000269|PubMed:33563959"
SQ SEQUENCE 540 AA; 56461 MW; 171DF129FF5720D1 CRC64;
MMGSPVSHLL AGFCVWVVLG WVGGSVPNLG PAEQEQNHYL AQLFGLYGEN GTLTAGGLAR
LLHSLGLGRV QGLRLGQHGP LTGRAASPAA DNSTHRPQNP ELSVDVWAGM PLGPSGWGDL
EESKAPHLPR GPAPSGLDLL HRLLLLDHSL ADHLNEDCLN GSQLLVNFGL SPAAPLTPRQ
FALLCPALLY QIDSRVCIGA PAPAPPGDLL SALLQSALAV LLLSLPSPLS LLLLRLLGPR
LLRPLLGFLG ALAVGTLCGD ALLHLLPHAQ EGRHAGPGGL PEKDLGPGLS VLGGLFLLFV
LENMLGLLRH RGLRPRCCRR KRRNLETRNL DPENGSGMAL QPLQAAPEPG AQGQREKNSQ
HPPALAPPGH QGHSHGHQGG TDITWMVLLG DGLHNLTDGL AIGAAFSDGF SSGLSTTLAV
FCHELPHELG DFAMLLQSGL SFRRLLLLSL VSGALGLGGA VLGVGLSLGP VPLTPWVFGV
TAGVFLYVAL VDMLPALLRP PEPLPTPHVL LQGLGLLLGG GLMLAITLLE ERLLPVTTEG
