SLC39A4
entrez
55630
canonical
uniprot
Q6P5W5
canonical
ensembl
ENSG00000147804
resolver
ensp
ENSP00000276833
resolver
ensp
ENSP00000301305
resolver
genesymbol
SLC39A4
resolver
genesymbol_syn
ZIP4
resolver
hgnc
HGNC:17129
resolver
uniprot
Q7L5S5
resolver
uniprot
Q9H6T8
resolver
uniprot
Q9NX22
resolver
uniprot
Q9NXC4
resolver
uniprot_entry
Q9NX22_HUMAN
resolver
uniprot_entry
S39A4_HUMAN
resolver
uniprot_sec
Q7L5S5
resolver
uniprot_sec
Q9H6T8
resolver
uniprot_sec
Q9NXC4
resolver
activity_regulation
ACTIVITY REGULATION: The Zn(2+) uniporter activity is regulated by zinc availability (PubMed:17202136, PubMed:32348750). Extracellular acidification stimulated SLC39A4-dependent Zn(2+) uptake (PubMed:31979155). {ECO:0000269|PubMed:17202136, ECO:0000269|PubMed:31979155, ECO:0000269|PubMed:32348750}.
uniprot
proteins
amino_acid_sequence
MASLVSLELGLLLAVLVVTATASPPAGLLSLLTSGQGALDQEALGGLLNTLADRVHCANGPCGKCLSVEDALGLGEPEGSGLPPGPVLEARYVARLSAAAVLYLSNPEGTCEDARAGLWASHADHLLALLESPKALTPGLSWLLQRMQARAAGQTPKMACVDIPQLLEEAVGAGAPGSAGGVLAALLDHVRSGSCFHALPSPQYFVDFVFQQHSSEVPMTLAELSALMQRLGVGREAHSDHSHRHRGASSRDPVPLISSSNSSSVWDTVCLSARDVMAAYGLSEQAGVTPEAWAQLSPALLQQQLSGACTSQSRPPVQDQLSQSERYLYGSLATLLICLCAVFGLLLLTCTGCRGVTHYILQTFLSLAVGAVTGDAVLHLTPKVLGLHTHSEEGLSPQPTWRLLAMLAGLYAFFLFENLFNLLLPRDPEDLEDGPCGHSSHSHGGHSHGVSLQLAPSELRQPKPPHEGSRADLVAEESPELLNPEPRRLSPELRLLPYMITLGDAVHNFADGLAVGAAFASSWKTGLATSLAVFCHELPHELGDFAALLHAGLSVRQALLLNLASALTAFAGLYVALAVGVSEESEAWILAVATGLFLYVALCDMLPAMLKVRDPRPWLLFLLHNVGLLGGWTVLLLLSLYEDDITF
uniprot
proteins
disease_involvement
DISEASE: Acrodermatitis enteropathica, zinc-deficiency type (AEZ) [MIM:201100]: A rare autosomal recessive disease caused by the inability to absorb sufficient zinc. The clinical features are growth retardation, immune-system dysfunction, alopecia, severe dermatitis, diarrhea and occasionally mental disorders. {ECO:0000269|PubMed:12032886, ECO:0000269|PubMed:12068297, ECO:0000269|PubMed:12787121, ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:33837739}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Selective transporter that mediates the uptake of Zn(2+) (PubMed:17202136, PubMed:22242765, PubMed:27321477, PubMed:28875161, PubMed:31164399, PubMed:31914589, PubMed:31979155, PubMed:33837739, PubMed:36473915). Plays an essential role for dietary zinc uptake from small intestine (By similarity). The Zn(2+) uniporter activity is regulated by zinc availability (PubMed:17202136, PubMed:32348750). Also exhibits polyspecific binding and transport of Cu(2+), Cd(2+) and possibly Ni(2+) but at higher concentrations (PubMed:22242765, PubMed:31914589). {ECO:0000250|UniProtKB:Q78IQ7, ECO:0000269|PubMed:17202136, ECO:0000269|PubMed:22242765, ECO:0000269|PubMed:27321477, ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31164399, ECO:0000269|PubMed:31914589, ECO:0000269|PubMed:31979155, ECO:0000269|PubMed:32348750, ECO:0000269|PubMed:33837739, ECO:0000269|PubMed:36473915}.
uniprot
proteins
mass_dalton
68408
uniprot
proteins
mutagenesis
MUTAGEN 62; /note="C->R: Decreases location at cell membrane. Retained in the ER. Loss of zinc transport activity."; /evidence="ECO:0000269|PubMed:33837739"; MUTAGEN 99; /note="A->T: Loss of zinc transport activity."; /evidence="ECO:0000269|PubMed:33837739"; MUTAGEN 202; /note="P->A: Does not affect location at cell membrane. Does not affect zinc transport activity."; /evidence="ECO:0000269|PubMed:27321477"; MUTAGEN 238; /note="H->S: Decreases zinc transport activity; when associated with S-241; S-243; S-245. Decreases Vmax for Zn(2+) by 20% but does not affect the KM; when associated with S-241; S-243; S-245."; /evidence="ECO:0000269|PubMed:31164399"; MUTAGEN 241; /note="H->S: Decreases zinc transport activity; when associated with S-238; S-243 and S-245. Decreases Vmax for Zn(2+) by 20% does not affect the KM; when associated with S-238; S-243 and S-245."; /evidence="ECO:0000269|PubMed:31164399"; MUTAGEN 243; /note="H->S: Decreases zinc transport activity; when associated with S-238; S-241 and S-245. Decreases Vmax for Zn(2+) by 20% does not affect the KM; when associated with S-238; S-241 and S-245."; /evidence="ECO:0000269|PubMed:31164399"; MUTAGEN 245; /note="H->S: Decreases zinc transport activity; when associated with S-238; S-241 and S-243. Decreases Vmax for Zn(2+) by 20% but does not affect the KM; when associated with S-238; S-241 and S-243."; /evidence="ECO:0000269|PubMed:31164399"; MUTAGEN 261; /note="N->Q: Decreases location at cell membrane; retained in the ER."; /evidence="ECO:0000269|PubMed:33837739"; MUTAGEN 266; /note="W->A: No glycosylated. Very low cell surface expression. Decreases zinc uptake activity."; /evidence="ECO:0000269|PubMed:27321477"; MUTAGEN 275; /note="D->A: Decreases zinc uptake activity."; /evidence="ECO:0000269|PubMed:27321477"; MUTAGEN 303; /note="Q->A: Reduces glycosylation level. Reduces cell surface expression. Decreases zinc uptake activity."; /evidence="ECO:0000269|PubMed:27321477"; MUTAGEN 375; /note="D->A: Reduces zinc transport activity; when associated with A-379."; /evidence="ECO:0000269|PubMed:28875161"; MUTAGEN 379; /note="H->A: Reduces zinc transport activity; when associated with A-375."; /evidence="ECO:0000269|PubMed:28875161"; MUTAGEN 388; /note="H->A: Does not affect zinc sensing."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 390; /note="H->A: Does not affect zinc sensing."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 452..454; /note="LQL->AAA: Abrogates endocytosis of the A-511 mutant which undergoes zinc-independent endocytosis."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 452; /note="L->A: Abrogates endocytosis."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 453; /note="Q->A: Reduces endocytosis."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 454; /note="L->A: Abrogates endocytosis."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 463; /note="K->R: No effect on SLC39A4 endocytosis. No effect on SLC39A4 endocytosis; when associated with R-611."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 481; /note="L->A: No effect on SLC39A4 endocytosis. No effect on SLC39A4 endocytosis; when associated with A-482."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 482; /note="L->A: No effect on SLC39A4 endocytosis. No effect on SLC39A4 endocytosis; when associated with A-481."; /evidence="ECO:0000269|PubMed:32348750"; MUTAGEN 507; /note="H->A: Moderately reduces zinc transport activity. Completely abrogated zinc transport activity; when associated with A-536 and A-540."; /evidence="ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31914589"; MUTAGEN 507; /note="H->R: Abolishes zinc transport activity."; /evidence="ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31914589"; MUTAGEN 508; /note="N->A: Moderately Reduces zinc transport activity. Reduced zinc transmembrane transporter activity; when associated with A-537. Does not affect substrate specificity; when associated with A-537. Exhibits a zinc transport activity dependent on pH; when associated with A-537."; /evidence="ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31914589"; MUTAGEN 508; /note="N->R: Reduces zinc transport activity by 60%."; /evidence="ECO:0000269|PubMed:28875161"; MUTAGEN 508; /note="N->S: Strong reduction of zinc transport activity; when associated with K-537."; /evidence="ECO:0000269|PubMed:31914589"; MUTAGEN 511; /note="D->A: Strongly reduced zinc transport activity. Loss of zinc-sensing function; endocytosis of this mutant becomes a zinc-independent process."; /evidence="ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:32348750"; MUTAGEN 536; /note="H->A: Moderately reduces zinc transport activity. Completely abrogates zinc transport activity; when associated with A-507 and A-540."; /evidence="ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31914589"; MUTAGEN 536; /note="H->R: Abolishes zinc transport activity."; /evidence="ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31914589"; MUTAGEN 537; /note="E->A: Moderately reduces zinc transport activity. Reduces zinc transmembrane transporter activity; when associated with A-508. Does not affect substrate specificity; when associated with A-508. Exhibits a zinc transport activity dependent on pH; when associated with A-508."; /evidence="ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31914589"; MUTAGEN 537; /note="E->K: Strong reduction of zinc transport activity; when associated with S-537."; /evidence="ECO:0000269|PubMed:31914589"; MUTAGEN 537; /note="E->R: Abolishes zinc transport activity."; /evidence="ECO:0000269|PubMed:28875161"; MUTAGEN 540; /note="H->A: Increases zinc transport activity. Reduces affinity toward zinc. No defect in endocytosis or zinc sensing. Completely abrogated zinc transport activity; when associated with A-507 and A-536."; /evidence="ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31914589, ECO:0000269|PubMed:32348750"; MUTAGEN 540; /note="H->R: Does not affect zinc transport activity."; /evidence="ECO:0000269|PubMed:28875161"; MUTAGEN 611; /note="K->R: No effect on SLC39A4 endocytosis. No effect on SLC39A4 endocytosis; when associated with R-463."; /evidence="ECO:0000269|PubMed:32348750
uniprot
proteins
post_translational_modification
PTM: The extracellular N-terminal ectodomain is cleaved when cells are Zn(2+) deficient, N-terminally cleaved SLC39A4 is internalized at a faster rate. {ECO:0000250|UniProtKB:Q78IQ7}.; PTM: Under excess Zn(2+) conditions, SLC39A4 on the cell surface is rapidly endocytosed, ubiquitinated and degraded. {ECO:0000269|PubMed:17202136}.; PTM: Glycosylated. {ECO:0000269|PubMed:17202136, ECO:0000269|PubMed:27321477, ECO:0000269|PubMed:33837739}.
uniprot
proteins
protein_family
ZIP transporter (TC 2.A.5) family
uniprot
proteins
pubmed
12032886
uniprot
proteins
pubmed
12068297
uniprot
proteins
pubmed
12787121
uniprot
proteins
pubmed
14612438
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
17202136
uniprot
proteins
pubmed
22242765
uniprot
proteins
pubmed
27321477
uniprot
proteins
pubmed
28875161
uniprot
proteins
pubmed
30874431
uniprot
proteins
pubmed
31164399
uniprot
proteins
pubmed
31914589
uniprot
proteins
pubmed
31979155
uniprot
proteins
pubmed
32348750
uniprot
proteins
pubmed
33837739
uniprot
proteins
pubmed
36473915
uniprot
proteins
sequence_length
647
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14612438, ECO:0000269|PubMed:17202136, ECO:0000269|PubMed:30874431, ECO:0000269|PubMed:31164399, ECO:0000269|PubMed:32348750, ECO:0000269|PubMed:36473915}; Multi-pass membrane protein {ECO:0000250|UniProtKB:A0A0H3LM39}. Recycling endosome membrane {ECO:0000269|PubMed:14612438}; Multi-pass membrane protein {ECO:0000250|UniProtKB:A0A0H3LM39}. Apical cell membrane {ECO:0000250|UniProtKB:Q78IQ7}; Multi-pass membrane protein {ECO:0000250|UniProtKB:A0A0H3LM39}. Note=Colocalized with TFRC in the recycling endosomes. Cycles between endosomal compartments and the plasma membrane in response to Zn(2+) availability. Zn(2+) deficiency promotes accumulation of SLC39A4 on the surface membrane, whereas high extracellular Zn(2+) levels induce internalization of SLC39A4, but also trigger drastic removal of cellular SLC39A4 via proteasomal and lysosomal degradation pathways. {ECO:0000250|UniProtKB:Q78IQ7, ECO:0000269|PubMed:17202136, ECO:0000269|PubMed:32348750}.
uniprot
proteins
transmembrane_region
TRANSMEM 328..348; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:A0A0H3LM39"; TRANSMEM 360..380; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:A0A0H3LM39"; TRANSMEM 403..423; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:A0A0H3LM39"; TRANSMEM 499..518; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:A0A0H3LM39"; TRANSMEM 527..553; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:A0A0H3LM39"; TRANSMEM 559..579; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:A0A0H3LM39"; TRANSMEM 587..607; /note="Helical; Name=7"; /evidence="ECO:0000250|UniProtKB:A0A0H3LM39"; TRANSMEM 618..638; /note="Helical; Name=8"; /evidence="ECO:0000250|UniProtKB:A0A0H3LM39
uniprot
proteins