S39AE_BOVIN
ID S39AE_BOVIN Reviewed; 490 AA.
AC A5D7L5;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Metal cation symporter ZIP14 {ECO:0000250|UniProtKB:Q15043};
DE AltName: Full=Solute carrier family 39 member 14 {ECO:0000250|UniProtKB:Q15043};
DE AltName: Full=Zrt- and Irt-like protein 14 {ECO:0000250|UniProtKB:Q15043};
DE Short=ZIP-14 {ECO:0000250|UniProtKB:Q15043};
DE Flags: Precursor;
GN Name=SLC39A14 {ECO:0000250|UniProtKB:Q15043};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal skin;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Electroneutral transporter of the plasma membrane mediating
CC the cellular uptake of the divalent metal cations zinc, manganese and
CC iron that are important for tissue homeostasis, metabolism, development
CC and immunity (By similarity). Functions as an energy-dependent
CC symporter, transporting through the membranes an electroneutral complex
CC composed of a divalent metal cation and two bicarbonate anions. Beside
CC these endogenous cellular substrates, can also import cadmium a non-
CC essential metal which is cytotoxic and carcinogenic (By similarity).
CC {ECO:0000250|UniProtKB:Q15043, ECO:0000250|UniProtKB:Q75N73}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 hydrogencarbonate(out) + Zn(2+)(out) = 2
CC hydrogencarbonate(in) + Zn(2+)(in); Xref=Rhea:RHEA:62252,
CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q75N73};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62253;
CC Evidence={ECO:0000250|UniProtKB:Q75N73};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 hydrogencarbonate(out) + Mn(2+)(out) = 2
CC hydrogencarbonate(in) + Mn(2+)(in); Xref=Rhea:RHEA:62260,
CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q75N73};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62261;
CC Evidence={ECO:0000250|UniProtKB:Q75N73};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe(2+)(out) + 2 hydrogencarbonate(out) = Fe(2+)(in) + 2
CC hydrogencarbonate(in); Xref=Rhea:RHEA:62368, ChEBI:CHEBI:17544,
CC ChEBI:CHEBI:29033; Evidence={ECO:0000250|UniProtKB:Q75N73};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62369;
CC Evidence={ECO:0000250|UniProtKB:Q75N73};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cd(2+)(out) + 2 hydrogencarbonate(out) = Cd(2+)(in) + 2
CC hydrogencarbonate(in); Xref=Rhea:RHEA:62256, ChEBI:CHEBI:17544,
CC ChEBI:CHEBI:48775; Evidence={ECO:0000250|UniProtKB:Q75N73};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62257;
CC Evidence={ECO:0000250|UniProtKB:Q75N73};
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:Q15043}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q15043};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein
CC {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q15043};
CC Multi-pass membrane protein {ECO:0000255}. Late endosome membrane
CC {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q15043}; Multi-
CC pass membrane protein {ECO:0000255}.
CC -!- PTM: Ubiquitinated. Ubiquitination occurs upon iron depletion. The
CC ubiquitinated form undergoes proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q15043}.
CC -!- PTM: N-glycosylated. N-glycosylation at Asn-100 is required for iron-
CC regulated extraction of the transporter from membranes and subsequent
CC proteasomal degradation. {ECO:0000250|UniProtKB:Q15043}.
CC -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family.
CC {ECO:0000305}.
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DR EMBL; BC140602; AAI40603.1; -; mRNA.
DR RefSeq; NP_001091505.1; NM_001098036.1.
DR RefSeq; XP_005210309.1; XM_005210252.3.
DR AlphaFoldDB; A5D7L5; -.
DR SMR; A5D7L5; -.
DR STRING; 9913.ENSBTAP00000025599; -.
DR PaxDb; A5D7L5; -.
DR PeptideAtlas; A5D7L5; -.
DR PRIDE; A5D7L5; -.
DR Ensembl; ENSBTAT00000025599; ENSBTAP00000025599; ENSBTAG00000019225.
DR GeneID; 515437; -.
DR KEGG; bta:515437; -.
DR CTD; 23516; -.
DR VEuPathDB; HostDB:ENSBTAG00000019225; -.
DR VGNC; VGNC:34862; SLC39A14.
DR eggNOG; KOG2693; Eukaryota.
DR GeneTree; ENSGT00940000157986; -.
DR HOGENOM; CLU_015114_13_0_1; -.
DR InParanoid; A5D7L5; -.
DR OrthoDB; 657777at2759; -.
DR TreeFam; TF318470; -.
DR Proteomes; UP000009136; Chromosome 8.
DR Bgee; ENSBTAG00000019225; Expressed in liver and 103 other tissues.
DR ExpressionAtlas; A5D7L5; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0015296; F:anion:cation symporter activity; ISS:UniProtKB.
DR GO; GO:0015086; F:cadmium ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015093; F:ferrous iron transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; ISS:UniProtKB.
DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl.
DR GO; GO:0098739; P:import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0033212; P:iron import into cell; ISS:UniProtKB.
DR GO; GO:0034755; P:iron ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0055071; P:manganese ion homeostasis; ISS:UniProtKB.
DR GO; GO:0071421; P:manganese ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051344; P:negative regulation of cyclic-nucleotide phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0010817; P:regulation of hormone levels; IEA:Ensembl.
DR GO; GO:0071578; P:zinc ion import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0071577; P:zinc ion transmembrane transport; ISS:UniProtKB.
DR InterPro; IPR003689; ZIP.
DR Pfam; PF02535; Zip; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Endosome; Glycoprotein; Ion transport; Lysosome; Membrane;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation; Zinc; Zinc transport.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..490
FT /note="Metal cation symporter ZIP14"
FT /id="PRO_0000312193"
FT TOPO_DOM 29..155
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..184
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..222
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 244..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..416
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 417..422
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 444..459
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 460..480
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 481..490
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 127..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 249..256
FT /note="HHHGHXHX-motif"
FT /evidence="ECO:0000250|UniProtKB:Q15043"
FT MOTIF 374..379
FT /note="XEXPHE-motif"
FT /evidence="ECO:0000250|UniProtKB:Q15043"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 490 AA; 53934 MW; FBFE403CF1D56A94 CRC64;
MELLRPALPS YFLLTLLSIW TAASEARAVS TGMPTISAAS FLQNLMHRYG EGDSLTLQQL
KALLNHLDVG VGRGNISQPV QGPRNLSTCF SSGELFAAHN LSHQSQIGER EFQEFCPTIL
QQLDSRACSS ENQENEENEQ TEEGRPSSVE VWGYGLLCVT VISLCSLLGA SVVPFMKKTF
YKRLLLYFIA LAIGTLYSNA LFQLIPEAFG FNPMEDYYVS KSAVVFGGFY LFFFTEKILK
MLLKQKNEHH HGHSHYTSET LPSQKDQEEG VTEKLQNGDL DHMIPQHCSG ELDGKTPVVD
EKVIVGSLSV QDLQASQSAC HWLKGVRYSD IGTLAWMITL SDGLHNFIDG LAIGASFTVS
VFQGISTSVA ILCEEFPHEL GDFVILLNAG MSLQQALFFN FLSACCCYVG LGFGILAGSH
FSANWIFALA GGMFLYISLA DMFPEMNEVS QEDERKGSAL IPFVIQNLGL LTGFGIMLVL
TMYSGHIQIG
