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S39AE_XENTR
ID   S39AE_XENTR             Reviewed;         462 AA.
AC   A4IGY6;
DT   04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2007, sequence version 1.
DT   03-AUG-2022, entry version 75.
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   Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX   NCBI_TaxID=8364;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (MAR-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   -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family.
CC       {ECO:0000305}.
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DR   EMBL; BC135298; AAI35299.1; -; mRNA.
DR   RefSeq; NP_001090864.1; NM_001097395.1.
DR   AlphaFoldDB; A4IGY6; -.
DR   SMR; A4IGY6; -.
DR   PaxDb; A4IGY6; -.
DR   GeneID; 100038282; -.
DR   KEGG; xtr:100038282; -.
DR   CTD; 23516; -.
DR   Xenbase; XB-GENE-982219; slc39a14.
DR   eggNOG; KOG2693; Eukaryota.
DR   HOGENOM; CLU_015114_13_0_1; -.
DR   InParanoid; A4IGY6; -.
DR   OrthoDB; 657777at2759; -.
DR   Reactome; R-XTR-442380; Zinc influx into cells by the SLC39 gene family.
DR   Proteomes; UP000008143; Chromosome 3.
DR   Proteomes; UP000790000; Unplaced.
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: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:0098739; P:import across plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098662; P:inorganic cation transmembrane transport; ISS:UniProtKB.
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: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   Zinc; Zinc transport.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..462
FT                   /note="Metal cation symporter ZIP14"
FT                   /id="PRO_0000312197"
FT   TOPO_DOM        17..138
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        139..159
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        160..167
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        168..188
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        189..201
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        202..222
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        223..322
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        323..343
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        344..367
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        368..388
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        389..396
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        397..417
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        418..431
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        432..452
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        453..462
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          235..285
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           230..237
FT                   /note="HHHGHXHX-motif"
FT                   /evidence="ECO:0000250|UniProtKB:Q15043"
FT   MOTIF           346..351
FT                   /note="XEXPHE-motif"
FT                   /evidence="ECO:0000250|UniProtKB:Q15043"
FT   COMPBIAS        235..255
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        265..279
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        42
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        68
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        83
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        119
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   462 AA;  50190 MW;  CE028E55D5702EAD CRC64;
     MPLLLLSALL PFSLMAGPTP STGKELSAAS FLQDILQRYG ENESLSMPQL QSLLENLEVG
     KGGGNQRNMS QCLSSSTLFA AHNLTSGSVV DAEGFQSFCP TILQQLETRA CQESPAFQNE
     TTPGAEGRPS PGEVWGYGFL CVTVISLCSL FGAGVVPFMK KACYKRLLLF CIALAIGTLF
     SNALFQLIPE AFGFNPLEDS YVFTSSVIFG GFYLFFFTEK VLKMMLKQKH EHGHSHYSAD
     TSKRDAEEGV TEKLQNGDLD HMIPPPHGSE SDLRGDEKAV QQQDLPGQQS SCYWLKGIRY
     SDIGTLAWMI TLSDGLHNFI DGLAIGASFT VSVFQGVSTS IAILCEEFPH ELGDFVILLN
     AGMSIPQALF FNFLSACCCY LGLAFGILAG SHFSSNWIFA LAGGMFLYIA LSDMFPEMNE
     VSKEDEEGGR AFSAFMIQNA GLLTGFAIML LLTTFSGQIQ LG
 
 
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