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Protein

Solute carrier family 12 member 1

Gene

Slc12a1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.

Enzyme regulationi

Activated by WNK3.By similarity

GO - Molecular functioni

  • sodium:potassium:chloride symporter activity Source: MGI

GO - Biological processi

  • cellular hyperosmotic salinity response Source: MGI
  • chemical homeostasis Source: MGI
  • excretion Source: MGI
  • kidney development Source: MGI
  • positive regulation of calcineurin-NFAT signaling cascade Source: MGI
  • potassium ion transport Source: UniProtKB-KW
  • sodium ion transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Potassium, Sodium

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 12 member 1
Alternative name(s):
BSC1
Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2
Kidney-specific Na-K-Cl symporter
Gene namesi
Name:Slc12a1
Synonyms:Nkcc2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:103150. Slc12a1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 173173CytoplasmicSequence analysisAdd
BLAST
Transmembranei174 – 19421HelicalSequence analysisAdd
BLAST
Transmembranei198 – 21821HelicalSequence analysisAdd
BLAST
Topological domaini219 – 25537CytoplasmicSequence analysisAdd
BLAST
Transmembranei256 – 27621HelicalSequence analysisAdd
BLAST
Transmembranei299 – 31921HelicalSequence analysisAdd
BLAST
Topological domaini320 – 3234CytoplasmicSequence analysis
Transmembranei324 – 34421HelicalSequence analysisAdd
BLAST
Transmembranei376 – 39621HelicalSequence analysisAdd
BLAST
Topological domaini397 – 41317CytoplasmicSequence analysisAdd
BLAST
Transmembranei414 – 43421HelicalSequence analysisAdd
BLAST
Transmembranei481 – 50121HelicalSequence analysisAdd
BLAST
Topological domaini502 – 54645CytoplasmicSequence analysisAdd
BLAST
Transmembranei547 – 56721HelicalSequence analysisAdd
BLAST
Transmembranei568 – 58821HelicalSequence analysisAdd
BLAST
Topological domaini589 – 60517CytoplasmicSequence analysisAdd
BLAST
Transmembranei606 – 62621HelicalSequence analysisAdd
BLAST
Transmembranei789 – 80921HelicalSequence analysisAdd
BLAST
Topological domaini810 – 1095286CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10951095Solute carrier family 12 member 1PRO_0000178019Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei57 – 571PhosphoserineCombined sources
Modified residuei96 – 961PhosphothreonineCombined sources
Modified residuei101 – 1011PhosphothreonineCombined sources
Modified residuei114 – 1141PhosphothreonineBy similarity
Modified residuei116 – 1161PhosphoserineBy similarity
Modified residuei126 – 1261Phosphoserine; by AMPKBy similarity
Modified residuei144 – 1441PhosphoserineBy similarity
Glycosylationi442 – 4421N-linked (GlcNAc...)Sequence analysis
Glycosylationi452 – 4521N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP55014.
PaxDbiP55014.
PeptideAtlasiP55014.
PRIDEiP55014.

PTM databases

iPTMnetiP55014.
PhosphoSiteiP55014.

Expressioni

Tissue specificityi

Predominant in kidney. Isoform F is most highly expressed in the inner stripe of outer medulla, isoform A is most highly expressed in the outer stripe of the outer medulla, and isoform B is most highly expressed in the cortical thick ascending limb.

Gene expression databases

CleanExiMM_SLC12A1.

Interactioni

Protein-protein interaction databases

BioGridi203276. 1 interaction.
IntActiP55014. 4 interactions.
MINTiMINT-4133657.
STRINGi10090.ENSMUSP00000028630.

Family & Domainsi

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2083. Eukaryota.
COG0531. LUCA.
HOGENOMiHOG000062855.
HOVERGENiHBG052851.
InParanoidiP55014.
KOiK14425.
PhylomeDBiP55014.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR002443. Na/K/Cl_cotranspt.
IPR018491. SLC12_C.
IPR002445. Slc12a1.
IPR004842. SLC12A_fam.
[Graphical view]
PANTHERiPTHR11827:SF45. PTHR11827:SF45. 3 hits.
PfamiPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
PF03522. SLC12. 1 hit.
[Graphical view]
PRINTSiPR01207. NAKCLTRNSPRT.
PR01209. NAKCLTRSPRT2.
TIGRFAMsiTIGR00930. 2a30. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: P55014-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSVSIPSNSV PSSASRFQVH VINEGHGSAA AVGDSADPPH YEETSFGDEA
60 70 80 90 100
QNRLRISFRP GNQECYDNFL QTGETAKTDT TFHAYDSHTN TYYLQTFGHN
110 120 130 140 150
TMDAVPKIEY YRNTGSVSGP KVNRPSLLEI HEQLAKNVTV APGSADRVAN
160 170 180 190 200
GDGMPGDEQA ENKEEDMTGV VKFGWVKGVL VRCMLNIWGV MLFIRLSWIV
210 220 230 240 250
GEAGIGLGVL IILLSTMVTS ITGLSTSAIA TNGFVRGGGA YYLISRSLGP
260 270 280 290 300
EFGGSIGLIF AFANAVAVAM YVVGFAETVV DLLKESDSMM VDPTNDIRII
310 320 330 340 350
GSITVVILLG ISVAGMEWEA KAQVILLVIL LIAIANFFIG TVIPSNNEKK
360 370 380 390 400
SRGFFNYQAS IFAENFGPSF TKGEGFFSVF AIFFPAATGI LAGANISGDL
410 420 430 440 450
EDPQDAIPRG TMLAIFITTV AYIGVAICVA ACVVRDATGS MNDTIVSGMN
460 470 480 490 500
CNGSAACGLG YDFSRCQHEP CQYGLMNNFQ VMSMVSGFGP LITAGIFSAT
510 520 530 540 550
LSSALASLVS APKVFQALCK DNIFKGLQFF AKGYGKNNEP LRGYFLTFVI
560 570 580 590 600
AMAFILIAEL NVIAPIISNF FLASYALINF SCFHASYAKS PGWRPAYGIY
610 620 630 640 650
NMWVSLFGAI LCCAVMFVIN WWAAVITYVI ELFLYIYVTY KKPDVNWGSS
660 670 680 690 700
TQALSYVSAL DNALELTTVE DHVKNFRPQC IVLTGGPMTR PALLDITHAF
710 720 730 740 750
TKNSGLCICC EVFVGPRKLC VKEMNSGMAK KQAWLIKNKI KAFYAAVAAD
760 770 780 790 800
CFRDGVRSLL QASGLGRMKP NTLVIGYKKN WRKAPLSELE NYVGIIHDAF
810 820 830 840 850
DFEIGVVIVR ISQGFDISPV LQVQDELEKL EQERLALEAA IKDNECEEGK
860 870 880 890 900
GGIRGLFKKA GKLNITKPAP KKDGNISSIQ SMHVGEFNQK LVEASAQFKK
910 920 930 940 950
KQGKGTIDVW WLFDDGGLTL LIPYILTLRK KWKDCKLRIY VGGKITRIEE
960 970 980 990 1000
EKISMASLLS KFRIKFADIH IIGDINIKPN KESWKVFEEM IEPYRLHESH
1010 1020 1030 1040 1050
KDLTTAEKLK RESPWKITDA ELEAVKEKSY RQVRLNELLQ EHSRAANLIV
1060 1070 1080 1090
LSLPVARKGS ISDLLYMAWL EILTKNLPPV LLVRGNHKNV LTFYS
Length:1,095
Mass (Da):120,355
Last modified:December 13, 2002 - v2
Checksum:iE3E134016ECCE3B0
GO
Isoform A4 (identifier: P55014-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     715-1059: Missing.
     1060-1095: SISDLLYMAW...NHKNVLTFYS → VRATSSGSSA...TNKQCNRGCK

Show »
Length:770
Mass (Da):83,220
Checksum:i0944BB79FCED7FC6
GO
Isoform B (identifier: P55014-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     210-234: LIILLSTMVTSITGLSTSAIATNGF → IIIGLAVTVTAITGLSTSAIATNGY

Show »
Length:1,095
Mass (Da):120,251
Checksum:i7E83EB36EE81CDCA
GO
Isoform F (identifier: P55014-4) [UniParc]FASTAAdd to basket

Also known as: C9

The sequence of this isoform differs from the canonical sequence as follows:
     210-234: LIILLSTMVTSITGLSTSAIATNGF → IIIGLSVVVTTLTGISMSAICTNGV

Show »
Length:1,095
Mass (Da):120,293
Checksum:i4EA5A8F7D59C5068
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti30 – 301A → S in AAC52632 (PubMed:7573490).Curated
Sequence conflicti30 – 301A → S in AAB03495 (PubMed:7573490).Curated
Sequence conflicti30 – 301A → S in AAC52633 (PubMed:7573490).Curated
Sequence conflicti48 – 481D → G in AAC52632 (PubMed:7573490).Curated
Sequence conflicti48 – 481D → G in AAB03495 (PubMed:7573490).Curated
Sequence conflicti48 – 481D → G in AAC52633 (PubMed:7573490).Curated
Sequence conflicti599 – 5991I → T in AAC52632 (PubMed:7573490).Curated
Sequence conflicti599 – 5991I → T in AAB03495 (PubMed:7573490).Curated
Sequence conflicti599 – 5991I → T in AAC52633 (PubMed:7573490).Curated
Sequence conflicti773 – 7731L → P in AAC52632 (PubMed:7573490).Curated
Sequence conflicti773 – 7731L → P in AAB03495 (PubMed:7573490).Curated
Sequence conflicti773 – 7731L → P in AAC52633 (PubMed:7573490).Curated
Sequence conflicti873 – 8731D → G in AAB65150 (PubMed:10070158).Curated
Sequence conflicti946 – 9461T → N in AAB65150 (PubMed:10070158).Curated
Sequence conflicti946 – 9461T → N in AAH16888 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei210 – 23425LIILL…ATNGF → IIIGLAVTVTAITGLSTSAI ATNGY in isoform B. 1 PublicationVSP_006099Add
BLAST
Alternative sequencei210 – 23425LIILL…ATNGF → IIIGLSVVVTTLTGISMSAI CTNGV in isoform F. 2 PublicationsVSP_006100Add
BLAST
Alternative sequencei715 – 1059345Missing in isoform A4. 1 PublicationVSP_006101Add
BLAST
Alternative sequencei1060 – 109536SISDL…LTFYS → VRATSSGSSAFSLCSQWVML GGTEDTHGNRKEKKRLGQEF TSLKKQTNKQCNRGCK in isoform A4. 1 PublicationVSP_006102Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20973 mRNA. Translation: AAC52632.1.
U20974 mRNA. Translation: AAB03495.1.
U20975 mRNA. Translation: AAC52633.1.
U94518 mRNA. Translation: AAB65150.1.
U61381 mRNA. Translation: AAD00091.1.
BC016888 mRNA. Translation: AAH16888.1.
CCDSiCCDS50693.1. [P55014-1]
CCDS50694.1. [P55014-4]
PIRiI49268.
I49269.
I49270.
RefSeqiNP_001073158.1. NM_001079690.1.
NP_899197.2. NM_183354.2.
UniGeneiMm.3914.

Genome annotation databases

GeneIDi20495.
KEGGimmu:20495.
UCSCiuc008mcg.1. mouse. [P55014-1]
uc008mch.1. mouse. [P55014-4]
uc008mci.1. mouse. [P55014-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20973 mRNA. Translation: AAC52632.1.
U20974 mRNA. Translation: AAB03495.1.
U20975 mRNA. Translation: AAC52633.1.
U94518 mRNA. Translation: AAB65150.1.
U61381 mRNA. Translation: AAD00091.1.
BC016888 mRNA. Translation: AAH16888.1.
CCDSiCCDS50693.1. [P55014-1]
CCDS50694.1. [P55014-4]
PIRiI49268.
I49269.
I49270.
RefSeqiNP_001073158.1. NM_001079690.1.
NP_899197.2. NM_183354.2.
UniGeneiMm.3914.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203276. 1 interaction.
IntActiP55014. 4 interactions.
MINTiMINT-4133657.
STRINGi10090.ENSMUSP00000028630.

PTM databases

iPTMnetiP55014.
PhosphoSiteiP55014.

Proteomic databases

MaxQBiP55014.
PaxDbiP55014.
PeptideAtlasiP55014.
PRIDEiP55014.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi20495.
KEGGimmu:20495.
UCSCiuc008mcg.1. mouse. [P55014-1]
uc008mch.1. mouse. [P55014-4]
uc008mci.1. mouse. [P55014-2]

Organism-specific databases

CTDi6557.
MGIiMGI:103150. Slc12a1.

Phylogenomic databases

eggNOGiKOG2083. Eukaryota.
COG0531. LUCA.
HOGENOMiHOG000062855.
HOVERGENiHBG052851.
InParanoidiP55014.
KOiK14425.
PhylomeDBiP55014.

Miscellaneous databases

PROiP55014.
SOURCEiSearch...

Gene expression databases

CleanExiMM_SLC12A1.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR002443. Na/K/Cl_cotranspt.
IPR018491. SLC12_C.
IPR002445. Slc12a1.
IPR004842. SLC12A_fam.
[Graphical view]
PANTHERiPTHR11827:SF45. PTHR11827:SF45. 3 hits.
PfamiPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
PF03522. SLC12. 1 hit.
[Graphical view]
PRINTSiPR01207. NAKCLTRNSPRT.
PR01209. NAKCLTRSPRT2.
TIGRFAMsiTIGR00930. 2a30. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter."
    Igarashi P., Vanden Heuvel G.B., Payne J.A., Forbush B. III
    Am. J. Physiol. 269:F405-F418(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND F).
    Tissue: Kidney.
  2. "Isoforms of the Na-K-2Cl cotransporter in murine TAL I. Molecular characterization and intrarenal localization."
    Mount D.B., Baekgaard A., Hall A.E., Plata C., Xu J., Beier D.R., Gamba G., Hebert S.C.
    Am. J. Physiol. 276:F347-F358(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A4 AND F).
    Strain: CD-1.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
    Tissue: Kidney.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57; THR-96 AND THR-101, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney.

Entry informationi

Entry nameiS12A1_MOUSE
AccessioniPrimary (citable) accession number: P55014
Secondary accession number(s): O35938, Q91W55, Q9Z1E0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 13, 2002
Last modified: July 6, 2016
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.