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Protein

Serine/threonine-protein kinase WNK3

Gene

Wnk3

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

Functioni

Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SLC12A1, SLC12A2, SLC12A3, SCNN1A, SCNN1B, SCNN1D and SGK1. Inhibits SLC12A4, SLC12A5, SLC12A6 and SLC12A7. Phosphorylates WNK4. Increases Ca2+ influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway. Inhibits KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activation requires autophosphorylation of Ser-307. Phosphorylation of Ser-303 also promotes increased activity. Kinase activity is inhibited by WNK4 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei158 – 1581ATPPROSITE-ProRule annotation
Active sitei274 – 2741Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi152 – 1609ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. chloride channel inhibitor activity Source: MGI
  3. protein kinase activity Source: UniProtKB
  4. protein serine/threonine kinase activity Source: MGI

GO - Biological processi

  1. negative regulation of apoptotic process Source: MGI
  2. positive regulation of calcium ion transport Source: MGI
  3. positive regulation of establishment of protein localization to plasma membrane Source: UniProtKB
  4. positive regulation of ion transmembrane transporter activity Source: UniProtKB
  5. positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
  6. positive regulation of rubidium ion transmembrane transporter activity Source: UniProtKB
  7. positive regulation of rubidium ion transport Source: UniProtKB
  8. positive regulation of sodium ion transmembrane transporter activity Source: UniProtKB
  9. positive regulation of sodium ion transport Source: UniProtKB
  10. protein autophosphorylation Source: UniProtKB
  11. regulation of ion homeostasis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_196640. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase WNK3 (EC:2.7.11.1)
Alternative name(s):
Protein kinase lysine-deficient 3
Protein kinase with no lysine 3
Gene namesi
Name:Wnk3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome X

Organism-specific databases

MGIiMGI:2652875. Wnk3.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. adherens junction Source: BHF-UCL
  2. cytoplasm Source: MGI
  3. tight junction Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 17571757Serine/threonine-protein kinase WNK3PRO_0000278775Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei62 – 621PhosphoserineBy similarity
Modified residuei303 – 3031Phosphoserine; by autocatalysisBy similarity
Modified residuei307 – 3071Phosphoserine; by autocatalysisBy similarity

Post-translational modificationi

Ubiquitinated by the BCR(KLHL2) complex, leading to its degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ80XP9.
PaxDbiQ80XP9.
PRIDEiQ80XP9.

PTM databases

PhosphoSiteiQ80XP9.

Expressioni

Gene expression databases

CleanExiMM_WNK3.
ExpressionAtlasiQ80XP9. baseline and differential.
GenevestigatoriQ80XP9.

Interactioni

Subunit structurei

Interacts with WNK1 and WNK4.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000094005.

Structurei

3D structure databases

ProteinModelPortaliQ80XP9.
SMRiQ80XP9. Positions 135-497.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini146 – 404259Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074385.
HOVERGENiHBG050346.
InParanoidiQ80XP9.
KOiK08867.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q80XP9-1) [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
MATDSGEPAS TEDSEKPDGV SFENRAARAV APLTVEARIK EKYSTFSASG
60 70 80 90 100
ENIERKRFFR KSVEMTEDDK VAESSRRDER KAATNISRVD KVPTNVLRGG
110 120 130 140 150
QEVKYEQCSK ATSESSKDCF KEKTEKEMEE EAEMKAVATS PSGRFLKFDI
160 170 180 190 200
ELGRGAFKTV YKGLDTETWV EVAWCELQDR KLTKAEQQRF KEEAEMLKGL
210 220 230 240 250
QHPNIVRFYD SWESTLKGKK CIVLVTELMT SGTLKTYLKR FKVMKPKVLR
260 270 280 290 300
SWCRQILKGL QFLHTRTPPI IHRDLKCDNI FITGPTGSVK IGDLGLATLM
310 320 330 340 350
RTSFAKSVIG TPEFMAPEMY EEHYDESVDV YAFGMCMLEM ATSEYPYSEC
360 370 380 390 400
QNAAQIYRKV TSGIKPASFN KVTDPEVKEI IEGCIRQNKS ERLSIKDLLN
410 420 430 440 450
HAFFAEDTGL RVELAEEDDC SNSSLALRLW VEDPKKLKGK HKDNEAIEFS
460 470 480 490 500
FNLEADTPEE VAYEMVKSGF FHESDSKAVA KSIRDRVTLI KKIREKKPAG
510 520 530 540 550
CLEERRDSQC KYVRNVLPQQ QTATLQPTPG PHTAAEYEET EVDQHVRQQF
560 570 580 590 600
LQGKPQQQSS SVRGDTSSEP TAGPVLHSDT SSHPTVAYSS NQTTSSQEQP
610 620 630 640 650
KLTQSPVLPV VQGQSSVMPI YAAGVGVVSQ SQISPLTIQK VSQIKPVSQP
660 670 680 690 700
IGAEQQATLQ NPDFVRSLNQ DVTSVKENTN NPDTPSGNGK QDRNKQRRAS
710 720 730 740 750
CPRPEKGTKF QLTVLQVSVS GDNMVECQLE THNNKMVTFK FDVDGDAPED
760 770 780 790 800
IADYMVEDNF VLENEKEKFV EELRAIVGQA QEILHVHSAV EKSIGVDSVA
810 820 830 840 850
LESNSNQTGS SEQVLINSAS TQTSNESAPQ SSPVGRWRFC INQTIKNREA
860 870 880 890 900
QSPPSLQPSM AMVPGLHPFP SSRNTSNQAI SQNTVFTIEN NPGHRELFTS
910 920 930 940 950
KLDHKDVVDG KIGEHASIET EQSSISYQVE DDRQIMTPAT DNSNYSAALV
960 970 980 990 1000
CPVPGECEAL TSQAGMFMPT YPNQQAAVLA DVHIAYPGES VPIGGNAALT
1010 1020 1030 1040 1050
SVLVSSDQKP QSLSVQQPTI DAEFISKEGE TTVNTETSSP KAVIATQTPG
1060 1070 1080 1090 1100
FEPAVILPAT ILESDGERPP KMEFADNRIK TLDEKLRNLL YQEHSISSIC
1110 1120 1130 1140 1150
PESQKDTQSI DSPFSSSAED ILSYSMPEVI AISHCGIQDS PAQSPNFQQT
1160 1170 1180 1190 1200
GSKILSNVAA SQPAHISVFK KDLNVITSVP SELCLHEMSP DASLPGDPEA
1210 1220 1230 1240 1250
YPAAVSSDGT IHLQTGGGYF GLSFTCPSLK NPISRKSWTR KLKSWAYRLR
1260 1270 1280 1290 1300
QSTSFFKRSK VRQVETEDKR SAIASDPIPL TREFSSDTRA LSRCKAMSGS
1310 1320 1330 1340 1350
FQRGRFQVIT VPQQQPVKMM SFGKDHRPPF NKTTVQSSEQ ALTFAEAAVS
1360 1370 1380 1390 1400
QLIEVEPAMP THKASVSSRK LRTLYETFKE DKGDPEQGDI VSYSTACETS
1410 1420 1430 1440 1450
VSSVATEKNV TSTTEVSVQS GSEPLDKEKN ESTPGKQTCT NEFSATLAGN
1460 1470 1480 1490 1500
RKSVTKTRPE GDQYLPLREE QAYAQTQNSL FYSPSSPMSS DNESEIEDED
1510 1520 1530 1540 1550
LKVELQRLRE KHIQEVVSLQ TQQNKELQEL YERLRATKDN KAQSSEVPLS
1560 1570 1580 1590 1600
PASPRRPRSF KSKLRSRPQS MTHSDNLVVK DALGVESNTV SCQQSPASKK
1610 1620 1630 1640 1650
GMFTDDLHKL VDDWTRETVG HFPSKPSLNQ LKQSQQKSEA ENWNKSCEST
1660 1670 1680 1690 1700
PSTMGYTSNW ISSLSQIRGA APTSLPQGLP LPSFHGPLAS YGMPHVCQYN
1710 1720 1730 1740 1750
AVGAAGYPVQ WVGISGPAQQ SVVLPTQSGG LFQPGMNLQS FPAPPVQNPA

SIPPGPK
Length:1,757
Mass (Da):193,991
Last modified:January 9, 2013 - v3
Checksum:i3E5B070772BE6725
GO
Isoform 2 (identifier: Q80XP9-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1217-1263: Missing.

Note: No experimental confirmation available.

Show »
Length:1,710
Mass (Da):188,423
Checksum:iD825CA0153EC71F6
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1217 – 126347Missing in isoform 2. 1 PublicationVSP_041934Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JQ247189 mRNA. Translation: AEZ01402.1.
JQ247190 mRNA. Translation: AEZ01403.1.
AL732420 Genomic DNA. No translation available.
AL807396 Genomic DNA. No translation available.
BC043119 mRNA. Translation: AAH43119.1.
BC060731 mRNA. Translation: AAH60731.1.
CCDSiCCDS72450.1. [Q80XP9-2]
CCDS72451.1. [Q80XP9-1]
RefSeqiNP_001258607.1. NM_001271678.1. [Q80XP9-1]
NP_001258608.1. NM_001271679.1. [Q80XP9-2]
XP_006528933.1. XM_006528870.1. [Q80XP9-1]
XP_006528934.1. XM_006528871.1. [Q80XP9-1]
XP_006528935.1. XM_006528872.1. [Q80XP9-1]
XP_006528936.1. XM_006528873.1. [Q80XP9-1]
XP_006528937.1. XM_006528874.1. [Q80XP9-2]
UniGeneiMm.441474.

Genome annotation databases

EnsembliENSMUST00000184392; ENSMUSP00000139037; ENSMUSG00000041245. [Q80XP9-1]
ENSMUST00000184730; ENSMUSP00000138822; ENSMUSG00000041245. [Q80XP9-2]
GeneIDi279561.
KEGGimmu:279561.
UCSCiuc009upa.2. mouse. [Q80XP9-2]
uc029xnn.1. mouse. [Q80XP9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JQ247189 mRNA. Translation: AEZ01402.1.
JQ247190 mRNA. Translation: AEZ01403.1.
AL732420 Genomic DNA. No translation available.
AL807396 Genomic DNA. No translation available.
BC043119 mRNA. Translation: AAH43119.1.
BC060731 mRNA. Translation: AAH60731.1.
CCDSiCCDS72450.1. [Q80XP9-2]
CCDS72451.1. [Q80XP9-1]
RefSeqiNP_001258607.1. NM_001271678.1. [Q80XP9-1]
NP_001258608.1. NM_001271679.1. [Q80XP9-2]
XP_006528933.1. XM_006528870.1. [Q80XP9-1]
XP_006528934.1. XM_006528871.1. [Q80XP9-1]
XP_006528935.1. XM_006528872.1. [Q80XP9-1]
XP_006528936.1. XM_006528873.1. [Q80XP9-1]
XP_006528937.1. XM_006528874.1. [Q80XP9-2]
UniGeneiMm.441474.

3D structure databases

ProteinModelPortaliQ80XP9.
SMRiQ80XP9. Positions 135-497.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000094005.

PTM databases

PhosphoSiteiQ80XP9.

Proteomic databases

MaxQBiQ80XP9.
PaxDbiQ80XP9.
PRIDEiQ80XP9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000184392; ENSMUSP00000139037; ENSMUSG00000041245. [Q80XP9-1]
ENSMUST00000184730; ENSMUSP00000138822; ENSMUSG00000041245. [Q80XP9-2]
GeneIDi279561.
KEGGimmu:279561.
UCSCiuc009upa.2. mouse. [Q80XP9-2]
uc029xnn.1. mouse. [Q80XP9-1]

Organism-specific databases

CTDi65267.
MGIiMGI:2652875. Wnk3.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074385.
HOVERGENiHBG050346.
InParanoidiQ80XP9.
KOiK08867.

Enzyme and pathway databases

ReactomeiREACT_196640. Stimuli-sensing channels.

Miscellaneous databases

NextBioi35562242.
PROiQ80XP9.
SOURCEiSearch...

Gene expression databases

CleanExiMM_WNK3.
ExpressionAtlasiQ80XP9. baseline and differential.
GenevestigatoriQ80XP9.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mouse Wnk3 gene encodes multiple continuous open reading frames."
    Shmukler B.E., Alper S.L.
    Submitted (DEC-2011) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  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] OF 1296-1757.
    Strain: C57BL/6.
    Tissue: Embryonic brain.
  4. "Renal and brain isoforms of WNK3 have opposite effects on NCCT expression."
    Glover M., Zuber A.M., O'Shaughnessy K.M.
    J. Am. Soc. Nephrol. 20:1314-1322(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ALTERNATIVE SPLICING.

Entry informationi

Entry nameiWNK3_MOUSE
AccessioniPrimary (citable) accession number: Q80XP9
Secondary accession number(s): H6WJI2, H6WJI3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: January 9, 2013
Last modified: February 4, 2015
This is version 86 of the entry and version 3 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.