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Q80XP9 (WNK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Wnk3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1757 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.4

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

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

Subunit structure

Interacts with WNK1 and WNK4 By similarity.

Subcellular location

Cytoplasm By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.

Contains 1 protein kinase domain.

Caution

Cys-175 is present instead of the conserved Lys which is expected to be an active site residue. Lys-158 appears to fulfill the required catalytic function.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processpositive regulation of establishment of protein localization to plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-threonine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of rubidium ion transmembrane transporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of rubidium ion transport

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of sodium ion transmembrane transporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of sodium ion transport

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentadherens junction

Inferred from direct assay PubMed 16275913. Source: BHF-UCL

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

tight junction

Inferred from direct assay PubMed 16275913. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q80XP9-1)

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.
Isoform 2 (identifier: Q80XP9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1217-1263: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 17571757Serine/threonine-protein kinase WNK3
PRO_0000278775

Regions

Domain146 – 404259Protein kinase
Nucleotide binding152 – 1609ATP By similarity

Sites

Active site2741Proton acceptor By similarity
Binding site1581ATP By similarity

Amino acid modifications

Modified residue621Phosphoserine By similarity
Modified residue3031Phosphoserine; by autocatalysis By similarity
Modified residue3071Phosphoserine; by autocatalysis By similarity

Natural variations

Alternative sequence1217 – 126347Missing in isoform 2.
VSP_041934

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 9, 2013. Version 3.
Checksum: 3E5B070772BE6725

FASTA1,757193,991
        10         20         30         40         50         60 
MATDSGEPAS TEDSEKPDGV SFENRAARAV APLTVEARIK EKYSTFSASG ENIERKRFFR 

        70         80         90        100        110        120 
KSVEMTEDDK VAESSRRDER KAATNISRVD KVPTNVLRGG QEVKYEQCSK ATSESSKDCF 

       130        140        150        160        170        180 
KEKTEKEMEE EAEMKAVATS PSGRFLKFDI ELGRGAFKTV YKGLDTETWV EVAWCELQDR 

       190        200        210        220        230        240 
KLTKAEQQRF KEEAEMLKGL QHPNIVRFYD SWESTLKGKK CIVLVTELMT SGTLKTYLKR 

       250        260        270        280        290        300 
FKVMKPKVLR SWCRQILKGL QFLHTRTPPI IHRDLKCDNI FITGPTGSVK IGDLGLATLM 

       310        320        330        340        350        360 
RTSFAKSVIG TPEFMAPEMY EEHYDESVDV YAFGMCMLEM ATSEYPYSEC QNAAQIYRKV 

       370        380        390        400        410        420 
TSGIKPASFN KVTDPEVKEI IEGCIRQNKS ERLSIKDLLN HAFFAEDTGL RVELAEEDDC 

       430        440        450        460        470        480 
SNSSLALRLW VEDPKKLKGK HKDNEAIEFS FNLEADTPEE VAYEMVKSGF FHESDSKAVA 

       490        500        510        520        530        540 
KSIRDRVTLI KKIREKKPAG CLEERRDSQC KYVRNVLPQQ QTATLQPTPG PHTAAEYEET 

       550        560        570        580        590        600 
EVDQHVRQQF LQGKPQQQSS SVRGDTSSEP TAGPVLHSDT SSHPTVAYSS NQTTSSQEQP 

       610        620        630        640        650        660 
KLTQSPVLPV VQGQSSVMPI YAAGVGVVSQ SQISPLTIQK VSQIKPVSQP IGAEQQATLQ 

       670        680        690        700        710        720 
NPDFVRSLNQ DVTSVKENTN NPDTPSGNGK QDRNKQRRAS CPRPEKGTKF QLTVLQVSVS 

       730        740        750        760        770        780 
GDNMVECQLE THNNKMVTFK FDVDGDAPED IADYMVEDNF VLENEKEKFV EELRAIVGQA 

       790        800        810        820        830        840 
QEILHVHSAV EKSIGVDSVA LESNSNQTGS SEQVLINSAS TQTSNESAPQ SSPVGRWRFC 

       850        860        870        880        890        900 
INQTIKNREA QSPPSLQPSM AMVPGLHPFP SSRNTSNQAI SQNTVFTIEN NPGHRELFTS 

       910        920        930        940        950        960 
KLDHKDVVDG KIGEHASIET EQSSISYQVE DDRQIMTPAT DNSNYSAALV CPVPGECEAL 

       970        980        990       1000       1010       1020 
TSQAGMFMPT YPNQQAAVLA DVHIAYPGES VPIGGNAALT SVLVSSDQKP QSLSVQQPTI 

      1030       1040       1050       1060       1070       1080 
DAEFISKEGE TTVNTETSSP KAVIATQTPG FEPAVILPAT ILESDGERPP KMEFADNRIK 

      1090       1100       1110       1120       1130       1140 
TLDEKLRNLL YQEHSISSIC PESQKDTQSI DSPFSSSAED ILSYSMPEVI AISHCGIQDS 

      1150       1160       1170       1180       1190       1200 
PAQSPNFQQT GSKILSNVAA SQPAHISVFK KDLNVITSVP SELCLHEMSP DASLPGDPEA 

      1210       1220       1230       1240       1250       1260 
YPAAVSSDGT IHLQTGGGYF GLSFTCPSLK NPISRKSWTR KLKSWAYRLR QSTSFFKRSK 

      1270       1280       1290       1300       1310       1320 
VRQVETEDKR SAIASDPIPL TREFSSDTRA LSRCKAMSGS FQRGRFQVIT VPQQQPVKMM 

      1330       1340       1350       1360       1370       1380 
SFGKDHRPPF NKTTVQSSEQ ALTFAEAAVS QLIEVEPAMP THKASVSSRK LRTLYETFKE 

      1390       1400       1410       1420       1430       1440 
DKGDPEQGDI VSYSTACETS VSSVATEKNV TSTTEVSVQS GSEPLDKEKN ESTPGKQTCT 

      1450       1460       1470       1480       1490       1500 
NEFSATLAGN RKSVTKTRPE GDQYLPLREE QAYAQTQNSL FYSPSSPMSS DNESEIEDED 

      1510       1520       1530       1540       1550       1560 
LKVELQRLRE KHIQEVVSLQ TQQNKELQEL YERLRATKDN KAQSSEVPLS PASPRRPRSF 

      1570       1580       1590       1600       1610       1620 
KSKLRSRPQS MTHSDNLVVK DALGVESNTV SCQQSPASKK GMFTDDLHKL VDDWTRETVG 

      1630       1640       1650       1660       1670       1680 
HFPSKPSLNQ LKQSQQKSEA ENWNKSCEST PSTMGYTSNW ISSLSQIRGA APTSLPQGLP 

      1690       1700       1710       1720       1730       1740 
LPSFHGPLAS YGMPHVCQYN AVGAAGYPVQ WVGISGPAQQ SVVLPTQSGG LFQPGMNLQS 

      1750 
FPAPPVQNPA SIPPGPK 

« Hide

Isoform 2 [UniParc].

Checksum: D825CA0153EC71F6
Show »

FASTA1,710188,423

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001258607.1. NM_001271678.1.
NP_001258608.1. NM_001271679.1.
XP_006528933.1. XM_006528870.1.
XP_006528934.1. XM_006528871.1.
XP_006528935.1. XM_006528872.1.
XP_006528936.1. XM_006528873.1.
XP_006528937.1. XM_006528874.1.
UniGeneMm.441474.

3D structure databases

ProteinModelPortalQ80XP9.
SMRQ80XP9. Positions 135-497.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000094005.

PTM databases

PhosphoSiteQ80XP9.

Proteomic databases

PaxDbQ80XP9.
PRIDEQ80XP9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000184392; ENSMUSP00000139037; ENSMUSG00000041245. [Q80XP9-1]
ENSMUST00000184730; ENSMUSP00000138822; ENSMUSG00000041245. [Q80XP9-2]
GeneID279561.
KEGGmmu:279561.
UCSCuc009upa.2. mouse. [Q80XP9-2]
uc029xnn.1. mouse. [Q80XP9-1]

Organism-specific databases

CTD65267.
MGIMGI:2652875. Wnk3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074385.
HOVERGENHBG050346.
InParanoidQ80XP9.
KOK08867.

Gene expression databases

CleanExMM_WNK3.
GenevestigatorQ80XP9.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio35562242.
PROQ80XP9.
SOURCESearch...

Entry information

Entry nameWNK3_MOUSE
AccessionPrimary (citable) accession number: Q80XP9
Secondary accession number(s): H6WJI2, H6WJI3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: January 9, 2013
Last modified: March 19, 2014
This is version 78 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot