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Protein

Serine/threonine-protein kinase WNK2

Gene

Wnk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5. Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression. Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1. WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activation requires autophosphorylation of Ser-356. Phosphorylation of Ser-352 also promotes increased activity (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei207ATPPROSITE-ProRule annotation1
Active sitei323Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi201 – 209ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase WNK2 (EC:2.7.11.1)
Alternative name(s):
Protein kinase lysine-deficient 2
Protein kinase with no lysine 2
Gene namesi
Name:Wnk2
Synonyms:Kiaa1760
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1922857. Wnk2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002787741 – 2149Serine/threonine-protein kinase WNK2Add BLAST2149

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Omega-N-methylarginineCombined sources1
Modified residuei30Omega-N-methylarginineCombined sources1
Modified residuei45PhosphoserineBy similarity1
Modified residuei352Phosphoserine; by autocatalysisBy similarity1
Modified residuei356Phosphoserine; by autocatalysisBy similarity1
Modified residuei560PhosphoserineBy similarity1
Modified residuei1098PhosphoserineBy similarity1
Modified residuei1210PhosphoserineBy similarity1
Modified residuei1507PhosphoserineBy similarity1
Modified residuei1566Phosphoserine1 Publication1
Modified residuei1594PhosphoserineBy similarity1
Modified residuei1725PhosphoserineCombined sources1
Modified residuei1726PhosphoserineCombined sources1
Modified residuei1770Phosphoserine1 Publication1
Modified residuei1797Phosphoserine1 Publication1
Modified residuei1962PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated.By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiQ3UH66.
PaxDbiQ3UH66.
PeptideAtlasiQ3UH66.
PRIDEiQ3UH66.

PTM databases

iPTMnetiQ3UH66.
PhosphoSitePlusiQ3UH66.

Expressioni

Tissue specificityi

Brain and heart.1 Publication

Gene expression databases

BgeeiENSMUSG00000037989.
CleanExiMM_WNK2.

Interactioni

Subunit structurei

Forms a complex with the phosphorylated form of STK39 in the brain.

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000089212.

Structurei

3D structure databases

ProteinModelPortaliQ3UH66.
SMRiQ3UH66.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini195 – 453Protein kinasePROSITE-ProRule annotationAdd BLAST259

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi172 – 177Poly-Glu6
Compositional biasi645 – 1080Pro-richAdd BLAST436
Compositional biasi1430 – 1496Pro-richAdd BLAST67
Compositional biasi1594 – 1597Poly-Ser4

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

eggNOGiKOG0584. Eukaryota.
ENOG410XQWZ. LUCA.
HOGENOMiHOG000139922.
HOVERGENiHBG050345.
InParanoidiQ3UH66.
KOiK08867.
PhylomeDBiQ3UH66.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
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 (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3UH66-1) [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
MDGDGGRRDA PGALMEAGRG TGSAGMAEPR ARAARLGPQR FLRRSVVESD
60 70 80 90 100
QEEPPGLEAA ETPSAQPPQP LQRRVLLLCK TRRLIAERAR GRPAAPAPAA
110 120 130 140 150
PAAPPGSPSV PSDPGPERAG TQEPSPDPTT ASAAATQVPD GGPRQEEAPA
160 170 180 190 200
PTQEDAGTTE AKPEPGRARK DEPEEEEDDE DDLKAVATSL DGRFLKFDIE
210 220 230 240 250
LGRGSFKTVY KGLDTETWVE VAWCELQDRK LTKLERQRFK EEAEMLKGLQ
260 270 280 290 300
HPNIVRFYDF WESSAKGKRC IVLVTELMTS GTLKTYLKRF KVMKPKVLRS
310 320 330 340 350
WCRQILKGLL FLHTRTPPII HRDLKCDNIF ITGPTGSVKI GDLGLATLKR
360 370 380 390 400
ASFAKSVIGT PEFMAPEMYE EHYDESVDVY AFGMCMLEMA TSEYPYSECQ
410 420 430 440 450
NAAQIYRKVT CGIKPASFEK VHDPEIKEII GECICKNKEE RYEIKDLLSH
460 470 480 490 500
AFFAEDTGVR VELAEEDHGR KSTIALRLWV EDPKKLKGKP KDNGAIEFTF
510 520 530 540 550
DLEKETPDEV AQEMIDSGFF HESDVKIVAK SIRDRVALIQ WRRERIWPAL
560 570 580 590 600
QSQEPKDSGS PDKARGLPAP LQVQVTYHAQ SGQPGQPEPE EPEADQHLLP
610 620 630 640 650
PTLPASVTSL ASDSTFDSGQ GSTVYSDSQS SQQSMVLSSL VDTAPTPASC
660 670 680 690 700
VCSPPVSEGP GLTHSLPTLG AFQQPATVPG LSVGPVPPPA RPPLLQQHFP
710 720 730 740 750
ESSMSFTPVL PPPSTPVPTG PSQPAPPVQQ PLPMAQPPTL PQVLAPQPMG
760 770 780 790 800
TVQPVPSHLP PYLAPTSQVV APAQLKPLQM PQPPLQPLAQ VPPQMPQMPV
810 820 830 840 850
VPPITPLTGL DGLPQTLTDL PAANVAPVPP PQYFSPAVIL PSLTTPLPTS
860 870 880 890 900
PALPMQAVKL PHPPGTPLAV PCQTIVPNAP AAIPLLAVAP QGVAALSIHP
910 920 930 940 950
AVAQIPAQPV YPAAFPQMVP GDIPPSPHHT VQSLRATPPQ LASPVPPQPV
960 970 980 990 1000
QPSVIHLPEQ AAPTAASGTQ VLLGHPPSYT ADVAAPVSAV SLPPAVLSPP
1010 1020 1030 1040 1050
LPDTLLPTVP DLLPKVPSSL APTVVAASQS APAQTSSLLL PTNPPLPTGP
1060 1070 1080 1090 1100
AVAGPCPAVQ LMVEVAQEEQ VSQDKPPGPP QSSESFGGSD VTSGRDLSDS
1110 1120 1130 1140 1150
CEGTFGGGRL EGRTARKHHR RSTRARSRQE RASRPRLTIL NVCNTGDKMV
1160 1170 1180 1190 1200
ECQLETHNHK MVTFKFDLDG DAPDEIATYM VEHDFILPAE RETFIEQMKD
1210 1220 1230 1240 1250
VMDKAEDMLS EDTDADHGSD TGTSPPHLGT CGLATGEENR QSQANAPVYQ
1260 1270 1280 1290 1300
QNVLHTGKRW FIICPVAEHP ATDTSESSPP LPLSSLQPEA SQDPAPYPDQ
1310 1320 1330 1340 1350
LSLTDKPSFP AAQQLLSQAG SSNPPGGASA PLAPSSPPVT TVIPAAPATS
1360 1370 1380 1390 1400
TVPESAAGTA MQAGGPGTHQ GPASVHETLQ PLAETRSAQC TAQPLSTGQG
1410 1420 1430 1440 1450
PCTPALEASR CSTGLGEPIS TREVSTQGEP LPASVPEPSP PTGATQSVPG
1460 1470 1480 1490 1500
QPPPPLPITV GAISLAAPQL PSPPLGPTAP PPPPSALESD GEGPPPRVGF
1510 1520 1530 1540 1550
VDNTIKSLDE KLRTLLYQEH VPTSSASAGT PMEASDRDFT LEPLRGDLPS
1560 1570 1580 1590 1600
ALSDKTPSLT QQTQPSLEKS ETAPAGWALA QREQGASSPM TAESSSSNTL
1610 1620 1630 1640 1650
GCDSDAGQVA SDSSTAPSVP QDASGSSVPT HMDPKDQNSS VPREALAAPM
1660 1670 1680 1690 1700
QSGPGSFTVG SPAQLRGARD SGSPHKRPGQ QDNSSPAKTV GRFSVVSTQD
1710 1720 1730 1740 1750
EWTLASPHSL RYSAPPDVYL DEIPSSPEVK LAVRRVQTAS SIEVGVEEPA
1760 1770 1780 1790 1800
SSDSGDERPR RRSQVQKQSS LPGTGGVASD FVKKATAFLH RSSRAGSLGP
1810 1820 1830 1840 1850
ETPSRAGVKV PTISITSFHS QSSYISSDND SEFEDADIKK ELRSLREKHL
1860 1870 1880 1890 1900
KEISELQSQQ KQEIEALYRR LGKPLPPNVG FFHTAPPMGR RRKTSKSKLK
1910 1920 1930 1940 1950
AGKLLNPLVQ QLKVVASSTG HLSDSSRGPP TKDPRGTKAV QTQQPCSVRA
1960 1970 1980 1990 2000
SLSTDICSGL ASDGGGARGQ GWTVYHPTSE RGAYKSSSKP RARFLSGPVS
2010 2020 2030 2040 2050
VSIWSALKRL CLGKEHSSSL YDSPGSSTSS LAPGPEPGPQ PTLHVQAQVN
2060 2070 2080 2090 2100
NSNNKKGTFT DDLHKLVDEW TTKTVGAAQV KPTLNQLKQT QKLHDMEASG
2110 2120 2130 2140
DARATSVPRA AVGASCLAPA PGPLSTTATP GATPALPVPI PDPESEKPD
Note: No experimental confirmation available.
Length:2,149
Mass (Da):227,527
Last modified:February 20, 2007 - v2
Checksum:iA4BBF1D391FE9BEC
GO
Isoform 2 (identifier: Q3UH66-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1921-2004: Missing.

Note: No experimental confirmation available.
Show »
Length:2,065
Mass (Da):218,728
Checksum:iCF4AE4A4DC664F90
GO
Isoform 3 (identifier: Q3UH66-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1935-1935: R → AHASTPP
     2019-2025: SLYDSPG → R

Note: No experimental confirmation available.
Show »
Length:2,149
Mass (Da):227,469
Checksum:i98AD382CFD4CFE45
GO
Isoform 4 (identifier: Q3UH66-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1935-1935: R → AHASTPP
     1971-2024: Missing.

Note: No experimental confirmation available.
Show »
Length:2,101
Mass (Da):222,082
Checksum:i953172919B0CBF8D
GO
Isoform 5 (identifier: Q3UH66-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1935-1935: R → AHASTPP
     2019-2025: SLYDSPG → R
     2142-2149: DPESEKPD → GTVHSSLSGP...STPGPRLHIT

Note: No experimental confirmation available.
Show »
Length:2,213
Mass (Da):234,069
Checksum:i0BE7B0D8B10819E2
GO
Isoform 6 (identifier: Q3UH66-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     731-742: Missing.
     971-1068: Missing.
     1935-1935: R → AHASTPP
     1971-2024: Missing.

Note: No experimental confirmation available.
Show »
Length:1,991
Mass (Da):211,147
Checksum:i1177FFA99C62BFD0
GO
Isoform 7 (identifier: Q3UH66-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     971-1068: Missing.
     1592-1593: AE → E
     1935-1935: R → AHASTPP
     2019-2025: SLYDSPG → R
     2142-2149: DPESEKPD → EACALPTPPCKFLSRPSSGQPTEGRSISGGFHDTCPGGERGDENSLTPSG

Note: No experimental confirmation available.
Show »
Length:2,092
Mass (Da):221,908
Checksum:i581DA7240F2E5FE5
GO

Sequence cautioni

The sequence AAH46464 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH55795 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAE20646 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti761 – 794PYLAP…QVPPQ → RRYLWPIFCSPQGWGTRPWT RPVHACLQGLLARE in BAC98249 (PubMed:14621295).CuratedAdd BLAST34

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023366731 – 742Missing in isoform 6. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_023367971 – 1068Missing in isoform 6 and isoform 7. 2 PublicationsAdd BLAST98
Alternative sequenceiVSP_0233681592 – 1593AE → E in isoform 7. 1 Publication2
Alternative sequenceiVSP_0233691921 – 2004Missing in isoform 2. 1 PublicationAdd BLAST84
Alternative sequenceiVSP_0233701935R → AHASTPP in isoform 3, isoform 4, isoform 5, isoform 6 and isoform 7. 3 Publications1
Alternative sequenceiVSP_0233711971 – 2024Missing in isoform 4 and isoform 6. 1 PublicationAdd BLAST54
Alternative sequenceiVSP_0233722019 – 2025SLYDSPG → R in isoform 3, isoform 5 and isoform 7. 3 Publications7
Alternative sequenceiVSP_0233732142 – 2149DPESEKPD → GTVHSSLSGPPCTLPLCQYG GLLPDPVSWGPWVASGNPEG SWGSQSPTQVPVFPVFLRPP VISTPGPRLHIT in isoform 5. 1 Publication8
Alternative sequenceiVSP_0233742142 – 2149DPESEKPD → EACALPTPPCKFLSRPSSGQ PTEGRSISGGFHDTCPGGER GDENSLTPSG in isoform 7. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CAAA01187366 Genomic DNA. No translation available.
AC140284 Genomic DNA. No translation available.
AK044381 mRNA. Translation: BAE20646.1. Different initiation.
AK147550 mRNA. Translation: BAE27991.1.
BC046464 mRNA. Translation: AAH46464.1. Different initiation.
BC055795 mRNA. Translation: AAH55795.1. Different initiation.
BC060187 mRNA. Translation: AAH60187.1.
AK129439 mRNA. Translation: BAC98249.1.
CCDSiCCDS70454.1. [Q3UH66-5]
CCDS70455.1. [Q3UH66-3]
RefSeqiNP_001277240.1. NM_001290311.1.
NP_001277242.1. NM_001290313.1.
NP_083637.2. NM_029361.4.
UniGeneiMm.342723.

Genome annotation databases

GeneIDi75607.
KEGGimmu:75607.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CAAA01187366 Genomic DNA. No translation available.
AC140284 Genomic DNA. No translation available.
AK044381 mRNA. Translation: BAE20646.1. Different initiation.
AK147550 mRNA. Translation: BAE27991.1.
BC046464 mRNA. Translation: AAH46464.1. Different initiation.
BC055795 mRNA. Translation: AAH55795.1. Different initiation.
BC060187 mRNA. Translation: AAH60187.1.
AK129439 mRNA. Translation: BAC98249.1.
CCDSiCCDS70454.1. [Q3UH66-5]
CCDS70455.1. [Q3UH66-3]
RefSeqiNP_001277240.1. NM_001290311.1.
NP_001277242.1. NM_001290313.1.
NP_083637.2. NM_029361.4.
UniGeneiMm.342723.

3D structure databases

ProteinModelPortaliQ3UH66.
SMRiQ3UH66.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000089212.

PTM databases

iPTMnetiQ3UH66.
PhosphoSitePlusiQ3UH66.

Proteomic databases

MaxQBiQ3UH66.
PaxDbiQ3UH66.
PeptideAtlasiQ3UH66.
PRIDEiQ3UH66.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi75607.
KEGGimmu:75607.

Organism-specific databases

CTDi65268.
MGIiMGI:1922857. Wnk2.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0584. Eukaryota.
ENOG410XQWZ. LUCA.
HOGENOMiHOG000139922.
HOVERGENiHBG050345.
InParanoidiQ3UH66.
KOiK08867.
PhylomeDBiQ3UH66.

Miscellaneous databases

ChiTaRSiWnk2. mouse.
PROiQ3UH66.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037989.
CleanExiMM_WNK2.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
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...

Entry informationi

Entry nameiWNK2_MOUSE
AccessioniPrimary (citable) accession number: Q3UH66
Secondary accession number(s): Q3V387
, Q6PAN9, Q6ZPI6, Q7TNS1, Q811F2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: November 2, 2016
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Cys-224 is present instead of the conserved Lys which is expected to be an active site residue. Lys-207 appears to fulfill the required catalytic function.Curated

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

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.