WNK2

Protein identityUniProt · HPA

UniProt accession

Q9Y3S1

Gene

WNK2

Ensembl

ENSG00000165238

Chromosome

9

Canonical length

2297 aa

Protein class

Enzymes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

The protein encoded by this gene is a cytoplasmic serine-threonine kinase that belongs to the protein kinase superfamily. The protein plays an important role in the regulation of electrolyte homeostasis, cell signaling survival, and proliferation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Canonical amino-acid sequenceUniProt

2297 residues, UniProt reviewed canonical sequence.

>Q9Y3S1|WNK2
     1  MDGDGGRRDV PGTLMEPGRG AGPAGMAEPR AKAARPGPQR FLRRSVVESD QEEPPGLEAA
    61  EAPGPQPPQP LQRRVLLLCK TRRLIAERAR GRPAAPAPAA LVAQPGAPGA PADAGPEPVG
   121  TQEPGPDPIA AAVETAPAPD GGPREEAAAT VRKEDEGAAE AKPEPGRTRR DEPEEEEDDE
   181  DDLKAVATSL DGRFLKFDIE LGRGSFKTVY KGLDTETWVE VAWCELQDRK LTKLERQRFK
   241  EEAEMLKGLQ HPNIVRFYDF WESSAKGKRC IVLVTELMTS GTLKTYLKRF KVMKPKVLRS
   301  WCRQILKGLL FLHTRTPPII HRDLKCDNIF ITGPTGSVKI GDLGLATLKR ASFAKSVIGT
   361  PEFMAPEMYE EHYDESVDVY AFGMCMLEMA TSEYPYSECQ NAAQIYRKVT CGIKPASFEK
   421  VHDPEIKEII GECICKNKEE RYEIKDLLSH AFFAEDTGVR VELAEEDHGR KSTIALRLWV
   481  EDPKKLKGKP KDNGAIEFTF DLEKETPDEV AQEMIESGFF HESDVKIVAK SIRDRVALIQ
   541  WRRERIWPAL QPKEQQDVGS PDKARGPPVP LQVQVTYHAQ AGQPGPPEPE EPEADQHLLP
   601  PTLPTSATSL ASDSTFDSGQ GSTVYSDSQS SQQSVMLGSL ADAAPSPAQC VCSPPVSEGP
   661  VLPQSLPSLG AYQQPTAAPG LPVGSVPAPA CPPSLQQHFP DPAMSFAPVL PPPSTPMPTG
   721  PGQPAPPGQQ PPPLAQPTPL PQVLAPQPVV PLQPVPPHLP PYLAPASQVG APAQLKPLQM
   781  PQAPLQPLAQ VPPQMPPIPV VPPITPLAGI DGLPPALPDL PTATVPPVPP PQYFSPAVIL
   841  PSLAAPLPPA SPALPLQAVK LPHPPGAPLA MPCRTIVPNA PATIPLLAVA PPGVAALSIH
   901  SAVAQLPGQP VYPAAFPQMA PTDVPPSPHH TVQNMRATPP QPALPPQPTL PPQPVLPPQP
   961  TLPPQPVLPP QPTRPPQPVL PPQPMLPPQP VLPPQPALPV RPEPLQPHLP EQAAPAATPG
  1021  SQILLGHPAP YAVDVAAQVP TVPVPPAAVL SPPLPEVLLP AAPELLPQFP SSLATVSASV
  1081  QSVPTQTATL LPPANPPLPG GPGIASPCPT VQLTVEPVQE EQASQDKPPG LPQSCESYGG
  1141  SDVTSGKELS DSCEGAFGGG RLEGRAARKH HRRSTRARSR QERASRPRLT ILNVCNTGDK
  1201  MVECQLETHN HKMVTFKFDL DGDAPDEIAT YMVEHDFILQ AERETFIEQM KDVMDKAEDM
  1261  LSEDTDADRG SDPGTSPPHL STCGLGTGEE SRQSQANAPV YQQNVLHTGK RWFIICPVAE
  1321  HPAPEAPESS PPLPLSSLPP EASQGPCRGL TLPCLPWRRA ACGAVFLSLF SAESAQSKQP
  1381  PDSAPYKDQL SSKEQPSFLA SQQLLSQAGP SNPPGAPPAP LAPSSPPVTA LPQDGAAPAT
  1441  STMPEPASGT ASQAGGPGTP QGLTSELETS QPLAETHEAP LAVQPLVVGL APCTPAPEAA
  1501  STRDASAPRE PLPPPAPEPS PHSGTPQPAL GQPAPLLPAA VGAVSLATSQ LPSPPLGPTV
  1561  PPQPPSALES DGEGPPPRVG FVDSTIKSLD EKLRTLLYQE HVPTSSASAG TPVEVGDRDF
  1621  TLEPLRGDQP RSEVCGGDLA LPPVPKEAVS GRVQLPQPLV EKSELAPTRG AVMEQGTSSS
  1681  MTAESSPRSM LGYDRDGRQV ASDSHVVPSV PQDVPAFVRP ARVEPTDRDG GEAGESSAEP
  1741  PPSDMGTVGG QASHPQTLGA RALGSPRKRP EQQDVSSPAK TVGRFSVVST QDEWTLASPH
  1801  SLRYSAPPDV YLDEAPSSPD VKLAVRRAQT ASSIEVGVGE PVSSDSGDEG PRARPPVQKQ
  1861  ASLPVSGSVA GDFVKKATAF LQRPSRAGSL GPETPSRVGM KVPTISVTSF HSQSSYISSD
  1921  NDSELEDADI KKELQSLREK HLKEISELQS QQKQEIEALY RRLGKPLPPN VGFFHTAPPT
  1981  GRRRKTSKSK LKAGKLLNPL VRQLKVVASS TGHLADSSRG PPAKDPAQAS VGLTADSTGL
  2041  SGKAVQTQQP CSVRASLSSD ICSGLASDGG GARGQGWTVY HPTSERVTYK SSSKPRARFL
  2101  SGPVSVSIWS ALKRLCLGKE HSSRSSTSSL APGPEPGPQP ALHVQAQVNN SNNKKGTFTD
  2161  DLHKLVDEWT SKTVGAAQLK PTLNQLKQTQ KLQDMEAQAG WAAPGEARAM TAPRAGVGMP
  2221  RLPPAPGPLS TTVIPGAAPT LSVPTPDGAL GTARRNQVWF GLRVPPTACC GHSTQPRGGQ
  2281  RVGSKTASFA ASDPVRS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against WNK2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.61

Highest tissue expression

64 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about WNK2.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 3,151 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Inborn genetic diseases

Disease | ImmuneIEDB

Conditions an epitope on WNK2 was assayed in.

• castration-resistant prostate carcinoma B and T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.21

gnomAD pLI

1

gnomAD missense Z

2.58

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA damage response
• intracellular signal transduction
• monoatomic ion homeostasis
• negative regulation of cell population proliferation
• negative regulation of ERK1 and ERK2 cascade
• positive regulation of canonical Wnt signaling pathway
• positive regulation of sodium ion transmembrane transporter activity
• protein autophosphorylation
• protein phosphorylation

Molecular functions

• ATP binding
• protein serine kinase activity
• protein serine/threonine kinase activity

Cellular components

• cytoplasm
• cytosol
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• Serine/threonine-protein kinase OSR1/WNK, CCT domain
• With No Lysine (K) Ser/Thr Protein Kinase
• Serine/threonine-protein kinase WNK, CCTL2 domain
• Protein kinase domain
• Oxidative-stress-responsive kinase 1 C-terminal domain
• WNK CCTL2 domain

KeywordsUniProt

• ATP-binding
• Cell membrane
• Cytoplasm
• Kinase
• Membrane
• Methylation
• Nucleotide-binding
• Phosphoprotein
• Serine/threonine-protein kinase
• Transferase

InteractionsUniProt · HPA

Protein binding partners of WNK2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• OXSR1
• WNK1
• YWHAZ