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UniProtKB - Q9H4A3 (WNK1_HUMAN)

Protein

Serine/threonine-protein kinase WNK1

Gene

WNK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4, SLC26A6 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity).By similarity2 Publications
Isoform 3: Dominant-negative regulator of the longer isoform 1. Does not have kinase activity, does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport. Downregulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity. In kidney, may play an important role regulating sodium and potassium balance.By similarity

Caution

Was named WNK/'with no lysine(K)' because key residues for catalysis, including the lysine involved in ATP binding, are either not conserved or differ compared to the residues described in other kinase family proteins.1 Publication
HSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron. It has been shown to be a nervous system-specific exon of WNK1 included in isoform 4 and isoform 5 (PubMed:18521183).1 Publication
It is uncertain whether Met-1 or Met-214 is the initiator in isoform 4 and isoform 5.Curated

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Activity regulationi

By hypertonicity. Activation requires autophosphorylation of Ser-382, that may be regulated by calcium. Phosphorylation of Ser-378 also promotes increased activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei231ATP; via amide nitrogenCombined sources1 Publication1
Binding sitei351ATPCombined sources1 Publication1
Active sitei368Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi301 – 304ATPCombined sources1 Publication4

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • chloride channel inhibitor activity Source: UniProtKB
  • magnesium ion binding Source: Ensembl
  • phosphatase binding Source: UniProtKB
  • potassium channel inhibitor activity Source: GO_Central
  • protein kinase activator activity Source: ParkinsonsUK-UCL
  • protein kinase activity Source: ParkinsonsUK-UCL
  • protein kinase binding Source: ParkinsonsUK-UCL
  • protein serine/threonine kinase activity Source: UniProtKB
  • protein serine/threonine kinase inhibitor activity Source: Ensembl
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Protein kinase inhibitor, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
SignaLinkiQ9H4A3
SIGNORiQ9H4A3

Protein family/group databases

MoonDBiQ9H4A3 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase WNK1Curated (EC:2.7.11.11 Publication)
Alternative name(s):
Erythrocyte 65 kDa protein
Short name:
p65
Kinase deficient protein
Protein kinase lysine-deficient 1Imported
Protein kinase with no lysine 11 Publication
Short name:
hWNK1
Gene namesi
Name:WNK1Imported
Synonyms:HSN21 Publication, KDP, KIAA0344Imported, PRKWNK1Imported
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000060237.16
HGNCiHGNC:14540 WNK1
MIMi605232 gene
neXtProtiNX_Q9H4A3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Pseudohypoaldosteronism 2C (PHA2C)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics.
See also OMIM:614492
Neuropathy, hereditary sensory and autonomic, 2A (HSAN2A)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves.
See also OMIM:201300

Keywords - Diseasei

Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi65125
GeneReviewsiWNK1
MalaCardsiWNK1
MIMi201300 phenotype
614492 phenotype
OpenTargetsiENSG00000060237
Orphaneti970 Hereditary sensory and autonomic neuropathy type 2
88940 Pseudohypoaldosteronism type 2C
PharmGKBiPA134944932
PA33782

Chemistry databases

ChEMBLiCHEMBL1075173
GuidetoPHARMACOLOGYi2280

Polymorphism and mutation databases

BioMutaiWNK1
DMDMi296453029

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000868191 – 2382Serine/threonine-protein kinase WNK1Add BLAST2382

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19PhosphoserineCombined sources1
Modified residuei167PhosphoserineCombined sources1
Modified residuei174PhosphoserineCombined sources1
Modified residuei378Phosphoserine; by autocatalysisBy similarity1
Modified residuei382Phosphoserine; by autocatalysisBy similarity1
Modified residuei1261PhosphoserineCombined sources1
Modified residuei1978PhosphoserineCombined sources1
Modified residuei2002PhosphoserineCombined sources1
Modified residuei2011PhosphoserineCombined sources1
Modified residuei2012PhosphoserineCombined sources1
Modified residuei2027PhosphoserineCombined sources1
Modified residuei2029PhosphoserineCombined sources1
Modified residuei2032PhosphoserineCombined sources1
Modified residuei2121PhosphoserineCombined sources1
Modified residuei2270PhosphoserineBy similarity1
Modified residuei2286PhosphoserineBy similarity1
Modified residuei2370PhosphoserineCombined sources1
Modified residuei2372PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylation at Ser-382 is inhibited by intracellular calcium.By similarity
May be O-glycosylated.1 Publication
Ubiquitinated in vitro by the BCR(KLHL3) complex and in vivo by a BCR(KLHL2) complex, leading to proteasomal degradation.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9H4A3
MaxQBiQ9H4A3
PaxDbiQ9H4A3
PeptideAtlasiQ9H4A3
PRIDEiQ9H4A3
ProteomicsDBi80804
80805 [Q9H4A3-2]
80806 [Q9H4A3-4]
80807 [Q9H4A3-5]
80808 [Q9H4A3-6]

PTM databases

iPTMnetiQ9H4A3
PhosphoSitePlusiQ9H4A3

Expressioni

Tissue specificityi

Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle. Isoform 3 is kidney-specific and specifically expressed in the distal convoluted tubule (DCT) and connecting tubule (CNT) of the nephron.4 Publications

Gene expression databases

BgeeiENSG00000060237 Expressed in 240 organ(s), highest expression level in corpus callosum
CleanExiHS_WNK1
ExpressionAtlasiQ9H4A3 baseline and differential
GenevisibleiQ9H4A3 HS

Organism-specific databases

HPAiHPA046541
HPA059157

Interactioni

Subunit structurei

Interacts with SYT2 (By similarity). Interacts with WNK3 and WNK4 (By similarity). Interacts with KLHL3 (PubMed:23387299, PubMed:23576762). Isoform 3: Interacts with isoform 1 (By similarity).By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi122403, 71 interactors
CORUMiQ9H4A3
DIPiDIP-32648N
ELMiQ9H4A3
IntActiQ9H4A3, 65 interactors
MINTiQ9H4A3
STRINGi9606.ENSP00000313059

Chemistry databases

BindingDBiQ9H4A3

Structurei

Secondary structure

12382
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9H4A3
SMRiQ9H4A3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini221 – 479Protein kinasePROSITE-ProRule annotationAdd BLAST259

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni488 – 555Autoinhibitory domainBy similarityAdd BLAST68

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0584 Eukaryota
ENOG410XQWZ LUCA
GeneTreeiENSGT00800000124049
HOVERGENiHBG048577
InParanoidiQ9H4A3
KOiK08867
OMAiHFLPMGQ
OrthoDBiEOG091G06LL
PhylomeDBiQ9H4A3
TreeFamiTF315363

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR024678 Kinase_OSR1/WNK_CCT
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF12202 OSR1_C, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (6+)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket
Note: WNK1 is a complex 33-exons gene, in total 9 WNK1 exons are alternatively spliced, some expressed in a tissue-specific manner. Additional isoforms seems to exist.

This entry has 6 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All

Isoform 11 Publication (identifier: Q9H4A3-1) [UniParc]FASTAAdd to basket
Also known as: L-WNK1

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
MSGGAAEKQS STPGSLFLSP PAPAPKNGSS SDSSVGEKLG AAAADAVTGR 
        60         70         80         90        100
TEEYRRRRHT MDKDSRGAAA TTTTTEHRFF RRSVICDSNA TALELPGLPL 
       110        120        130        140        150
SLPQPSIPAA VPQSAPPEPH REETVTATAT SQVAQQPPAA AAPGEQAVAG 
       160        170        180        190        200
PAPSTVPSST SKDRPVSQPS LVGSKEEPPP ARSGSGGGSA KEPQEERSQQ 
       210        220        230        240        250
QDDIEELETK AVGMSNDGRF LKFDIEIGRG SFKTVYKGLD TETTVEVAWC 
       260        270        280        290        300
ELQDRKLTKS ERQRFKEEAE MLKGLQHPNI VRFYDSWEST VKGKKCIVLV 
       310        320        330        340        350
TELMTSGTLK TYLKRFKVMK IKVLRSWCRQ ILKGLQFLHT RTPPIIHRDL 
       360        370        380        390        400
KCDNIFITGP TGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD 
       410        420        430        440        450
ESVDVYAFGM CMLEMATSEY PYSECQNAAQ IYRRVTSGVK PASFDKVAIP 
       460        470        480        490        500
EVKEIIEGCI RQNKDERYSI KDLLNHAFFQ EETGVRVELA EEDDGEKIAI 
       510        520        530        540        550
KLWLRIEDIK KLKGKYKDNE AIEFSFDLER DVPEDVAQEM VESGYVCEGD 
       560        570        580        590        600
HKTMAKAIKD RVSLIKRKRE QRQLVREEQE KKKQEESSLK QQVEQSSASQ 
       610        620        630        640        650
TGIKQLPSAS TGIPTASTTS ASVSTQVEPE EPEADQHQQL QYQQPSISVL 
       660        670        680        690        700
SDGTVDSGQG SSVFTESRVS SQQTVSYGSQ HEQAHSTGTV PGHIPSTVQA 
       710        720        730        740        750
QSQPHGVYPP SSVAQGQSQG QPSSSSLTGV SSSQPIQHPQ QQQGIQQTAP 
       760        770        780        790        800
PQQTVQYSLS QTSTSSEATT AQPVSQPQAP QVLPQVSAGK QLPVSQPVPT 
       810        820        830        840        850
IQGEPQIPVA TQPSVVPVHS GAHFLPVGQP LPTPLLPQYP VSQIPISTPH 
       860        870        880        890        900
VSTAQTGFSS LPITMAAGIT QPLLTLASSA TTAAIPGVST VVPSQLPTLL 
       910        920        930        940        950
QPVTQLPSQV HPQLLQPAVQ SMGIPANLGQ AAEVPLSSGD VLYQGFPPRL 
       960        970        980        990       1000
PPQYPGDSNI APSSNVASVC IHSTVLSPPM PTEVLATPGY FPTVVQPYVE 
      1010       1020       1030       1040       1050
SNLLVPMGGV GGQVQVSQPG GSLAQAPTTS SQQAVLESTQ GVSQVAPAEP 
      1060       1070       1080       1090       1100
VAVAQTQATQ PTTLASSVDS AHSDVASGMS DGNENVPSSS GRHEGRTTKR 
      1110       1120       1130       1140       1150
HYRKSVRSRS RHEKTSRPKL RILNVSNKGD RVVECQLETH NRKMVTFKFD 
      1160       1170       1180       1190       1200
LDGDNPEEIA TIMVNNDFIL AIERESFVDQ VREIIEKADE MLSEDVSVEP 
      1210       1220       1230       1240       1250
EGDQGLESLQ GKDDYGFSGS QKLEGEFKQP IPASSMPQQI GIPTSSLTQV 
      1260       1270       1280       1290       1300
VHSAGRRFIV SPVPESRLRE SKVFPSEITD TVAASTAQSP GMNLSHSASS 
      1310       1320       1330       1340       1350
LSLQQAFSEL RRAQMTEGPN TAPPNFSHTG PTFPVVPPFL SSIAGVPTTA 
      1360       1370       1380       1390       1400
AATAPVPATS SPPNDISTSV IQSEVTVPTE EGIAGVATST GVVTSGGLPI 
      1410       1420       1430       1440       1450
PPVSESPVLS SVVSSITIPA VVSISTTSPS LQVPTSTSEI VVSSTALYPS 
      1460       1470       1480       1490       1500
VTVSATSASA GGSTATPGPK PPAVVSQQAA GSTTVGATLT SVSTTTSFPS 
      1510       1520       1530       1540       1550
TASQLCIQLS SSTSTPTLAE TVVVSAHSLD KTSHSSTTGL AFSLSAPSSS 
      1560       1570       1580       1590       1600
SSPGAGVSSY ISQPGGLHPL VIPSVIASTP ILPQAAGPTS TPLLPQVPSI 
      1610       1620       1630       1640       1650
PPLVQPVANV PAVQQTLIHS QPQPALLPNQ PHTHCPEVDS DTQPKAPGID 
      1660       1670       1680       1690       1700
DIKTLEEKLR SLFSEHSSSG AQHASVSLET SLVIESTVTP GIPTTAVAPS 
      1710       1720       1730       1740       1750
KLLTSTTSTC LPPTNLPLGT VALPVTPVVT PGQVSTPVST TTSGVKPGTA 
      1760       1770       1780       1790       1800
PSKPPLTKAP VLPVGTELPA GTLPSEQLPP FPGPSLTQSQ QPLEDLDAQL 
      1810       1820       1830       1840       1850
RRTLSPEMIT VTSAVGPVSM AAPTAITEAG TQPQKGVSQV KEGPVLATSS 
      1860       1870       1880       1890       1900
GAGVFKMGRF QVSVAADGAQ KEGKNKSEDA KSVHFESSTS ESSVLSSSSP 
      1910       1920       1930       1940       1950
ESTLVKPEPN GITIPGISSD VPESAHKTTA SEAKSDTGQP TKVGRFQVTT 
      1960       1970       1980       1990       2000
TANKVGRFSV SKTEDKITDT KKEGPVASPP FMDLEQAVLP AVIPKKEKPE 
      2010       2020       2030       2040       2050
LSEPSHLNGP SSDPEAAFLS RDVDDGSGSP HSPHQLSSKS LPSQNLSQSL 
      2060       2070       2080       2090       2100
SNSFNSSYMS SDNESDIEDE DLKLELRRLR DKHLKEIQDL QSRQKHEIES 
      2110       2120       2130       2140       2150
LYTKLGKVPP AVIIPPAAPL SGRRRRPTKS KGSKSSRSSS LGNKSPQLSG 
      2160       2170       2180       2190       2200
NLSGQSAASV LHPQQTLHPP GNIPESGQNQ LLQPLKPSPS SDNLYSAFTS 
      2210       2220       2230       2240       2250
DGAISVPSLS APGQGTSSTN TVGATVNSQA AQAQPPAMTS SRKGTFTDDL 
      2260       2270       2280       2290       2300
HKLVDNWARD AMNLSGRRGS KGHMNYEGPG MARKFSAPGQ LCISMTSNLG 
      2310       2320       2330       2340       2350
GSAPISAASA TSLGHFTKSM CPPQQYGFPA TPFGAQWSGT GGPAPQPLGQ 
      2360       2370       2380 
FQPVGTASLQ NFNISNLQKS ISNPPGSNLR TT
Note: Strong expression in dorsal root ganglia and spinal cord.
Length:2,382
Mass (Da):250,794
Last modified:May 18, 2010 - v2
Checksum:i426785F98A452A0A
GO
Isoform 21 Publication (identifier: Q9H4A3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     740-740: Missing.
     792-1037: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:2,135
Mass (Da):225,560
Checksum:i2961D903C013A22C
GO
Isoform 3 (identifier: Q9H4A3-4) [UniParc]FASTAAdd to basket
Also known as: KS-WNK1, Kidney-Specific

The sequence of this isoform differs from the canonical sequence as follows:
     1-407: Missing.
     408-437: FGMCMLEMATSEYPYSECQNAAQIYRRVTS → MDIKKKDFCSVFVIINSHCCCCPQKDCINE

Note: Kinase-defective isoform. Produced by alternative promoter usage and alternative splicing.
Show »
Length:1,975
Mass (Da):206,646
Checksum:iB03B35C0321782D3
GO
Isoform 4 (identifier: Q9H4A3-5) [UniParc]FASTAAdd to basket
Also known as: Brain and spinal cord variant

The sequence of this isoform differs from the canonical sequence as follows:
     714-1037: AQGQSQGQPS...TTSSQQAVLE → PRRGRSMSVC...VLPQVSAGKQ

Note: Contains the nervous system-specific exon HSN2. Produced by alternative splicing.
Show »
Length:2,634
Mass (Da):279,538
Checksum:i2F95DCDA28619B4C
GO
Isoform 5 (identifier: Q9H4A3-6) [UniParc]FASTAAdd to basket
Also known as: Dorsal root ganglia and sciatic nerve variant, DRG and sciatic nerve variant

The sequence of this isoform differs from the canonical sequence as follows:
     713-713: V → VPQSMAHPCG...SSGGSALHPQ
     792-944: Missing.

Note: Contains the nervous system-specific exon HSN2. Produced by alternative splicing.
Show »
Length:2,642
Mass (Da):279,713
Checksum:iD0AB5C95ABFF46A4
GO
Isoform 6 (identifier: Q9H4A3-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     713-713: V → VPQSMAHPCG...SSGGSALHPQ
     2215-2215: G → GCAKFNCASEQVTFKPGGRRTRFLRKMVKKVCPCNQLCR

Note: Contains the nervous system-specific exon HSN2. Produced by alternative splicing.
Show »
Length:2,833
Mass (Da):299,725
Checksum:i24CA46FC81669858
GO

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5GWT4F5GWT4_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
2,134Annotation score:
F6UYG0F6UYG0_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
393Annotation score:
A0A0B4J299A0A0B4J299_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
434Annotation score:
H0YFF1H0YFF1_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
218Annotation score:
H0YF81H0YF81_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
76Annotation score:
I3L251I3L251_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
240Annotation score:
H0YH79H0YH79_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
176Annotation score:
H0YFK5H0YFK5_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
67Annotation score:
H0YFP5H0YFP5_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
245Annotation score:
H0YH68H0YH68_HUMAN
Serine/threonine-protein kinase WNK...
WNK1
194Annotation score:

Sequence cautioni

The sequence AAF31483 differs from that shown. Contaminating sequence. Sequence of unknown origin in the C-terminal part.Curated
The sequence AAI30468 differs from that shown. Probable cloning artifact.Curated
The sequence AAI30470 differs from that shown. Probable cloning artifact.Curated
The sequence DAA04494 differs from that shown. Reason: Erroneous gene model prediction. Includes 3' and 3' intronic sequences.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti164R → S AA sequence (PubMed:2507249).Curated1
Sequence conflicti1836Missing in BAA20802 (PubMed:9205841).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041309141A → T1 PublicationCorresponds to variant dbSNP:rs11554421EnsemblClinVar.1
Natural variantiVAR_041310149A → V1 PublicationCorresponds to variant dbSNP:rs34880640EnsemblClinVar.1
Natural variantiVAR_041311419E → Q in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041312509I → T1 PublicationCorresponds to variant dbSNP:rs34728563EnsemblClinVar.1
Natural variantiVAR_041313527D → G1 PublicationCorresponds to variant dbSNP:rs34408667Ensembl.1
Natural variantiVAR_019992665T → I1 PublicationCorresponds to variant dbSNP:rs2286007EnsemblClinVar.1
Natural variantiVAR_041314674T → A1 PublicationCorresponds to variant dbSNP:rs11833299EnsemblClinVar.1
Natural variantiVAR_041315823H → R1 PublicationCorresponds to variant dbSNP:rs56015776EnsemblClinVar.1
Natural variantiVAR_0590331056T → P3 PublicationsCorresponds to variant dbSNP:rs956868EnsemblClinVar.1
Natural variantiVAR_0356401199E → G in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_0590341506C → S3 PublicationsCorresponds to variant dbSNP:rs7955371EnsemblClinVar.1
Natural variantiVAR_0413161546A → V1 PublicationCorresponds to variant dbSNP:rs56351358Ensembl.1
Natural variantiVAR_0356411799Q → E in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications1
Natural variantiVAR_0413171808M → I3 PublicationsCorresponds to variant dbSNP:rs12828016EnsemblClinVar.1
Natural variantiVAR_0413181823P → L1 PublicationCorresponds to variant dbSNP:rs17755373EnsemblClinVar.1
Natural variantiVAR_0413191957R → H1 PublicationCorresponds to variant dbSNP:rs36083875Ensembl.1
Natural variantiVAR_0413202190S → C in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0413212362F → L in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0413222380R → W1 PublicationCorresponds to variant dbSNP:rs56262445EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0506341 – 407Missing in isoform 3. CuratedAdd BLAST407
Alternative sequenceiVSP_050637408 – 437FGMCM…RRVTS → MDIKKKDFCSVFVIINSHCC CCPQKDCINE in isoform 3. CuratedAdd BLAST30
Alternative sequenceiVSP_040267713V → VPQSMAHPCGGTPTYPESQI FFPTIHERPVSFSPPPTCPP KVAISQRRKSTSFLEAQTHH FQPLLRTVGQSLLPPGGSPT NWTPEAVVMLGTTASRVTGE SCEIQVHPMFEPSQVYSDYR PGLVLPEEAHYFIPQEAVYV AGVHYQARVAEQYEGIPYNS SVLSSPMKQIPEQKPVQGGP TSSSVFEFPSGQAFLVGHLQ NLRLDSGLGPGSPLSSISAP ISTDATRLKFHPVFVPHSAP AVLTHNNESRSNCVFEFHVH TPSSSSGEGGGILPQRVYRN RQVAVDLNQEELPPQSVGLH GYLQPVTEEKHNYHAPELTV SVVEPIGQNWPIGSPEYSSD SSQITSSDPSDFQSPPPTGG AAAPFGSDVSMPFIHLPQTV LQESPLFFCFPQGTTSQQVL TASFSSGGSALHPQ in isoform 5 and isoform 6. 1 Publication1
Alternative sequenceiVSP_040268714 – 1037AQGQS…QAVLE → PRRGRSMSVCVPIFLLLPLC PASLPVLFHPTASTVCTSFS FPPPDCPEETFAEKLSKALE SVLPMHSASQRKHRRSSLPS LFVSTPQSMAHPCGGTPTYP ESQIFFPTIHERPVSFSPPP TCPPKVAISQRRKSTSFLEA QTHHFQPLLRTVGQSLLPPG GSPTNWTPEAVVMLGTTASR VTGESCEIQVHPMFEPSQVY SDYRPGLVLPEEAHYFIPQE AVYVAGVHYQARVAEQYEGI PYNSSVLSSPMKQIPEQKPV QGGPTSSSVFEFPSGQAFLV GHLQNLRLDSGLGPGSPLSS ISAPISTDATRLKFHPVFVP HSAPAVLTHNNESRSNCVFE FHVHTPSSSSGEGGGILPQR VYRNRQVAVDLNQEELPPQS VGLHGYLQPVTEEKHNYHAP ELTVSVVEPIGQNWPIGSPE YSSDSSQITSSDPSDFQSPP PTGGAAAPFGSDVSMPFIHL PQTVLQESPLFFCFPQGTTS QQVLTASFSSGGSALHPQAQ GQSQGQPSSSSLTGVSSSQP IQHPQQQQGIQQTAPPQQTV QYSLSQTSTSSEATTAQPVS QPQAPQVLPQVSAGKQ in isoform 4. CuratedAdd BLAST324
Alternative sequenceiVSP_040269740Missing in isoform 2. 1 Publication1
Alternative sequenceiVSP_050638792 – 1037Missing in isoform 2. 1 PublicationAdd BLAST246
Alternative sequenceiVSP_040270792 – 944Missing in isoform 5. CuratedAdd BLAST153
Alternative sequenceiVSP_0537672215G → GCAKFNCASEQVTFKPGGRR TRFLRKMVKKVCPCNQLCR in isoform 6. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ296290 mRNA Translation: CAC15059.1
JQ358908 mRNA Translation: AEY99342.1
FJ515833 Genomic DNA Translation: ACS13726.1
FJ515833 Genomic DNA Translation: ACS13727.1
FJ515833 Genomic DNA Translation: ACS13728.1
AC004765 Genomic DNA No translation available.
AC004803 Genomic DNA No translation available.
AF061944 mRNA Translation: AAF31483.1 Sequence problems.
AB002342 mRNA Translation: BAA20802.2
AY231477 mRNA Translation: AAO46160.1
BC013629 mRNA Translation: AAH13629.2
BC130467 mRNA Translation: AAI30468.1 Sequence problems.
BC130469 mRNA Translation: AAI30470.1 Sequence problems.
BK004108 Genomic DNA Translation: DAA04494.1 Sequence problems.
CCDSiCCDS73419.1 [Q9H4A3-5]
CCDS8506.1 [Q9H4A3-1]
RefSeqiNP_001171914.1, NM_001184985.1 [Q9H4A3-6]
NP_055638.2, NM_014823.2
NP_061852.3, NM_018979.3 [Q9H4A3-1]
NP_998820.3, NM_213655.4 [Q9H4A3-5]
XP_016875326.1, XM_017019837.1
XP_016875327.1, XM_017019838.1 [Q9H4A3-2]
UniGeneiHs.744906

Genome annotation databases

EnsembliENST00000315939; ENSP00000313059; ENSG00000060237 [Q9H4A3-1]
ENST00000340908; ENSP00000341292; ENSG00000060237 [Q9H4A3-5]
ENST00000530271; ENSP00000433548; ENSG00000060237 [Q9H4A3-7]
ENST00000537687; ENSP00000444465; ENSG00000060237 [Q9H4A3-6]
GeneIDi65125
KEGGihsa:65125
UCSCiuc001qio.4 human [Q9H4A3-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ296290 mRNA Translation: CAC15059.1
JQ358908 mRNA Translation: AEY99342.1
FJ515833 Genomic DNA Translation: ACS13726.1
FJ515833 Genomic DNA Translation: ACS13727.1
FJ515833 Genomic DNA Translation: ACS13728.1
AC004765 Genomic DNA No translation available.
AC004803 Genomic DNA No translation available.
AF061944 mRNA Translation: AAF31483.1 Sequence problems.
AB002342 mRNA Translation: BAA20802.2
AY231477 mRNA Translation: AAO46160.1
BC013629 mRNA Translation: AAH13629.2
BC130467 mRNA Translation: AAI30468.1 Sequence problems.
BC130469 mRNA Translation: AAI30470.1 Sequence problems.
BK004108 Genomic DNA Translation: DAA04494.1 Sequence problems.
CCDSiCCDS73419.1 [Q9H4A3-5]
CCDS8506.1 [Q9H4A3-1]
RefSeqiNP_001171914.1, NM_001184985.1 [Q9H4A3-6]
NP_055638.2, NM_014823.2
NP_061852.3, NM_018979.3 [Q9H4A3-1]
NP_998820.3, NM_213655.4 [Q9H4A3-5]
XP_016875326.1, XM_017019837.1
XP_016875327.1, XM_017019838.1 [Q9H4A3-2]
UniGeneiHs.744906

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PWNX-ray1.84A210-482[»]
5TF9X-ray2.50A/B206-483[»]
5WDYX-ray2.46A/B206-483[»]
5WE8X-ray2.01A/B206-483[»]
6FBKX-ray1.74P1247-1269[»]
ProteinModelPortaliQ9H4A3
SMRiQ9H4A3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122403, 71 interactors
CORUMiQ9H4A3
DIPiDIP-32648N
ELMiQ9H4A3
IntActiQ9H4A3, 65 interactors
MINTiQ9H4A3
STRINGi9606.ENSP00000313059

Chemistry databases

BindingDBiQ9H4A3
ChEMBLiCHEMBL1075173
GuidetoPHARMACOLOGYi2280

Protein family/group databases

MoonDBiQ9H4A3 Predicted

PTM databases

iPTMnetiQ9H4A3
PhosphoSitePlusiQ9H4A3

Polymorphism and mutation databases

BioMutaiWNK1
DMDMi296453029

Proteomic databases

EPDiQ9H4A3
MaxQBiQ9H4A3
PaxDbiQ9H4A3
PeptideAtlasiQ9H4A3
PRIDEiQ9H4A3
ProteomicsDBi80804
80805 [Q9H4A3-2]
80806 [Q9H4A3-4]
80807 [Q9H4A3-5]
80808 [Q9H4A3-6]

Protocols and materials databases

DNASUi65125
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000315939; ENSP00000313059; ENSG00000060237 [Q9H4A3-1]
ENST00000340908; ENSP00000341292; ENSG00000060237 [Q9H4A3-5]
ENST00000530271; ENSP00000433548; ENSG00000060237 [Q9H4A3-7]
ENST00000537687; ENSP00000444465; ENSG00000060237 [Q9H4A3-6]
GeneIDi65125
KEGGihsa:65125
UCSCiuc001qio.4 human [Q9H4A3-1]

Organism-specific databases

CTDi65125
DisGeNETi65125
EuPathDBiHostDB:ENSG00000060237.16
GeneCardsiWNK1
GeneReviewsiWNK1
H-InvDBiHIX0010312
HGNCiHGNC:14540 WNK1
HPAiHPA046541
HPA059157
MalaCardsiWNK1
MIMi201300 phenotype
605232 gene
614492 phenotype
neXtProtiNX_Q9H4A3
OpenTargetsiENSG00000060237
Orphaneti970 Hereditary sensory and autonomic neuropathy type 2
88940 Pseudohypoaldosteronism type 2C
PharmGKBiPA134944932
PA33782
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0584 Eukaryota
ENOG410XQWZ LUCA
GeneTreeiENSGT00800000124049
HOVERGENiHBG048577
InParanoidiQ9H4A3
KOiK08867
OMAiHFLPMGQ
OrthoDBiEOG091G06LL
PhylomeDBiQ9H4A3
TreeFamiTF315363

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
SignaLinkiQ9H4A3
SIGNORiQ9H4A3

Miscellaneous databases

ChiTaRSiWNK1 human
GeneWikiiWNK1
GenomeRNAii65125
PROiPR:Q9H4A3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000060237 Expressed in 240 organ(s), highest expression level in corpus callosum
CleanExiHS_WNK1
ExpressionAtlasiQ9H4A3 baseline and differential
GenevisibleiQ9H4A3 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR024678 Kinase_OSR1/WNK_CCT
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF12202 OSR1_C, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiWNK1_HUMAN
AccessioniPrimary (citable) accession number: Q9H4A3
Secondary accession number(s): A1L4B0
, C5HTZ5, C5HTZ6, C5HTZ7, H6WZW3, O15052, P54963, Q4VBX9, Q6IFS5, Q86WL5, Q8N673, Q96CZ6, Q9P1S9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 190 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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