Reviewed, UniProtKB/Swiss-Prot Q9JIH7 (WNK1_RAT)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase WNK1
    EC=2.7.11.1
Alternative name(s):
    Protein kinase with no lysine 1
    Protein kinase, lysine-deficient 1

Gene names

Name:	Wnk1
Synonyms:	Prkwnk1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	2126 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Controls sodium and chloride ion transport by inhibiting the activity of WNK4, potentially 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 By similarity. UniProtKB Q9H4A3 UniProtKB P83741
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1
Cofactor	Magnesium. Ref.1
Enzyme regulation	By hypertonicity. Activation requires autophosphorylation of Ser-382. Phosphorylation of Ser-378 also promotes increased activity. Ref.1 Ref.2
Subunit structure	Interacts with SYT2. Ref.3
Subcellular location	Cytoplasm Ref.1.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. Contains 1 protein kinase domain.
Caution	Cys-250 is present instead of the conserved Lys which is expected to be an active site residue. Lys-233 appears to fulfill the required catalytic function. Ref.1 Ref.2

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Protein kinase inhibitor Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	ion transport Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of kinase activity Inferred from direct assay. Source: RGD protein amino acid autophosphorylation Ref.1 Inferred from direct assay. Source: RGD protein kinase cascade Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: UniProtKB insoluble fraction Ref.1 Inferred from direct assay. Source: RGD
Molecular function	ATP binding Ref.1 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.1 Inferred from mutant phenotype. Source: RGD potassium channel inhibitor activity Inferred from direct assay. Source: RGD protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB protein serine/threonine kinase inhibitor activity Inferred from direct assay. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Syt2	P29101	2	EBI-457953,EBI-458017

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2126

2126

Serine/threonine-protein kinase WNK1

PRO_0000086821

Regions

Domain

221 – 479

259

Protein kinase

Nucleotide binding

227 – 235

9

ATP By similarity UniProtKB Q8TDX7

Sites

Active site

349

1

Proton acceptor By similarity UniProtKB Q8TDX7

Binding site

233

1

ATP Ref.1

Amino acid modifications

Modified residue

17

1

Phosphoserine By similarity

Modified residue

165

1

Phosphoserine By similarity

Modified residue

172

1

Phosphoserine By similarity

Modified residue

378

1

Phosphoserine; by autocatalysis Ref.2

Modified residue

382

1

Phosphoserine; by autocatalysis Ref.2

Modified residue

1007

1

Phosphoserine By similarity

Modified residue

1043

1

Phosphoserine By similarity

Modified residue

1046

1

Phosphoserine By similarity

Modified residue

1723

1

Phosphoserine By similarity

Modified residue

1755

1

Phosphoserine By similarity

Modified residue

1756

1

Phosphoserine By similarity

Modified residue

1771

1

Phosphoserine By similarity

Modified residue

1773

1

Phosphoserine By similarity

Modified residue

1776

1

Phosphoserine By similarity

Modified residue

1782

1

Phosphoserine By similarity

Modified residue

1865

1

Phosphoserine By similarity

Modified residue

2116

1

Phosphoserine By similarity

Experimental info

Mutagenesis

233

1

K → G: Loss of kinase activity; when associated with K-250. Ref.1 Ref.2

Mutagenesis

233

1

K → M: Loss of kinase activity. Ref.1 Ref.2

Mutagenesis

250

1

C → A: No effect on kinase activity. Ref.1 Ref.2

Mutagenesis

250

1

C → K: Reduced kinase activity. Loss of kinase activity; when associated with G-233. Ref.1 Ref.2

Mutagenesis

256

1

K → M: No effect on kinase activity. Ref.1

Mutagenesis

259

1

K → M: No effect on kinase activity. Ref.1

Mutagenesis

378

1

S → A: Reduced kinase activity. Ref.2

Mutagenesis

378

1

S → D: Increased kinase activity. Ref.2

Mutagenesis

382

1

S → A: Loss of kinase activity. Ref.2

Mutagenesis

382

1

S → D: Loss of kinase activity. Ref.2

Mutagenesis

524

1

F → A: Reduced ability of autoinhibitory domain to regulate kinase activity. Ref.2

Mutagenesis

526

1

F → A: Reduced ability of autoinhibitory domain to regulate kinase activity. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

2126

Helix Strand Turn

Details...

Beta strand

220 – 229

10

Beta strand

231 – 240

10

Turn

241 – 243

3

Beta strand

246 – 253

8

Helix

254 – 256

3

Helix

259 – 272

14

Beta strand

283 – 293

11

Beta strand

295 – 302

8

Helix

309 – 316

8

Helix

321 – 339

19

Beta strand

341 – 343

3

Helix

352 – 354

3

Beta strand

355 – 359

5

Beta strand

364 – 366

3

Helix

371 – 374

4

Beta strand

379 – 383

5

Helix

392 – 396

5

Helix

402 – 417

16

Turn

421 – 424

4

Helix

428 – 435

8

Turn

436 – 438

3

Helix

442 – 446

5

Helix

450 – 459

10

Helix

464 – 466

3

Helix

470 – 474

5

Helix

477 – 479

3

Sequences

	Sequence		Length	Mass (Da)
	Q9JIH7-1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 7137BCC45A54402F	FASTA	2,126	225,216
	10 20 30 40 50 60 MSDGTAEKQS GTPGFLSPPA PVPKNGSSSD SSVGEKLGAA VADSGIGRTE EYRRRRHTMD 70 80 90 100 110 120 KDSRGAAATT TPTEHRFFRR SVICDSNATA LELPGLPLSI PQPSVPAVVP QSAPPEPHRE 130 140 150 160 170 180 ETLTATVASQ VSQQPSAAAS PGEQAVVGSA TATVPSSTSK DRPVSQPSLV GSKEEPPPSR 190 200 210 220 230 240 SGSGSGGASA KEPQEERNQQ QDDIEELETK AVGMSNDGRF LKFDIEIGRG SFKTVYKGLD 250 260 270 280 290 300 TETTVEVAWC ELQDRKLTKS ERQRFKEEAE MLKGLQHPNI VRFYDSWEST VKGKKCIVLV 310 320 330 340 350 360 TELMTSGTLK TYLKRFKVMK IKVLRSWCRQ ILKGLQFLHT RTPPIIHRDL KCDNIFITGP 370 380 390 400 410 420 TGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD ESVDVYAFGM CMLEMATSEY 430 440 450 460 470 480 PYSECQNAAQ IYRRVTSGVK PASFDKVAIP EVKEIIEGCI RQNKDERYSI KDLLNHAFFQ 490 500 510 520 530 540 EETGVRVELA EEDDGEKIAI KLWLRIEDIK KLKGKYKDNE AIEFSFDLER DVPEDVAQEM 550 560 570 580 590 600 VESGYVCEGD HKTMAKAIKD RVSLIKRKRE QRQLVREEQE KRKQEESSFK QQNEQQASVS 610 620 630 640 650 660 QAGIQPLSVA STGIPTAPTT SASVSTQVEP EEPEADQHQQ LQYQQPSISV LSDGTVDSGQ 670 680 690 700 710 720 GSSVFTESRV SSQQTVSYGS QHEQAHSIGT APGHTVSSIQ AQSQPHGVYP PSSMAQGQNQ 730 740 750 760 770 780 GQPSSSLAGV LSSQPVQHPQ QQGIQPTVPP QQAVQYSLPQ AASSSEGTVQ PVSQPQVSAG 790 800 810 820 830 840 TQSSTQGVSQ AAPPEQTPIT QSQPTQPVPL VSSVDSAHSD VASGMSDGNE NAPSSSGRHE 850 860 870 880 890 900 GRTTKRHYRK SVRSRSRHEK TSRPKLRILN VSNKGDRVVE CQLETHNRKM VTFKFDLDGD 910 920 930 940 950 960 NPEEIATIMV NNDFILAIER ESFVAQVREI IEKADEMLSE DVSVEPEGDQ GLESLQGKDD 970 980 990 1000 1010 1020 YGFPGSQKLE GEFKQPIAVS SMPQQIGVPT SSLTQVVHSA GRRFIVSPVP ESRLRESKIF 1030 1040 1050 1060 1070 1080 TSEIPDPVAA STSQGPGMNL SHSASSLSLQ QAFSELKHGQ MTEGPNTAPP NFNHPGPTFS 1090 1100 1110 1120 1130 1140 PFLTSIAGVQ TVAASTPSVS VPITSSPLND ISTSVMQSEG ALPTDKGIGG VTTSTGVVAS 1150 1160 1170 1180 1190 1200 GGLTTLSVSE TPTLSSAVSS STAPAVVTVS TTSQPVQAFT SGSIASSTGS FPSGTFSTTT 1210 1220 1230 1240 1250 1260 GTTVSSVAVP NAKPPTVLLQ QVAGNTAGVA IVTSVSTTTP FPAMASQPSL PLGSSTSAPT 1270 1280 1290 1300 1310 1320 LAETVVVSAH SLDKASHSST AGLGLSFCAP SSSSSSGTAV SSSVSQPGIV HPLVISSAIA 1330 1340 1350 1360 1370 1380 STPVLPQPAV PTSTPLLPQV PNIPPLVQPV ANVPAVQQTL IHSQPQPALL PNQPHTHCPE 1390 1400 1410 1420 1430 1440 MDADTQSKAP GIDDIKTLEE KLRSLFSEHS SSGTQHASVS LETPLVVETV TPGIPTTAVA 1450 1460 1470 1480 1490 1500 PSKLMTSTTS TCLPPTNLPL GTAGMPVMPV GTPGQVSTPG THASAPASTA TGAKPGTTPP 1510 1520 1530 1540 1550 1560 KPSLTKTVVP PVGTELSAGT VPCEQLPPFP GPSLIQTQQP LEDLDAQLRR TLSPETIPVT 1570 1580 1590 1600 1610 1620 PAVGPLSTMS STAVTEAGSQ PQKDGTEVHV TASSSGAGVV KMGRFQVSVT MDDAQKERKN 1630 1640 1650 1660 1670 1680 RSEDTKSVHF ESSTSESSVL SSSSPESTLV KPEPNGITVS GISLDVPDST HRTPTPEAKS 1690 1700 1710 1720 1730 1740 ETGQPTKVGR FQVTTTANKV GRFSVSRTED KVTELKKEGP VTSPFRDSEQ TVIPAAIPKK 1750 1760 1770 1780 1790 1800 EKPELAEPSH LNGPSSDLEA AFLSRGGEDG SGSPHSPPHL CSKSLPIQTL SQSLSNSFNS 1810 1820 1830 1840 1850 1860 SYMSSDNESD IEDEDLRLEL RRLREKHLKE IQDLQSRQKH EIESLYTKLG KVPPAVIIPP 1870 1880 1890 1900 1910 1920 AAPLSGRRRR PTKSKGSKSS RSSSLGNKSP QLSGNLSGQS GTSVLNPQQT LHPPGNTPET 1930 1940 1950 1960 1970 1980 GHNQLLQPLK PSPSSDNLYS AFTSDGAISI PSLSAPGQGT SSTNTVGGTV SSQAAQAQPP 1990 2000 2010 2020 2030 2040 AMTSSRKGTF TDDLHKLVDN WARDAMNLSG RRGSKGHMNY EGPGMARKFS APGQLCISMT 2050 2060 2070 2080 2090 2100 SNMGGSTPIS AASATSLGHF TKSMCPPQQY GFPAAPFGTQ WSGTGGPAPQ PLGQFQPVGT 2110 2120 TSLQNFNISN LQKSISNPPS SNLRTT

References

[1]	"WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II." Xu B.-E., English J.M., Wilsbacher J.L., Stippec S., Goldsmith E.J., Cobb M.H. J. Biol. Chem. 275:16795-16801(2000) [PubMed: 10828064] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-233; CYS-250; LYS-256 AND LYS-259.
[2]	"Regulation of WNK1 by an autoinhibitory domain and autophosphorylation." Xu B.-E., Min X., Stippec S., Lee B.H., Goldsmith E.J., Cobb M.H. J. Biol. Chem. 277:48456-48462(2002) [PubMed: 12374799] [Abstract] Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-378 AND SER-382, MUTAGENESIS OF LYS-233; CYS-250; SER-378; SER-382; PHE-524 AND PHE-526.
[3]	"Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension." Min X., Lee B.-H., Cobb M.H., Goldsmith E.J. Structure 12:1303-1311(2004) [PubMed: 15242606] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 194-483 OF MUTANT ALA-382, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF227741 mRNA. Translation: AAF74258.1.

IPI

IPI00200557.

RefSeq

NP_446246.1.

UniGene

Rn.27409

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3FPQ	X-ray	1.80	A/B	194-483	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9JIH7. 7 interactions.

STRING

Q9JIH7.

PTM databases

PhosphoSite

Q9JIH7.

Genome annotation databases

Ensembl

ENSRNOT00000013621; ENSRNOP00000013622; ENSRNOG00000009956; Rattus norvegicus. [Genome view]

GeneID

116477.

KEGG

rno:116477.

Organism-specific databases

CTD

116477.

RGD

621141. Prkwnk1.

Phylogenomic databases

HOVERGEN

Q9JIH7.

Enzyme and pathway databases

BRENDA

2.7.11.1. 248.

Gene expression databases

ArrayExpress

Q9JIH7.

Genevestigator

Q9JIH7.

GermOnline

ENSRNOG00000009956. Rattus norvegicus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

619039.

Entry information

Entry name

WNK1_RAT

Accession

Primary (citable) accession number: Q9JIH7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	October 1, 2000
Last modified:	November 24, 2009
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)