Q9JIH7 (WNK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase WNK1
EC=2.7.11.1

Alternative name(s):
Protein kinase lysine-deficient 1
Protein kinase with no lysine 1

Gene names

Name:	Wnk1
Synonyms:	Hsn2, 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.
Protein existence	Evidence at protein 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 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. Ref.5 Ref.6
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.4
Subunit structure	Interacts with SYT2. Interacts with WNK3 and WNK4. Ref.5 Ref.7
Subcellular location	Cytoplasm Ref.1.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. Ref.4
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.4 HSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron. It has been shown to be an alternative exon of the WNK1 gene in other mammalian species, including human and mouse. Isoforms bearing this exon (isoform 2 and isoform 3 in this entry) are specifically expressed in the nervous system in these species. system.
Sequence caution	The sequence DAA04492.1 differs from that shown. Reason: Erroneous gene model prediction. Includes 3' and 3' intronic sequences.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Protein kinase inhibitor Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular protein kinase cascade Inferred from direct assay Ref.1. Source: UniProtKB ion transport Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.1. Source: RGD
Cellular component	cytoplasm Inferred from direct assay Ref.1. Source: UniProtKB insoluble fraction Inferred from direct assay Ref.1. Source: RGD
Molecular function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB magnesium ion binding Inferred from mutant phenotype Ref.1. Source: RGD phosphatase binding Inferred from sequence or structural similarity. Source: UniProtKB potassium channel inhibitor activity Inferred from direct assay. Source: RGD protein kinase binding Inferred from physical interaction. Source: RGD protein serine/threonine kinase activity Inferred from direct assay Ref.1. 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	9	EBI-457953,EBI-458017

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9JIH7-1)

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: Q9JIH7-3)

Also known as: Brain and spinal cord variant;

The sequence of this isoform differs from the canonical sequence as follows:
     714-714: M → MPRRGRSMSV...SSGGSALHPQ

Note: This isoform which includes the HSN2 exon has been identified in human and mouse. The sequence shown here is the result of gene prediction.

Isoform 3 (identifier: Q9JIH7-2)

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:
     714-714: M → MPQSVAHPCG...SSGGSALHPQ
     782-782: Q → QGFPSRLPPQ...TTSSQQAVLE

Note: This isoform which includes the HSN2 exon has been identified in human and mouse. The sequence shown here is the result of gene prediction.

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.4

Modified residue

382

1

Phosphoserine; by autocatalysis Ref.4

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

Natural variations

Alternative sequence

714

1

M → MPRRGRSMSVCVPHLSAVPS LSRISPSAPSTPPPVLSAPL CPSLLRSAPEETFAEKLSKA LESVLPMHSASQRKHRRSSL PSLFVTTPQSVAHPCGGTPT YPESQIFFPTIHERPVSFSP PPTCPPKVAISQRRKSTSFL EAQTRHFQPLLRTVGQNHLP PGGSPTNWTPEAIVMLGTTA NRVNRELCEMQVQPVFETTQ IYSDYRPGLVLAEEAHYFIP QETVYLAGVHYQAHAAGQYE GISYNSPVLSSPMKQITEQK PVPGCPASSSVFEFPSGQAF LVGHLQNLRLDSGPSPASPL SSISAPNSTDATHLKFHPVF VPHSAPAVLTHSNENRSNCV FEFHAQTPSSSSGEGGGILP QRVYRNRQVAVDSSQEELSP QSVGLHCHLQPVTEEQRNNH TPELTISVVEPMGQNWPVGS PEYSSDSSQITSSDISDFQS PPPTGGTAAPFGSDVSLPYI RLPQTVLQESPLFFCFPQGT TSQQVLSASYSSGGSALHPQ in isoform 2.

VSP_040279

Alternative sequence

714

1

M → MPQSVAHPCGGTPTYPESQI FFPTIHERPVSFSPPPTCPP KVAISQRRKSTSFLEAQTRH FQPLLRTVGQNHLPPGGSPT NWTPEAIVMLGTTANRVNRE LCEMQVQPVFETTQIYSDYR PGLVLAEEAHYFIPQETVYL AGVHYQAHAAGQYEGISYNS PVLSSPMKQITEQKPVPGCP ASSSVFEFPSGQAFLVGHLQ NLRLDSGPSPASPLSSISAP NSTDATHLKFHPVFVPHSAP AVLTHSNENRSNCVFEFHAQ TPSSSSGEGGGILPQRVYRN RQVAVDSSQEELSPQSVGLH CHLQPVTEEQRNNHTPELTI SVVEPMGQNWPVGSPEYSSD SSQITSSDISDFQSPPPTGG TAAPFGSDVSLPYIRLPQTV LQESPLFFCFPQGTTSQQVL SASYSSGGSALHPQ in isoform 3.

VSP_040278

Alternative sequence

782

1

Q → QGFPSRLPPQYPGDSNIAPS SNVASVCIHSTVLAPPPMPT EALATQGYFPTVVQPYVEST PLVPMGSVGGQVQVSQPAVS LSQQPPTTSSQQAVLE in isoform 3.

VSP_040280

Experimental info

Mutagenesis

233

1

K → G: Loss of kinase activity; when associated with K-250. Ref.1 Ref.4

Mutagenesis

233

1

K → M: Loss of kinase activity. Ref.1 Ref.4

Mutagenesis

250

1

C → A: No effect on kinase activity. Ref.1 Ref.4

Mutagenesis

250

1

C → K: Reduced kinase activity. Loss of kinase activity; when associated with G-233. Ref.1 Ref.4

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.4

Mutagenesis

378

1

S → D: Increased kinase activity. Ref.4

Mutagenesis

382

1

S → A: Loss of kinase activity. Ref.4

Mutagenesis

382

1

S → D: Loss of kinase activity. Ref.4

Mutagenesis

524

1

F → A: Reduced ability of autoinhibitory domain to regulate kinase activity. Ref.4

Mutagenesis

526

1

F → A: Reduced ability of autoinhibitory domain to regulate kinase activity. Ref.4

Sequence conflict

1179

1

S → F in AAF74258. Ref.1

Sequence conflict

1950

1

V → I in AAF74258. Ref.1

Sequence conflict

2120

1

G → S in AAF74258. Ref.1

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)
	Isoform 1 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: 89AC72F9CC8B07DF	FASTA	2,126	225,112
	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 TTSQPVQAST 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 AFTSDGAISV 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 LQKSISNPPG SNLRTT
	Isoform 2 (Brain and spinal cord variant) [UniParc]. Checksum: 3A08561C46528F28	FASTA	2,625	278,978
	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 PSSMPRRGRS 730 740 750 760 770 780 MSVCVPHLSA VPSLSRISPS APSTPPPVLS APLCPSLLRS APEETFAEKL SKALESVLPM 790 800 810 820 830 840 HSASQRKHRR SSLPSLFVTT PQSVAHPCGG TPTYPESQIF FPTIHERPVS FSPPPTCPPK 850 860 870 880 890 900 VAISQRRKST SFLEAQTRHF QPLLRTVGQN HLPPGGSPTN WTPEAIVMLG TTANRVNREL 910 920 930 940 950 960 CEMQVQPVFE TTQIYSDYRP GLVLAEEAHY FIPQETVYLA GVHYQAHAAG QYEGISYNSP 970 980 990 1000 1010 1020 VLSSPMKQIT EQKPVPGCPA SSSVFEFPSG QAFLVGHLQN LRLDSGPSPA SPLSSISAPN 1030 1040 1050 1060 1070 1080 STDATHLKFH PVFVPHSAPA VLTHSNENRS NCVFEFHAQT PSSSSGEGGG ILPQRVYRNR 1090 1100 1110 1120 1130 1140 QVAVDSSQEE LSPQSVGLHC HLQPVTEEQR NNHTPELTIS VVEPMGQNWP VGSPEYSSDS 1150 1160 1170 1180 1190 1200 SQITSSDISD FQSPPPTGGT AAPFGSDVSL PYIRLPQTVL QESPLFFCFP QGTTSQQVLS 1210 1220 1230 1240 1250 1260 ASYSSGGSAL HPQAQGQNQG QPSSSLAGVL SSQPVQHPQQ QGIQPTVPPQ QAVQYSLPQA 1270 1280 1290 1300 1310 1320 ASSSEGTVQP VSQPQVSAGT QSSTQGVSQA APPEQTPITQ SQPTQPVPLV SSVDSAHSDV 1330 1340 1350 1360 1370 1380 ASGMSDGNEN APSSSGRHEG RTTKRHYRKS VRSRSRHEKT SRPKLRILNV SNKGDRVVEC 1390 1400 1410 1420 1430 1440 QLETHNRKMV TFKFDLDGDN PEEIATIMVN NDFILAIERE SFVAQVREII EKADEMLSED 1450 1460 1470 1480 1490 1500 VSVEPEGDQG LESLQGKDDY GFPGSQKLEG EFKQPIAVSS MPQQIGVPTS SLTQVVHSAG 1510 1520 1530 1540 1550 1560 RRFIVSPVPE SRLRESKIFT SEIPDPVAAS TSQGPGMNLS HSASSLSLQQ AFSELKHGQM 1570 1580 1590 1600 1610 1620 TEGPNTAPPN FNHPGPTFSP FLTSIAGVQT VAASTPSVSV PITSSPLNDI STSVMQSEGA 1630 1640 1650 1660 1670 1680 LPTDKGIGGV TTSTGVVASG GLTTLSVSET PTLSSAVSSS TAPAVVTVST TSQPVQASTS 1690 1700 1710 1720 1730 1740 GSIASSTGSF PSGTFSTTTG TTVSSVAVPN AKPPTVLLQQ VAGNTAGVAI VTSVSTTTPF 1750 1760 1770 1780 1790 1800 PAMASQPSLP LGSSTSAPTL AETVVVSAHS LDKASHSSTA GLGLSFCAPS SSSSSGTAVS 1810 1820 1830 1840 1850 1860 SSVSQPGIVH PLVISSAIAS TPVLPQPAVP TSTPLLPQVP NIPPLVQPVA NVPAVQQTLI 1870 1880 1890 1900 1910 1920 HSQPQPALLP NQPHTHCPEM DADTQSKAPG IDDIKTLEEK LRSLFSEHSS SGTQHASVSL 1930 1940 1950 1960 1970 1980 ETPLVVETVT PGIPTTAVAP SKLMTSTTST CLPPTNLPLG TAGMPVMPVG TPGQVSTPGT 1990 2000 2010 2020 2030 2040 HASAPASTAT GAKPGTTPPK PSLTKTVVPP VGTELSAGTV PCEQLPPFPG PSLIQTQQPL 2050 2060 2070 2080 2090 2100 EDLDAQLRRT LSPETIPVTP AVGPLSTMSS TAVTEAGSQP QKDGTEVHVT ASSSGAGVVK 2110 2120 2130 2140 2150 2160 MGRFQVSVTM DDAQKERKNR SEDTKSVHFE SSTSESSVLS SSSPESTLVK PEPNGITVSG 2170 2180 2190 2200 2210 2220 ISLDVPDSTH RTPTPEAKSE TGQPTKVGRF QVTTTANKVG RFSVSRTEDK VTELKKEGPV 2230 2240 2250 2260 2270 2280 TSPFRDSEQT VIPAAIPKKE KPELAEPSHL NGPSSDLEAA FLSRGGEDGS GSPHSPPHLC 2290 2300 2310 2320 2330 2340 SKSLPIQTLS QSLSNSFNSS YMSSDNESDI EDEDLRLELR RLREKHLKEI QDLQSRQKHE 2350 2360 2370 2380 2390 2400 IESLYTKLGK VPPAVIIPPA APLSGRRRRP TKSKGSKSSR SSSLGNKSPQ LSGNLSGQSG 2410 2420 2430 2440 2450 2460 TSVLNPQQTL HPPGNTPETG HNQLLQPLKP SPSSDNLYSA FTSDGAISVP SLSAPGQGTS 2470 2480 2490 2500 2510 2520 STNTVGGTVS SQAAQAQPPA MTSSRKGTFT DDLHKLVDNW ARDAMNLSGR RGSKGHMNYE 2530 2540 2550 2560 2570 2580 GPGMARKFSA PGQLCISMTS NMGGSTPISA ASATSLGHFT KSMCPPQQYG FPAAPFGTQW 2590 2600 2610 2620 SGTGGPAPQP LGQFQPVGTT SLQNFNISNL QKSISNPPGS NLRTT
	Isoform 3 (Dorsal root ganglia and sciatic nerve variant) (DRG and sciatic nerve variant) [UniParc]. Checksum: 16F6B2F0666858C7	FASTA	2,634	279,566
	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 PSSMPQSVAH 730 740 750 760 770 780 PCGGTPTYPE SQIFFPTIHE RPVSFSPPPT CPPKVAISQR RKSTSFLEAQ TRHFQPLLRT 790 800 810 820 830 840 VGQNHLPPGG SPTNWTPEAI VMLGTTANRV NRELCEMQVQ PVFETTQIYS DYRPGLVLAE 850 860 870 880 890 900 EAHYFIPQET VYLAGVHYQA HAAGQYEGIS YNSPVLSSPM KQITEQKPVP GCPASSSVFE 910 920 930 940 950 960 FPSGQAFLVG HLQNLRLDSG PSPASPLSSI SAPNSTDATH LKFHPVFVPH SAPAVLTHSN 970 980 990 1000 1010 1020 ENRSNCVFEF HAQTPSSSSG EGGGILPQRV YRNRQVAVDS SQEELSPQSV GLHCHLQPVT 1030 1040 1050 1060 1070 1080 EEQRNNHTPE LTISVVEPMG QNWPVGSPEY SSDSSQITSS DISDFQSPPP TGGTAAPFGS 1090 1100 1110 1120 1130 1140 DVSLPYIRLP QTVLQESPLF FCFPQGTTSQ QVLSASYSSG GSALHPQAQG QNQGQPSSSL 1150 1160 1170 1180 1190 1200 AGVLSSQPVQ HPQQQGIQPT VPPQQAVQYS LPQAASSSEG TVQPVSQPQV SAGTQGFPSR 1210 1220 1230 1240 1250 1260 LPPQYPGDSN IAPSSNVASV CIHSTVLAPP PMPTEALATQ GYFPTVVQPY VESTPLVPMG 1270 1280 1290 1300 1310 1320 SVGGQVQVSQ PAVSLSQQPP TTSSQQAVLE SSTQGVSQAA PPEQTPITQS QPTQPVPLVS 1330 1340 1350 1360 1370 1380 SVDSAHSDVA SGMSDGNENA PSSSGRHEGR TTKRHYRKSV RSRSRHEKTS RPKLRILNVS 1390 1400 1410 1420 1430 1440 NKGDRVVECQ LETHNRKMVT FKFDLDGDNP EEIATIMVNN DFILAIERES FVAQVREIIE 1450 1460 1470 1480 1490 1500 KADEMLSEDV SVEPEGDQGL ESLQGKDDYG FPGSQKLEGE FKQPIAVSSM PQQIGVPTSS 1510 1520 1530 1540 1550 1560 LTQVVHSAGR RFIVSPVPES RLRESKIFTS EIPDPVAAST SQGPGMNLSH SASSLSLQQA 1570 1580 1590 1600 1610 1620 FSELKHGQMT EGPNTAPPNF NHPGPTFSPF LTSIAGVQTV AASTPSVSVP ITSSPLNDIS 1630 1640 1650 1660 1670 1680 TSVMQSEGAL PTDKGIGGVT TSTGVVASGG LTTLSVSETP TLSSAVSSST APAVVTVSTT 1690 1700 1710 1720 1730 1740 SQPVQASTSG SIASSTGSFP SGTFSTTTGT TVSSVAVPNA KPPTVLLQQV AGNTAGVAIV 1750 1760 1770 1780 1790 1800 TSVSTTTPFP AMASQPSLPL GSSTSAPTLA ETVVVSAHSL DKASHSSTAG LGLSFCAPSS 1810 1820 1830 1840 1850 1860 SSSSGTAVSS SVSQPGIVHP LVISSAIAST PVLPQPAVPT STPLLPQVPN IPPLVQPVAN 1870 1880 1890 1900 1910 1920 VPAVQQTLIH SQPQPALLPN QPHTHCPEMD ADTQSKAPGI DDIKTLEEKL RSLFSEHSSS 1930 1940 1950 1960 1970 1980 GTQHASVSLE TPLVVETVTP GIPTTAVAPS KLMTSTTSTC LPPTNLPLGT AGMPVMPVGT 1990 2000 2010 2020 2030 2040 PGQVSTPGTH ASAPASTATG AKPGTTPPKP SLTKTVVPPV GTELSAGTVP CEQLPPFPGP 2050 2060 2070 2080 2090 2100 SLIQTQQPLE DLDAQLRRTL SPETIPVTPA VGPLSTMSST AVTEAGSQPQ KDGTEVHVTA 2110 2120 2130 2140 2150 2160 SSSGAGVVKM GRFQVSVTMD DAQKERKNRS EDTKSVHFES STSESSVLSS SSPESTLVKP 2170 2180 2190 2200 2210 2220 EPNGITVSGI SLDVPDSTHR TPTPEAKSET GQPTKVGRFQ VTTTANKVGR FSVSRTEDKV 2230 2240 2250 2260 2270 2280 TELKKEGPVT SPFRDSEQTV IPAAIPKKEK PELAEPSHLN GPSSDLEAAF LSRGGEDGSG 2290 2300 2310 2320 2330 2340 SPHSPPHLCS KSLPIQTLSQ SLSNSFNSSY MSSDNESDIE DEDLRLELRR LREKHLKEIQ 2350 2360 2370 2380 2390 2400 DLQSRQKHEI ESLYTKLGKV PPAVIIPPAA PLSGRRRRPT KSKGSKSSRS SSLGNKSPQL 2410 2420 2430 2440 2450 2460 SGNLSGQSGT SVLNPQQTLH PPGNTPETGH NQLLQPLKPS PSSDNLYSAF TSDGAISVPS 2470 2480 2490 2500 2510 2520 LSAPGQGTSS TNTVGGTVSS QAAQAQPPAM TSSRKGTFTD DLHKLVDNWA RDAMNLSGRR 2530 2540 2550 2560 2570 2580 GSKGHMNYEG PGMARKFSAP GQLCISMTSN MGGSTPISAA SATSLGHFTK SMCPPQQYGF 2590 2600 2610 2620 2630 PAAPFGTQWS GTGGPAPQPL GQFQPVGTTS LQNFNISNLQ KSISNPPGSN LRTT

References

	« Hide 'large scale' referencesShow 'large scale' 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] (ISOFORM 1), ENZYME REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-233; CYS-250; LYS-256 AND LYS-259.
[2]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed: 15057822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 312-2126. Strain: Brown Norway.
[3]	"Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian genetic isolates." Lafreniere R.G., MacDonald M.L.E., Dube M.-P., MacFarlane J., O'Driscoll M., Brais B., Meilleur S., Brinkman R.R., Dadivas O., Pape T., Platon C., Radomski C., Risler J., Thompson J., Guerra-Escobio A.-M., Davar G., Breakefield X.O., Pimstone S.N. , Green R., Pryse-Phillips W., Goldberg Y.P., Younghusband H.B., Hayden M.R., Sherrington R., Rouleau G.A., Samuels M.E. Am. J. Hum. Genet. 74:1064-1073(2004) [PubMed: 15060842] [Abstract] Cited for: IDENTIFICATION OF THE HSN2 EXON.
[4]	"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.
[5]	"The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex." Yang C.L., Zhu X., Ellison D.H. J. Clin. Invest. 117:3403-3411(2007) [PubMed: 17975670] [Abstract] Cited for: FUNCTION, INTERACTION WITH WNK3 AND WNK4.
[6]	"Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members." Heise C.J., Xu B.E., Deaton S.L., Cha S.K., Cheng C.J., Earnest S., Sengupta S., Juang Y.C., Stippec S., Xu Y., Zhao Y., Huang C.L., Cobb M.H. J. Biol. Chem. 285:25161-25167(2010) [PubMed: 20525693] [Abstract] Cited for: FUNCTION.
[7]	"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

EMBL
GenBank
DDBJ

AF227741 mRNA. Translation: AAF74258.1.
AC106348 Genomic DNA. No translation available.
BK004106 Genomic DNA. Translation: DAA04492.1. Sequence problems.

IPI

IPI00200557.
IPI00972852.
IPI00972854.

RefSeq

NP_001002823.2. NM_001002823.2.
NP_001186024.1. NM_001199095.1.
NP_446246.2. NM_053794.2.

UniGene

Rn.27409.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

Q9JIH7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9JIH7. 6 interactions.

STRING

Q9JIH7.

PTM databases

PhosphoSite

Q9JIH7.

Proteomic databases

PRIDE

Q9JIH7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000013621; ENSRNOP00000013622; ENSRNOG00000009956.

GeneID

116477.

KEGG

rno:116477.

Organism-specific databases

CTD

65125.

RGD

621141. Wnk1.

Phylogenomic databases

GeneTree

ENSGT00550000074385.

HOVERGEN

HBG048577.

OrthoDB

EOG4DFPN4.

Gene expression databases

ArrayExpress

Q9JIH7.

Genevestigator

Q9JIH7.

GermOnline

ENSRNOG00000009956. Rattus norvegicus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_cat_dom.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

KO

K08867.

Pfam

PF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

NextBio

619039.

Entry information

Entry name

WNK1_RAT

Accession

Primary (citable) accession number: Q9JIH7
Secondary accession number(s): Q6IFS7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	November 30, 2010
Last modified:	January 25, 2012
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program