WNK1_PIG
ID WNK1_PIG Reviewed; 2376 AA.
AC Q6R2V0; F1SHS6;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2017, sequence version 3.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Serine/threonine-protein kinase WNK1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q9H4A3};
GN Name=WNK1 {ECO:0000250|UniProtKB:Q9H4A3};
GN Synonyms=HSN2 {ECO:0000303|PubMed:15060842};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Duroc;
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15060842; DOI=10.1086/420795;
RA Lafreniere R.G., MacDonald M.L.E., Dube M.-P., MacFarlane J.,
RA O'Driscoll M., Brais B., Meilleur S., Brinkman R.R., Dadivas O., Pape T.,
RA Platon C., Radomski C., Risler J., Thompson J., Guerra-Escobio A.-M.,
RA Davar G., Breakefield X.O., Pimstone S.N., Green R., Pryse-Phillips W.,
RA Goldberg Y.P., Younghusband H.B., Hayden M.R., Sherrington R.,
RA Rouleau G.A., Samuels M.E.;
RT "Identification of a novel gene (HSN2) causing hereditary sensory and
RT autonomic neuropathy type II through the study of Canadian genetic
RT isolates.";
RL Am. J. Hum. Genet. 74:1064-1073(2004).
CC -!- FUNCTION: Serine/threonine kinase which plays an important role in the
CC regulation of electrolyte homeostasis, cell signaling, survival, and
CC proliferation. Acts as an activator and inhibitor of sodium-coupled
CC chloride cotransporters and potassium-coupled chloride cotransporters
CC respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls
CC sodium and chloride ion transport by inhibiting the activity of WNK4,
CC by either phosphorylating the kinase or via an interaction between WNK4
CC and the autoinhibitory domain of WNK1. WNK4 regulates the activity of
CC the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by
CC phosphorylation. WNK1 may also play a role in actin cytoskeletal
CC reorganization. Phosphorylates NEDD4L. Acts as a scaffold to inhibit
CC SLC4A4, SLC26A6 as well as CFTR activities and surface expression,
CC recruits STK39 which mediates the inhibition (By similarity).
CC {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9H4A3,
CC ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q9H4A3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q9H4A3};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9H4A3};
CC -!- ACTIVITY REGULATION: By hypertonicity (By similarity). Activation
CC requires autophosphorylation of Ser-380, that may be regulated by
CC calcium. Phosphorylation of Ser-376 also promotes increased activity
CC (By similarity). {ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- SUBUNIT: Interacts with SYT2. Interacts with WNK3 and WNK4. Interacts
CC with KLHL3. {ECO:0000250|UniProtKB:Q9H4A3,
CC ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- PTM: Autophosphorylation at Ser-380 is inhibited by intracellular
CC calcium. {ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- PTM: Ubiquitinated in vitro by the BCR(KLHL3) complex and in vivo by a
CC BCR(KLHL2) complex, leading to proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. WNK subfamily. {ECO:0000305}.
CC -!- CAUTION: Was named WNK/'with no lysine(K)' because key residues for
CC catalysis, including the lysine involved in ATP binding, are either not
CC conserved or differ compared to the residues described in other kinase
CC family proteins. {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- CAUTION: HSN2 was originally thought to be an intronless gene lying
CC within a WNK1 gene intron. However, it is most probably an alternative
CC exon which has been also described in alternative splicing products of
CC the human and mouse WNK1 genes. Isoforms bearing this exon are
CC specifically expressed in the nervous system in these species.
CC {ECO:0000305|PubMed:15060842}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAS86809.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; CU463193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU915332; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP340582; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY517853; AAS86809.1; ALT_SEQ; mRNA.
DR AlphaFoldDB; Q6R2V0; -.
DR SMR; Q6R2V0; -.
DR STRING; 9823.ENSSSCP00000000801; -.
DR Ensembl; ENSSSCT00040102601; ENSSSCP00040046393; ENSSSCG00040074009.
DR eggNOG; KOG0584; Eukaryota.
DR InParanoid; Q6R2V0; -.
DR TreeFam; TF315363; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019869; F:chloride channel inhibitor activity; IBA:GO_Central.
DR GO; GO:0019902; F:phosphatase binding; ISS:UniProtKB.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IBA:GO_Central.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0050801; P:ion homeostasis; IBA:GO_Central.
DR GO; GO:0010766; P:negative regulation of sodium ion transport; IBA:GO_Central.
DR GO; GO:1903288; P:positive regulation of potassium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:2000651; P:positive regulation of sodium ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024678; Kinase_OSR1/WNK_CCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF12202; OSR1_C; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Phosphoprotein;
KW Protein kinase inhibitor; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..2376
FT /note="Serine/threonine-protein kinase WNK1"
FT /id="PRO_0000223947"
FT DOMAIN 219..477
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 486..553
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT REGION 571..641
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..799
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1026..1118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1459..1478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1734..1770
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1862..1942
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1991..2033
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2110..2239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..176
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 571..587
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 588..628
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 701..770
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 771..785
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1026..1043
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1058..1091
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1095..1115
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1742..1756
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1863..1879
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1880..1900
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1916..1942
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2127..2238
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 366
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT BINDING 229
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT BINDING 299..302
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT BINDING 349
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 376
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 380
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 1261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1972
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1996
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2005
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2006
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2021
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2023
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2026
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2264
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P83741"
FT MOD_RES 2280
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P83741"
FT MOD_RES 2364
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
SQ SEQUENCE 2376 AA; 248976 MW; 508CB7AC7C4A057C CRC64;
MSGGGADQQS SPPGSLFLSP PAPAPKNGSS SDSSVGEKLG AAAADAGAGR TEEYRRRRHT
MDKDSRGAAA TTTTEHRFFR RSVICDSNAT ALELPGLPLP LPQPGAAAVA QQRSPPEPHR
EETLTPAVAH VAQQPPAAAT PGEPAAAVPA AASAPGSASR DRQVAQPSQA GSKEEPPSAR
SGSGGGSAKE PQEERSQQQD DIEELETKAV GMSNDGRFLK FDIEIGRGSF KTVYKGLDTE
TTVEVAWCEL QDRKLTKSER QRFKEEAEML KGLQHPNIVR FYDSWESTVK GKKCIVLVTE
LMTSGTLKTY LKRFKVMKIK VLRSWCRQIL KGLQFLHTRT PPIIHRDLKC DNIFITGPTG
SVKIGDLGLA TLKRASFAKS VIGTPEFMAP EMYEEKYDES VDVYAFGMCM LEMATSEYPY
SECQNAAQIY RRVTSGVKPA SFDKVAIPEV KEIIEGCIRQ NKDERYSIKD LLNHAFFQEE
TGVRVELAEE DDGEKIAIKL WLRIEDIKKL KGKYKDNEAI EFSFDLERDV PEDVAQEMVE
SGYVCEGDHK TMAKAIKDRV SLIKRKREQR QLVREEQEKR KQEESSLKQQ GEQQSSASQA
GILQPSSAST GLPAAATTSA SVSTQVEPEE PEADQHQQLQ YQQPSISVLS DGTVDSGQGS
SVFTESRVSS QQTVSYGSQH EQAHSTCTLP GHTASVVQAQ AQPHGGYPPS SMAQGQSQGQ
PSSSSLTGIP SSQPVQHSQQ QQGVQQTAPS QQTVQYSLPQ TSAPSEPTTA QPASQPQPPQ
VLPPVSAGKQ LPVSQPVPTI QGEPQISVAT QPSVVPVHSG AHFLPVGQPL PPSLLPQYPV
SQVPSAPHVS AAQPGFSPLP VTAAAGVNQP LLTLASSAAA AAVPGGSTVV PSQLPTLLQP
VTQLPSQAHP QLLQTAVQSM GIPANLGQTA EAPLPSGDVL YQGFPPRLPP QYPGDSNIAP
SSSVASVCIP STVLSPPRPT EALAAPGYFP TVVQSYAESN LLVPVGSIGG QIQVSQPAVS
LAQAPTTSSQ QAALESTQGV SQVAPPEPVP AAPPQPTQPT TLVSSIDRSA HSDVASGMSD
GNENVPSSSG RHEGRTIKRH YRKSVRSRSR HEKTSRPKLR ILNVSNKGDR VVECQLETHN
RKMVTFKFDL DGDNPEEIAT IMVNNDFILA IEREAFVDQV REIIEKADEM LSEDVSVEPE
GDQGLENLQG KDDYGFSGSQ KLEGEFKQPI PASSMPQQIA GLPTSSLTQV VHSAGRRFIV
SPVPESRLRE SKVFTSEISD TVAASTSPGT GMNLSHSASS LSLQQAFSEL RRAQMTEGPS
TAPPHFSHTG PTFPVVPPSM SSIAGAAATP SVSVPATSCP FSDISTSVTP SEVTASTEKG
IAGVATCTGV ISSSGLTVPP ASDSPILSSV VSSITVPVAV SVSTTSLSVQ APTPGSIVSN
TGTFPSISVA MTSASAVSST AAPGAKPPPV SSQQVSGSTA GITTLASVPT TAPAPSVASQ
PSLSLSSSTS APTLAETIVV SAHSLDKASH SSTAGLALSL PASSSSASPA AGVSSSVSQP
GVAHPLVIPS AVASIPVLSQ AGPTCAPLLP QVPGIPPLVQ PAASVPAVQQ TLVHSQPQPA
LLPNQPHTHC PEMDADAQPR APGIDDIKTL EEKLRSLFSE HSSSGTQHAS VSLETSLVVE
TTVTPGIPTT AVAPGKLMTS TTSTCLPPTS LPLGTTGLSI LPVVTPGQVS TPVSTIPAVK
PGTAPSKPPS TKPPVLPLGT ELPAGTPPSE QLPPFPGPSL MQAQQPLEDL DAQLRRTLSP
ETVVLTSTVG PVSVVAPTAA VEAGAQLQKD VSQVTEGPIP APTSGTGVFQ MGRFQVSVAM
DDTQKEGKNK SEDVKSVHFE SSTSESSVLS SSSPESTLVK PEPNGTAIRG ISSDMPDSAH
KTSASEAKSE AGQPTKVGRF QVTTTADKVG RFSVSRTEDA IAEAKKEGPV ASPPFMDLEH
SILPAVIPKK EKPELSEPSH LNGPSSDLEA AFLSRDGDDG SGSPHSPPQL CSKSLPIQSL
SQSLSNSFNS SYMSSDNESD IEDEDLKLEL RRLREKHLKE IQDLQSRQKH EIESLYTRLG
KAPPAVIIPA AAPLAGRRRR PTKSKGSKSS RSSSLGNKSP GPAGNLSGQS TATVLHPQQT
LPAPGNIPET GQNQLLQPLK PSPSSDNLYS AFTSDGAISV PSLSAPGQGT SSTNTVGGTV
SSQAAQAQPP TMTSSRKGTF TDDLHKLVDN WARDAMNLSG RRGSKGHMSY EGPGMARKFS
APGQLCISMT SNLGGSAPIS AASATSLGHF TKSMCPPQQY GFPAPPFGTQ WSGTGGPAPQ
PLSQFQPVGT ASLQNFNISN LQKSISNPPG SNLRTT
