(data stored in ACNUC9435 zone)

HOGENOM: HS12_PE30

ID   HS12_PE30                            STANDARD;      PRT;   2382 AA.
AC   HS12_PE30;
DT   00-JAN-0000 (Rel. 1, Created)
DT   00-JAN-0000 (Rel. 2, Last sequence update)
DT   00-JAN-0000 (Rel. 3, Last annotation update)
DE   RecName: Full=Serine/threonine-protein kinase WNK1; EC=2.7.11 1;AltName:
DE   Full=Erythrocyte 65 kDa protein; Short=p65;AltName: Full=Kinase deficient
DE   protein;AltName: Full=Protein kinase lysine-deficient 1;AltName:
DE   Full=Protein kinase with no lysine 1; Short=hWNK1; (HS12.PE30).
GN   Name=WNK1; Synonyms=HSN2, KDP, KIAA0344, PRKWNK1;
OS   HOMO SAPIENS.
OC   Eukaryota; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia;
OC   Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi;
OC   Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria;
OC   Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini;
OC   Hominoidea; Hominidae; Homininae; Homo.
OX   NCBI_TaxID=9606;
RN   [0]
RP   -.;
RG   -.;
RL   -.;
CC   -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS HS12.PE30.
CC       Homo sapiens chromosome 12 GRCh37  sequence 1..133841895 annotated by
CC       Ensembl
CC   -!- ANNOTATIONS ORIGIN:WNK1_HUMAN
CC   -!- FUNCTION: Controls sodium and chloride ion transport by inhibiting
CC       the activity of WNK4, potentially by either phosphorylating the
CC       kinase or via an interaction between WNK4 and the autoinhibitory
CC       domain of WNK1. WNK4 regulates the activity of the thiazide-
CC       sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1
CC       may also play a role in actin cytoskeletal reorganization.
CC   -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC   -!- COFACTOR: Magnesium.
CC   -!- ENZYME REGULATION: By hypertonicity. Activation requires
CC       autophosphorylation of Ser-382. Phosphorylation of Ser-378 also
CC       promotes increased activity (By similarity).
CC   -!- SUBUNIT: Interacts with SYT2 (By similarity).
CC   -!- INTERACTION:
CC       P29101:Syt2 (xeno); NbExp=2; IntAct=EBI-457907, EBI-458017;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage, Alternative splicing; Named isoforms=5;
CC       Name=1;
CC         IsoId=Q9H4A3-1; Sequence=Displayed;
CC         Note=Produced by alternative promoter usage;
CC       Name=2;
CC         IsoId=Q9H4A3-2; Sequence=VSP_040269, VSP_050638;
CC         Note=No experimental confirmation available;
CC       Name=3;
CC         IsoId=Q9H4A3-4; Sequence=VSP_050634, VSP_050637;
CC         Note=Kinase-defective isoform. Produced by alternative promoter
CC         usage and alternative splicing;
CC       Name=4; Synonyms=Brain and spinal cord variant;
CC         IsoId=Q9H4A3-5; Sequence=VSP_040268;
CC         Note=Contain the nervous system-specific exon HSN2. Produced by
CC         alternative splicing;
CC       Name=5; Synonyms=Dorsal root ganglia and sciatic nerve variant,
CC       DRG and sciatic nerve variant;
CC         IsoId=Q9H4A3-6; Sequence=VSP_040267, VSP_040270;
CC         Note=Contain the nervous system-specific exon HSN2. Produced by
CC         alternative splicing;
CC   -!- TISSUE SPECIFICITY: Widely expressed, with highest levels observed
CC       in the testis, heart, kidney and skeletal muscle. Isoform 3 is
CC       kidney-specific.
CC   -!- PTM: O-glycosylated.
CC   -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
CC   -!- DISEASE: Defects in WNK1 are a cause of pseudohypoaldosteronism
CC       type II (PHAII) [MIM:145260]. PHAII is an autosomal dominant
CC       disease characterized by severe hypertension, hyperkalemia, and
CC       sensitivity to thiazide diuretics which may result from a chloride
CC       shunt in the renal distal nephron.
CC   -!- DISEASE: Defects in WNK1 are a cause of hereditary sensory and
CC       autonomic neuropathy type 2A (HSAN2A) [MIM:201300]. A form of
CC       hereditary sensory and autonomic neuropathy, a genetically and
CC       clinically heterogeneous group of disorders characterized by
CC       degeneration of dorsal root and autonomic ganglion cells, and by
CC       sensory and/or autonomic abnormalities. HSAN2A is an autosomal
CC       recessive disorder characterized by impairment of pain,
CC       temperature and touch sensation, onset of symptoms in infancy or
CC       early childhood, occurrence of distal extremity pathologies
CC       (paronychia, whitlows, ulcers, and Charcot joints), frequent
CC       amputations, sensory loss that affects all modalities of sensation
CC       (lower and upper limbs and perhaps the trunk as well), absence or
CC       diminution of tendon reflexes (usually in all limbs), minimal
CC       autonomic dysfunction, absence of sensory nerve action potentials,
CC       and virtual absence of myelinated fibers with decreased numbers of
CC       unmyelinated fibers in sural nerves.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
CC       protein kinase family. WNK subfamily.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC   -!- CAUTION: PubMed:2507249 describes a peptide sequence containing a
CC       GlcNAc glycosylated Ser in position 164 while it is an Arg residue
CC       according to others.
CC   -!- CAUTION: Cys-250 is present instead of the conserved Lys which is
CC       expected to be an active site residue. Lys-233 appears to fulfill
CC       the required catalytic function.
CC   -!- CAUTION: HSN2 was originally thought to be an intronless gene
CC       lying within a WNK1 gene intron. It has been shown to be a nervous
CC       system-specific exon of WNK1 included in isoform 4 and isoform 5
CC       (PubMed:18521183).
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-214 is the initiator
CC       in isoform 4 and isoform 5.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF31483.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part;
CC       Sequence=AAI30468.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;
CC       Sequence=AAI30470.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;
CC       Sequence=DAA04494.1; Type=Erroneous gene model prediction; Note=Includes 3' and 3' intronic sequences;
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/WNK1";
CC   -!- GENE_FAMILY: HOG000168221 [ FAMILY / ALN / TREE ]
DR   HOGENOM:Homo_sapiens;ENSG00000060237;ENST00000315939;ENSP00000313059.
DR   EMBL; AB002342; - ;
DR   EMBL; AC004765; - ;
DR   EMBL; AC004803; - ;
DR   EMBL; AF061944; - ;
DR   EMBL; AJ296290; - ;
DR   EMBL; AY231477; - ;
DR   EMBL; BC013629; - ;
DR   EMBL; CH471116; - ;
DR   EMBL; FJ515833; - ;
DR   UniProtKB/Swiss-Prot; Q9H4A3; A1L4B0; C5HTZ5; C5HTZ6; C5HTZ7; O15052; P54963; Q4VBX9; -.
DR   UniProtKB/Swiss-Prot; Q6IFS5; Q86WL5; Q8N673; Q9P1S9; -.
DR   EMBL; AJ296290; CAC15059.1; -; mRNA.
DR   EMBL; FJ515833; ACS13726.1; -; Genomic_DNA.
DR   EMBL; FJ515833; ACS13727.1; -; Genomic_DNA.
DR   EMBL; FJ515833; ACS13728.1; -; Genomic_DNA.
DR   EMBL; AC004765; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC004803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF061944; AAF31483.1; ALT_SEQ; mRNA.
DR   EMBL; AB002342; BAA20802.2; -; mRNA.
DR   EMBL; AY231477; AAO46160.1; -; mRNA.
DR   EMBL; BC130467; AAI30468.1; ALT_SEQ; mRNA.
DR   EMBL; BC130469; AAI30470.1; ALT_SEQ; mRNA.
DR   EMBL; BK004108; DAA04494.1; ALT_SEQ; Genomic_DNA.
DR   IPI; IPI00004472; -.
DR   IPI; IPI00397592; -.
DR   IPI; IPI00412748; -.
DR   IPI; IPI00972952; -.
DR   IPI; IPI01013396; -.
DR   RefSeq; NP_001171914.1; NM_001184985.1.
DR   RefSeq; NP_055638.2; NM_014823.2.
DR   RefSeq; NP_061852.3; NM_018979.3.
DR   RefSeq; NP_998820.3; NM_213655.4.
DR   UniGene; Hs.726723; -.
DR   UniGene; Hs.728846; -.
DR   ProteinModelPortal; Q9H4A3; -.
DR   SMR; Q9H4A3; 210-481.
DR   IntAct; Q9H4A3; 45.
DR   MINT; MINT-4651503; -.
DR   STRING; Q9H4A3; -.
DR   PhosphoSite; Q9H4A3; -.
DR   PRIDE; Q9H4A3; -.
DR   Ensembl; ENST00000252477; ENSP00000252477; ENSG00000060237.
DR   Ensembl; ENST00000315939; ENSP00000313059; ENSG00000060237.
DR   Ensembl; ENST00000340908; ENSP00000341292; ENSG00000060237.
DR   GeneID; 65125; -.
DR   KEGG; hsa:65125; -.
DR   UCSC; uc001qin.2; human.
DR   UCSC; uc001qio.2; human.
DR   UCSC; uc001qip.2; human.
DR   CTD; 65125; -.
DR   GeneCards; GC12P000733; -.
DR   H-InvDB; HIX0010312; -.
DR   HGNC; HGNC:14540; WNK1.
DR   MIM; 145260; phenotype.
DR   MIM; 201300; phenotype.
DR   MIM; 605232; gene.
DR   neXtProt; NX_Q9H4A3; -.
DR   Orphanet; 970; Hereditary sensory and autonomic neuropathy type 2.
DR   Orphanet; 88940; Pseudohypoaldosteronism type 2C.
DR   PharmGKB; PA33782; -.
DR   eggNOG; prNOG06337; -.
DR   GeneTree; ENSGT00550000074385; -.
DR   InParanoid; Q9H4A3; -.
DR   OMA; GPGMNLS; -.
DR   OrthoDB; EOG4C5CKQ; -.
DR   NextBio; 67340; -.
DR   ArrayExpress; Q9H4A3; -.
DR   Bgee; Q9H4A3; -.
DR   CleanEx; HS_WNK1; -.
DR   Genevestigator; Q9H4A3; -.
DR   GermOnline; ENSG00000060237; Homo sapiens.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
DR   GO; GO:0006811; P:ion transport; ISS:UniProtKB.
DR   GO; GO:0048666; P:neuron development; NAS:UniProtKB.
DR   InterPro; IPR011009; Kinase-like_dom.
DR   InterPro; IPR000719; Prot_kinase_cat_dom.
DR   InterPro; IPR017442; Se/Thr_kinase-like_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   Pfam; PF00069; Pkinase; 1.
DR   SUPFAM; SSF56112; Kinase_like; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   HOGENOMDNA; HS12.PE30; -.
KW   ENSG000000602371755old_1320000031; ENSP000003130597901old_1320000031;
KW   D3DUP1_HUMAN; Q96CZ6_HUMAN; AB002342; AC004765; AC004803; AF061944;
KW   AY231477; BC013629; CH471116; FJ515833;
KW   Alternative promoter usage; Alternative splicing; ATP-binding;
KW   Complete proteome; Cytoplasm; Direct protein sequencing; Glycoprotein;
KW   Kinase; Neuropathy; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW   Protein kinase inhibitor; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase.
SQ   SEQUENCE   2382 AA;  UNKNOWN MW;  UNKNOWN CRC64;
     MSGGAAEKQS STPGSLFLSP PAPAPKNGSS SDSSVGEKLG AAAADAVTGR TEEYRRRRHT
     MDKDSRGAAA TTTTTEHRFF RRSVICDSNA TALELPGLPL SLPQPSIPAA VPQSAPPEPH
     REETVTATAT SQVAQQPPAA AAPGEQAVAG PAPSTVPSST SKDRPVSQPS LVGSKEEPPP
     ARSGSGGGSA KEPQEERSQQ QDDIEELETK AVGMSNDGRF LKFDIEIGRG SFKTVYKGLD
     TETTVEVAWC ELQDRKLTKS ERQRFKEEAE MLKGLQHPNI VRFYDSWEST VKGKKCIVLV
     TELMTSGTLK TYLKRFKVMK IKVLRSWCRQ ILKGLQFLHT RTPPIIHRDL KCDNIFITGP
     TGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD ESVDVYAFGM CMLEMATSEY
     PYSECQNAAQ IYRRVTSGVK PASFDKVAIP EVKEIIEGCI RQNKDERYSI KDLLNHAFFQ
     EETGVRVELA EEDDGEKIAI KLWLRIEDIK KLKGKYKDNE AIEFSFDLER DVPEDVAQEM
     VESGYVCEGD HKTMAKAIKD RVSLIKRKRE QRQLVREEQE KKKQEESSLK QQVEQSSASQ
     TGIKQLPSAS TGIPTASTTS ASVSTQVEPE EPEADQHQQL QYQQPSISVL SDGTVDSGQG
     SSVFTESRVS SQQTVSYGSQ HEQAHSTGTV PGHIPSTVQA QSQPHGVYPP SSVAQGQSQG
     QPSSSSLTGV SSSQPIQHPQ QQQGIQQTAP PQQTVQYSLS QTSTSSEATT AQPVSQPQAP
     QVLPQVSAGK QLPVSQPVPT IQGEPQIPVA TQPSVVPVHS GAHFLPVGQP LPTPLLPQYP
     VSQIPISTPH VSTAQTGFSS LPITMAAGIT QPLLTLASSA TTAAIPGVST VVPSQLPTLL
     QPVTQLPSQV HPQLLQPAVQ SMGIPANLGQ AAEVPLSSGD VLYQGFPPRL PPQYPGDSNI
     APSSNVASVC IHSTVLSPPM PTEVLATPGY FPTVVQPYVE SNLLVPMGGV GGQVQVSQPG
     GSLAQAPTTS SQQAVLESTQ GVSQVAPAEP VAVAQTQATQ PTTLASSVDS AHSDVASGMS
     DGNENVPSSS GRHEGRTTKR HYRKSVRSRS RHEKTSRPKL RILNVSNKGD RVVECQLETH
     NRKMVTFKFD LDGDNPEEIA TIMVNNDFIL AIERESFVDQ VREIIEKADE MLSEDVSVEP
     EGDQGLESLQ GKDDYGFSGS QKLEGEFKQP IPASSMPQQI GIPTSSLTQV VHSAGRRFIV
     SPVPESRLRE SKVFPSEITD TVAASTAQSP GMNLSHSASS LSLQQAFSEL RRAQMTEGPN
     TAPPNFSHTG PTFPVVPPFL SSIAGVPTTA AATAPVPATS SPPNDISTSV IQSEVTVPTE
     EGIAGVATST GVVTSGGLPI PPVSESPVLS SVVSSITIPA VVSISTTSPS LQVPTSTSEI
     VVSSTALYPS VTVSATSASA GGSTATPGPK PPAVVSQQAA GSTTVGATLT SVSTTTSFPS
     TASQLCIQLS SSTSTPTLAE TVVVSAHSLD KTSHSSTTGL AFSLSAPSSS SSPGAGVSSY
     ISQPGGLHPL VIPSVIASTP ILPQAAGPTS TPLLPQVPSI PPLVQPVANV PAVQQTLIHS
     QPQPALLPNQ PHTHCPEVDS DTQPKAPGID DIKTLEEKLR SLFSEHSSSG AQHASVSLET
     SLVIESTVTP GIPTTAVAPS KLLTSTTSTC LPPTNLPLGT VALPVTPVVT PGQVSTPVST
     TTSGVKPGTA PSKPPLTKAP VLPVGTELPA GTLPSEQLPP FPGPSLTQSQ QPLEDLDAQL
     RRTLSPEMIT VTSAVGPVSM AAPTAITEAG TQPQKGVSQV KEGPVLATSS GAGVFKMGRF
     QVSVAADGAQ KEGKNKSEDA KSVHFESSTS ESSVLSSSSP ESTLVKPEPN GITIPGISSD
     VPESAHKTTA SEAKSDTGQP TKVGRFQVTT TANKVGRFSV SKTEDKITDT KKEGPVASPP
     FMDLEQAVLP AVIPKKEKPE LSEPSHLNGP SSDPEAAFLS RDVDDGSGSP HSPHQLSSKS
     LPSQNLSQSL SNSFNSSYMS SDNESDIEDE DLKLELRRLR DKHLKEIQDL QSRQKHEIES
     LYTKLGKVPP AVIIPPAAPL SGRRRRPTKS KGSKSSRSSS LGNKSPQLSG NLSGQSAASV
     LHPQQTLHPP GNIPESGQNQ LLQPLKPSPS SDNLYSAFTS DGAISVPSLS APGQGTSSTN
     TVGATVNSQA AQAQPPAMTS SRKGTFTDDL HKLVDNWARD AMNLSGRRGS KGHMNYEGPG
     MARKFSAPGQ LCISMTSNLG GSAPISAASA TSLGHFTKSM CPPQQYGFPA TPFGAQWSGT
     GGPAPQPLGQ FQPVGTASLQ NFNISNLQKS ISNPPGSNLR TT
//

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