KCNA5_HUMAN
ID KCNA5_HUMAN Reviewed; 613 AA.
AC P22460; Q4KKT8; Q4VAJ1; Q4VAJ2; Q9UDA4;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 4.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Potassium voltage-gated channel subfamily A member 5;
DE AltName: Full=HPCN1;
DE AltName: Full=Voltage-gated potassium channel HK2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv1.5;
GN Name=KCNA5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=2001794; DOI=10.1096/fasebj.5.3.2001794;
RA Tamkun M.M., Knoth K.M., Walbridge J.A., Kroemer H., Roden D.M.,
RA Glover D.M.;
RT "Molecular cloning and characterization of two voltage-gated K+ channel
RT cDNAs from human ventricle.";
RL FASEB J. 5:331-337(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Insulinoma;
RX PubMed=1986382; DOI=10.1073/pnas.88.1.53;
RA Philipson L.H., Hice R.E., Schaefer K., Lamendola J., Bell G.I.,
RA Nelson D.J., Steiner D.F.;
RT "Sequence and functional expression in Xenopus oocytes of a human
RT insulinoma and islet potassium channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:53-57(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=1349297; DOI=10.1016/0888-7543(92)90302-9;
RA Curran M.E., Landes G.M., Keating M.T.;
RT "Molecular cloning, characterization, and genomic localization of a human
RT potassium channel gene.";
RL Genomics 12:729-737(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8505626; DOI=10.1085/jgp.101.4.513;
RA Snyders D.J., Tamkun M.M., Bennett P.B.;
RT "A rapidly activating and slowly inactivating potassium channel cloned from
RT human heart. Functional analysis after stable mammalian cell culture
RT expression.";
RL J. Gen. Physiol. 101:513-543(1993).
RN [6]
RP FUNCTION, AND ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
RX PubMed=11524461; DOI=10.1085/jgp.118.3.315;
RA Kurata H.T., Soon G.S., Fedida D.;
RT "Altered state dependence of c-type inactivation in the long and short
RT forms of human Kv1.5.";
RL J. Gen. Physiol. 118:315-332(2001).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KCNAB1.
RX PubMed=12130714; DOI=10.1124/jpet.102.033357;
RA Williams C.P., Hu N., Shen W., Mashburn A.B., Murray K.T.;
RT "Modulation of the human Kv1.5 channel by protein kinase C activation: role
RT of the Kvbeta1.2 subunit.";
RL J. Pharmacol. Exp. Ther. 302:545-550(2002).
RN [8]
RP INTERACTION WITH DLG1, AND MUTAGENESIS OF THR-15.
RX PubMed=16466689; DOI=10.1016/j.bbrc.2006.01.110;
RA Mathur R., Choi W.S., Eldstrom J., Wang Z., Kim J., Steele D.F., Fedida D.;
RT "A specific N-terminal residue in Kv1.5 is required for upregulation of the
RT channel by SAP97.";
RL Biochem. Biophys. Res. Commun. 342:1-8(2006).
RN [9]
RP INVOLVEMENT IN ATFB7.
RX PubMed=16772329; DOI=10.1093/hmg/ddl143;
RA Olson T.M., Alekseev A.E., Liu X.K., Park S., Zingman L.V.,
RA Bienengraeber M., Sattiraju S., Ballew J.D., Jahangir A., Terzic A.;
RT "Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human
RT atrial fibrillation.";
RL Hum. Mol. Genet. 15:2185-2191(2006).
RN [10]
RP SUMOYLATION AT LYS-221 AND LYS-536, INTERACTION WITH UBE2I, AND MUTAGENESIS
RP OF ILE-220; LYS-221; LEU-535 AND LYS-536.
RX PubMed=17261810; DOI=10.1073/pnas.0606702104;
RA Benson M.D., Li Q.J., Kieckhafer K., Dudek D., Whorton M.R., Sunahara R.K.,
RA Iniguez-Lluhi J.A., Martens J.R.;
RT "SUMO modification regulates inactivation of the voltage-gated potassium
RT channel Kv1.5.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1805-1810(2007).
RN [11]
RP VARIANT [LARGE SCALE ANALYSIS] SER-300.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [12]
RP VARIANTS HIS-42; MET-85; PRO-114; ARG-170 AND PRO-184.
RX PubMed=24936649; DOI=10.1371/journal.pone.0100261;
RA Pousada G., Baloira A., Vilarino C., Cifrian J.M., Valverde D.;
RT "Novel mutations in BMPR2, ACVRL1 and KCNA5 genes and hemodynamic
RT parameters in patients with pulmonary arterial hypertension.";
RL PLoS ONE 9:E100261-E100261(2014).
CC -!- FUNCTION: Voltage-gated potassium channel that mediates transmembrane
CC potassium transport in excitable membranes. Forms tetrameric potassium-
CC selective channels through which potassium ions pass in accordance with
CC their electrochemical gradient. The channel alternates between opened
CC and closed conformations in response to the voltage difference across
CC the membrane. Can form functional homotetrameric channels and
CC heterotetrameric channels that contain variable proportions of KCNA1,
CC KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel
CC properties depend on the type of alpha subunits that are part of the
CC channel (PubMed:12130714). Channel properties are modulated by
CC cytoplasmic beta subunits that regulate the subcellular location of the
CC alpha subunits and promote rapid inactivation (PubMed:12130714).
CC Homotetrameric channels display rapid activation and slow inactivation
CC (PubMed:8505626, PubMed:12130714). May play a role in regulating the
CC secretion of insulin in normal pancreatic islets. Isoform 2 exhibits a
CC voltage-dependent recovery from inactivation and an excessive
CC cumulative inactivation (PubMed:11524461).
CC {ECO:0000269|PubMed:11524461, ECO:0000269|PubMed:12130714,
CC ECO:0000269|PubMed:8505626}.
CC -!- SUBUNIT: Homotetramer and heterotetramer of potassium channel proteins.
CC Interacts with DLG1, which enhances channel currents. Forms a ternary
CC complex with DLG1 and CAV3 (By similarity). Interacts with KCNAB1
CC (PubMed:12130714). Interacts with UBE2I (PubMed:17261810).
CC {ECO:0000250|UniProtKB:P19024, ECO:0000269|PubMed:11524461,
CC ECO:0000269|PubMed:12130714, ECO:0000269|PubMed:16466689,
CC ECO:0000269|PubMed:17261810, ECO:0000269|PubMed:8505626}.
CC -!- INTERACTION:
CC P22460; P35609: ACTN2; NbExp=6; IntAct=EBI-6426121, EBI-77797;
CC P22460; Q14160: SCRIB; NbExp=2; IntAct=EBI-6426121, EBI-357345;
CC P22460; Q6UX40: TMEM107; NbExp=3; IntAct=EBI-6426121, EBI-12845616;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12130714,
CC ECO:0000269|PubMed:8505626}; Multi-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P22460-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P22460-2; Sequence=VSP_037110;
CC -!- TISSUE SPECIFICITY: Pancreatic islets and insulinoma.
CC -!- DOMAIN: The amino terminus may be important in determining the rate of
CC inactivation of the channel while the C-terminal PDZ-binding motif may
CC play a role in modulation of channel activity and/or targeting of the
CC channel to specific subcellular compartments.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Channel opening and closing is effected by a
CC conformation change that affects the position and orientation of the
CC voltage-sensor paddle formed by S3 and S4 within the membrane. A
CC transmembrane electric field that is positive inside would push the
CC positively charged S4 segment outwards, thereby opening the pore, while
CC a field that is negative inside would pull the S4 segment inwards and
CC close the pore. Changes in the position and orientation of S4 are then
CC transmitted to the activation gate formed by the inner helix bundle via
CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}.
CC -!- PTM: Sumoylated on Lys-221, and Lys-536, preferentially with SUMO3.
CC Sumoylation regulates the voltage sensitivity of the channel.
CC {ECO:0000269|PubMed:17261810}.
CC -!- DISEASE: Atrial fibrillation, familial, 7 (ATFB7) [MIM:612240]: A
CC familial form of atrial fibrillation, a common sustained cardiac rhythm
CC disturbance. Atrial fibrillation is characterized by disorganized
CC atrial electrical activity and ineffective atrial contraction promoting
CC blood stasis in the atria and reduces ventricular filling. It can
CC result in palpitations, syncope, thromboembolic stroke, and congestive
CC heart failure. {ECO:0000269|PubMed:16772329}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the potassium channel family. A (Shaker) (TC
CC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60146.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M60451; AAA61276.1; -; mRNA.
DR EMBL; M55513; AAA36422.1; -; mRNA.
DR EMBL; M83254; AAA60146.1; ALT_FRAME; mRNA.
DR EMBL; BC096357; AAH96357.1; -; mRNA.
DR EMBL; BC096358; AAH96358.3; -; mRNA.
DR EMBL; BC099665; AAH99665.3; -; mRNA.
DR EMBL; BC099666; AAH99666.3; -; mRNA.
DR CCDS; CCDS8536.1; -. [P22460-1]
DR PIR; A56031; A56031.
DR RefSeq; NP_002225.2; NM_002234.3. [P22460-1]
DR AlphaFoldDB; P22460; -.
DR SMR; P22460; -.
DR BioGRID; 109943; 81.
DR DIP; DIP-42010N; -.
DR IntAct; P22460; 38.
DR MINT; P22460; -.
DR STRING; 9606.ENSP00000252321; -.
DR BindingDB; P22460; -.
DR ChEMBL; CHEMBL4306; -.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB06217; Vernakalant.
DR DrugCentral; P22460; -.
DR GuidetoPHARMACOLOGY; 542; -.
DR TCDB; 1.A.1.2.4; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; P22460; -.
DR PhosphoSitePlus; P22460; -.
DR SwissPalm; P22460; -.
DR BioMuta; KCNA5; -.
DR DMDM; 146345443; -.
DR jPOST; P22460; -.
DR MassIVE; P22460; -.
DR PaxDb; P22460; -.
DR PeptideAtlas; P22460; -.
DR PRIDE; P22460; -.
DR ProteomicsDB; 53993; -. [P22460-1]
DR ProteomicsDB; 53994; -. [P22460-2]
DR Antibodypedia; 22318; 292 antibodies from 34 providers.
DR DNASU; 3741; -.
DR Ensembl; ENST00000252321.5; ENSP00000252321.3; ENSG00000130037.5. [P22460-1]
DR GeneID; 3741; -.
DR KEGG; hsa:3741; -.
DR MANE-Select; ENST00000252321.5; ENSP00000252321.3; NM_002234.4; NP_002225.2.
DR UCSC; uc001qni.5; human. [P22460-1]
DR CTD; 3741; -.
DR DisGeNET; 3741; -.
DR GeneCards; KCNA5; -.
DR HGNC; HGNC:6224; KCNA5.
DR HPA; ENSG00000130037; Group enriched (choroid plexus, heart muscle).
DR MalaCards; KCNA5; -.
DR MIM; 176267; gene.
DR MIM; 612240; phenotype.
DR neXtProt; NX_P22460; -.
DR OpenTargets; ENSG00000130037; -.
DR Orphanet; 334; Familial atrial fibrillation.
DR PharmGKB; PA208; -.
DR VEuPathDB; HostDB:ENSG00000130037; -.
DR eggNOG; KOG1545; Eukaryota.
DR GeneTree; ENSGT00940000161860; -.
DR HOGENOM; CLU_011722_4_0_1; -.
DR InParanoid; P22460; -.
DR OMA; MNNTLSC; -.
DR OrthoDB; 695337at2759; -.
DR PhylomeDB; P22460; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; P22460; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; P22460; -.
DR BioGRID-ORCS; 3741; 11 hits in 1059 CRISPR screens.
DR GeneWiki; KCNA5; -.
DR GenomeRNAi; 3741; -.
DR Pharos; P22460; Tclin.
DR PRO; PR:P22460; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P22460; protein.
DR Bgee; ENSG00000130037; Expressed in cardiac muscle of right atrium and 137 other tissues.
DR Genevisible; P22460; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR GO; GO:0046691; C:intracellular canaliculus; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0034705; C:potassium channel complex; IDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:BHF-UCL.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0051393; F:alpha-actinin binding; IPI:BHF-UCL.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; IDA:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0086089; F:voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization; IMP:BHF-UCL.
DR GO; GO:0086087; F:voltage-gated potassium channel activity involved in bundle of His cell action potential repolarization; IMP:BHF-UCL.
DR GO; GO:0086090; F:voltage-gated potassium channel activity involved in SA node cell action potential repolarization; IMP:BHF-UCL.
DR GO; GO:0086014; P:atrial cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0060081; P:membrane hyperpolarization; IMP:BHF-UCL.
DR GO; GO:0098914; P:membrane repolarization during atrial cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0086050; P:membrane repolarization during bundle of His cell action potential; IMP:BHF-UCL.
DR GO; GO:0086052; P:membrane repolarization during SA node cell action potential; IMP:BHF-UCL.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:2000288; P:positive regulation of myoblast proliferation; IEA:Ensembl.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0055075; P:potassium ion homeostasis; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; IDA:MGI.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0060372; P:regulation of atrial cardiac muscle cell membrane repolarization; IMP:BHF-UCL.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0050796; P:regulation of insulin secretion; TAS:BHF-UCL.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:BHF-UCL.
DR GO; GO:0043266; P:regulation of potassium ion transport; IMP:BHF-UCL.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0010033; P:response to organic substance; IEA:Ensembl.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; IPR003972; K_chnl_volt-dep_Kv1.
DR InterPro; IPR004052; K_chnl_volt-dep_Kv1.5.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01512; KV15CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01496; SHAKERCHANEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Atrial fibrillation; Cell membrane; Ion channel;
KW Ion transport; Isopeptide bond; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Potassium; Potassium channel; Potassium transport;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..613
FT /note="Potassium voltage-gated channel subfamily A member
FT 5"
FT /id="PRO_0000053985"
FT TOPO_DOM 1..247
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 248..269
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 270..323
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 324..345
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 346..356
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 357..377
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 378..395
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 396..416
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 417..431
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 432..453
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 454..467
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 468..479
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 480..487
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 488..494
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 495..523
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 524..613
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REPEAT 61..71
FT /note="1"
FT REPEAT 72..82
FT /note="2"
FT REGION 1..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..82
FT /note="2 X 11 AA tandem repeat of D-[SP]-G-V-R-P-L-P-P-L-P"
FT REGION 282..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..431
FT /note="S4-S5 linker"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 532..559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 480..485
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOTIF 611..613
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 66..86
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 557
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT LIPID 346
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CROSSLNK 221
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:17261810"
FT CROSSLNK 536
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:17261810"
FT VAR_SEQ 1..209
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_037110"
FT VARIANT 42
FT /note="L -> H (found in a patient with pulmonary arterial
FT hypertension; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24936649"
FT /id="VAR_079602"
FT VARIANT 85
FT /note="L -> M"
FT /evidence="ECO:0000269|PubMed:24936649"
FT /id="VAR_079603"
FT VARIANT 114
FT /note="T -> P (found in a patient with pulmonary arterial
FT hypertension; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24936649"
FT /id="VAR_079604"
FT VARIANT 170
FT /note="P -> R (found in a patient with pulmonary arterial
FT hypertension; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24936649"
FT /id="VAR_079605"
FT VARIANT 184
FT /note="R -> P (found in a patient with pulmonary arterial
FT hypertension; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24936649"
FT /id="VAR_079606"
FT VARIANT 228
FT /note="P -> S (in dbSNP:rs1056464)"
FT /id="VAR_053856"
FT VARIANT 300
FT /note="G -> S (in a breast cancer sample; somatic mutation;
FT dbSNP:rs148708451)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035770"
FT VARIANT 578
FT /note="R -> K (in dbSNP:rs12720445)"
FT /id="VAR_054786"
FT MUTAGEN 15
FT /note="T->A: Loss of DLG1 effect on channel current."
FT /evidence="ECO:0000269|PubMed:16466689"
FT MUTAGEN 220
FT /note="I->N: Reduces sumoylation; when associated with N-
FT 535."
FT /evidence="ECO:0000269|PubMed:17261810"
FT MUTAGEN 221
FT /note="K->R: Abolishes sumoylation; when associated with R-
FT 536."
FT /evidence="ECO:0000269|PubMed:17261810"
FT MUTAGEN 535
FT /note="L->N: Reduces sumoylation; when associated with N-
FT 220."
FT /evidence="ECO:0000269|PubMed:17261810"
FT MUTAGEN 536
FT /note="K->R: Abolishes sumoylation; when associated with R-
FT 221."
FT /evidence="ECO:0000269|PubMed:17261810"
FT CONFLICT 55
FT /note="Missing (in Ref. 1; AAA61276)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="L -> Q (in Ref. 2; AAA36422)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="R -> P (in Ref. 1; AAA61276 and 2; AAA36422)"
FT /evidence="ECO:0000305"
FT CONFLICT 187..188
FT /note="RP -> G (in Ref. 1; AAA61276)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="R -> G (in Ref. 2; AAA36422)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="P -> V (in Ref. 2; AAA36422)"
FT /evidence="ECO:0000305"
FT CONFLICT 282
FT /note="L -> V (in Ref. 3; AAA60146)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="P -> A (in Ref. 1; AAA61276)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 613 AA; 67228 MW; A5B02B27F8396E3D CRC64;
MEIALVPLEN GGAMTVRGGD EARAGCGQAT GGELQCPPTA GLSDGPKEPA PKGRGAQRDA
DSGVRPLPPL PDPGVRPLPP LPEELPRPRR PPPEDEEEEG DPGLGTVEDQ ALGTASLHHQ
RVHINISGLR FETQLGTLAQ FPNTLLGDPA KRLRYFDPLR NEYFFDRNRP SFDGILYYYQ
SGGRLRRPVN VSLDVFADEI RFYQLGDEAM ERFREDEGFI KEEEKPLPRN EFQRQVWLIF
EYPESSGSAR AIAIVSVLVI LISIITFCLE TLPEFRDERE LLRHPPAPHQ PPAPAPGANG
SGVMAPPSGP TVAPLLPRTL ADPFFIVETT CVIWFTFELL VRFFACPSKA GFSRNIMNII
DVVAIFPYFI TLGTELAEQQ PGGGGGGQNG QQAMSLAILR VIRLVRVFRI FKLSRHSKGL
QILGKTLQAS MRELGLLIFF LFIGVILFSS AVYFAEADNQ GTHFSSIPDA FWWAVVTMTT
VGYGDMRPIT VGGKIVGSLC AIAGVLTIAL PVPVIVSNFN YFYHRETDHE EPAVLKEEQG
TQSQGPGLDR GVQRKVSGSR GSFCKAGGTL ENADSARRGS CPLEKCNVKA KSNVDLRRSL
YALCLDTSRE TDL
