ID S12A5_MOUSE Reviewed; 1138 AA. AC Q91V14; A2A5L0; Q3UHQ2; Q7TQC9; Q80TI5; Q9Z0M7; DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot. DT 04-DEC-2007, sequence version 2. DT 27-MAR-2024, entry version 179. DE RecName: Full=Solute carrier family 12 member 5; DE AltName: Full=Electroneutral potassium-chloride cotransporter 2; DE AltName: Full=K-Cl cotransporter 2; DE Short=mKCC2 {ECO:0000303|PubMed:33597714}; DE AltName: Full=Neuronal K-Cl cotransporter; GN Name=Slc12a5; Synonyms=Kcc2 {ECO:0000303|PubMed:33597714}, Kiaa1176; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC STRAIN=ILS, and ISS; RX PubMed=11471062; DOI=10.1007/s00335-001-1001-x; RA Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J., RA Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.; RT "High-throughput sequence identification of gene coding variants within RT alcohol-related QTLs."; RL Mamm. Genome 12:657-663(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=12693553; DOI=10.1093/dnares/10.1.35; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., RA Nakajima D., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II. RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 10:35-48(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Brain; 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 [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-227 (ISOFORM 2). RX PubMed=10077537; RA Haapa S., Suomalainen S., Eerikaeinen S., Airaksinen M., Paulin L., RA Savilahti H.; RT "An efficient DNA sequencing strategy based on bacteriophage Mu in vitro RT DNA transposition reaction."; RL Genome Res. 9:308-315(1999). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72 (ISOFORM 1), TISSUE SPECIFICITY, RP AND DISRUPTION PHENOTYPE. RX PubMed=17715129; DOI=10.1074/jbc.m705095200; RA Uvarov P., Ludwig A., Markkanen M., Pruunsild P., Kaila K., Delpire E., RA Timmusk T., Rivera C., Airaksinen M.S.; RT "A novel N-terminal isoform of the neuron-specific K-Cl cotransporter RT KCC2."; RL J. Biol. Chem. 282:30570-30576(2007). RN [8] RP PROTEIN SEQUENCE OF 532-538; 726-747; 813-819; 833-843; 952-961; 1042-1052; RP 1078-1085 AND 1091-1101, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=C57BL/6J; TISSUE=Brain; RA Lubec G., Kang S.U.; RL Submitted (APR-2007) to UniProtKB. RN [9] RP SUBCELLULAR LOCATION. RX PubMed=11395011; DOI=10.1016/s0896-6273(01)00297-5; RA Huebner C.A., Stein V., Hermans-Borgmeyer I., Meyer T., Ballanyi K., RA Jentsch T.J.; RT "Disruption of KCC2 reveals an essential role of K-Cl cotransport already RT in early synaptic inhibition."; RL Neuron 30:515-524(2001). RN [10] RP INTERACTION WITH AP2A1, AND MUTAGENESIS OF 680-LEU-LEU-681 AND RP 684-GLU-GLU-685. RX PubMed=18625303; DOI=10.1016/j.cellsig.2008.06.011; RA Zhao B., Wong A.Y.C., Murshid A., Bowie D., Presley J.F., Bedford F.K.; RT "Identification of a novel di-leucine motif mediating K(+)/Cl(-) RT cotransporter KCC2 constitutive endocytosis."; RL Cell. Signal. 20:1769-1779(2008). RN [11] RP ACTIVITY REGULATION, AND PHOSPHORYLATION AT THR-929 AND THR-1029. RX PubMed=19665974; DOI=10.1016/j.cell.2009.05.031; RA Rinehart J., Maksimova Y.D., Tanis J.E., Stone K.L., Hodson C.A., Zhang J., RA Risinger M., Pan W., Wu D., Colangelo C.M., Forbush B., Joiner C.H., RA Gulcicek E.E., Gallagher P.G., Lifton R.P.; RT "Sites of regulated phosphorylation that control K-Cl cotransporter RT activity."; RL Cell 138:525-536(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1044; SER-1047 AND SER-1048, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [13] {ECO:0007744|PDB:7D14} RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS), AND SUBUNIT. RX PubMed=33597714; DOI=10.1038/s42003-021-01750-w; RA Zhang S., Zhou J., Zhang Y., Liu T., Friedel P., Zhuo W., Somasekharan S., RA Roy K., Zhang L., Liu Y., Meng X., Deng H., Zeng W., Li G., Forbush B., RA Yang M.; RT "The structural basis of function and regulation of neuronal cotransporters RT NKCC1 and KCC2."; RL Commun. Biol. 4:226-226(2021). CC -!- FUNCTION: Mediates electroneutral potassium-chloride cotransport in CC mature neurons and is required for neuronal Cl(-) homeostasis (By CC similarity). As major extruder of intracellular chloride, it CC establishes the low neuronal Cl(-) levels required for chloride influx CC after binding of GABA-A and glycine to their receptors, with subsequent CC hyperpolarization and neuronal inhibition (By similarity). Involved in CC the regulation of dendritic spine formation and maturation (By CC similarity). {ECO:0000250|UniProtKB:Q63633, CC ECO:0000250|UniProtKB:Q9H2X9}. CC -!- CATALYTIC ACTIVITY: CC Reaction=chloride(in) + K(+)(in) = chloride(out) + K(+)(out); CC Xref=Rhea:RHEA:72427, ChEBI:CHEBI:17996, ChEBI:CHEBI:29103; CC Evidence={ECO:0000250|UniProtKB:Q9H2X9}; CC -!- ACTIVITY REGULATION: Inhibited following phosphorylation by OXSR1/OSR1 CC and STK39/SPAK: phosphorylation takes place downstream of WNK kinases CC (WNK1, WNK2, WNK3 or WNK4) in response to hyperosmotic stress and CC subsequent cell shrinkage. {ECO:0000269|PubMed:19665974}. CC -!- SUBUNIT: Homodimer (PubMed:33597714). Heteromultimer with other K-Cl CC cotransporters (By similarity). Interacts with AP2A1 (PubMed:18625303). CC {ECO:0000250|UniProtKB:Q63633, ECO:0000269|PubMed:18625303, CC ECO:0000269|PubMed:33597714}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11395011}; CC Multi-pass membrane protein {ECO:0000269|PubMed:11395011, CC ECO:0000269|PubMed:33597714}. Cell projection, dendrite CC {ECO:0000269|PubMed:11395011}. Note=Detected on dendrites, but not on CC axons of spinal cord neurons and at GPHN-positive inhibitory synapses. CC {ECO:0000269|PubMed:11395011}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=KCC2a; CC IsoId=Q91V14-1; Sequence=Displayed; CC Name=2; Synonyms=KCC2b; CC IsoId=Q91V14-2; Sequence=VSP_029910; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in brainstem, spinal cord CC and olfactory bulb of 17 dpc embryos. Expressed in all parts of the CC brain and spinal cord in postnatal day 14 mice. CC {ECO:0000269|PubMed:17715129}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in brainstem and spinal cord CC of 17 dpc embryos. Expressed in all parts of the brain and spinal cord CC in postnatal day 14 mice. {ECO:0000269|PubMed:17715129}. CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: Predominant isoform in 17 dpc brain. CC {ECO:0000269|PubMed:17715129}. CC -!- DEVELOPMENTAL STAGE: [Isoform 2]: Predominant isoform during postnatal CC development. Detected in the ventral horns of the spinal cord at 12.5 CC dpc, and throughout the spinal cord at birth. CC {ECO:0000269|PubMed:17715129}. CC -!- PTM: Phosphorylated at Thr-929 and Thr-1029 by OXSR1/OSR1 and CC STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), CC inhibiting the potassium-chloride cotransport activity. CC {ECO:0000269|PubMed:19665974}. CC -!- DISRUPTION PHENOTYPE: Death at birth due to severe motor deficits CC including respiratory failure. {ECO:0000269|PubMed:11395011}. CC -!- DISRUPTION PHENOTYPE: [Isoform 2]: Mice lacking isoform 2 die within 2 CC weeks after birth. {ECO:0000269|PubMed:17715129}. CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC65742.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF332063; AAK56092.1; -; mRNA. DR EMBL; AF332064; AAK56093.1; -; mRNA. DR EMBL; AK122460; BAC65742.1; ALT_INIT; mRNA. DR EMBL; AK147262; BAE27805.1; -; mRNA. DR EMBL; AL591495; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC054808; AAH54808.1; -; mRNA. DR EMBL; AJ011033; CAA09464.1; -; Genomic_DNA. DR CCDS; CCDS38332.1; -. [Q91V14-2] DR CCDS; CCDS89581.1; -. [Q91V14-1] DR RefSeq; NP_065066.2; NM_020333.2. [Q91V14-2] DR RefSeq; XP_006500006.2; XM_006499943.3. DR PDB; 7D14; EM; 3.80 A; A/B=1-1138. DR PDBsum; 7D14; -. DR AlphaFoldDB; Q91V14; -. DR EMDB; EMD-30543; -. DR SMR; Q91V14; -. DR BioGRID; 208213; 12. DR IntAct; Q91V14; 6. DR MINT; Q91V14; -. DR STRING; 10090.ENSMUSP00000096690; -. DR DrugBank; DB01216; Finasteride. DR GlyConnect; 2730; 5 N-Linked glycans (3 sites). DR GlyCosmos; Q91V14; 5 sites, 5 glycans. DR GlyGen; Q91V14; 6 sites, 5 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q91V14; -. DR PhosphoSitePlus; Q91V14; -. DR SwissPalm; Q91V14; -. DR MaxQB; Q91V14; -. DR PaxDb; 10090-ENSMUSP00000096690; -. DR PeptideAtlas; Q91V14; -. DR ProteomicsDB; 253339; -. [Q91V14-1] DR ProteomicsDB; 253340; -. [Q91V14-2] DR ABCD; Q91V14; 1 sequenced antibody. DR Antibodypedia; 1580; 390 antibodies from 29 providers. DR DNASU; 57138; -. DR Ensembl; ENSMUST00000099092.8; ENSMUSP00000096690.5; ENSMUSG00000017740.18. [Q91V14-2] DR Ensembl; ENSMUST00000202623.4; ENSMUSP00000144623.2; ENSMUSG00000017740.18. [Q91V14-1] DR GeneID; 57138; -. DR KEGG; mmu:57138; -. DR UCSC; uc056zqu.1; mouse. [Q91V14-1] DR AGR; MGI:1862037; -. DR CTD; 57468; -. DR MGI; MGI:1862037; Slc12a5. DR VEuPathDB; HostDB:ENSMUSG00000017740; -. DR eggNOG; KOG2082; Eukaryota. DR GeneTree; ENSGT00940000160827; -. DR HOGENOM; CLU_001883_1_2_1; -. DR InParanoid; Q91V14; -. DR OMA; AMFPANT; -. DR OrthoDB; 5490251at2759; -. DR PhylomeDB; Q91V14; -. DR TreeFam; TF313657; -. DR Reactome; R-MMU-426117; Cation-coupled Chloride cotransporters. DR BioGRID-ORCS; 57138; 2 hits in 80 CRISPR screens. DR ChiTaRS; Slc12a5; mouse. DR PRO; PR:Q91V14; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q91V14; Protein. DR Bgee; ENSMUSG00000017740; Expressed in retrosplenial region and 190 other cell types or tissues. DR ExpressionAtlas; Q91V14; baseline and differential. DR GO; GO:0071944; C:cell periphery; IDA:ARUK-UCL. DR GO; GO:0032590; C:dendrite membrane; ISO:MGI. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0043005; C:neuron projection; ISO:MGI. DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL. DR GO; GO:0043204; C:perikaryon; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0008519; F:ammonium transmembrane transporter activity; ISO:MGI. DR GO; GO:0015108; F:chloride transmembrane transporter activity; ISO:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0015379; F:potassium:chloride symporter activity; IMP:MGI. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0072488; P:ammonium transmembrane transport; ISO:MGI. DR GO; GO:0006884; P:cell volume homeostasis; IBA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; IMP:MGI. DR GO; GO:0055064; P:chloride ion homeostasis; IBA:GO_Central. DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central. DR GO; GO:0006821; P:chloride transport; IMP:MGI. DR GO; GO:0060996; P:dendritic spine development; ISO:MGI. DR GO; GO:0006971; P:hypotonic response; ISS:UniProtKB. DR GO; GO:0030644; P:intracellular chloride ion homeostasis; ISO:MGI. DR GO; GO:0051452; P:intracellular pH reduction; ISO:MGI. DR GO; GO:0007612; P:learning; IMP:MGI. DR GO; GO:0006811; P:monoatomic ion transport; ISS:UniProtKB. DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI. DR GO; GO:0055075; P:potassium ion homeostasis; IBA:GO_Central. DR GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB. DR GO; GO:0006813; P:potassium ion transport; ISO:MGI. DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:MGI. DR GO; GO:0040040; P:thermosensory behavior; IMP:MGI. DR Gene3D; 1.20.1740.10; Amino acid/polyamine transporter I; 1. DR InterPro; IPR004841; AA-permease/SLC12A_dom. DR InterPro; IPR000076; KCL_cotranspt. DR InterPro; IPR018491; SLC12_C. DR InterPro; IPR004842; SLC12A_fam. DR NCBIfam; TIGR00930; 2a30; 1. DR PANTHER; PTHR11827:SF54; SOLUTE CARRIER FAMILY 12 MEMBER 5; 1. DR PANTHER; PTHR11827; SOLUTE CARRIER FAMILY 12, CATION COTRANSPORTERS; 1. DR Pfam; PF00324; AA_permease; 2. DR Pfam; PF03522; SLC12; 3. DR PRINTS; PR01081; KCLTRNSPORT. DR Genevisible; Q91V14; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cell projection; KW Chloride; Direct protein sequencing; Disulfide bond; Glycoprotein; KW Ion transport; Membrane; Metal-binding; Phosphoprotein; Potassium; KW Potassium transport; Reference proteome; Symport; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..1138 FT /note="Solute carrier family 12 member 5" FT /id="PRO_0000178035" FT TOPO_DOM 1..122 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 123..143 FT /note="Discontinuously helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 144..151 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 152..176 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 177..197 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 198..227 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 228..251 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 252..273 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 274..299 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 300..422 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 423..443 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 444..452 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 453..476 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 477..508 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 509..537 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 538..557 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 558..574 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 575..576 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 577..601 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 602..618 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 619..636 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 637 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TRANSMEM 638..655 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT TOPO_DOM 656..1138 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:33597714, FT ECO:0007744|PDB:7D14" FT REGION 1..62 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 96..116 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 943..1051 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 23..44 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 98..112 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 943..966 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 980..996 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1014..1039 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 133 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 134 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 218 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 432 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 435 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 436 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 437 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 438 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 592 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT BINDING 592 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT MOD_RES 57 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q63633" FT MOD_RES 929 FT /note="Phosphothreonine; by OXSR1 and STK39" FT /evidence="ECO:0000269|PubMed:19665974" FT MOD_RES 1029 FT /note="Phosphothreonine; by OXSR1 and STK39" FT /evidence="ECO:0000269|PubMed:19665974" FT MOD_RES 1044 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1047 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1048 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT CARBOHYD 314 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 333 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 351 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 362 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 310..325 FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT DISULFID 345..354 FT /evidence="ECO:0000250|UniProtKB:Q9UP95" FT VAR_SEQ 1..40 FT /note="MSRRFTVTSLPPAASAASADPESRRHSVADPRRLPREDVK -> MLNNLTDC FT EDGDGGANP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11471062, FT ECO:0000303|PubMed:12693553, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16141072" FT /id="VSP_029910" FT MUTAGEN 680..681 FT /note="LL->AA: Inhibits endocytosis. Abolishes interaction FT with AP2A1." FT /evidence="ECO:0000269|PubMed:18625303" FT MUTAGEN 684..685 FT /note="EE->AA: Decreases endocytosis." FT /evidence="ECO:0000269|PubMed:18625303" FT CONFLICT 64 FT /note="Missing (in Ref. 5; AAH54808)" FT /evidence="ECO:0000305" FT CONFLICT 859 FT /note="G -> D (in Ref. 3; BAE27805)" FT /evidence="ECO:0000305" SQ SEQUENCE 1138 AA; 126271 MW; 56059F065B89C407 CRC64; MSRRFTVTSL PPAASAASAD PESRRHSVAD PRRLPREDVK GDGNPKESSP FINSTDTEKG REYDGRNMAL FEEEMDTSPM VSSLLSGLAN YTNLPQGSRE HEEAENNEGG KKKPVQAPRM GTFMGVYLPC LQNIFGVILF LRLTWVVGIA GIMESFCMVF ICCSCTMLTA ISMSAIATNG VVPAGGSYYM ISRSLGPEFG GAVGLCFYLG TTFAGAMYIL GTIEILLAYL FPAMAIFKAE DASGEAAAML NNMRVYGTCV LTCMATVVFV GVKYVNKFAL VFLGCVILSI LAIYAGVIKS AFDPPNFPIC LLGNRTLSRH GFDVCAKLAW EGNETVTTRL WGLFCSSRLL NATCDEYFTR NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERRGMPSV GLADGTPVDM DHPYVFSDMT SYFTLLVGIY FPSVTGIMAG SNRSGDLRDA QKSIPTGTIL AIATTSAVYI SSVVLFGACI EGVVLRDKFG EAVNGNLVVG TLAWPSPWVI VIGSFFSTCG AGLQSLTGAP RLLQAISRDG IVPFLQVFGH GKANGEPTWA LLLTACICEI GILIASLDEV APILSMFFLM CYMFVNLACA VQTLLRTPNW RPRFRYYHWT LSFLGMSLCL ALMFICSWYY ALVAMLIAGL IYKYIEYRGA EKEWGDGIRG LSLSAARYAL LRLEEGPPHT KNWRPQLLVL VRVDQDQNVV HPQLLSLTSQ LKAGKGLTIV GSVLEGTFLD NHPQAQRAEE SIRRLMEAEK VKGFCQVVIS SNLRDGVSHL IQSGGLGGLQ HNTVLVGWPR NWRQKEDHQT WRNFIELVRE TTAGHLALLV TKNVSMFPGN PERFSEGSID VWWIVHDGGM LMLLPFLLRH HKVWRKCKMR IFTVAQMDDN SIQMKKDLTT FLYHLRITAE VEVVEMHESD ISAYTYEKTL VMEQRSQILK QMHLTKNERE REIQSITDES RGSIRRKNPA NPRLRLNVPE ETACDNEEKP EEEVQLIHDQ SAPSCPSSSP SPGEEPEGER ETDPEVHLTW TKDKSVAEKN KGPSPVSSEG IKDFFSMKPE WENLNQSNVR RMHTAVRLNE VIVNKSRDAK LVLLNMPGPP RNRNGDENYM EFLEVLTEQL DRVMLVRGGG REVITIYS //