S12A7_RAT
ID S12A7_RAT Reviewed; 1083 AA.
AC Q5RK27; Q6T7Y5; Q6TUA1; Q6TUA2;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Solute carrier family 12 member 7;
DE AltName: Full=Electroneutral potassium-chloride cotransporter 4;
DE AltName: Full=K-Cl cotransporter 4;
GN Name=Slc12a7 {ECO:0000312|EMBL:AAH86339.1, ECO:0000312|RGD:1359672};
GN Synonyms=Kcc4 {ECO:0000312|EMBL:AAQ93481.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000269|PubMed:15057822};
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAH86339.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-213.
RC TISSUE=Ovary {ECO:0000312|EMBL:AAH86339.1};
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 [3] {ECO:0000312|EMBL:AAR10805.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-159.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAR10805.1};
RC TISSUE=Pancreas {ECO:0000312|EMBL:AAR10805.1};
RA Le Rouzic P., Stanley S.J., Luckman S.M.;
RT "Rattus norvegicus K-CL cotransporter KCC4.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAR10805.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 80-105 AND 113-129.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAQ93481.1};
RA Lopez N.C., Michea L.;
RT "Aldosterone up regulates K+-Cl- cotransporter expression and activity in
RT arterial tissue.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=16872584; DOI=10.1016/j.brainres.2006.06.055;
RA Le Rouzic P., Ivanov T.R., Stanley P.J., Baudoin F.M.-H., Chan F.,
RA Pinteaux E., Brown P.D., Luckman S.M.;
RT "KCC3 and KCC4 expression in rat adult forebrain.";
RL Brain Res. 1110:39-45(2006).
CC -!- FUNCTION: Mediates electroneutral potassium-chloride cotransport when
CC activated by cell swelling. May mediate K(+) uptake into Deiters' cells
CC in the cochlea and contribute to K(+) recycling in the inner ear.
CC Important for the survival of cochlear outer and inner hair cells and
CC the maintenance of the organ of Corti. May be required for basolateral
CC Cl(-) extrusion in the kidney and contribute to renal acidification (By
CC similarity). {ECO:0000250|UniProtKB:Q9WVL3}.
CC -!- ACTIVITY REGULATION: Inhibited by WNK3. {ECO:0000250}.
CC -!- SUBUNIT: Homomultimer and heteromultimer with other K-Cl
CC cotransporters. {ECO:0000250|UniProtKB:Q9WVL3}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:Q9WVL3}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in kidney,
CC liver and pancreas. Expressed in choroid plexus and suprachiasmatic
CC nucleus. {ECO:0000269|PubMed:16872584}.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH86339.1; Type=Miscellaneous discrepancy; Note=Intron retention. This sequence is incomplete at its 3'end and extensively differs from that shown in positions 214-251.; Evidence={ECO:0000305};
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DR EMBL; AABR03000133; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC086339; AAH86339.1; ALT_SEQ; mRNA.
DR EMBL; AY429042; AAR10805.1; -; mRNA.
DR EMBL; AY387486; AAQ93480.1; -; mRNA.
DR EMBL; AY387487; AAQ93481.1; -; mRNA.
DR RefSeq; NP_001013162.2; NM_001013144.2.
DR AlphaFoldDB; Q5RK27; -.
DR SMR; Q5RK27; -.
DR IntAct; Q5RK27; 1.
DR STRING; 10116.ENSRNOP00000022635; -.
DR GlyGen; Q5RK27; 3 sites.
DR iPTMnet; Q5RK27; -.
DR PhosphoSitePlus; Q5RK27; -.
DR PaxDb; Q5RK27; -.
DR PRIDE; Q5RK27; -.
DR GeneID; 308069; -.
DR KEGG; rno:308069; -.
DR UCSC; RGD:1359672; rat.
DR CTD; 10723; -.
DR RGD; 1359672; Slc12a7.
DR VEuPathDB; HostDB:ENSRNOG00000016372; -.
DR eggNOG; KOG2082; Eukaryota.
DR HOGENOM; CLU_001883_1_2_1; -.
DR InParanoid; Q5RK27; -.
DR OrthoDB; 349744at2759; -.
DR PhylomeDB; Q5RK27; -.
DR TreeFam; TF313657; -.
DR Reactome; R-RNO-426117; Cation-coupled Chloride cotransporters.
DR PRO; PR:Q5RK27; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016372; Expressed in heart and 18 other tissues.
DR ExpressionAtlas; Q5RK27; baseline and differential.
DR Genevisible; Q5RK27; RN.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0008519; F:ammonium transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015379; F:potassium:chloride symporter activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0140157; P:ammonium import across plasma membrane; ISO:RGD.
DR GO; GO:0006884; P:cell volume homeostasis; IMP:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
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:0055075; P:potassium ion homeostasis; IBA:GO_Central.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR InterPro; IPR004841; AA-permease/SLC12A_dom.
DR InterPro; IPR030354; KCC4.
DR InterPro; IPR000076; KCL_cotranspt.
DR InterPro; IPR018491; SLC12_C.
DR InterPro; IPR004842; SLC12A_fam.
DR PANTHER; PTHR11827; PTHR11827; 1.
DR PANTHER; PTHR11827:SF47; PTHR11827:SF47; 1.
DR Pfam; PF00324; AA_permease; 2.
DR Pfam; PF03522; SLC12; 2.
DR PRINTS; PR01081; KCLTRNSPORT.
DR TIGRFAMs; TIGR00930; 2a30; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Chloride; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Potassium; Potassium transport; Reference proteome;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1083
FT /note="Solute carrier family 12 member 7"
FT /id="PRO_0000299076"
FT TOPO_DOM 1..118
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..139
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..200
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 274..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..455
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 456..476
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 494..514
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 515..553
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 554..574
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 577..597
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 598..624
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 625..645
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 845..865
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 866..1083
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVL3"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVL3"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y666"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y666"
FT MOD_RES 973
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVL3"
FT MOD_RES 980
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVL3"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 125
FT /note="Y -> F (in Ref. 4; AAQ93481)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1083 AA; 119378 MW; 111C2D9EE0A16BA5 CRC64;
MPTNFTVVPV EARADGAGDE AAERTEEPGS PESADPACPT PGDGNPRENS PFINNVEVER
ESYFEGKNMA LFEEEMDSNP MVSSLLNKLA NYTNLSQGVV EHEEDEDSRR REIKAPRMGT
FIGVYLPCLQ NILGVILFLR LTWIVGAAGV LESFLIVAMC CTCTMLTAIS MSAIATNGVV
PAGGSYYMIS RSLGPEFGGA VGLCFYLGTT FAGAMYILGT IEIFLTYISP SAAIFQAETA
DGEAAALLNN MRVYGSCALA LMAVVVFVGV KYVNKLALVF LACVVLSILA IYAGVIKTAF
APPDIPVCLL GNRTLANRNF DTCAKMQVVS NGTVTTALWR LFCNGSSLGA SCDEYFVQNN
VTEIQGIPGV ASGVFLDNLW STYSDKGAFV EKKGVSSVPV SEESRPGGLP YVLTDIMTYF
TMLVGIYFPS VTGIMAGSNR SGDLKDAQKS IPTGTILAIV TTSFIYLSCI VLFGACIEGV
VLRDKFGEAL QGNLVIGMLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIARDGIIP
FLQVFGHGKA NGEPTWALLL TALICETGIL IASLDSVAPI LSMFFLMCYM FVNLACAVQT
LLRTPNWRPR FKFYHWTLSF LGMSLCLALM FICSWYYALF AMLIAGCIYK YIEYRGAEKE
WGDGIRGLSL NAARYALLRV EHGPPHTKNW RPQVLVMLNL DSEQCVKHPR LLSFTSQLKA
GKGLTIVGSV LEGTYLDKHV EAQRAEENIR SLMSAEKMKG FCQLVVSSNL RDGASHLIQS
AGLGGMKHNT VLMAWPEAWK QADNPFSWKN FVDTVRDTTA AHQALLVAKN IDLFPQNQER
FSDGNIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQVDDNSIQ MKKDLQMFLY
HLRISAEVEV VEMVENDISA FTYEKTLMME QRSQMLKQMQ LSKNEREREA QLIHDRNTAS
HTVATARTEA PPTPDKVQMT WTKEKLIAEK HRNKDTGTSG FKDLFSLKPD QSNVRRMHTA
VKLNGVVLNK SQDAQLVLLN MPGPPKSRQG DENYMEFLEV LTEGLNRVLL VRGGGREVIT
IYS
