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2.A.30.1.14
KCl symporter KCC2. It influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines (Gauvain et al., 2011). It plays a role in inhibitory and excitatory neurotransmission in neurons (Chamma et al., 2012). KCC2 transport activity requires the highly conserved L(675) in the C-terminal β1 strand (Döding et al., 2012). Direct physical coupling between the GABA-A receptor and the KCC2 chloride transporter underlies ionic plasticity in cerebellar purkinje neurons in response to brain-derived neurotrophic factor (BDNF) (Huang et al., 2013).  KCC2 is neuron-specific and is essential for Cl(-) homeostasis and fast inhibitory synaptic transmission in the mature CNS. KCC2 is regulated by the single-pass transmembrane protein neuropilin and tolloid like-2 (Neto2). Neto2 is required to maintain the normal abundance of KCC2 and specifically associates with the active oligomeric form of the transporter (Ivakine et al. 2013). Loss of the Neto2:KCC2 interaction reduced KCC2-mediated Cl- extrusion, resulting in decreased synaptic inhibition in hippocampal neurons.  KCC2 mediates the efflux of Cl-out of neurons and plays a role in inhibitory GABAergic and glycinergic neurotransmission. It also participates in the regulation of various physiological processes of neurons, including cell migration, dendritic outgrowth, spine morphology, and dendritic synaptogenesis (Wu et al. 2016). Down-regulation of KCC2 is associated with multiple neurological diseases and is particularly relevant to acute central nervous system (CNS) injury.

Accession Number:Q63633
Protein Name:SLC12A5 aka KCC2
Length:1139
Molecular Weight:126247.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

Genevestigator: Q63633
eggNOG: maNOG13119
RefSeq: NP_599190.1   
Entrez Gene ID: 171373   
Pfam: PF00324   
KEGG: rno:171373   

Gene Ontology

GO:0032590 C:dendrite membrane
GO:0016021 C:integral to membrane
GO:0043204 C:perikaryon
GO:0051739 F:ammonia transmembrane transporter activity
GO:0015379 F:potassium:chloride symporter activity
GO:0005515 F:protein binding
GO:0015696 P:ammonium transport
GO:0006821 P:chloride transport
GO:0051452 P:intracellular pH reduction
GO:0006813 P:potassium ion transport
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport

References (4)

[1] “Molecular characterization of a putative K-Cl cotransporter in rat brain. A neuronal-specific isoform.”  Payne J.A.et.al.   8663311
[2] “A novel N-terminal isoform of the neuron-specific K-Cl cotransporter KCC2.”  Uvarov P.et.al.   17715129
[3] “The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation.”  Rivera C.et.al.   9930699
[4] “A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity.”  Casula S.et.al.   11551954

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MSRRFTVTSL PPAASAASAD PESRRHSVAD PRRLPREDVK GDGNPKESSP FINSTDTEKG 
61:	REYDGRNMAL FEEEMDTSPM VSSLLSGLAN YTNLPQGSKE HEEAENNEGG KKKPVQAPRM 
121:	GTFMGVYLPC LQNIFGVILF LRLTWVVGIA GIMESFCMVF ICCSCTMLTA ISMSAIATNG 
181:	VVPAGGSYYM ISRSLGPEFG GAVGLCFYLG TTFAGAMYIL GTIEILLAYL FPAMAIFKAE 
241:	DASGEAAAML NNMRVYGTCV LTCMATVVFV GVKYVNKFAL VFLGCVILSI LAIYAGVIKS 
301:	AFDPPNFPIC LLGNRTLSRH GFDVCAKLAW EGNETVTTRL WGLFCSSRLL NATCDEYFTR 
361:	NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERRGMPSV GLADGTPVDM DHPYVFSDMT 
421:	SYFTLLVGIY FPSVTGIMAG SNRSGDLRDA QKSIPTGTIL AIATTSAVYI SSVVLFGACI 
481:	EGVVLRDKFG EAVNGNLVVG TLAWPSPWVI VIGSFFSTCG AGLQSLTGAP RLLQAISRDG 
541:	IVPFLQVFGH GKANGEPTWA LLLTACICEI GILIASLDEV APILSMFFLM CYMFVNLACA 
601:	VQTLLRTPNW RPRFRYYHWT LSFLGMSLCL ALMFICSWYY ALVAMLIAGL IYKYIEYRGA 
661:	EKEWGDGIRG LSLSAARYAL LRLEEGPPHT KNWRPQLLVL VRVDQDQNVV HPQLLSLTSQ 
721:	LKAGKGLTIV GSVLEGTFLD NHPQAQRAEE SIRRLMEAEK VKGFCQVVIS SNLRDGVSHL 
781:	IQSGGLGGLQ HNTVLVGWPR NWRQKEDHQT WRNFIELVRE TTAGHLALLV TKNVSMFPGN 
841:	PERFSEGSID VWWIVHDGGM LMLLPFLLRH HKVWRKCKMR IFTVAQMDDN SIQMKKDLTT 
901:	FLYHLRITAE VEVVEMHESD ISAYTYEKTL VMEQRSQILK QMHLTKNERE REIQSITDES 
961:	RGSIRRKNPA NTRLRLNVPE ETACDNEEKP EEEVQLIHDQ SAPSCPSSSP SPGEEPEGEG 
1021:	ETDPEKVHLT WTKDKSAAQK NKGPSPVSSE GIKDFFSMKP EWENLNQSNV RRMHTAVRLN 
1081:	EVIVNKSRDA KLVLLNMPGP PRNRNGDENY MEFLEVLTEQ LDRVMLVRGG GREVITIYS