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PR01082

Identifier
KCLTRNSPORT1  [View Relations]  [View Alignment]  
Accession
PR01082
No. of Motifs
4
Creation Date
03-MAR-1999  (UPDATE 07-JUN-1999)
Title
K-Cl co-transporter type 1 (KCC1) signature
Database References
PRINTS; PR01081 KCLTRNSPORT
PRODOM; PD010750; PD010749
INTERPRO; IPR000622
Literature References
1. GILLEN, C.M., BRILL, S., PAYNE, J.A. AND FORBUSH, B. III.
Molecular cloning and functional expression of the K-Cl co-transporter from rabbit,
rat and human. A new member of the cation-chloride co-transporter family.
J.BIOL.CHEM. 271 16237-16244 (1996).
 
2. PAYNE, J.A. STEVENSON, T.J. AND DONALDSON, L.F.
Molecular characterization of a putative K-Cl co-transporter in rat brain. 
A neuronal-specific isoform.
J.BIOL.CHEM. 271 16245-16252 (1996).
 
3. RIVERA, C., VOIPIO, J., PAYNE, J.A., RUUSUVUORI, E., LAHTINEN, H., 
LAMSA, K., PIRVOLA, U., SAARMA, M. AND KAILA, K.
The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal
maturation.
NATURE 397 251-255 (1999).

Documentation
The K-Cl co-transporter (KCC) mediates the coupled movement of K+ and Cl- 
ions across the plasma membrane of many animal cells. This transport is
involved in the regulatory volume decrease in response to cell swelling in
red blood cells, and has been proposed to play a role in the vectorial
movement of Cl- across kidney epithelia. The transport process involves one
for one electroneutral movement of K+ together with Cl-, and, in all
known mammalian cells, the net movement is outward [1].
 
In neurones, it appears to play a unique role in maintaining low intra-
cellular Cl-concentration, which is required for the functioning of Cl- 
dependent fast synaptic inhibition, mediated by certain neurotransmitters,
such as gamma-aminobutyric acid (GABA) and glycine.
 
Two isoforms of the K-Cl co-transporter have been described, termed KCC1 and
KCC2, containing 1085 and 1116 amino acids, respectively. They are both 
predicted to have 12 transmembrane (TM) regions in a central hydrophobic 
domain, together with hydrophilic N- and C-termini that are likely
cytoplasmic. Comparison of their sequences with those of other ion-
tranporting membrane proteins reveals that they are part of a new super-
family of cation-chloride co-transporters, which includes the Na-Cl and 
Na-K-2Cl co-transporters. KCC1 is widely expressed in human tissues, while
KCC2 is expressed only in brain neurones, making it likely that this is the
isoform responsible for maintaining low Cl- concentration in neurones [2,3].
 
KCC1 is widely expressed in human tissues, and when heterologously expressed,
possesses the functional characteristics of the well-studied red blood cell
K-Cl co-transporter, including stimulation by both swelling and
N-ethylmaleimide. Several splice variants have also been identified.
 
KCLTRNSPORT1 is a 4-element fingerprint that provides a signature for the 
K-Cl co-transporter type 1 isoform. The fingerprint was derived from an 
initial alignment of 5 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those 
sections that characterise the K-Cl co-transporter type 1 isoform but
distinguish it from type 2 - motifs 1 and 2 lie within the putative
cytoplasmic N-terminus; and motifs 3 and 4 lie near the extremity of the
presumed cytoplasmic, C-terminal hydrophilic domain. Two iterations on
OWL31.1 were required to reach converegence, at which point a true set
comprising 7 sequences was identified.
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
46666
30000
20000
1234
True Positives
O18887        O55069        O60632        Q13953        
Q28677 Q63632
Sequence Titles
O18887      K-CL COTRANSPORTER - SUS SCROFA (PIG).        
O55069 ERYTHROID K:CL COTRANSPORTER - MUS MUSCULUS (MOUSE).
O60632 ERYTHROID K:CL COTRANSPORTER SPLICING ISOFORM 2 - HOMO SAPIENS (HUMAN).
Q13953 K-CL COTRANSPORTER - HOMO SAPIENS (HUMAN).
Q28677 K-CL COTRANSPORTER - ORYCTOLAGUS CUNICULUS (RABBIT).
Q63632 FUROSEMIDE-SENSITIVE K-CL COTRANSPORTER - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    2  300  NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
MPHFTVVPVDGPRR AF028807 1 1 -
MPHFTVVPVDGPRR OCKCC 1 1 -
MPHFTVVPVDGPRR AF047338 1 1 -
MPHFTVVPVDGPRR AF054506 1 1 -
MPHFTVVPVDGPRR AF054505 1 1 -

Motif 2 width=8
Element Seqn Id St Int Rpt
EDSDGHGN AF028807 35 20 -
EDPDGHGN OCKCC 35 20 -
DDSDGHGN AF047338 35 20 -
DDSDGHGN AF054506 35 20 -
DDSDGHGN AF054505 35 20 -

Motif 3 width=13
Element Seqn Id St Int Rpt
VKDRHSALRLESL AF028807 953 910 -
VKDRHSALRLESL OCKCC 953 910 -
VKDRHSALRLESL AF047338 953 910 -
VKDRHSALRLESL AF054506 953 910 -
VKDRHSALRLESL AF054505 953 910 -

Motif 4 width=17
Element Seqn Id St Int Rpt
YSDEEDESVAGTDKIQM AF028807 966 0 -
YSDEEDEAAAGADKIQM OCKCC 966 0 -
YSDEEDESAVGADKIQM AF047338 966 0 -
YSDEEDESAVGADKIQM AF054506 966 0 -
YSDEEDESAVGADKIQM AF054505 966 0 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
MPHFTVVPVDGPRR O18887 1 1 -
MPHFTVVPVDGPRR O60632 1 1 -
MPHFTVVPVDGPRR Q13953 1 1 -
MPHFTVVPVDGPRR Q63632 1 1 -
MPHFTVVPVDGPRR O55069 1 1 -
MPHFTVVPVDGPRR Q28677 1 1 -

Motif 2 width=8
Element Seqn Id St Int Rpt
EDSDGHGN O18887 35 20 -
DDSDGHGN O60632 35 20 -
DDSDGHGN Q13953 35 20 -
EDSDGQGN Q63632 35 20 -
EDSDGQGN O55069 35 20 -
EDPDGHGN Q28677 35 20 -

Motif 3 width=13
Element Seqn Id St Int Rpt
VKDRHSALRLESL O18887 953 910 -
VKDRHSALRLESL O60632 953 910 -
VKDRHSALRLESL Q13953 953 910 -
VKDRHSALRLESL Q63632 953 910 -
VKDRHSALRLESL O55069 953 910 -
VKDRHSALRLESL Q28677 953 910 -

Motif 4 width=17
Element Seqn Id St Int Rpt
YSDEEDESVAGTDKIQM O18887 966 0 -
YSDEEDESAVGADKIQM O60632 966 0 -
YSDEEDESAVGADKIQM Q13953 966 0 -
YSDEEDESVTGADKIQM Q63632 966 0 -
YSDEEEESVAGADKIQM O55069 966 0 -
YSDEEDEAAAGADKIQM Q28677 966 0 -