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PR01260

Identifier
NACAEXCHNGR1  [View Relations]  [View Alignment]  
Accession
PR01260
No. of Motifs
4
Creation Date
06-DEC-1999
Title
Na+/Ca2+ exchanger isoform 1 signature
Database References

PFAM; PF01699 Na_Ca_Ex
PRODOM; PD024407
INTERPRO; IPR002987
Literature References
1. NICOLL, D.A., LONGONI, S. AND PHILIPSON, K.D.
Molecular cloning and functional expression of the cardiac sarcolemmal
Na+-Ca2+ exchanger.
SCIENCE 250 562-565 (1990).
 
2. LI, Z., MATSUOKA, S., HRYSHKO, L.V., NICOLL, D.A., BERSOHN, M.M.,
BURKE, E.P., LIFTON, R.P. AND PHILIPSON, K.D.
Cloning of the NCX2 isoform of the plasma membrane Na+/Ca2+ exchanger.
J.BIOL.CHEM. 269 17434-17439 (1994).
 
3. NICOLL, D.A., QUEDNAU, B.D., QUI, Z., XIA, Y-R., LUSIS, A.J. AND
PHILIPSON, K.D.
Cloning of a third mammalian Na+-Ca2+ exchanger, NCX3.
J.BIOL.CHEM. 271 24914-24921 (1996).

Documentation
Na+/Ca2+ exchange proteins are involved in maintaining Ca2+ homeostasis in
a wide variety of cell types. They are found in both the plasma membrane
and intracellular organellar membranes, where they exchange Na+ for Ca2+ in
an electrogenic manner. When located in the plasma membrane, they generally
utilise the transmembrane (TM) Na+ concentration gradient in order to
extrude Ca2+ from cells. Three mammalian isoforms have been cloned to date
(NCX1-3), which consist of 920-970 amino acid residues that are predicted
to possess 11 or 12 TM domains. Interestingly, they possess a short motif 
(~30 residues) that is similar to the Na+/K+-ATPase, although its function
is unknown [1-3].
 
NCX1 is the principal Na+/Ca2+ exchanger of cardiac myocytes, where it is
thought to play an important role in excitation-contraction coupling. It is
also found in a variety of other tissues, suggesting it serves as a house-
keeping protein, maintaining low cytosolic Ca2+ concentration. Alternatively
spliced variants of NCX1 have been identified, expression of which is cell 
type-specific. Sequence analysis reveals two sets of tandem repeats are 
found within the NCX1 protein sequence, which are usually referred to as
alpha and beta. The alpha repeats are thought to be involved in the ion
binding and translocation reactions of the exchanger, and the first beta 
repeat may be part of a regulatory site that responds to Ca2+ concentration.
 
NACAEXCHNGR1 is a 4-element fingerprint that provides a signature for
Na+/Ca2+ exchanger isoform 1. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from conserved regions
from the N-terminal half of the alignment length, focusing on those sections
that characterise isoform 1 but distinguish it from other Na+/Ca2+ exchanger
isoforms - motifs 1-2 lie on the N-terminal signal sequence that is presumed
to be cleaved in order to generate the mature protein; motif 3 encodes part 
of the first putative extracellular domain; and motif 4 is located on the
long cytoplasmic loop that connects the N- and C-terminal hydrophobic 
regions, which contain the putative TM domains. Two iterations on SPTR37_10f
were required to reach convergence, at which point a true set comprising 10
sequences was identified.
Summary Information
10 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
410101010
30000
20000
1234
True Positives
NAC1_BOVIN    NAC1_CANFA    NAC1_CAVPO    NAC1_FELCA    
NAC1_HUMAN NAC1_MOUSE NAC1_RAT O35157
O97801 Q28662
Sequence Titles
NAC1_BOVIN  SODIUM/CALCIUM EXCHANGER 1 PRECURSOR (NA+/CA2+-EXCHANGE PROTEIN 1) - BOS TAURUS  
NAC1_CANFA SODIUM/CALCIUM EXCHANGER 1 PRECURSOR (NA+/CA2+-EXCHANGE PROTEIN 1) - CANIS FAMIL
NAC1_CAVPO SODIUM/CALCIUM EXCHANGER 1 PRECURSOR (NA+/CA2+-EXCHANGE PROTEIN 1) - CAVIA PORCE
NAC1_FELCA SODIUM/CALCIUM EXCHANGER 1 PRECURSOR (NA+/CA2+-EXCHANGE PROTEIN 1) - FELIS SILVE
NAC1_HUMAN SODIUM/CALCIUM EXCHANGER 1 PRECURSOR (NA+/CA2+-EXCHANGE PROTEIN 1) - HOMO SAPIEN
NAC1_MOUSE SODIUM/CALCIUM EXCHANGER 1 PRECURSOR (NA+/CA2+-EXCHANGE PROTEIN 1) - MUS MUSCULU
NAC1_RAT SODIUM/CALCIUM EXCHANGER 1 PRECURSOR (NA+/CA2+-EXCHANGE PROTEIN 1) - RATTUS NORV
O35157 SOLUTE CARRIER FAMILY 8 (SODIUM/CALCIUM EXCHANGER), MEMBER 1 - MUS MUSCULUS (MOU
O97801 SODIUM-CALCIUM EXCHANGER ISOFORM NCX1.3 - MACACA MULATTA (RHESUS MACAQUE).
Q28662 RENAL NA/CA EXCHANGER NACA-2 - ORYCTOLAGUS CUNICULUS (RABBIT).
Scan History
SPTR37_10f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
SMGFHLLVTVSLL NAC1_HUMAN 11 11 -
SMGFRLVALVALL NAC1_MOUSE 11 11 -
SMGFRLVALVALL O35157 11 11 -
SMGFHVIAMVALL NAC1_BOVIN 11 11 -
SMGFHLLAIVALF Q28662 11 11 -
SLGFHLLAMMTLL NAC1_CAVPO 11 11 -
SMGFRLVTLVALL NAC1_RAT 11 11 -

Motif 2 width=12
Element Seqn Id St Int Rpt
FSHVDHVIAETE NAC1_HUMAN 24 0 -
FSHVDHITADTE NAC1_MOUSE 24 0 -
FSHVDHITADTE O35157 24 0 -
FSHVDHISAETE NAC1_BOVIN 24 0 -
FFRVDHVSAETE Q28662 24 0 -
ISHVDHITAETE NAC1_CAVPO 24 0 -
FTHVDHITADTE NAC1_RAT 24 0 -

Motif 3 width=10
Element Seqn Id St Int Rpt
ECTGSYYCKK NAC1_HUMAN 45 9 -
ECTGSYYCKK NAC1_MOUSE 45 9 -
ECTGSYYCKK O35157 45 9 -
ECTGSYYCKK NAC1_BOVIN 45 9 -
ECTGSYYCKK Q28662 45 9 -
ECTGSYYCKK NAC1_CAVPO 45 9 -
ECTGSYYCKK NAC1_RAT 45 9 -

Motif 4 width=13
Element Seqn Id St Int Rpt
SEDGILEANHVST NAC1_HUMAN 502 447 -
SEDGILESNHASS NAC1_MOUSE 502 447 -
SEDGILESNHASS O35157 502 447 -
SEDGILEASHVST NAC1_BOVIN 502 447 -
SEDGILEANHIST Q28662 502 447 -
SEDGILEANHIST NAC1_CAVPO 502 447 -
SEDGILDSNHVSA NAC1_RAT 502 447 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
SMGFHLLVIVALL O97801 11 11 -
SMGCHLLAVVALL NAC1_CANFA 11 11 -
SMGFHLLVTVSLL NAC1_HUMAN 11 11 -
SMGFRLVALVALL NAC1_MOUSE 11 11 -
SMGFRLVALVALL O35157 11 11 -
SMGFHVIAMVALL NAC1_BOVIN 11 11 -
SVGFHLLAFVPLL NAC1_FELCA 11 11 -
SMGFHLLAIVALF Q28662 11 11 -
SLGFHLLAMMTLL NAC1_CAVPO 11 11 -
SMGFRLVTLVALL NAC1_RAT 11 11 -

Motif 2 width=12
Element Seqn Id St Int Rpt
FSHVDYVIAETE O97801 24 0 -
FSHVDLISAETE NAC1_CANFA 24 0 -
FSHVDHVIAETE NAC1_HUMAN 24 0 -
FSHVDHITADTE NAC1_MOUSE 24 0 -
FSHVDHITADTE O35157 24 0 -
FSHVDHISAETE NAC1_BOVIN 24 0 -
FSHVDLISADTE NAC1_FELCA 24 0 -
FFRVDHVSAETE Q28662 24 0 -
ISHVDHITAETE NAC1_CAVPO 24 0 -
FTHVDHITADTE NAC1_RAT 24 0 -

Motif 3 width=10
Element Seqn Id St Int Rpt
ECTGSYYCKK O97801 45 9 -
ECTGSYYCKK NAC1_CANFA 45 9 -
ECTGSYYCKK NAC1_HUMAN 45 9 -
ECTGSYYCKK NAC1_MOUSE 45 9 -
ECTGSYYCKK O35157 45 9 -
ECTGSYYCKK NAC1_BOVIN 45 9 -
ECTGSYYCKK NAC1_FELCA 45 9 -
ECTGSYYCKK Q28662 45 9 -
ECTGSYYCKK NAC1_CAVPO 45 9 -
ECTGSYYCKK NAC1_RAT 45 9 -

Motif 4 width=13
Element Seqn Id St Int Rpt
SEDGILEANHVST O97801 502 447 -
SEDGILEANHVSA NAC1_CANFA 502 447 -
SEDGILEANHVST NAC1_HUMAN 502 447 -
SEDGILESNHASS NAC1_MOUSE 502 447 -
SEDGILESNHASS O35157 502 447 -
SEDGILEASHVST NAC1_BOVIN 502 447 -
SEDGILEANHVST NAC1_FELCA 502 447 -
SEDGILEANHIST Q28662 502 447 -
SEDGILEANHIST NAC1_CAVPO 502 447 -
SEDGILDSNHVSA NAC1_RAT 502 447 -