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PR01087

Identifier
NAHEXCHNGR3  [View Relations]  [View Alignment]  
Accession
PR01087
No. of Motifs
16
Creation Date
20-JAN-1999  (UPDATE 07-JUN-1999)
Title
Na+/H+ exchanger isoform 3 (NHE3) signature
Database References
PRINTS; PR01084 NAHEXCHNGR
PRODOM; PD017855; PD024500
INTERPRO; IPR001118
Literature References
1. ORLOWSKI, J. AND GRINSTEIN, S.
Na+/H+ exchangers of mammalian cells.
J.BIOL.CHEM. 272 22373-22376 (1997).
 
2. NUMATA, M., PETRECCA, K., LAKE, N. AND ORLOWSKI, J.
Identification of a mitochondrial Na+/H+ exchanger.
J.BIOL.CHEM. 273 6951-6959 (1998).
 
3. DIBROV, P. AND FLIEGEL, L.
Comparative molecular analysis of Na+/H+ exchangers: a unified model for
Na+/H+ antiport.
FEBS LETT. 424 1-5 (1998).

Documentation
Na+/H+ exchange proteins eject protons from cells, effectively eliminating
excess acid from actively metabolising cells. Na+/H+ exchange activity is
also crucial for the regulation of cell volume, and for the reabsorption of
NaCl across renal, intestinal, and other epithelia. These antiports exchange
Na+ for H+ in an electroneutral manner, and this activity is carried out by
a family of Na+/H+ exchangers, or NHEs, which are known to be present in
both prokaryotic and eukaryotic cells. In mammalian cells, Na+/H+ exchange
activity is found in both the plasma membrane and inner mitochondrial
membrane. To date, six mammalian isoforms have been identified (designated
NHE1-NHE6) [1,2]. These exchangers are highly-regulated (glyco)phospho-
proteins, which, based on their primary structure, appear to contain 10-12
membrane-spanning regions at the N-terminus and a large cytoplasmic region
at the C-terminus. There is some evidence that they may exist in the cell
membrane as homodimers, but little is currently known about the mechanism
of their antiport [3].
 
NHE3, which shares around 40% amino acid identity with NHE1, appears not to
be glycosylated, and is found preferentially in the gastrointestinal tract
and the kidney. It is not readily inhibited by the diuretic amiloride, and 
immunological studies have localised it to the apical membranes of the renal
proximal tubule and intestinal epithelia, implicating this isoform in Na+
absorption.
 
NAHEXCHNGR3 is a 16-element fingerprint that provides a signature for the 
Na+/H+ exchanger isoform 3 (NHE3). The fingerprint was derived from an 
initial alignment of 3 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise NHE3 but distinguish it from other NHE isoforms -
motif 1 lies within the first putative extracellular loop; motif 2 encodes
about half the second transmembrane (TM) domain; motif 3 spans the third TM 
domain and the following extracellular loop; motifs 4 and 5 encode the third
and fourth extracellular loops; motif 6 spans the C-terminus of the sixth 
TM domain and a portion of the following cytoplasmic loop; motif 7 spans the
seventh TM domain and the fifth extracellular loop; and the remaining motifs,
8-16, reside at the cytoplasmic C-terminus. Two iterations on OWL31.1 were
required to reach convergence, at which point a true set comprising 4 
sequences was identified. Two partial matches were also found, CLU75970 and
MUU93492, both of which are NHE3 protein fragments, from black-tailed
prairie dog, and Mongolian gerbil, respectively.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 codes involving 16 elements
0 codes involving 15 elements
0 codes involving 14 elements
0 codes involving 13 elements
0 codes involving 12 elements
0 codes involving 11 elements
0 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
164444444444444444
150000000000000000
140000000000000000
130000000000000000
120000000000000000
110000000000000000
100000000000000000
90000000000000000
80000000000000000
70000000000000000
60000000000000000
50000000000000000
40000000000000000
30000000000000000
20000000000000000
12345678910111213141516
True Positives
NAH3_DIDMA    NAH3_HUMAN    NAH3_RABIT    NAH3_RAT      
Sequence Titles
NAH3_DIDMA  SODIUM/HYDROGEN EXCHANGER 3 (NA(+)/H(+) EXCHANGER 3) (NHE-3) - DIDELPHIS MARSUPIALIS VIRGINIANA (NORTH AMERICAN OPOSSUM). 
NAH3_HUMAN SODIUM/HYDROGEN EXCHANGER 3 (NA(+)/H(+) EXCHANGER 3) (NHE-3) - HOMO SAPIENS (HUMAN).
NAH3_RABIT SODIUM/HYDROGEN EXCHANGER 3 (NA(+)/H(+) EXCHANGER 3) (NHE-3) - ORYCTOLAGUS CUNICULUS (RABBIT).
NAH3_RAT SODIUM/HYDROGEN EXCHANGER 3 (NA(+)/H(+) EXCHANGER 3) (NHE-3) - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    2  100  NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=7
Element Seqn Id St Int Rpt
QDPYIIA NAH3_RABIT 52 52 -
QDPYIIA NAH3_DIDMA 58 58 -
QDPYVIA NAH3_HUMAN 53 53 -

Motif 2 width=8
Element Seqn Id St Int Rpt
LSHKVTSV NAH3_RABIT 73 14 -
LSHKVTSV NAH3_DIDMA 79 14 -
LSHKVTSV NAH3_HUMAN 74 14 -

Motif 3 width=7
Element Seqn Id St Int Rpt
ASFTLTP NAH3_RABIT 105 24 -
ASFTLTP NAH3_DIDMA 111 24 -
ASFTLTP NAH3_HUMAN 106 24 -

Motif 4 width=11
Element Seqn Id St Int Rpt
GVFLSGIMGEL NAH3_RABIT 163 51 -
GVYLSGIMGDL NAH3_DIDMA 169 51 -
GVFLSGLMGDL NAH3_HUMAN 164 51 -

Motif 5 width=10
Element Seqn Id St Int Rpt
DKVTGVDCVK NAH3_RABIT 239 65 -
DKVTGVDCVK NAH3_DIDMA 245 65 -
DNVTGVDCVK NAH3_HUMAN 240 65 -

Motif 6 width=8
Element Seqn Id St Int Rpt
FAFLLSLV NAH3_RABIT 267 18 -
FAFLLSLV NAH3_DIDMA 273 18 -
FAFLLSLV NAH3_HUMAN 268 18 -

Motif 7 width=13
Element Seqn Id St Int Rpt
ILAITFCGICCQK NAH3_RABIT 308 33 -
ILAITFCGICCQK NAH3_DIDMA 314 33 -
ILAITFCGICCQK NAH3_HUMAN 309 33 -

Motif 8 width=11
Element Seqn Id St Int Rpt
EHREPKLNEKL NAH3_RABIT 468 147 -
EHREPKLNEKL NAH3_DIDMA 474 147 -
EHREPRLNEKL NAH3_HUMAN 469 147 -

Motif 9 width=10
Element Seqn Id St Int Rpt
GRAFDHILSA NAH3_RABIT 480 1 -
GRAFDHILSA NAH3_DIDMA 486 1 -
GRAFDHILSA NAH3_HUMAN 481 1 -

Motif 10 width=16
Element Seqn Id St Int Rpt
SAQKSRDRILNVFHEL NAH3_RABIT 522 32 -
SAQKSRDRILNVFHEL NAH3_DIDMA 528 32 -
SAQKSRDRILNVFHEL NAH3_HUMAN 523 32 -

Motif 11 width=19
Element Seqn Id St Int Rpt
NLKDAISYVTEGERRGSLA NAH3_RABIT 538 0 -
NLKDAISYVAEGERRGSLA NAH3_DIDMA 544 0 -
NLKDAISYVAEGERRGSLA NAH3_HUMAN 539 0 -

Motif 12 width=14
Element Seqn Id St Int Rpt
IRSPSTDNMVNVDF NAH3_RABIT 558 1 -
IRSPSTDNIVNVDF NAH3_DIDMA 564 1 -
IRSPSTDNVVNVDF NAH3_HUMAN 559 1 -

Motif 13 width=22
Element Seqn Id St Int Rpt
HHTLQQYLYKPRQEYKHLYSRH NAH3_RABIT 617 45 -
HHTLQQYLYKPRQEYKHLYSRH NAH3_DIDMA 623 45 -
HHTLQQYLYKPRQEYKHLYSRH NAH3_HUMAN 617 44 -

Motif 14 width=22
Element Seqn Id St Int Rpt
DEKQDKEIFHRTMRKRLESFKS NAH3_RABIT 645 6 -
DEKQDKEIFHRTMRKRLESFKS NAH3_DIDMA 651 6 -
DEKQDREIFHRTMRKRLESFKS NAH3_HUMAN 645 6 -

Motif 15 width=15
Element Seqn Id St Int Rpt
MSGGIEFLASVTKDT NAH3_RABIT 733 66 -
MSGGIEFLANVTQDT NAH3_DIDMA 737 64 -
MSGGIEFLASVTKDT NAH3_HUMAN 730 63 -

Motif 16 width=26
Element Seqn Id St Int Rpt
QIPYSPGNFRRLAPFRLSNKSVDSFL NAH3_RABIT 793 45 -
QIPYSPSNFRRLTPIRLSTKSVDSFL NAH3_DIDMA 795 43 -
QIPYSPGTFRRLMPFRLSSKSVDSFL NAH3_HUMAN 790 45 -
Final Motifs
Motif 1  width=7
Element Seqn Id St Int Rpt
QDPYIIA NAH3_RABIT 52 52 -
QDPYIIA NAH3_RAT 50 50 -
QDPYIIA NAH3_DIDMA 58 58 -
QDPYVIA NAH3_HUMAN 53 53 -

Motif 2 width=8
Element Seqn Id St Int Rpt
LSHKVTSV NAH3_RABIT 73 14 -
LSHKVTSV NAH3_RAT 71 14 -
LSHKVTSV NAH3_DIDMA 79 14 -
LSHKVTSV NAH3_HUMAN 74 14 -

Motif 3 width=7
Element Seqn Id St Int Rpt
ASFTLTP NAH3_RABIT 105 24 -
ASFTLTP NAH3_RAT 103 24 -
ASFTLTP NAH3_DIDMA 111 24 -
ASFTLTP NAH3_HUMAN 106 24 -

Motif 4 width=11
Element Seqn Id St Int Rpt
GVFLSGIMGEL NAH3_RABIT 163 51 -
GVFLSGLMGEL NAH3_RAT 161 51 -
GVYLSGIMGDL NAH3_DIDMA 169 51 -
GVFLSGLMGDL NAH3_HUMAN 164 51 -

Motif 5 width=10
Element Seqn Id St Int Rpt
DKVTGVDCVK NAH3_RABIT 239 65 -
DAVTGVDCVK NAH3_RAT 237 65 -
DKVTGVDCVK NAH3_DIDMA 245 65 -
DNVTGVDCVK NAH3_HUMAN 240 65 -

Motif 6 width=8
Element Seqn Id St Int Rpt
FAFLLSLV NAH3_RABIT 267 18 -
FAFLLSLV NAH3_RAT 265 18 -
FAFLLSLV NAH3_DIDMA 273 18 -
FAFLLSLV NAH3_HUMAN 268 18 -

Motif 7 width=13
Element Seqn Id St Int Rpt
ILAITFCGICCQK NAH3_RABIT 308 33 -
ILAITFCGICCQK NAH3_RAT 306 33 -
ILAITFCGICCQK NAH3_DIDMA 314 33 -
ILAITFCGICCQK NAH3_HUMAN 309 33 -

Motif 8 width=11
Element Seqn Id St Int Rpt
EHREPKLNEKL NAH3_RABIT 468 147 -
EQREPKLNEKL NAH3_RAT 466 147 -
EHREPKLNEKL NAH3_DIDMA 474 147 -
EHREPRLNEKL NAH3_HUMAN 469 147 -

Motif 9 width=10
Element Seqn Id St Int Rpt
GRAFDHILSA NAH3_RABIT 480 1 -
GRAFDHILSA NAH3_RAT 478 1 -
GRAFDHILSA NAH3_DIDMA 486 1 -
GRAFDHILSA NAH3_HUMAN 481 1 -

Motif 10 width=16
Element Seqn Id St Int Rpt
SAQKSRDRILNVFHEL NAH3_RABIT 522 32 -
SAQKSRDRILNVFHEL NAH3_RAT 520 32 -
SAQKSRDRILNVFHEL NAH3_DIDMA 528 32 -
SAQKSRDRILNVFHEL NAH3_HUMAN 523 32 -

Motif 11 width=19
Element Seqn Id St Int Rpt
NLKDAISYVTEGERRGSLA NAH3_RABIT 538 0 -
NLKDAISYVAEGERRGSLA NAH3_RAT 536 0 -
NLKDAISYVAEGERRGSLA NAH3_DIDMA 544 0 -
NLKDAISYVAEGERRGSLA NAH3_HUMAN 539 0 -

Motif 12 width=14
Element Seqn Id St Int Rpt
IRSPSTDNMVNVDF NAH3_RABIT 558 1 -
IRSPSTDNMVNVDF NAH3_RAT 556 1 -
IRSPSTDNIVNVDF NAH3_DIDMA 564 1 -
IRSPSTDNVVNVDF NAH3_HUMAN 559 1 -

Motif 13 width=22
Element Seqn Id St Int Rpt
HHTLQQYLYKPRQEYKHLYSRH NAH3_RABIT 617 45 -
HHTLQQYLYKPRQEYKHLYSRH NAH3_RAT 615 45 -
HHTLQQYLYKPRQEYKHLYSRH NAH3_DIDMA 623 45 -
HHTLQQYLYKPRQEYKHLYSRH NAH3_HUMAN 617 44 -

Motif 14 width=22
Element Seqn Id St Int Rpt
DEKQDKEIFHRTMRKRLESFKS NAH3_RABIT 645 6 -
DEKQDKEIFHRTMRKRLESFKS NAH3_RAT 643 6 -
DEKQDKEIFHRTMRKRLESFKS NAH3_DIDMA 651 6 -
DEKQDREIFHRTMRKRLESFKS NAH3_HUMAN 645 6 -

Motif 15 width=15
Element Seqn Id St Int Rpt
MSGGIEFLASVTKDT NAH3_RABIT 733 66 -
ISGGIEFLASVTKDV NAH3_RAT 727 62 -
MSGGIEFLANVTQDT NAH3_DIDMA 737 64 -
MSGGIEFLASVTKDT NAH3_HUMAN 730 63 -

Motif 16 width=26
Element Seqn Id St Int Rpt
QIPYSPGNFRRLAPFRLSNKSVDSFL NAH3_RABIT 793 45 -
QIPNSPSNFRRLTPFRLSNKSVDSFL NAH3_RAT 787 45 -
QIPYSPSNFRRLTPIRLSTKSVDSFL NAH3_DIDMA 795 43 -
QIPYSPGTFRRLMPFRLSSKSVDSFL NAH3_HUMAN 790 45 -