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PR01086

Identifier
NAHEXCHNGR2  [View Relations]  [View Alignment]  
Accession
PR01086
No. of Motifs
9
Creation Date
20-JAN-1999  (UPDATE 07-JUN-1999)
Title
Na+/H+ exchanger isoform 2 (NHE2) signature
Database References
PRINTS; PR01084 NAHEXCHNGR
PRODOM; PD040826; PF024503
INTERPRO; IPR001953
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].
 
NHE2, which shares around 50% amino acid identity with NHE1, has a limited 
expression pattern, being found preferentially in the gastrointestinal tract
and the kidney. It is also much less sensitive to the inhibitory diuretic 
amiloride than the more ubiquitous NHE1. The targeting of NHE2 in polarised
epithelial cells is controversial, some studies reporting basolateral, and
others reporting apical localisation. When transfected into mutagenised 
cells devoid of endogenous NHE activity, NHE2 is capable of regulating pH,
cellular volume, and proliferation, in a manner similar to NHE1.
 
NAHEXCHNGR2 is a 9-element fingerprint that provides a signature for the 
Na+/H+ exchanger isoform 2 (NHE2). The fingerprint was derived from an 
initial alignment of 4 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise NHE2 but distinguish it from other NHE isoforms -
motif 1 encodes the first putative extracellular domain; and motifs 2-9 span
the C-terminal putative cytoplasmic domain. A single iteration on OWL31.1
was required to reach convergence, no further sequences being identified
beyond the starting set. Two partial matches were found, S83549 and AF012894,
which are NHE2 protein fragments, from human and prairie dog, respectively.
 
An update on SPTR37_9f identified a true set of 3 sequences.
Summary Information
3 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
9333333333
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
NAH2_RABIT    NAH2_RAT      Q16434        
Sequence Titles
NAH2_RABIT  SODIUM/HYDROGEN EXCHANGER 2 (NA(+)/H(+) EXCHANGER 2) (NHE-2) - ORYCTOLAGUS CUNICULUS (RABBIT). 
NAH2_RAT SODIUM/HYDROGEN EXCHANGER 2 (NA(+)/H(+) EXCHANGER 2) (NHE-2) (H7) - RATTUS NORVEGICUS (RAT).
Q16434 NA+/H+ EXCHANGER - HOMO SAPIENS (HUMAN).
Scan History
OWL31_1    1  100  NSINGLE    
SPTR37_9f 2 4 NSINGLE
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
FGVDEKSPPAMKTD RATNHE2X 11 11 -
FGVDEKSPPAMKTD A57644 11 11 -
FGVDEKSPPAMKTD NAH2_RAT 127 127 -
FGVDEKSPPAMKTD NAH2_RABIT 126 126 -

Motif 2 width=30
Element Seqn Id St Int Rpt
FASLNDCREEKIRKLTPGEMDEIREILSRN A57644 465 440 -
FASLNDCREEKIRKLTPGEMDEIREILSRN NAH2_RAT 580 439 -
FASLNDCREEKIRKLTPGEMDEIREILSRN NAH2_RABIT 579 439 -
FASLNDCREEKIRKLTPGEMDEIREILSRN RATNHE2X 464 439 -

Motif 3 width=12
Element Seqn Id St Int Rpt
TADTSERQAKEI RATNHE2X 510 16 -
TADTSERQAKEI A57644 511 16 -
TADTSERQAKEI NAH2_RABIT 625 16 -
TADTSERQAKEI NAH2_RAT 626 16 -

Motif 4 width=21
Element Seqn Id St Int Rpt
SLPKNTKLPEKLQKKNKVSNA A57644 555 32 -
SLPKNTKLPEKLQKKNKVSNA NAH2_RAT 670 32 -
SLPKNTKLPEKLQKRKNISNA NAH2_RABIT 669 32 -
SLPKNTKLPEKLQKKNKVSNA RATNHE2X 554 32 -

Motif 5 width=21
Element Seqn Id St Int Rpt
GTTVLNLQPRARRFLPDQFSK RATNHE2X 585 10 -
GTTVLNLQPRARRFLPDQFSK A57644 586 10 -
GTTVLNLQPRARRFLPEPFSK NAH2_RABIT 701 11 -
GTTVLNLQPRARRFLPDQFSK NAH2_RAT 701 10 -

Motif 6 width=17
Element Seqn Id St Int Rpt
ASPAYKMEWKNEVDVGS A57644 608 1 -
ASQAYKMEWKNEVDAGS NAH2_RABIT 723 1 -
ASPAYKMEWKNEVDVGS NAH2_RAT 723 1 -
ASPAYKMEWKNEVDVGS RATNHE2X 607 1 -

Motif 7 width=25
Element Seqn Id St Int Rpt
PSVTPAPRSKEGGTQTPGVLRQPLL RATNHE2X 628 4 -
PSVTPAPRSKEGGTQTPGVLRQPLL A57644 629 4 -
PSVTPAPRSKEGGTQTPGVLRQPLL NAH2_RAT 744 4 -
PSPPAAPRSKEGGTQTPAVLRQPLL NAH2_RABIT 744 4 -

Motif 8 width=19
Element Seqn Id St Int Rpt
GREDSLTEDVPPKPPPRLV A57644 662 8 -
GREDSLTEGGRPKPPPRLV NAH2_RABIT 773 4 -
GREDSLTEDVPPKPPPRLV NAH2_RAT 777 8 -
GREDSLTEDGPPKPPPRLV RATNHE2X 661 8 -

Motif 9 width=18
Element Seqn Id St Int Rpt
RRASEPGNRKGRLGNEKP RATNHE2X 680 0 -
RRASEPGNRKGRLGNEKP A57644 681 0 -
RRASEPGNRKSRLGSDKP NAH2_RABIT 792 0 -
RRASEPGNRKGRLGNEKP NAH2_RAT 796 0 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
FGVDEKSPPAMKTD NAH2_RAT 127 127 -
FGVDEKSPPAMKTD Q16434 11 11 -
FGVDEKSPPAMKTD NAH2_RABIT 126 126 -

Motif 2 width=30
Element Seqn Id St Int Rpt
FASLNDCREEKIRKLTPGEMDEIREILSRN NAH2_RAT 580 439 -
FASLNDCREEKIRKLTPGEMDEIREILSRN Q16434 465 440 -
FASLNDCREEKIRKLTPGEMDEIREILSRN NAH2_RABIT 579 439 -

Motif 3 width=12
Element Seqn Id St Int Rpt
TADTSERQAKEI NAH2_RAT 626 16 -
TADTSERQAKEI Q16434 511 16 -
TADTSERQAKEI NAH2_RABIT 625 16 -

Motif 4 width=21
Element Seqn Id St Int Rpt
SLPKNTKLPEKLQKKNKVSNA NAH2_RAT 670 32 -
SLPKNTKLPEKLQKKNKVSNA Q16434 555 32 -
SLPKNTKLPEKLQKRKNISNA NAH2_RABIT 669 32 -

Motif 5 width=21
Element Seqn Id St Int Rpt
GTTVLNLQPRARRFLPDQFSK NAH2_RAT 701 10 -
GTTVLNLQPRARRFLPDQFSK Q16434 586 10 -
GTTVLNLQPRARRFLPEPFSK NAH2_RABIT 701 11 -

Motif 6 width=17
Element Seqn Id St Int Rpt
ASPAYKMEWKNEVDVGS NAH2_RAT 723 1 -
ASPAYKMEWKNEVDVGS Q16434 608 1 -
ASQAYKMEWKNEVDAGS NAH2_RABIT 723 1 -

Motif 7 width=25
Element Seqn Id St Int Rpt
PSVTPAPRSKEGGTQTPGVLRQPLL NAH2_RAT 744 4 -
PSVTPAPRSKEGGTQTPGVLRQPLL Q16434 629 4 -
PSPPAAPRSKEGGTQTPAVLRQPLL NAH2_RABIT 744 4 -

Motif 8 width=19
Element Seqn Id St Int Rpt
GREDSLTEDVPPKPPPRLV NAH2_RAT 777 8 -
GREDSLTEDVPPKPPPRLV Q16434 662 8 -
GREDSLTEGGRPKPPPRLV NAH2_RABIT 773 4 -

Motif 9 width=18
Element Seqn Id St Int Rpt
RRASEPGNRKGRLGNEKP NAH2_RAT 796 0 -
RRASEPGNRKGRLGNEKP Q16434 681 0 -
RRASEPGNRKSRLGSDKP NAH2_RABIT 792 0 -