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PR01088

Identifier
NAHEXCHNGR6  [View Relations]  [View Alignment]  
Accession
PR01088
No. of Motifs
15
Creation Date
03-FEB-1999  (UPDATE 03-JUL-1999)
Title
Na+/H+ exchanger isoform 6 (NHE6) signature
Database References
PRINTS; PR01084 NAHEXCHNGR
INTERPRO; IPR002090
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].
 
NHE6 is a putative human mitochondrial Na+/H+ exchanger that is similar to
NHa2, an S.cerevisiae mitochondrial Na+/H+ exchanger [2]. NHE6 (although
ubquitously expressed) is particularly abundant in mitochondrion-rich
tissues such as brain, skeletal muscle and heart.
 
NAHEXCHNGR6 is a 15-element fingerprint that provides a signature for the
Na+/H+ exchanger isoform 6 (NHE6). The fingerprint was derived from an 
initial alignment of 2 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise NHE6 but distinguish it from other NHE isoforms -
motif 1 resides within the N-terminal putative cytoplasmic domain; motif 2
spans part of the N-terminus and transmembrane (TM) domain 1; motif 3 spans
the C-terminus of TM domain 1 and the following extracellular loop; motif 4 
spans the C-terminus of the first extracellular loop and about half the 
following TM domain; motif 5 encodes the remainder of TM domain 2, the first
cytoplasmic loop, and the first residues of TM domain 3; motif 6 encodes the
remainder of TM domain 3 and part of the second extracellular loop; motif 7
resides within the second extracellular loop; motif 8 encodes the C-terminus
of TM domain 7 and the following extracellular loop; motif 9 spans TM domain
8 and the following cytoplasmic loop; and the remaining motifs, 10-15, reside
within the C-terminal cytoplasmic region. A single iteration on OWL31.1 was
required to reach convergence, no further sequences being identified beyond
the starting set. A single partial match was found, HS71L161, a human
sequence containing a putative Na+/H+ exchanger that matches motifs 8-10.
 
An update on OWL31_3 identified a true set of 2 sequences, and 2
partial matches.
Summary Information
   2 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
1 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
15222222222222222
14000000000000000
13000000000000000
12000000000000000
11000000000000000
10000000000000000
9000000000000000
8000000000000000
7000000000000000
6000000011111100
5000000000000000
4000000000000000
3000000000000000
2000000000000000
123456789101112131415
True Positives
AF030409      D87743        
True Positive Partials
Codes involving 6 elements
HS71L161
Sequence Titles
AF030409    AF030409 NID: g2944232 - human.               
D87743 D87743 NID: g1665826 - Homo sapiens male bone marrow Myeloblast...

HS71L161 HS71L16 NID: g3281985 - human.
Scan History
OWL31_1    1  100  NSINGLE    
OWL31_3 1 10 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
WRRAPLRRGVGSSPRARRL AF030409 6 6 -
WRRAPLRRGVGSSPRARRL D87743 3 3 -

Motif 2 width=19
Element Seqn Id St Int Rpt
MRPLWLLLAVGVFDWAGAS AF030409 25 0 -
MRPLWLLLAVGVFDWAGAS D87743 22 0 -

Motif 3 width=20
Element Seqn Id St Int Rpt
DGGGGEARAMDEEIVSEKQA AF030409 44 0 -
DGGGGEARAMDEEIVSEKQA D87743 41 0 -

Motif 4 width=25
Element Seqn Id St Int Rpt
EESHRQDSANLLIFILLLTLTILTI AF030409 64 0 -
EESHRQDSANLLIFILLLTLTILTI D87743 61 0 -

Motif 5 width=19
Element Seqn Id St Int Rpt
WLFKHRRARFLHETGLAMI AF030409 89 0 -
WLFKHRRARFLHETGLAMI D87743 86 0 -

Motif 6 width=27
Element Seqn Id St Int Rpt
YGLLVGLVLRYGIHVPSDVNNVTLSCE AF030409 108 0 -
YGLLVGLVLRYGIHVPSDVNNVTLSCE D87743 105 0 -

Motif 7 width=14
Element Seqn Id St Int Rpt
QSSPTTLLVTFDPE AF030409 136 1 -
QSSPTTLLVTFDPE D87743 133 1 -

Motif 8 width=18
Element Seqn Id St Int Rpt
SSSIVAYQPAGDNSHTFD AF030409 267 117 -
SSSIVAYQPAGDNSHTFD D87743 264 117 -

Motif 9 width=20
Element Seqn Id St Int Rpt
TAMFKSIGIFLGIFSGSFAM AF030409 286 1 -
TAMFKSIGIFLGIFSGSFAM D87743 283 1 -

Motif 10 width=27
Element Seqn Id St Int Rpt
TTAMLSCLHIRVGVDSDQEHLGVPENE AF030409 497 191 -
TTAMLSCLHIRVGVDSDQEHLGVPENE D87743 494 191 -

Motif 11 width=19
Element Seqn Id St Int Rpt
RRTTKAESAWLFRMWYNFD AF030409 524 0 -
RRTTKAESAWLFRMWYNFD D87743 521 0 -

Motif 12 width=29
Element Seqn Id St Int Rpt
PLLTHSGPPLTTTLPACCGPIARCLTSPQ AF030409 548 5 -
PLLTHSGPPLTTTLPACCGPIARCLTSPQ D87743 545 5 -

Motif 13 width=28
Element Seqn Id St Int Rpt
AYENQEQLKDDDSDLILNDGDISLTYGD AF030409 577 0 -
AYENQEQLKDDDSDLILNDGDISLTYGD D87743 574 0 -

Motif 14 width=22
Element Seqn Id St Int Rpt
TEPATSSAPRRFMGNSSEDALD AF030409 609 4 -
TEPATSSAPRRFMGNSSEDALD D87743 606 4 -

Motif 15 width=30
Element Seqn Id St Int Rpt
DHELVIRGTRLVLPMDDSEPPLNLLDNTRH AF030409 633 2 -
DHELVIRGTRLVLPMDDSEPPLNLLDNTRH D87743 630 2 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
WRRAPLRRGVGSSPRARRL AF030409 6 6 -
WRRAPLRRGVGSSPRARRL D87743 3 3 -

Motif 2 width=19
Element Seqn Id St Int Rpt
MRPLWLLLAVGVFDWAGAS AF030409 25 0 -
MRPLWLLLAVGVFDWAGAS D87743 22 0 -

Motif 3 width=20
Element Seqn Id St Int Rpt
DGGGGEARAMDEEIVSEKQA AF030409 44 0 -
DGGGGEARAMDEEIVSEKQA D87743 41 0 -

Motif 4 width=25
Element Seqn Id St Int Rpt
EESHRQDSANLLIFILLLTLTILTI AF030409 64 0 -
EESHRQDSANLLIFILLLTLTILTI D87743 61 0 -

Motif 5 width=19
Element Seqn Id St Int Rpt
WLFKHRRARFLHETGLAMI AF030409 89 0 -
WLFKHRRARFLHETGLAMI D87743 86 0 -

Motif 6 width=27
Element Seqn Id St Int Rpt
YGLLVGLVLRYGIHVPSDVNNVTLSCE AF030409 108 0 -
YGLLVGLVLRYGIHVPSDVNNVTLSCE D87743 105 0 -

Motif 7 width=14
Element Seqn Id St Int Rpt
QSSPTTLLVTFDPE AF030409 136 1 -
QSSPTTLLVTFDPE D87743 133 1 -

Motif 8 width=18
Element Seqn Id St Int Rpt
SSSIVAYQPAGDNSHTFD AF030409 267 117 -
SSSIVAYQPAGDNSHTFD D87743 264 117 -

Motif 9 width=20
Element Seqn Id St Int Rpt
TAMFKSIGIFLGIFSGSFAM AF030409 286 1 -
TAMFKSIGIFLGIFSGSFAM D87743 283 1 -

Motif 10 width=27
Element Seqn Id St Int Rpt
TTAMLSCLHIRVGVDSDQEHLGVPENE AF030409 497 191 -
TTAMLSCLHIRVGVDSDQEHLGVPENE D87743 494 191 -

Motif 11 width=19
Element Seqn Id St Int Rpt
RRTTKAESAWLFRMWYNFD AF030409 524 0 -
RRTTKAESAWLFRMWYNFD D87743 521 0 -

Motif 12 width=29
Element Seqn Id St Int Rpt
PLLTHSGPPLTTTLPACCGPIARCLTSPQ AF030409 548 5 -
PLLTHSGPPLTTTLPACCGPIARCLTSPQ D87743 545 5 -

Motif 13 width=28
Element Seqn Id St Int Rpt
AYENQEQLKDDDSDLILNDGDISLTYGD AF030409 577 0 -
AYENQEQLKDDDSDLILNDGDISLTYGD D87743 574 0 -

Motif 14 width=22
Element Seqn Id St Int Rpt
TEPATSSAPRRFMGNSSEDALD AF030409 609 4 -
TEPATSSAPRRFMGNSSEDALD D87743 606 4 -

Motif 15 width=30
Element Seqn Id St Int Rpt
DHELVIRGTRLVLPMDDSEPPLNLLDNTRH AF030409 633 2 -
DHELVIRGTRLVLPMDDSEPPLNLLDNTRH D87743 630 2 -