2.A.53.2.15 Solute carrier family 26 member 9 (Anion transporter/exchanger protein 9; AE9). May play a role in chronic inflammatory airway diseases (Sala-Rabanal et al. 2015). The Cl--transporting proteins CFTR (TC# 3.A.1.202.1), SLC26A9, and anoctamin
(ANO1; ANO6) (see TC family 1.A.17) all participate in the pathogenic process and clinical outcomes of
airway and renal diseases (Kunzelmann et al. 2023). The molecular principles underlying diverse functions of the SLC26 family of proteins (Takahashi and Homma 2023). (i) The basic residue at the anion binding site is essential for both anion antiport of SLC26A4 and motor functions of SLC26A5, and its conversion to a nonpolar residue is crucial but not sufficient for the fast uncoupled anion transport in SLC26A9; (ii) the conserved polar residues in the N- and C-terminal cytosolic domains are likely involved in dynamic hydrogen-bonding networks and are essential for anion antiport of SLC26A4 but not for motor (SLC26A5) and uncoupled anion transport (SLC26A9) functions; (iii) the hydrophobic interaction between each protomer's last transmembrane helices, TM14, is not of functional significance in SLC26A9 but crucial for the functions of SLC26A4 and SLC26A5, likely contributing to optimally orient the axis of the relative movements of the core domain with respect to the gate domains within the cell membrane (Takahashi and Homma 2023). The anion exchanger solute carrier family 26 and its member, SLC26A9, consisting of
the transmembrane (TM) domain and the cytoplasmic STAS domain, plays an
essential role in regulating chloride transport (Omori et al. 2024). The removal of the C-terminus not only unblocks the access of ions to the
permeation pathway but also triggers STAS domain motion, gating the TM
domain to promote ions' entry into their binding site. The asymmetric motion of the STAS domain leads to the
expansion of the ion permeation pathway within the TM domain, resulting
in the stiffening of the flexible TM12 helix near the ion-binding site.
This structural change in the TM12 helix stabilizes chloride ion
binding, which is essential for SLC26A9's alternate-access mechanism (Omori et al. 2024). The asymmetric motion of the STAS domain leads to the expansion of the
ion permeation pathway within the TM domain, resulting in the stiffening
of the flexible TM12 helix near the ion-binding site. Use of the inhibitor, S9-A13, provided evidence that AE9 functions in the regulation of ASL pH and gastric proton/bicarbonate secSala-Rabanal et al. 2015). The Cl--transporting proteins CFTR (TC# 3.A.1.202.1), SLC26A9, and anoctamin
(ANO1; ANO6) (see TC family 1.A.17) all participate in the pathogenic process and clinical outcomes of
airway and renal diseases (Kunzelmann et al. 2023). The molecular principles underlying diverse functions of the SLC26 family of proteins (Takahashi and Homma 2023). (i) The basic residue at the anion binding site is essential for both anion antiport of SLC26A4 and motor functions of SLC26A5, and its conversion to a nonpolar residue is crucial but not sufficient for the fast uncoupled anion transport in SLC26A9; (ii) the conserved polar residues in the N- and C-terminal cytosolic domains are likely involved in dynamic hydrogen-bonding networks and are essential for anion antiport of SLC26A4 but not for motor (SLC26A5) and uncoupled anion transport (SLC26A9) functions; (iii) the hydrophobic interaction between each protomer's last transmembrane helices, TM14, is not of functional significance in SLC26A9 but crucial for the functions of SLC26A4 and SLC26A5, likely contributing to optimally orient the axis of the relative movements of the core domain with respect to the gate domains within the cell membrane (Takahashi and Homma 2023). The anion exchanger solute carrier family 26 and its member, SLC26A9, consisting of
the transmembrane (TM) domain and the cytoplasmic STAS domain, plays an
essential role in regulating chloride transport (Omori et al. 2024). The removal of the C-terminus not only unblocks the access of ions to the
permeation pathway but also triggers STAS domain motion, gating the TM
domain to promote ions' entry into their binding site. The asymmetric motion of the STAS domain leads to the
expansion of the ion permeation pathway within the TM domain, resulting
in the stiffening of the flexible TM12 helix near the ion-binding site.
This structural change in the TM12 helix stabilizes chloride ion
binding, which is essential for SLC26A9's alternate-access mechanism (Omori et al. 2024). The asymmetric motion of the STAS domain leads to the expansion of the
ion permeation pathway within the TM domain, resulting in the stiffening
of the flexible TM12 helix near the ion-binding site. Use of the inhibitor, S9-A13, provided evidence that AE9 functions in the regulation of ASL pH and gastric proton/bicarbonate secretion (Jo et al. 2022).
|
Accession Number: | Q7LBE3 |
Protein Name: | Solute carrier family 26 member 9 |
Length: | 791 |
Molecular Weight: | 86988.00 |
Species: | Homo sapiens (Human) [9606] |
Number of TMSs: | 11 |
Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
Substrate |
anion |
---|
Entrez Gene ID: |
115019
|
Pfam: |
PF01740
PF00916
|
KEGG: |
hsa:115019
|
|
[1] “Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9.” Lohi H. et.al. 11834742
[2] “The DNA sequence and biological annotation of human chromosome 1.” Gregory S.G. et.al. 16710414
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).” The MGC Project Team et.al. 15489334
[4] “SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl-/HCO3- exchange, and is inhibited by NH4+.” Xu J. et.al. 15800055
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1: MSQPRPRYVV DRAAYSLTLF DDEFEKKDRT YPVGEKLRNA FRCSSAKIKA VVFGLLPVLS
61: WLPKYKIKDY IIPDLLGGLS GGSIQVPQGM AFALLANLPA VNGLYSSFFP LLTYFFLGGV
121: HQMVPGTFAV ISILVGNICL QLAPESKFQV FNNATNESYV DTAAMEAERL HVSATLACLT
181: AIIQMGLGFM QFGFVAIYLS ESFIRGFMTA AGLQILISVL KYIFGLTIPS YTGPGSIVFT
241: FIDICKNLPH TNIASLIFAL ISGAFLVLVK ELNARYMHKI RFPIPTEMIV VVVATAISGG
301: CKMPKKYHMQ IVGEIQRGFP TPVSPVVSQW KDMIGTAFSL AIVSYVINLA MGRTLANKHG
361: YDVDSNQEMI ALGCSNFFGS FFKIHVICCA LSVTLAVDGA GGKSQVASLC VSLVVMITML
421: VLGIYLYPLP KSVLGALIAV NLKNSLKQLT DPYYLWRKSK LDCCIWVVSF LSSFFLSLPY
481: GVAVGVAFSV LVVVFQTQFR NGYALAQVMD TDIYVNPKTY NRAQDIQGIK IITYCSPLYF
541: ANSEIFRQKV IAKTGMDPQK VLLAKQKYLK KQEKRRMRPT QQRRSLFMKT KTVSLQELQQ
601: DFENAPPTDP NNNQTPANGT SVSYITFSPD SSSPAQSEPP ASAEAPGEPS DMLASVPPFV
661: TFHTLILDMS GVSFVDLMGI KALAKLSSTY GKIGVKVFLV NIHAQVYNDI SHGGVFEDGS
721: LECKHVFPSI HDAVLFAQAN ARDVTPGHNF QGAPGDAELS LYDSEEDIRS YWDLEQEMFG
781: SMFHAETLTA L