9.B.36 The Acid Resistance Membrane Protein (HdeD) Family The HdeD protein of E. coli is a 190 aa protein required for induction of acid resistance in response to overexpression of the AraC-type regulator, YdeO (Masuda and Church, 2003). It has 6 TMSs in a 2 + 2 + 2 arrangement. Evidence for an internally triplicated 2 TMS element was found. This protein may function with a 194 aa, 2 TMS protein (gi #3288672). Homologues of HdeD include the DR3 protein of the moss, Tortula rutalis (223 aas; AAN87348) which also has 6 putative TMSs. Other homologues are annotated 'putative permease.' Homologues are generally of 160-240 aas in length with 6 TMSs in a 2 + 2 + 2 or 3 + 3 TMS arrangement, where the latter proteins show the first 3 TMSs are separated by larger hydrophilic loops than the last 3 TMSs. They derive from proteobacteria, cyanobacteria, plants, low and high G C Gram-positive bacteria and archaea. Some are much bigger (>450 aas) due to the presence of large hydrophilic extensions. This is a large superfamily with over 10 families (see entries under 9.B.36). These proteins are known as the DUF4386 domain proteins.
References:
Banesh, S. and V. Trivedi. (2020). Therapeutic Potentials of Scavenger Receptor CD36 Mediated Innate Immune Responses Against Infectious and Non-Infectious Diseases. Curr Drug Discov Technol 17: 299-317.
Benton, R., K.S. Vannice, and L.B. Vosshall. (2007). An essential role for a CD36-related receptor in pheromone detection in Drosophila. Nature 450: 289-293.
Gomez-Diaz, C., B. Bargeton, L. Abuin, N. Bukar, J.H. Reina, T. Bartoi, M. Graf, H. Ong, M.H. Ulbrich, J.F. Masson, and R. Benton. (2016). A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism. Nat Commun 7: 11866.
Jin, X., T.S. Ha, and D.P. Smith. (2008). SNMP is a signaling component required for pheromone sensitivity in Drosophila. Proc. Natl. Acad. Sci. USA 105: 10996-11001.
Krin, E., A. Danchin, and O. Soutourina. (2010). Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli. BMC Microbiol 10: 273.
Lalaouna, D., K. Prévost, G. Laliberté, V. Houé, and E. Massé. (2018). Contrasting silencing mechanisms of the same target mRNA by two regulatory RNAs in Escherichia coli. Nucleic Acids Res 46: 2600-2612.
Masuda, N. and G.M. Church. (2003). Regulatory network of acid resistance genes in Escherichia coli. Mol. Microbiol. 48: 699-712.
Mates, A.K., A.K. Sayed, and J.W. Foster. (2007). Products of the Escherichia coli acid fitness island attenuate metabolite stress at extremely low pH and mediate a cell density-dependent acid resistance. J. Bacteriol. 189: 2759-2768.
Xu, S., A. Jay, K. Brunaldi, N. Huang, and J.A. Hamilton. (2013). CD36 Enhances Fatty Acid Uptake by Increasing the Rate of Intracellular Esterification but Not Transport across the Plasma Membrane. Biochemistry 52: 7254-7261.
Zhang, L., Y. Zhang, L. Zhang, X. Yang, and Z. Lv. (2009). Lupeol, a dietary triterpene, inhibited growth, and induced apoptosis through down-regulation of DR3 in SMMC7721 cells. Cancer Invest 27: 163-170.
Examples:
TC#	Name	Organismal Type	Example
9.B.36.1.1	The acid resistance 6 TMS HdeD protein of 190 aas. The yhiD and hdeD gene products participate in an acid resistance mechanism exhibited only at high cell densities (Mates et al. 2007). H-NS directly controls expression of the hedD gene (Krin et al. 2010). Both small RNAs, CyaR and RprA, interact with the 5'-UTR of hdeD mRNA, and binding to the RBS of hdeD, interfers with translational initiation. Lalaouna et al. 2018 identified an A/U-rich motif on hdeD, which is bound by the RNA chaperone Hfq. The results indicate that binding of this motif by Hfq is required for CyaR-induced degradation of hdeD mRNA, and two molecules of RprA must bind the 5'-UTR of hdeD to block translation initiation. While both CyaR and RprA sRNAs bind to the same motif on the hdeD mRNA, RprA solely acts at the translational level, leaving the target RNA intact (Lalaouna et al. 2018). Scavenger receptor CD36 mediates innate immune responses against infectious and non-infectious diseases (Banesh and Trivedi 2020).	Bacteria	*HdeD of E. coli* (P0AET5)**

9.B.36.1.2	Uncharacterized protein of 226 aas and 6 TM	Actinobacteria	Uncharacterized protein of Streptomyces coelicolor

9.B.36.1.3	PF03729 (DUF308) family protein	Actinobacteria	DUF308 family member of Bifidobacterium longum

9.B.36.1.4	HdeD family acid-resistance protein of 183 aas and 6 TMSs.		HdeD protein of Chitinophaga sp. MD30

9.B.36.1.5	Uncharacterized protein of 160 aas and 6 TMSs.		UP of Methanobrevibacter arboriphilus

9.B.36.1.6	Uncharacterized protein of 235 aas and 8 TMSs.		UP of Lokiarchaeum sp. GC14_75

9.B.36.1.7	Uncharacterized protein	Archaea	Uncharacterized protein of Methanosarcina mazei

Examples:
TC#	Name	Organismal Type	Example
9.B.36.10.1	Uncharacterized protein of 227 aas and 6 TMSs		UP of Candidatus Aminicenantes bacterium RBG_16_66_30 (subsurface metagenome)

9.B.36.10.2	Uncharacterized protein of 210 aas and 6 TMSs		UP of Marinilabiliales bacterium (bioreactor metagenome)

Examples:
TC#	Name	Organismal Type	Example
9.B.36.11.1	Uncharacterized protein of 2009 aas and 6 TMSs.		UP of Sphingobacteriales bacterium

9.B.36.11.2	Uncharacteerized protein of 212 aas and 6 TMSs		*UP of Brevundimonas* sp. Root1279**

9.B.36.11.3	Uncharacterized protein of 217 aas and 6 TMSs		UP of Gemmatimonas phototrophica

Examples:
TC#	Name	Organismal Type	Example
9.B.36.12.1	Uncharacterized protein of 227 aas and 6 TMSs.		UP of Geodermatophilus pulveris

9.B.36.12.2	Uncharacterized protein of 196 aas and 6 TMSs in a 3 + 3 TMS arrangement.		UP of Cryptosporangium sp.

9.B.36.12.3	Uncharacterized protein of 192 aas and 6 TMSs		UP of Paenibacillus hemerocallicola

9.B.36.12.4	Uncharacterized protein of 230 aas and 6 TMSs		UP of Rhodococcus maanshanensis

9.B.36.12.5	Uncharacterized protein of 219 aas and 6 TMSs.		UP of Arthrobacter globiformis

9.B.36.12.6	Uncharacterized protein of 237 aas and 6 or 7 TMSs.		UP of Pseudomonas fluvialis

9.B.36.12.7	Uncharacterized protein of 208 aas and 6 TMSs.		UP of Streptomyces aidingensis

9.B.36.12.8	Uncharacterized protein of 211 aas and 6 TMSs		UP of Ktedonobacter racemifer

9.B.36.12.9	Uncharacterized protein of 200 aas and 6 TMSs		UP of Ahrensia sp.

Examples:
TC#	Name	Organismal Type	Example
9.B.36.13.1	Uncharacterized protein of 477 aas and 12 TMSs in a 6 + 6 TMS, or 3 + 3 + 3 + 3 TMS arrangement. Also shows some similarity with an MFS protein (TC# 2.A.1.2.41).		UP of Sinomonas sp.

9.B.36.13.2	Uncharacterized protein of 6 TMSs		UP of Kribbella jejuensis

9.B.36.13.3	Uncharacterized protein of 457 aas and 12 TMSs in a 3 + 3 + 3 + 3 TMS arrangement.		UP of Streptomyces sp.

9.B.36.13.4	Uncharacterized protein of 463 aas and 12 TMSs in a 3 + 3 + 3 + 3 TMS arrangement.		UP of Asanoa ferruginea

9.B.36.13.5	Uncharacterized protein of 240 aas and 6 TMSs.		UP of Actinopolymorpha singaporensis

Examples:
TC#	Name	Organismal Type	Example
9.B.36.14.1	Uncharacterized protein of 251 aas and 6 TMSs in a 1 + 2 + 3 TMS arrangement.		UP of Rhodopseudomonas palustris (Rhodopseudomonas rutila)

9.B.36.14.2	Uncharacterized protein of 242 aas and 6 TMSs.		UP of Aspergillus parasiticus

9.B.36.14.3	Uncharacterized protein of 242 aas and 6 TMSs in a 1 + 2 + 3 TMS arrangement.		UP of Mycolicibacterium rhodesiae

9.B.36.14.4	Uncharacterized protein of 225 aas and 6 TMSs in a 1 + 2 + 3 TMS arrangement.		UP of Mycobacterium conspicuum

9.B.36.14.5	Uncharacterized protein of 434 aas and 11 TMSs, where the last 5 TMSs (domain 2) are homologous to members of the COX family (e.g., 3.D.4.10.1; e^-21) and the first 6 TMSs (domain 1) are homologous to 9.B.36.14.1; E^-19 and other members of the HdeD family). The C-terminal 5 TMSs occur in a 1 + 2 + 2 TMS arrangement.		UP of Novosphingobium lentum

Examples:
TC#	Name	Organismal Type	Example
9.B.36.2.1	*DR3 protein of 233 aas and 6 TMSs; involved in growth regulation and appoptosis (Zhang et al.* 2009).**	Plants	DR3 of Synthrichia (Tortula) ruralis

9.B.36.2.2	RD3 homologue of 174 aas	Plants (moss)	RD3 of Selaginella moellendorffii

Examples:
TC#	Name	Organismal Type	Example
9.B.36.3.1	Uncharacterized protein	Chlamydiae	Uncharacterized protein of Parchlamydia acanthamoebae

9.B.36.3.2	HdeD family acid-resistance protein of 187 aas and 6 TMSs.		HdeD protein of Martelella mediterranea

Examples:
TC#	Name	Organismal Type	Example
9.B.36.4.1	Uncharacterized protein of 189 aas and 6 TMSs.		UP of Crenarchaeota group-6 archaeon AD8-1 (sediment metagenome)

9.B.36.4.2	UP of 194 aas and 6 TMSs.		UP of Crenarchaeota group-1 archaeon SG8-32-1

9.B.36.4.3	Uncharacterized protein of 223 aas and 6 TMSs.		UP of Candidatus Lokiarchaeota archaeon (marine sediment metagenome)

9.B.36.4.4	Uncharacterized protein of 207 aas and 6 TMSs		UP of Candidatus Heimdallarchaeota archaeon (marine sediment metagenome)

9.B.36.4.5	Uncharacterized protein of 166 aas and 6 TMSs		UP of Candidatus Bathyarchaeota archaeon (sediment metagenome)

9.B.36.4.6	Uncharacterized protein of 189 aas and 6 TMSs		UP of Candidatus Methanoplasma termitum

9.B.36.4.7	Uncharacterized protein of 182 aas and 6 TMSs.		UP of Methanomassiliicoccales archaeon (marine sediment metagenome)

Examples:
TC#	Name	Organismal Type	Example
9.B.36.5.1	Uncharacterized protein of 249 aas and 6 TMSs.		UP of Actinopolyspora mortivallis

9.B.36.5.2	Uncharacterized protein of 229 aas and 6 TMSs.		UP of Nonomuraea fuscirosea

9.B.36.5.3	Uncharacterized protein of 226 aas and 6 TMSs		UP of Nocardia brasiliensis

Examples:
TC#	Name	Organismal Type	Example
9.B.36.6.1	Uncharacterized DUF4386 protein of 249 aas and 6 TMSs in a 3 + 3 TMS arrangement		DUF4386 protein of Bauldia litoralis

9.B.36.6.2	Uncharacterized DUF4368 domain protein of 232 aas and 6 TMSs		DUF4368 protein of Paenibacillus durus (Paenibacillus azotofixans)

9.B.36.6.3	Uncharacteerized DUF4368 domain protein of 240 aas and 6 TMSs.		UP of Permianibacter aggregans

9.B.36.6.4	Uncharacterized protein of 244 aas and 6 TMSs		UP of Chloroflexi bacterium UTCFX4 (bioreactor sludge metagenome)

Examples:
TC#	Name	Organismal Type	Example
9.B.36.7.1	Uncharacterized protein of 249 aas and 6 TMSs		UP of Candidatus Bathyarchaeota archaeon (soil metagenome)

9.B.36.7.2	Uncharacterized protein of 245 aas and 6 TMSs.		UP of Modestobacter multiseptatus

Examples:
TC#	Name	Organismal Type	Example
9.B.36.8.1	Uncharacterized protein of 222 aas and 6 TMSs		UP of Colwellia psychrerythraea

9.B.36.8.2	Uncharacterized DUF4368 domain protein of 230 aas and 6 TMSs.		DUF4368 protein of Halococcus saccharolyticus

9.B.36.8.3	Uncharacterized protein having 6 TMSs in a loose 3 TMS + tight 3 TMS arrangement with a DUF4386 domain.		UP of Candidatus Syntrophoarchaeum caldarius

9.B.36.8.4	Uncharacterized protein of 211 aas and 6 TMSs		UP of Terrabacteria group bacterium ANGP1 (soil metagenome)

9.B.36.8.5	Uncharacterized protein of 205 aas and 6 TMSs		UP of Candidatus Roizmanbacteria bacterium

9.B.36.8.6	DUF4386 domain-containing protein of 240 aas and 6 TMSs with the first 3 TMSs separated from each other more than the last 3 TMSs.		DUF4386 protein of Actinomadura fibrosa

Examples:
TC#	Name	Organismal Type	Example
9.B.36.9.1	Uncharacterized protein of 236 aas and 6 TMSs.		UP of Thaumarchaeota archaeon (soil metagenome)

9.B.36.9.2	DUF4368 domain protein of 235 aas and 6 TMSs		DUF4368 protein of Leptospira sarikeiensis

9.B.36.9.3	DUF4386 domain-containing protein of 247 aas and 6 TMSs.		DUF4368 domain protein of Trichormus variabilis