9.B.2 The Integral Membrane CAAX Protease-2 (CAAX Protease2) Family

The CAAX Protease2 family includes members that are similar in many ways to the CAAX protease family (9.B.1), but the sequence divergence is extensive. The latter proteins do not bring up members of the former family in PSI-BLAST searches, and vise versa. These proteins bring up 3.A.1.115.2 (NatB, the membrane constituent of the Na exporting ABC system, NatAB) and 3.A.1.110.1 (MceF, with 7 TMSs that may be a CAAX protease and not part of the transporter). These proteins may have a 2 + 2 + 2 TMS topology.  Sortases (TC# 9.B.297) are distantly related to members of the CAAX protease-2.1 subfamily, and some of these are listed under TC subfamily 9.B.2.14 (Haft 2024).



This family belongs to the CAAX Superfamily.

 

References:

Biswas, S. and I. Biswas. (2014). A conserved streptococcal membrane protein, LsrS, exhibits a receptor-like function for lantibiotics. J. Bacteriol. 196: 1578-1587.

Grell, T.A.J., W.M. Kincannon, N.A. Bruender, E.J. Blaesi, C. Krebs, V. Bandarian, and C.L. Drennan. (2018). Structural and spectroscopic analyses of the sporulation killing factor biosynthetic enzyme SkfB, a bacterial AdoMet radical sactisynthase. J. Biol. Chem. 293: 17349-17361.

Haft, D.H. (2024). discovery of the myxosortases that process MYXO-CTERM and three novel prokaryotic C-terminal protein-sorting signals that share invariant Cys residues. J. Bacteriol. 206: e0017323.

Pei, J. and N.V. Grishin. (2001). Type II CAAX prenyl endopeptidases belong to a novel superfamily of putative membrane-bound metalloproteases. Trends. Biochem. Sci. 26: 275-277.

Examples:

TC#NameOrganismal TypeExample
9.B.2.1.1

CAAX protease2 of 302aas and 8 TMSs

Chlamydiae

CAAX protease2 of Parachlamydia acanthamoebae (F8KZQ2)

 
9.B.2.1.10

CAAX protease involved in immunity against bacteriocins (Pei and Grishin 2001).

Firmicutes

CAAX protease of Streptococcus pyogenes

 
9.B.2.1.11

CAAX protease of 233 aas.

Algae (Cryptophyta)

CAAX protease of Guillardia theta

 
9.B.2.1.12

Abortive infection domain protein, Abi of 193 aas.  The C-terminal region has the Abi domain.

Proteobacteria

Putative CAAX protease of Marinobacter aquaeolei (Marinobacter hydrocarbonoclasticus)

 
9.B.2.1.13

Abortive infection-like protein of 323 aas with a C-terminal Abi domain.

Algae (Rhodophyta)

Abi protein of Galdieria sulphuraria

 
9.B.2.1.14

Abi domain-containing protein of 305 aas and 10 TMSs.

Proteobacteria

Abi protein of Koribacter versatilis

 
9.B.2.1.15

Abi domain-containing protein of 400 aas and 10 TMSs.

Red algae (Rhodophyta)

Abi protein of Galdieria sufphuraria

 
9.B.2.1.16

LsrS, a 229 aas CAAX peptidase that is required for receptor function for the killing activity of the lantibiiotics Smb and nisin (Biswas and Biswas 2014).  The peptidase activity is not required for receptor function.

Firmicutes

LsrS of Streptococcus mutans

 
9.B.2.1.17

CAAX protease of 223 aas and 7 TMSs

CAAX protease of Chlamydomonas reinhardtii

 
9.B.2.1.18

Putative CAAX protease of 215 aas and 6 TMSs

CAAX protease of Lactobacillus rhamnosus

 
9.B.2.1.19

Membrane peptidase, YdiL, of 293 aas.

YdiL of Capsicum annuum

 
9.B.2.1.2

CAAX protease2 of 258aas and 7 or 8 TMSs.

Chlamydiae

CAAX protease2 of Chlamydophila pecorum (F4DIL5)

 
9.B.2.1.20

Intramembrane metaloprotease of 195 aas and 7 TMSs.

Protease of Lactobacillus xiangfangensis

 
9.B.2.1.21

CPBP protease family member of 225 aas and 6 TMSs.

Protease of Bacillus cereus

 
9.B.2.1.22

CPBP integral membrane metaloprotease (sortase?) family member of 242 aas and 6 or 7 TMSs.

Protease of Dokdonella koreensis

 
9.B.2.1.23

CAAX amino terminal protease family protein of 351 aas and 8 TMSs.

CAAX protease of Clostridium methylpentosum

 
9.B.2.1.24

Uncharacterized putative integral membrane proteinof 240 aas and 6 TMSs.

UP of Mycobacterium tuberculosis

 
9.B.2.1.25

CAAX protease of 357 aas and 7 TMSs.

CAAX protease of Lokiarchaeum sp.

 
9.B.2.1.26

Uncharacterized putative peptidase of 163 aas and 5 putative TMSs.

UP of Candidatus Thorarchaeota archaeon AB_25 (marine sediment metagenome)

 
9.B.2.1.27

Uncharacterized protein of 325 aas and 8 TMSs

UP of Candidatus Thorarchaeota archaeon AB_25 (marine sedimet metagenome)

 
9.B.2.1.28

CPBP family intramembrane metalloprotease of 1141 aas and 7 TMSs, all at the C-terminus of the protein.

Protease of Bifidobacterium indicum

 
9.B.2.1.29

JDVT-CTERM system glutamic-type intramembrane protease of 163 aas and 5 TMSs. It may not be full length.

Protease of Noviherbaspirillum sp.

 
9.B.2.1.3

CAAX protease2 of 256aas and 7 or 8 TMSs

Chlamydiae

CAAX protease of Chlamydia trachomatis (Q3KMA8)

 
9.B.2.1.4

Uncharacterized protein of 420 aas

Euryarchaea

UP of Methanothermobacter thermautotrophicus

 
9.B.2.1.5

CAAX protease2 of 239aas and 5 or 6 TMSs

Bacteroidetes

CAAX protease2 of Porphyromonas catoniae (L1NER1)

 
9.B.2.1.6

Me2+-dependent protease of 303aas and 8 TMSs

Cyanobacteria

Protease of Acaryochloris marina (B0C1B4)

 
9.B.2.1.7

CAAX protease2 of 373aas and 11 TMSs

Archaea

CAAX protease2 of Natronolimnobius innermongolicus (L9XEM0)

 
9.B.2.1.8

CAAX protease2 of 230aas and 6 TMSs

Firmicutes

CAAX protease2 of Sporosarcina newyorkensis (F9DWD5)

 
9.B.2.1.9

MceF CAAX Protease

Bacteria

MceF of Klebsiella pneumoniae

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.10.1

The CPBP family intramembrane metalloprotease domain-containing protein of 468 aas and 7 TMSs.

CPBP protease of Methanomassiliicoccus luminyensis

 
9.B.2.10.2

Uncharacterized CPBP family intramembrane metalloprotease domain-containing protein of 366 aas and 8 TMSs.

UP of Aciduliprofundum boonei

 
9.B.2.10.3

Uncharacterized CPBP family intramembrane metalloprotease domain-containing protein of 369 aas and 7 TMSs.

UP of Candidatus Methanomethylophilus alvus

 
9.B.2.10.4

Uncharacterized CPBP family intramembrane metalloprotease domain-containing protein of 301 aas and 7 TMSs.

UP of methanogenic archaeon ISO4-H5

 
9.B.2.10.5

Uncharacterized CPBP family intramembrane metalloprotease domain-containing protein of 312 aas and 7 TMSs.

UP of Candidatus Nitrosopelagicus brevis

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.11.1

CPBP family intramembrane metalloprotease of 213 aas

Protease of Pseudoalteromonas

 
9.B.2.11.2

CPBP/CAAX family intramembrane metaloprotease of 221 aas and 6 TMSs.

Metaloprotease of Microbulbifer aggregans

 
9.B.2.11.3

CAAX amino terminal protease self-immunity of 194 aas and 6 TMSs in a 2 + 2 + 2 arrangement.

CAAX protease of Lokiarchaeum sp. GC14_75 (marine sediment metagenome)

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.12.1

Uncharacterized protein of 207 aas and 6 TMSs

UP of Candidatus Peribacter riflensis

 
9.B.2.12.2

Metaloprotease of 213 aas and 6 TMSs

Metaloprotease of Lewinella cohaerens

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.13.1

Putative CAAX protease of 496 aas and 7 TMSs in a 1 (N-terminal) + 6 (C-terminal) TMS arrangement. The gene for this protein is adjacent to an ABC transporter (TC# 3.A.1.128.10), probably specific for a sporulation killing factor, SkfB (Grell et al. 2018). This protease may therefore function to process SkfB.

Protease of Bacillus stratosphericus

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.14.1

Myxosortase X, MXAN-2755 or MrtX of 239 aas with 4 to 6 TMSs in a possibly 2 + 1 + 2 + 1 arrangement. It is a CPBP family intramembrane metalloprotease.  Other myxosortases include: MrtC (TC# 9.B.2.14.2), MrtP (TC# 9.B.2.14.3), MrtJ, MrtS and MrtA. All of these systems are present in Myxococcus xanthus (Haft 2024).

MrtX of Myxococcus xanthus

 
9.B.2.14.2

MrtC sortase; glutamic-type intramembrane protease of 247 aas and 6 TMSs.

 

MrtC of Polyangiaceae bacterium

 
9.B.2.14.3

Myxosortase MrtP OF 361 aas and 7 putative TMSs in a 3 (N-terminal) + 4 (C-terminal) TMS arrangement.

MrtP of Lujinxingia vulgaris

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.2.1

CAAX protease of 274 aas

Red algae (Rhodophyta)

CAAX protease of Galdieria sulphuraria

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.3.1

CAAX amino terminal protease of 306 aas and 8 TMSs.

Firmicutes

CAAX protease of Desulfitobacterium metallireducens

 
9.B.2.3.2

CAAX protease of 274 aas and 8 TMSs.

Chloroflexi

CAAX protease of Anaerolnea thermopila

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.4.1

Putative transporter of 206 aas and 6 TMSs.

Proteobacteeria

Putative transporter of Klebsiella pneumoniae

 
9.B.2.4.2

Uncharacterized protein of 217 aas and 6 TMSs.

Proteobacteria

UP of Vibrio fischeri

 
9.B.2.4.3

Putative Brp/Blh family of β-carotene monooxygenases of 221 aas and 6 TMSs

Bacteroidetes

UP of Psychroflexus torquis

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.5.1

Uncharacterized protein of 230 aas and 6 TMSs

Proteobacteria

UP of Deftia acidovorans

 
9.B.2.5.2

Uncharacterized protein of 206 aas and 6 TMSs

Firmicutes

UP of Acidaminococcus intestini

 
9.B.2.5.3

Uncharacterized protein of 215 aas and 6 TMSs

Proteobacteria

UP of Salmonella schwarzengrund

 
9.B.2.5.4

Uncharacterized protein of 215 aas and 6 TMSs

Firmicutes

UP of Megamonas hypermegale

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.6.1

Uncharacterized protein of 209 aas and 5 or 6 TMSs

Proteobacteria

UP of Geobacter sp.

 
9.B.2.6.2

Uncharacterized protein of 181 aas and 5 putative TMSs. 

Proteobacteria

UP of an uncultured Desulfobacterium

 
9.B.2.6.3

Uncharacterized protein of 228 aas and 6 TMSs

Proteobacteria

UP of Parvibaculum lavamentivorans

 
9.B.2.6.4

Uncharacterized protein of 181 aas and 5 TMSs.

Proteobacteria

UP of Thioalkalimicrobium cyclicum

 
9.B.2.6.5

Uncharacterized protein of 228 aas and 7 TMSs

Proteobacteria

UP of Phyllobacterium sp. YR531

 
9.B.2.6.6

Uncharacterized protein of 172 aas and 5 TMSs.

Euryarchaea

UP of Methanococcus maripaludis

 
9.B.2.6.7

Uncharacterized protein of 227 aas and 6 TMSs

Proteobacteria

UP of Rhizobium sp.

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.7.1

Uncharacterized protein of 213 aas and 6 TMSs.  This protein is the only member of its subfamily, but a protein from Zymophilus raffinosivorans (gi# 518382944), not in UniProt as of 5/5/14, shows similarity to it as well as members of subfamily 9.B.2.5.

Proteobacteria

UP of Octadecabacter antarcticus

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.8.1

Putative CPBP family membrane metaloprotease of 195 aas and 7 TMSs.

Protease of Streptococcus ferus

 
9.B.2.8.2

Putative membrane metaloprotease of 193 aas and 6 TMSs.

Protease of Candidatus Saccharibacteria bacterium

 
Examples:

TC#NameOrganismal TypeExample
9.B.2.9.1

Uncharacterized protein of 329 aas and 6 TMSs in a 1 + 2 + 3 TMS arrangement

UP of Natronorubrum tibetense