Conserved Protein Domain Family
CCL_ACL-C

?
cd06100: CCL_ACL-C 
Citryl-CoA lyase (CCL), the C-terminal portion of the single-subunit type ATP-citrate lyase (ACL) and the C-terminal portion of the large subunit of the two-subunit type ACL. CCL cleaves citryl-CoA (CiCoA) to acetyl-CoA (AcCoA) and oxaloacetate (OAA). ACL catalyzes an ATP- and a CoA- dependant cleavage of citrate to form AcCoA and OAA in a multistep reaction, the final step of which is likely to involve the cleavage of CiCoA to generate AcCoA and OAA. In fungi, yeast, plants, and animals ACL is cytosolic and generates AcCoA for lipogenesis. ACL may be required for fruiting body maturation in the filamentous fungus Sordaria macrospore. In several groups of autotrophic prokaryotes and archaea, ACL carries out the citrate-cleavage reaction of the reductive tricarboxylic acid (rTCA) cycle. In the family Aquificaceae this latter reaction in the rTCA cycle is carried out via a two enzyme system the second enzyme of which is CCL; the first enzyme is citryl-CoA synthetase (CCS) which is not included in this group. Chlorobium limicola ACL is an example of a two-subunit type ACL. It is comprised of a large and a small subunit; it has been speculated that the large subunit arose from a fusion of the small subunit of the two subunit CCS with CCL. The small ACL subunit is a homolog of the larger CCS subunit. Mammalian ACL is of the single-subunit type and may have arisen from the two-subunit ACL by another gene fusion. Mammalian ACLs are homotetramers; the ACLs of C. limicola and Arabidopsis are a heterooctomers (alpha4beta4). In cancer cells there is a shift in energy metabolism to aerobic glycolysis, the glycolytic end product pyruvate enters a truncated TCA cycle generating citrate which is cleaved in the cytosol by ACL. Inhibiting ACL limits the in-vitro proliferation and survival of these cancer cells, reduces in vivo tumor growth, and induces differentiation.
Statistics
?
PSSM-Id: 99854
View PSSM: cd06100
Aligned: 60 rows
Threshold Bit Score: 146.173
Threshold Setting Gi: 118745790
Created: 6-Nov-2007
Updated: 2-Oct-2020
Structure
?
Aligned Rows:
 
Feature 1:active site [active site]
Evidence:

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1                                                      #   #                              
BAD17841       21 GYRLL-DLVgnLSFAQAIYLILKGELPt-eRESRMMEAMLVSVIDHGiaPPSAIAARSVASGG--------NSLNVGVAA 90  Hydrogenobacte...
YP_706879      40 GYAIE-DLIptTSYAGMVWLMIRGQRPt-pWQERLLDAALVAAVDHGpqAPSIAASRMAATCG--------VGLNNVMAT 109 Rhodococcus sp...
NP_891342      27 GHRLS-DLIreQPFVASAFLLLTGRLPd-aGEARTLDAVLTACVDHGv-TPAAAIGRTFASYG--------APVAQAMAG 95  Bordetella bro...
ZP_01593755    31 GHDLHaELRd-MDWVELFVFGITGRRFt--PQQLRLLHAIWVYTSYP--DARIWNNRVAALAGssrstptlALAASLAVS 105 Geobacter lovl...
YP_343298      32 GYDVYgDLLgkASWVEYLYLLFKRERPs-sAEARLLEGLAVAIANPGprDHSIRAAMCAGVGGs-------TAASSLMAA 103 Nitrosococcus ...
YP_433789      31 GYDVYgDILtrASWFEYLYLLFRGEKPn-tDQARLLEKLAIALANPGprEASVRAAMNGGVGGc-------PHAASLMAS 102 Hahella chejue...
ZP_01593754    34 GYDVYgELLgqARWTEMLYLLFRGEAPt-dTQTRLLDTLALALANPGprDQSVHAAMCGGVGGs-------TAASCLIAA 105 Geobacter lovl...
jgi:Mmc1_3638 642 GVSNS-ELInsWSFTATAFLALFGRKPd-qNELYSFSVLLGLIITNGpgTISAQGAKGAVSADgpe--vsdRVQINKGYI 717 Magnetococcus ...
ZP_02122042   626 GVPNA-DLLtrRTLGEIGCLALLGREPadaGDVFVFETLVGLLLSNGpgTISAQGCKGAVSADgpe--speRVQLNKALI 702 Methylobacteri...
ZP_02859416    25 GYAMS-DLVgaIPFPGIAYLLIRGVLPt-rGQARMMDAIFSSILDYGlqKSGTVAARAVVSVNpam---taGLGAAVLAA 99  Rhizobium legu...
Feature 1                   ###  #   #                                                    ##### ##
BAD17841       91 GVLAF----GSAHGGAl-EDAMRFIQEGvssk--------------rsvEDIVKEYLETk-----------kPIPGY-GH 139 Hydrogenobacte...
YP_706879     110 GVGML----GDVHGGAg-EQCMSVLADIveqatda-------tdlrpvaDRIVADYRSAk-----------rYVPGF-GH 165 Rhodococcus sp...
NP_891342      96 AALLY----GDVAGGVg-DPLAAMMKQAiadagarnga-pgehdvdaaaGNLVAAALRAg-----------gRMPGF-GN 157 Bordetella bro...
ZP_01593755   106 EATVYg---GYPSISAf-DFFMRTRKKIaqg---------------ehvEEIIHSERQTr------------RIYGY-GR 153 Geobacter lovl...
YP_343298     104 LAVGA----GQLNGAR--EVALAMASWQecg---------------knlMAWQERLQHLpqeeradvwlsleHPPGFdPH 162 Nitrosococcus ...
YP_433789     103 LAVGA----GQYGGGH--EVYILMQLWRecg---------------tdmAQWRARLPSPvsdtrediwrpmeHAPGFdPN 161 Hahella chejue...
ZP_01593754   106 LAVGA----GQLSGGR--ELFLSMELWNacg---------------tdlASWYTRFAMPadttvs-lwpapaHPPGFdPH 163 Geobacter lovl...
jgi:Mmc1_3638 718 GFLTHt---GFAHGGNgfEAIAFLVDRFkdsgltdpgk-atsldlaemaLNYAKEYKKYknkakaegdlnyfKVPCI-NH 792 Magnetococcus ...
ZP_02122042   703 GFLTHa---GYAHGGNgyEGIAFLIEQFrdsgladpadpdhgidlqalaGRTAAEYARYksdrksagsldiqKIPGV-NH 778 Methylobacteri...
ZP_02859416   100 GEYALspedTGRFISTt-FAQWKDSGKPmde----------------aaANLVAELRAAk-----------rRVPGF-GH 150 Rhizobium legu...
Feature 1         #           #                                       #  # #                      
BAD17841      140 RYYk----DFDPRTKRLMDIARVlefyg-ehckFAEDVAEEIGRQKgk---kLVLNVDGAIAAIASEM----GFDw---- 203 Hydrogenobacte...
YP_706879     166 RFH-----PRDPRRDPLLSLVAAarddgavsgqYLHAALALEQSLAagrtrpVPMNIDGATAVVYAEL----GFPp---- 232 Rhodococcus sp...
NP_891342     158 PPH-----ARDPRPRVLLEVARRagtag-ihceLLLAAERHLAAAKgr---dIPINIDGIVAALALDL----GLPd---- 220 Bordetella bro...
ZP_01593755   154 PIT-----SADERLPWLLDCARElcldqgpylrLAFDVERVLLKDNp----lLRMNYAGLVAALSLDL----GFSare-- 218 Geobacter lovl...
YP_343298     163 GAS-----CATPVQQTLAFLVKNspge---tlpWLQTHRLELEAAAn-----SPLAMTGVAAAAMIDL----DFNm---- 221 Nitrosococcus ...
YP_433789     162 GES-----CPKPVRQVLEALAEIpcai---tvrWLAQHRQELEAAAd-----APLSLSGVAAAALHDL----AMNe---- 220 Hahella chejue...
ZP_01593754   164 GVS-----TATPVLQTLTCLAEIsdap---llpWLQAHLSDLETAAg-----LPLALSGVAAAALVDL----GFTp---- 222 Geobacter lovl...
jgi:Mmc1_3638 793 PVFknkdvNYDPREQFVNGLFKKrgdyn-vfldYYHELVNGLFKAGvsk-nvYCVNVDAVIAVILLKMlwssYSKgeisn 870 Magnetococcus ...
ZP_02122042   779 PVFkdkavNHDPREVWLHEQLAArgdsn-afhaYYRALVQALFEAGvsr-nvYCVNIDAVIAALLLKMlwrpYRTgelsa 856 Methylobacteri...
ZP_02859416   151 QVFr----IVDPRSEKLKKLAKEqgvwg-evneWYEAVHRAFQAASnk--pdLVLNDVGMLASIMVQM----GFSp---- 215 Rhizobium legu...
Feature 1                       #                     #  #     
BAD17841      204 ----rLGKGFFIIGRVPGLVAHVYEELTTekpfSKRLDEERDVEY 244 Hydrogenobacter thermophilus
YP_706879     233 ----pLGRGLFVLSRSVGILAHGWEQTQQ----GGRNKGPIPRTL 269 Rhodococcus sp. RHA1
NP_891342     221 ----gCAAALVMIARKFSVLTHYLEEKGQn--tKWRHVPQECVHY 259 Bordetella bronchiseptica RB50
ZP_01593755   219 ---fhLFRFPMTFAGMPPCFLESSQETEG----AFLPLSCAHIVY 256 Geobacter lovleyi SZ
YP_343298     222 ----qQSEMLYLLLRLPGAAAHALEQQAYg--wRRYPFFSHGLEL 260 Nitrosococcus oceani ATCC 19707
YP_433789     221 ----hAAVMLYLMLRLPGAAAHAIEQRDLg--wKMFPFYGEHIQL 259 Hahella chejuensis KCTC 2396
ZP_01593754   223 ----eQGEMLYLLLRLPGAAVHALEQKQL----GYKKFPFFSIEL 259 Geobacter lovleyi SZ
jgi:Mmc1_3638 871 dsmesAAFTTFLFGRMIGSAAEIDDHTNRgk-nMDTRTPASQVSS 914 Magnetococcus sp. MC-1
ZP_02122042   857 salesAAFTIFLFARMLGCAAEVDDHLNRgr-dMDTRTPASQCRF 900 Methylobacterium nodulans ORS 2060
ZP_02859416   216 ----aEMCGLAIISTMPGLVAHISEELQSg--vRNRLVPESHTEY 254 Rhizobium leguminosarum bv. trifolii WSM2304

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap