Conserved Protein Domain Family
CCL_ACL-C

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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
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PSSM-Id: 99854
View PSSM: cd06100
Aligned: 60 rows
Threshold Bit Score: 146.173
Threshold Setting Gi: 118745790
Created: 6-Nov-2007
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
Feature 1:active site [active site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                     #   #                              
gi 46849510   21 GYRLL-DLVgnLSFAQAIYLILKGELPt-eRESRMMEAMLVSVIDHGiaPPSAIAARSVASGG--------NSLNVGVAA 90
gi 111023907  40 GYAIE-DLIptTSYAGMVWLMIRGQRPt-pWQERLLDAALVAAVDHGpqAPSIAASRMAATCG--------VGLNNVMAT 109
gi 33603782   27 GHRLS-DLIreQPFVASAFLLLTGRLPd-aGEARTLDAVLTACVDHGv-TPAAAIGRTFASYG--------APVAQAMAG 95
gi 118745790  31 GHDLHaELRd-MDWVELFVFGITGRRFt--PQQLRLLHAIWVYTSYP--DARIWNNRVAALAGssrstptlALAASLAVS 105
gi 77164773   32 GYDVYgDLLgkASWVEYLYLLFKRERPs-sAEARLLEGLAVAIANPGprDHSIRAAMCAGVGGs-------TAASSLMAA 103
gi 83645354   31 GYDVYgDILtrASWFEYLYLLFRGEKPn-tDQARLLEKLAIALANPGprEASVRAAMNGGVGGc-------PHAASLMAS 102
gi 118745789  34 GYDVYgELLgqARWTEMLYLLFRGEAPt-dTQTRLLDTLALALANPGprDQSVHAAMCGGVGGs-------TAASCLIAA 105
gi 117610668 642 GVSNS-ELInsWSFTATAFLALFGRKPd-qNELYSFSVLLGLIITNGpgTISAQGAKGAVSADgpe--vsdRVQINKGYI 717
gi 163703209 626 GVPNA-DLLtrRTLGEIGCLALLGREPadaGDVFVFETLVGLLLSNGpgTISAQGCKGAVSADgpe--speRVQLNKALI 702
gi 169200134  25 GYAMS-DLVgaIPFPGIAYLLIRGVLPt-rGQARMMDAIFSSILDYGlqKSGTVAARAVVSVNpam---taGLGAAVLAA 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                  ###  #   #                                                    ##### ##
gi 46849510   91 GVLAF----GSAHGGAl-EDAMRFIQEGvssk--------------rsvEDIVKEYLETk-----------kPIPGY-GH 139
gi 111023907 110 GVGML----GDVHGGAg-EQCMSVLADIveqatda-------tdlrpvaDRIVADYRSAk-----------rYVPGF-GH 165
gi 33603782   96 AALLY----GDVAGGVg-DPLAAMMKQAiadagarnga-pgehdvdaaaGNLVAAALRAg-----------gRMPGF-GN 157
gi 118745790 106 EATVYg---GYPSISAf-DFFMRTRKKIaqg---------------ehvEEIIHSERQTr------------RIYGY-GR 153
gi 77164773  104 LAVGA----GQLNGAR--EVALAMASWQecg---------------knlMAWQERLQHLpqeeradvwlsleHPPGFdPH 162
gi 83645354  103 LAVGA----GQYGGGH--EVYILMQLWRecg---------------tdmAQWRARLPSPvsdtrediwrpmeHAPGFdPN 161
gi 118745789 106 LAVGA----GQLSGGR--ELFLSMELWNacg---------------tdlASWYTRFAMPadttvs-lwpapaHPPGFdPH 163
gi 117610668 718 GFLTHt---GFAHGGNgfEAIAFLVDRFkdsgltdpgk-atsldlaemaLNYAKEYKKYknkakaegdlnyfKVPCI-NH 792
gi 163703209 703 GFLTHa---GYAHGGNgyEGIAFLIEQFrdsgladpadpdhgidlqalaGRTAAEYARYksdrksagsldiqKIPGV-NH 778
gi 169200134 100 GEYALspedTGRFISTt-FAQWKDSGKPmde----------------aaANLVAELRAAk-----------rRVPGF-GH 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #           #                                       #  # #                      
gi 46849510  140 RYYk----DFDPRTKRLMDIARVlefyg-ehckFAEDVAEEIGRQKgk---kLVLNVDGAIAAIASEM----GFDw---- 203
gi 111023907 166 RFH-----PRDPRRDPLLSLVAAarddgavsgqYLHAALALEQSLAagrtrpVPMNIDGATAVVYAEL----GFPp---- 232
gi 33603782  158 PPH-----ARDPRPRVLLEVARRagtag-ihceLLLAAERHLAAAKgr---dIPINIDGIVAALALDL----GLPd---- 220
gi 118745790 154 PIT-----SADERLPWLLDCARElcldqgpylrLAFDVERVLLKDNp----lLRMNYAGLVAALSLDL----GFSare-- 218
gi 77164773  163 GAS-----CATPVQQTLAFLVKNspge---tlpWLQTHRLELEAAAn-----SPLAMTGVAAAAMIDL----DFNm---- 221
gi 83645354  162 GES-----CPKPVRQVLEALAEIpcai---tvrWLAQHRQELEAAAd-----APLSLSGVAAAALHDL----AMNe---- 220
gi 118745789 164 GVS-----TATPVLQTLTCLAEIsdap---llpWLQAHLSDLETAAg-----LPLALSGVAAAALVDL----GFTp---- 222
gi 117610668 793 PVFknkdvNYDPREQFVNGLFKKrgdyn-vfldYYHELVNGLFKAGvsk-nvYCVNVDAVIAVILLKMlwssYSKgeisn 870
gi 163703209 779 PVFkdkavNHDPREVWLHEQLAArgdsn-afhaYYRALVQALFEAGvsr-nvYCVNIDAVIAALLLKMlwrpYRTgelsa 856
gi 169200134 151 QVFr----IVDPRSEKLKKLAKEqgvwg-evneWYEAVHRAFQAASnk--pdLVLNDVGMLASIMVQM----GFSp---- 215
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
Feature 1                      #                     #  #     
gi 46849510  204 ----rLGKGFFIIGRVPGLVAHVYEELTTekpfSKRLDEERDVEY 244
gi 111023907 233 ----pLGRGLFVLSRSVGILAHGWEQTQQ----GGRNKGPIPRTL 269
gi 33603782  221 ----gCAAALVMIARKFSVLTHYLEEKGQn--tKWRHVPQECVHY 259
gi 118745790 219 ---fhLFRFPMTFAGMPPCFLESSQETEG----AFLPLSCAHIVY 256
gi 77164773  222 ----qQSEMLYLLLRLPGAAAHALEQQAYg--wRRYPFFSHGLEL 260
gi 83645354  221 ----hAAVMLYLMLRLPGAAAHAIEQRDLg--wKMFPFYGEHIQL 259
gi 118745789 223 ----eQGEMLYLLLRLPGAAVHALEQKQL----GYKKFPFFSIEL 259
gi 117610668 871 dsmesAAFTTFLFGRMIGSAAEIDDHTNRgk-nMDTRTPASQVSS 914
gi 163703209 857 salesAAFTIFLFARMLGCAAEVDDHLNRgr-dMDTRTPASQCRF 900
gi 169200134 216 ----aEMCGLAIISTMPGLVAHISEELQSg--vRNRLVPESHTEY 254

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