CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-003939
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Pyruvate carboxylase, mitochondrial 
Protein Synonyms/Alias
 Pyruvic carboxylase; PCB 
Gene Name
 PC 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
992LDLQALEKELVDRHGacetylation[1]
1090QLRSILVKDTQAMKEacetylation[2]
Reference
 [1] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 
Functional Description
 Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate. 
Sequence Annotation
 DOMAIN 36 486 Biotin carboxylation.
 DOMAIN 156 353 ATP-grasp.
 DOMAIN 563 832 Carboxyltransferase.
 DOMAIN 1110 1177 Biotinyl-binding.
 REGION 571 575 Substrate binding.
 ACT_SITE 328 328 By similarity.
 METAL 572 572 Manganese.
 METAL 741 741 Manganese; via carbamate group.
 METAL 771 771 Manganese.
 METAL 773 773 Manganese.
 BINDING 152 152 ATP (By similarity).
 BINDING 236 236 ATP (By similarity).
 BINDING 271 271 ATP (By similarity).
 BINDING 644 644 Substrate.
 BINDING 908 908 Substrate.
 MOD_RES 741 741 N6-carboxylysine.
 MOD_RES 1090 1090 N6-acetyllysine.
 MOD_RES 1144 1144 N6-biotinyllysine.  
Keyword
 3D-structure; Acetylation; ATP-binding; Biotin; Complete proteome; Disease mutation; Gluconeogenesis; Ligase; Lipid biosynthesis; Lipid metabolism; Manganese; Metal-binding; Mitochondrion; Multifunctional enzyme; Nucleotide-binding; Polymorphism; Pyruvate; Reference proteome; Transit peptide. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1178 AA 
Protein Sequence
MLKFRTVHGG LRLLGIRRTS TAPAASPNVR RLEYKPIKKV MVANRGEIAI RVFRACTELG 60
IRTVAIYSEQ DTGQMHRQKA DEAYLIGRGL APVQAYLHIP DIIKVAKENN VDAVHPGYGF 120
LSERADFAQA CQDAGVRFIG PSPEVVRKMG DKVEARAIAI AAGVPVVPGT DAPITSLHEA 180
HEFSNTYGFP IIFKAAYGGG GRGMRVVHSY EELEENYTRA YSEALAAFGN GALFVEKFIE 240
KPRHIEVQIL GDQYGNILHL YERDCSIQRR HQKVVEIAPA AHLDPQLRTR LTSDSVKLAK 300
QVGYENAGTV EFLVDRHGKH YFIEVNSRLQ VEHTVTEEIT DVDLVHAQIH VAEGRSLPDL 360
GLRQENIRIN GCAIQCRVTT EDPARSFQPD TGRIEVFRSG EGMGIRLDNA SAFQGAVISP 420
HYDSLLVKVI AHGKDHPTAA TKMSRALAEF RVRGVKTNIA FLQNVLNNQQ FLAGTVDTQF 480
IDENPELFQL RPAQNRAQKL LHYLGHVMVN GPTTPIPVKA SPSPTDPVVP AVPIGPPPAG 540
FRDILLREGP EGFARAVRNH PGLLLMDTTF RDAHQSLLAT RVRTHDLKKI APYVAHNFSK 600
LFSMENWGGA TFDVAMRFLY ECPWRRLQEL RELIPNIPFQ MLLRGANAVG YTNYPDNVVF 660
KFCEVAKENG MDVFRVFDSL NYLPNMLLGM EAAGSAGGVV EAAISYTGDV ADPSRTKYSL 720
QYYMGLAEEL VRAGTHILCI KDMAGLLKPT ACTMLVSSLR DRFPDLPLHI HTHDTSGAGV 780
AAMLACAQAG ADVVDVAADS MSGMTSQPSM GALVACTRGT PLDTEVPMER VFDYSEYWEG 840
ARGLYAAFDC TATMKSGNSD VYENEIPGGQ YTNLHFQAHS MGLGSKFKEV KKAYVEANQM 900
LGDLIKVTPS SKIVGDLAQF MVQNGLSRAE AEAQAEELSF PRSVVEFLQG YIGVPHGGFP 960
EPFRSKVLKD LPRVEGRPGA SLPPLDLQAL EKELVDRHGE EVTPEDVLSA AMYPDVFAHF 1020
KDFTATFGPL DSLNTRLFLQ GPKIAEEFEV ELERGKTLHI KALAVSDLNR AGQRQVFFEL 1080
NGQLRSILVK DTQAMKEMHF HPKALKDVKG QIGAPMPGKV IDIKVVAGAK VAKGQPLCVL 1140
SAMKMETVVT SPMEGTVRKV HVTKDMTLEG DDLILEIE 1178 
Gene Ontology
 GO:0005743; C:mitochondrial inner membrane; IEA:Compara.
 GO:0005759; C:mitochondrial matrix; TAS:Reactome.
 GO:0005524; F:ATP binding; TAS:ProtInc.
 GO:0009374; F:biotin binding; TAS:ProtInc.
 GO:0004075; F:biotin carboxylase activity; IEA:InterPro.
 GO:0003677; F:DNA binding; IEA:InterPro.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004736; F:pyruvate carboxylase activity; TAS:Reactome.
 GO:0006094; P:gluconeogenesis; TAS:Reactome.
 GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
 GO:0006107; P:oxaloacetate metabolic process; IEA:Compara.
 GO:0006090; P:pyruvate metabolic process; IEA:Compara.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome. 
Interpro
 IPR013785; Aldolase_TIM.
 IPR011761; ATP-grasp.
 IPR013815; ATP_grasp_subdomain_1.
 IPR013816; ATP_grasp_subdomain_2.
 IPR001882; Biotin_BS.
 IPR011764; Biotin_carboxylation_dom.
 IPR005482; Biotin_COase_C.
 IPR000089; Biotin_lipoyl.
 IPR005481; CarbamoylP_synth_lsu_N.
 IPR003379; Carboxylase_cons_dom.
 IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
 IPR009057; Homeodomain-like.
 IPR016185; PreATP-grasp_dom.
 IPR000891; PYR_CT.
 IPR005930; Pyruv_COase.
 IPR011054; Rudment_hybrid_motif.
 IPR011053; Single_hybrid_motif. 
Pfam
 PF02785; Biotin_carb_C
 PF00364; Biotin_lipoyl
 PF00289; CPSase_L_chain
 PF02786; CPSase_L_D2
 PF00682; HMGL-like
 PF02436; PYC_OADA 
SMART
 SM00878; Biotin_carb_C 
PROSITE
 PS50975; ATP_GRASP
 PS50979; BC
 PS00188; BIOTIN
 PS50968; BIOTINYL_LIPOYL
 PS50989; COA_CT_CTER
 PS50980; COA_CT_NTER
 PS50991; PYR_CT 
PRINTS