CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004956
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Cytoplasmic aconitate hydratase 
Protein Synonyms/Alias
 Aconitase; Citrate hydro-lyase; Ferritin repressor protein; Iron regulatory protein 1; IRP1; Iron-responsive element-binding protein 1; IRE-BP 1 
Gene Name
 ACO1 
Gene Synonyms/Alias
 IREB1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
20DPVQPGKKFFNLNKLubiquitination[1]
26KKFFNLNKLEDSRYGubiquitination[1, 2]
57CDEFLVKKQDIENILubiquitination[1]
79KNIEVPFKPARVILQubiquitination[1, 2, 3, 4]
105AAMRDAVKKLGGDPEubiquitination[3]
106AMRDAVKKLGGDPEKubiquitination[3]
141RRADSLQKNQDLEFEacetylation[5]
141RRADSLQKNQDLEFEubiquitination[1, 2, 3, 4, 6]
158RERFEFLKWGSQAFHubiquitination[1]
250IGYRLMGKPHPLVTSubiquitination[1]
335EKLKYIKKYLQAVGMubiquitination[1, 7]
386KVAVSDMKKDFESCLubiquitination[3]
387VAVSDMKKDFESCLGubiquitination[1]
396FESCLGAKQGFKGFQubiquitination[1]
455GAGLLAKKAVDAGLNubiquitination[1]
572TIRIDFEKEPLGVNAubiquitination[3]
580EPLGVNAKGQQVFLKubiquitination[1, 3, 4, 6, 7]
587KGQQVFLKDIWPTRDubiquitination[1]
610YVIPGMFKEVYQKIEubiquitination[1, 3]
615MFKEVYQKIETVNESubiquitination[3, 4]
632ALATPSDKLFFWNSKubiquitination[1, 3, 4]
639KLFFWNSKSTYIKSPubiquitination[1, 7, 8, 9]
644NSKSTYIKSPPFFENubiquitination[3, 4]
736LLNRFLNKQAPQTIHubiquitination[1, 3, 4, 6]
772PLIVLAGKEYGAGSSubiquitination[3, 4]
785SSRDWAAKGPFLLGIubiquitination[1, 2, 3, 4, 10]
844IIIPENLKPQMKVQVubiquitination[1, 3, 4]
852PQMKVQVKLDTGKTFubiquitination[1]
857QVKLDTGKTFQAVMRubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [6] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [8] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [9] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [10] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 Iron sensor. Binds a 4Fe-4S cluster and functions as aconitase when cellular iron levels are high. Functions as mRNA binding protein that regulates uptake, sequestration and utilization of iron when cellular iron levels are low. Binds to iron-responsive elements (IRES) in target mRNA species when iron levels are low. Binding of a 4Fe-4S cluster precludes RNA binding. 
Sequence Annotation
 REGION 205 207 Substrate binding (By similarity).
 REGION 779 780 Substrate binding (By similarity).
 METAL 437 437 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 503 503 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 506 506 Iron-sulfur (4Fe-4S) (By similarity).
 BINDING 86 86 Substrate (By similarity).
 BINDING 536 536 Substrate (By similarity).
 BINDING 541 541 Substrate (By similarity).
 BINDING 699 699 Substrate (By similarity).  
Keyword
 3D-structure; 4Fe-4S; Complete proteome; Cytoplasm; Direct protein sequencing; Iron; Iron-sulfur; Lyase; Metal-binding; Polymorphism; Reference proteome; RNA-binding; Tricarboxylic acid cycle. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 889 AA 
Protein Sequence
MSNPFAHLAE PLDPVQPGKK FFNLNKLEDS RYGRLPFSIR VLLEAAIRNC DEFLVKKQDI 60
ENILHWNVTQ HKNIEVPFKP ARVILQDFTG VPAVVDFAAM RDAVKKLGGD PEKINPVCPA 120
DLVIDHSIQV DFNRRADSLQ KNQDLEFERN RERFEFLKWG SQAFHNMRII PPGSGIIHQV 180
NLEYLARVVF DQDGYYYPDS LVGTDSHTTM IDGLGILGWG VGGIEAEAVM LGQPISMVLP 240
QVIGYRLMGK PHPLVTSTDI VLTITKHLRQ VGVVGKFVEF FGPGVAQLSI ADRATIANMC 300
PEYGATAAFF PVDEVSITYL VQTGRDEEKL KYIKKYLQAV GMFRDFNDPS QDPDFTQVVE 360
LDLKTVVPCC SGPKRPQDKV AVSDMKKDFE SCLGAKQGFK GFQVAPEHHN DHKTFIYDNT 420
EFTLAHGSVV IAAITSCTNT SNPSVMLGAG LLAKKAVDAG LNVMPYIKTS LSPGSGVVTY 480
YLQESGVMPY LSQLGFDVVG YGCMTCIGNS GPLPEPVVEA ITQGDLVAVG VLSGNRNFEG 540
RVHPNTRANY LASPPLVIAY AIAGTIRIDF EKEPLGVNAK GQQVFLKDIW PTRDEIQAVE 600
RQYVIPGMFK EVYQKIETVN ESWNALATPS DKLFFWNSKS TYIKSPPFFE NLTLDLQPPK 660
SIVDAYVLLN LGDSVTTDHI SPAGNIARNS PAARYLTNRG LTPREFNSYG SRRGNDAVMA 720
RGTFANIRLL NRFLNKQAPQ TIHLPSGEIL DVFDAAERYQ QAGLPLIVLA GKEYGAGSSR 780
DWAAKGPFLL GIKAVLAESY ERIHRSNLVG MGVIPLEYLP GENADALGLT GQERYTIIIP 840
ENLKPQMKVQ VKLDTGKTFQ AVMRFDTDVE LTYFLNGGIL NYMIRKMAK 889 
Gene Ontology
 GO:0005829; C:cytosol; IDA:HGNC.
 GO:0005783; C:endoplasmic reticulum; IDA:MGI.
 GO:0005794; C:Golgi apparatus; IDA:MGI.
 GO:0005739; C:mitochondrion; IDA:HPA.
 GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
 GO:0003994; F:aconitate hydratase activity; IDA:UniProtKB.
 GO:0052632; F:citrate hydro-lyase (cis-aconitate-forming) activity; IEA:EC.
 GO:0030350; F:iron-responsive element binding; IDA:UniProtKB.
 GO:0052633; F:isocitrate hydro-lyase (cis-aconitate-forming) activity; IEA:EC.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0006879; P:cellular iron ion homeostasis; IEA:Compara.
 GO:0006101; P:citrate metabolic process; IDA:UniProtKB.
 GO:0050892; P:intestinal absorption; IEA:Compara.
 GO:0009791; P:post-embryonic development; IEA:Compara.
 GO:0006417; P:regulation of translation; IEA:Compara.
 GO:0010040; P:response to iron(II) ion; IDA:UniProtKB.
 GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW. 
Interpro
 IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
 IPR015937; Acoase/IPM_deHydtase.
 IPR001030; Acoase/IPM_deHydtase_lsu_aba.
 IPR015928; Aconitase/3IPM_dehydase_swvl.
 IPR006249; Aconitase/Fe_reg_prot_2.
 IPR015934; Aconitase/Fe_reg_prot_2/AcnD.
 IPR015932; Aconitase/IPMdHydase_lsu_aba_2.
 IPR018136; Aconitase_4Fe-4S_BS.
 IPR000573; AconitaseA/IPMdHydase_ssu_swvl. 
Pfam
 PF00330; Aconitase
 PF00694; Aconitase_C 
SMART
  
PROSITE
 PS00450; ACONITASE_1
 PS01244; ACONITASE_2 
PRINTS
 PR00415; ACONITASE.