CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000757
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Alpha-actinin-4 
Protein Synonyms/Alias
 F-actin cross-linking protein; Non-muscle alpha-actinin 4 
Gene Name
 ACTN4 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
50LLDPAWEKQQRKTFTubiquitination[1]
54AWEKQQRKTFTAWCNubiquitination[2, 3]
83EDFRDGLKLMLLLEVubiquitination[1]
114HKINNVNKALDFIASacetylation[4]
122ALDFIASKGVKLVSIubiquitination[1]
181QRKTAPYKNVNVQNFubiquitination[2, 3, 5]
214PELIEYDKLRKDDPVacetylation[4]
217IEYDKLRKDDPVTNLubiquitination[1, 2]
233NAFEVAEKYLDIPKMubiquitination[3, 5]
239EKYLDIPKMLDAEDIubiquitination[2]
255NTARPDEKAIMTYVSubiquitination[6]
331TIQEMQQKLEDFRDYubiquitination[1]
350KPPKVQEKCQLEINFubiquitination[2, 7, 8]
378AFMPSEGKMVSDINNubiquitination[3, 9]
417RLDHLAEKFRQKASIacetylation[4]
417RLDHLAEKFRQKASIubiquitination[2, 3, 8]
421LAEKFRQKASIHEAWubiquitination[1, 2, 8]
592EAILAIHKEAQRIAEacetylation[4]
592EAILAIHKEAQRIAEubiquitination[2]
604IAESNHIKLSGSNPYubiquitination[1, 2]
622TPQIINSKWEKVQQLubiquitination[1]
625IINSKWEKVQQLVPKacetylation[4]
625IINSKWEKVQQLVPKubiquitination[1, 3, 5]
632KVQQLVPKRDHALLEubiquitination[3, 5]
668VGPWIQTKMEEIGRIubiquitination[1]
760QILTRDAKGISQEQMubiquitination[1]
859FKVLAGDKNFITAEEubiquitination[3, 5]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] Podocyte Injury Associated with Mutant α-Actinin-4.
 Cybulsky AV, Kennedy CR.
 J Signal Transduct. 2011;2011:563128. [PMID: 21808733]
 [7] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [8] 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]
 [9] Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry.
 Denis NJ, Vasilescu J, Lambert JP, Smith JC, Figeys D.
 Proteomics. 2007 Mar;7(6):868-74. [PMID: 17370265] 
Functional Description
 F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. 
Sequence Annotation
 DOMAIN 1 269 Actin-binding.
 DOMAIN 50 154 CH 1.
 DOMAIN 163 269 CH 2.
 REPEAT 293 403 Spectrin 1.
 REPEAT 413 518 Spectrin 2.
 REPEAT 528 639 Spectrin 3.
 REPEAT 649 752 Spectrin 4.
 DOMAIN 765 800 EF-hand 1.
 DOMAIN 806 841 EF-hand 2.
 REGION 177 192 Polyphosphoinositide (PIP2)-binding
 MOD_RES 114 114 N6-acetyllysine.
 MOD_RES 592 592 N6-acetyllysine.
 MOD_RES 625 625 N6-acetyllysine.
 CROSSLNK 378 378 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Actin-binding; Calcium; Complete proteome; Cytoplasm; Disease mutation; Isopeptide bond; Metal-binding; Nucleus; Protein transport; Reference proteome; Repeat; Transport; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 911 AA 
Protein Sequence
MVDYHAANQS YQYGPSSAGN GAGGGGSMGD YMAQEDDWDR DLLLDPAWEK QQRKTFTAWC 60
NSHLRKAGTQ IENIDEDFRD GLKLMLLLEV ISGERLPKPE RGKMRVHKIN NVNKALDFIA 120
SKGVKLVSIG AEEIVDGNAK MTLGMIWTII LRFAIQDISV EETSAKEGLL LWCQRKTAPY 180
KNVNVQNFHI SWKDGLAFNA LIHRHRPELI EYDKLRKDDP VTNLNNAFEV AEKYLDIPKM 240
LDAEDIVNTA RPDEKAIMTY VSSFYHAFSG AQKAETAANR ICKVLAVNQE NEHLMEDYEK 300
LASDLLEWIR RTIPWLEDRV PQKTIQEMQQ KLEDFRDYRR VHKPPKVQEK CQLEINFNTL 360
QTKLRLSNRP AFMPSEGKMV SDINNGWQHL EQAEKGYEEW LLNEIRRLER LDHLAEKFRQ 420
KASIHEAWTD GKEAMLKHRD YETATLSDIK ALIRKHEAFE SDLAAHQDRV EQIAAIAQEL 480
NELDYYDSHN VNTRCQKICD QWDALGSLTH SRREALEKTE KQLEAIDQLH LEYAKRAAPF 540
NNWMESAMED LQDMFIVHTI EEIEGLISAH DQFKSTLPDA DREREAILAI HKEAQRIAES 600
NHIKLSGSNP YTTVTPQIIN SKWEKVQQLV PKRDHALLEE QSKQQSNEHL RRQFASQANV 660
VGPWIQTKME EIGRISIEMN GTLEDQLSHL KQYERSIVDY KPNLDLLEQQ HQLIQEALIF 720
DNKHTNYTME HIRVGWEQLL TTIARTINEV ENQILTRDAK GISQEQMQEF RASFNHFDKD 780
HGGALGPEEF KACLISLGYD VENDRQGEAE FNRIMSLVDP NHSGLVTFQA FIDFMSRETT 840
DTDTADQVIA SFKVLAGDKN FITAEELRRE LPPDQAEYCI ARMAPYQGPD AVPGALDYKS 900
FSTALYGESD L 911 
Gene Ontology
 GO:0030863; C:cortical cytoskeleton; IEA:Compara.
 GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
 GO:0043234; C:protein complex; IDA:UniProtKB.
 GO:0031143; C:pseudopodium; TAS:UniProtKB.
 GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
 GO:0030018; C:Z disc; IEA:Compara.
 GO:0051015; F:actin filament binding; IDA:UniProtKB.
 GO:0005509; F:calcium ion binding; IEA:InterPro.
 GO:0005178; F:integrin binding; TAS:UniProtKB.
 GO:0001882; F:nucleoside binding; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; TAS:UniProtKB.
 GO:0051764; P:actin crosslink formation; IEA:InterPro.
 GO:0051017; P:actin filament bundle assembly; IEA:Compara.
 GO:0051271; P:negative regulation of cellular component movement; IEA:Compara.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0002576; P:platelet degranulation; TAS:Reactome.
 GO:0051272; P:positive regulation of cellular component movement; IDA:UniProtKB.
 GO:0048549; P:positive regulation of pinocytosis; IEA:Compara.
 GO:0032417; P:positive regulation of sodium:hydrogen antiporter activity; NAS:UniProtKB.
 GO:0015031; P:protein transport; IEA:UniProtKB-KW.
 GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
 GO:0001666; P:response to hypoxia; IEA:Compara. 
Interpro
 IPR001589; Actinin_actin-bd_CS.
 IPR026921; Alpha-actinin.
 IPR001715; CH-domain.
 IPR011992; EF-hand-like_dom.
 IPR014837; EF-hand_Ca_insen.
 IPR018247; EF_Hand_1_Ca_BS.
 IPR002048; EF_hand_dom.
 IPR018159; Spectrin/alpha-actinin.
 IPR002017; Spectrin_repeat. 
Pfam
 PF00307; CH
 PF13405; EF_hand_4
 PF08726; efhand_Ca_insen
 PF00435; Spectrin 
SMART
 SM00033; CH
 SM00054; EFh
 SM00150; SPEC 
PROSITE
 PS00019; ACTININ_1
 PS00020; ACTININ_2
 PS50021; CH
 PS00018; EF_HAND_1
 PS50222; EF_HAND_2 
PRINTS