UniProt Accession

 HERC4_HUMAN; Q5GLZ8; Q5GC98; Q5GC99; Q5GCA0; Q8IXP9; Q9HCH9 

Genbank Protein ID

 AY221963; AY650032; AY650033; AY650034; AB046813; AL356741; AC024258; AL133551; AL133551; AC024258; AL356741; BC039600 

Genbank Nucleotide ID

 AAO65480.1; AAV66578.1; AAV66579.1; AAV66580.1; BAB13419.1; CAH74148.1; CAH74148.1; CAH74148.1; CAI16032.1; CAI16032.1; CAI16032.1; AAH39600.1 

Protein Name

 Probable E3 ubiquitin-protein ligase HERC4 

Protein Synonyms/Alias

 HECT domain and RCC1-like domain-containing protein 4 

Gene Name

 HERC4 

Gene Synonyms/Alias

 KIAA1593 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
27	EIVLEPRKSDFFINK	ubiquitination	[1]
34	KSDFFINKRVRDVGC	ubiquitination	[1, 2]
70	LGQLGHEKSRKKPEQ	ubiquitination	[1]
165	VFCWGQNKYGQLGLG	ubiquitination	[1]
177	GLGTDCKKQTSPQLL	ubiquitination	[1]
218	IFGWGRNKFGQLGLN	ubiquitination	[1, 2, 3]
237	RYVPNLLKSLRSQKI	ubiquitination	[1]
243	LKSLRSQKIVYICCG	ubiquitination	[1]
336	TGSTSNRKSPFTVKG	ubiquitination	[1]
342	RKSPFTVKGNWYPYN	ubiquitination	[4]
365	SEEYFCVKRIFSGGD	ubiquitination	[4, 5, 6]
397	FRCPNPTKQIWTVNE	ubiquitination	[1, 4]
469	AARLLFHKLIQPDHP	ubiquitination	[1, 2, 3, 4, 6, 7, 8, 9]
488	QVAASLEKNLIPKLT	ubiquitination	[1, 3, 4, 7, 8, 9]
493	LEKNLIPKLTSSLPD	ubiquitination	[1, 2, 3, 4, 7, 9]
572	EVVVHLLKLYKIGIP	ubiquitination	[2]
606	ILHRVNEKMGQIIQY	ubiquitination	[2]
769	MRELLDPKYGMFRYY	ubiquitination	[1, 4]
828	YKKLLKKKPSLDDLK	ubiquitination	[4]
835	KPSLDDLKELMPDVG	ubiquitination	[4]
890	GADTAVNKQNRQEFV	ubiquitination	[1, 2, 3, 4, 7, 8, 9]
922	AFHAGFHKVCGGKVL	ubiquitination	[10]
959	LEKNTEYKGEYWAEH	ubiquitination	[4]
1003	RIPILGMKSLKLVIQ	ubiquitination	[4]
1006	ILGMKSLKLVIQSTG	ubiquitination	[4]
1033	FNLLDLPKYTEKETL	ubiquitination	[4]

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] 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] 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] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [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] 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] 

Functional Description

 Probable E3 ubiquitin-protein ligase involved in either protein trafficking or in the distribution of cellular structures. Required for spermatozoon maturation and fertility, and for the removal of the cytoplasmic droplet of the spermatozoon. E3 ubiquitin-protein ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfer it to targeted substrates (By similarity). 

Sequence Annotation

 REPEAT 1 51 RCC1 1.
 REPEAT 52 101 RCC1 2.
 REPEAT 102 154 RCC1 3.
 REPEAT 156 207 RCC1 4.
 REPEAT 208 259 RCC1 5.
 REPEAT 261 311 RCC1 6.
 REPEAT 313 368 RCC1 7.
 DOMAIN 730 1057 HECT.
 ACT_SITE 1025 1025 Glycyl thioester intermediate (By  

Keyword

 Alternative splicing; Complete proteome; Cytoplasm; Differentiation; Ligase; Reference proteome; Repeat; Spermatogenesis; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1057 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IBA:RefGenome.
 GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IBA:RefGenome.
 GO:0004842; F:ubiquitin-protein ligase activity; IBA:RefGenome.
 GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
 GO:0007283; P:spermatogenesis; ISS:UniProtKB. 

Interpro

 IPR000569; HECT.
 IPR009091; RCC1/BLIP-II.
 IPR000408; Reg_chr_condens. 

Pfam

 PF00632; HECT
 PF00415; RCC1 

SMART

 SM00119; HECTc 

PROSITE

 PS50237; HECT
 PS00625; RCC1_1
 PS00626; RCC1_2
 PS50012; RCC1_3 

PRINTS

 PR00633; RCCNDNSATION.