P62987 (RL40_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-60S ribosomal protein L40

Alternative name(s):
CEP52
Ubiquitin A-52 residue ribosomal protein fusion product 1

Cleaved into the following 2 chains:

1. Ubiquitin
2. 60S ribosomal protein L40

Gene names

Name:	UBA52
Synonyms:	UBCEP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	128 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. Ref.8 Ref.15 Ribosomal protein L40 is a component of the 60S subunit of the ribosome. Ref.8 Ref.15
Subunit structure	Ribosomal protein L40 is part of the 60S ribosomal subunit By similarity.
Subcellular location	Ubiquitin: Cytoplasm By similarity. Nucleus By similarity. 60S ribosomal protein L40: Cytoplasm By similarity.
Miscellaneous	Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains. For a better understanding, features related to ubiquitin are only indicated for the first chain.
Sequence similarities	In the N-terminal section; belongs to the ubiquitin family. In the C-terminal section; belongs to the ribosomal protein L40e family. Contains 1 ubiquitin-like domain.
Sequence caution	The sequence AAK31162.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Molecular function	Ribonucleoprotein Ribosomal protein
PTM	Acetylation Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Traceable author statement. Source: Reactome DNA repair Traceable author statement. Source: Reactome G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome I-kappaB kinase/NF-kappaB cascade Traceable author statement. Source: Reactome JNK cascade Traceable author statement. Source: Reactome M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome MyD88-independent toll-like receptor signaling pathway Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome activation of MAPK activity Traceable author statement. Source: Reactome anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome anti-apoptosis Traceable author statement. Source: Reactome antigen processing and presentation of peptide antigen via MHC class I Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome cellular membrane organization Traceable author statement. Source: Reactome endocrine pancreas development Traceable author statement. Source: Reactome endosome transport Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome induction of apoptosis by extracellular signals Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome mRNA metabolic process Traceable author statement. Source: Reactome negative regulation of epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of type I interferon production Traceable author statement. Source: Reactome negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Traceable author statement. Source: Reactome positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome protein polyubiquitination Traceable author statement. Source: Reactome stress-activated MAPK cascade Traceable author statement. Source: Reactome toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome translation Non-traceable author statement. Source: UniProtKB translational elongation Traceable author statement. Source: Reactome translational termination Traceable author statement. Source: Reactome viral transcription Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome cytosolic large ribosomal subunit Inferred from direct assay. Source: UniProtKB endocytic vesicle membrane Traceable author statement. Source: Reactome endosome membrane Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome ribosome Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction. Source: BHF-UCL structural constituent of ribosome Inferred from electronic annotation. Source: InterPro ubiquitin-protein ligase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 76	76	Ubiquitin		PRO_0000396433
	Chain	77 – 128	52	60S ribosomal protein L40		PRO_0000396434
Regions
	Domain	1 – 76	76	Ubiquitin-like
Sites
	Binding site	54	1	Activating enzyme
	Binding site	72	1	Activating enzyme
	Site	68	1	Essential for function
Amino acid modifications
	Modified residue	6	1	N6-acetyllysine Ref.14
	Modified residue	48	1	N6-acetyllysine Ref.14
	Modified residue	57	1	Phosphoserine By similarity
	Modified residue	65	1	Phosphoserine Ref.10
	Modified residue	98	1	N6,N6,N6-trimethyllysine By similarity
	Cross-link	6		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.6
	Cross-link	11		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.6 Ref.8
	Cross-link	27		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
	Cross-link	29		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.8
	Cross-link	33		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	48		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.6 Ref.8 Ref.11 Ref.12
	Cross-link	63		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.8 Ref.13
	Cross-link	76		Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)
Experimental info
	Mutagenesis	48	1	K → R: No effect on HLTF-mediated polyubiquitination of PCNA. Ref.13
	Mutagenesis	63	1	K → R: Abolishes HLTF-mediated polyubiquitination of PCNA. Ref.13

Sequences

	Sequence		Length	Mass (Da)
	P62987 [UniParc]. Last modified August 10, 2010. Version 2. Checksum: 7BCB602ABEFAD02A	FASTA	128	14,728
	10 20 30 40 50 60 MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN 70 80 90 100 110 120 IQKESTLHLV LRLRGGIIEP SLRQLAQKYN CDKMICRKCY ARLHPRAVNC RKKKCGHTNN LRPKKKVK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human ubiquitin-52 amino acid fusion protein gene shares several structural features with mammalian ribosomal protein genes." Baker R.T., Board P.G. Nucleic Acids Res. 19:1035-1040(1991) [PubMed: 1850507] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Adrenal gland, Lymphocyte and Placenta.
[2]	"Human ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) in salivary epithelial cells." Wang H., Zhang Y., Okamoto T. Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Hybrid troponin reconstituted from vertebrate and arthropod subunits." Schlesinger D.H., Goldstein G. Nature 255:423-424(1975) [PubMed: 124018] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-74.
[5]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-27; 30-42 AND 55-72, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[6]	"Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation." Cripps D., Thomas S.N., Jeng Y., Yang F., Davies P., Yang A.J. J. Biol. Chem. 281:10825-10838(2006) [PubMed: 16443603] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-27 AND 43-54, UBIQUITINATION AT LYS-6; LYS-11 AND LYS-48, MASS SPECTROMETRY.
[7]	"cDNA encoding a human homolog of yeast ubiquitin 1." Salvesen G., Lloyd C., Farley D. Nucleic Acids Res. 15:5485-5485(1987) [PubMed: 3037496] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 40-128.
[8]	"Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain." Huang F., Kirkpatrick D., Jiang X., Gygi S.P., Sorkin A. Mol. Cell 21:737-748(2006) [PubMed: 16543144] [Abstract] Cited for: FUNCTION, UBIQUITINATION AT LYS-11; LYS-29; LYS-48 AND LYS-63, MASS SPECTROMETRY.
[9]	"Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesis." Okumura F., Hatakeyama S., Matsumoto M., Kamura T., Nakayama K. J. Biol. Chem. 279:53533-53543(2004) [PubMed: 15466860] [Abstract] Cited for: UBIQUITINATION AT LYS-27.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Mass spectrometric characterization of the affinity-purified human 26S proteasome complex." Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L. Biochemistry 46:3553-3565(2007) [PubMed: 17323924] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-48, MASS SPECTROMETRY.
[12]	"The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells." Vasilescu J., Zweitzig D.R., Denis N.J., Smith J.C., Ethier M., Haines D.S., Figeys D. J. Proteome Res. 6:298-305(2007) [PubMed: 17203973] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-48, MASS SPECTROMETRY. Tissue: Lung adenocarcinoma.
[13]	"Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks." Motegi A., Liaw H.-J., Lee K.-Y., Roest H.P., Maas A., Wu X., Moinova H., Markowitz S.D., Ding H., Hoeijmakers J.H.J., Myung K. Proc. Natl. Acad. Sci. U.S.A. 105:12411-12416(2008) [PubMed: 18719106] [Abstract] Cited for: UBIQUITINATION AT LYS-63, MUTAGENESIS OF LYS-48 AND LYS-63.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6 AND LYS-48, MASS SPECTROMETRY.
[15]	"The emerging complexity of protein ubiquitination." Komander D. Biochem. Soc. Trans. 37:937-953(2009) [PubMed: 19754430] [Abstract] Cited for: REVIEW, FUNCTION.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X56998 mRNA. Translation: CAA40313.1. X56997 Genomic DNA. Translation: CAA40312.1. X56999 mRNA. Translation: CAA40314.1. AF348700 mRNA. Translation: AAK31162.1. Different initiation. AC005253 Genomic DNA. Translation: AAC25582.1. Y00361 mRNA. Translation: CAA68439.1.
IPI	IPI00456429.
PIR	UQHUR. S34428.
RefSeq	NP_001029102.1. NM_001033930.1. NP_003324.1. NM_003333.3.
UniGene	Hs.5308.
3D structure databases
ProteinModelPortal	P62987.
SMR	P62987. Positions 1-76, 89-128.
ModBase	Search...
Protein-protein interaction databases
IntAct	P62987. 2 interactions.
MINT	MINT-1137632.
STRING	P62987.
PTM databases
PhosphoSite	P62987.
Polymorphism databases
DMDM	302393718.
Proteomic databases
PRIDE	P62987.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000430157; ENSP00000396910; ENSG00000221983. ENST00000442744; ENSP00000388107; ENSG00000221983.
GeneID	7311.
KEGG	hsa:7311.
Organism-specific databases
CTD	7311.
GeneCards	GC19P018682.
HGNC	HGNC:12458. UBA52.
MIM	191321. gene.
neXtProt	NX_P62987.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07127.
HOVERGEN	HBG079132.
InParanoid	P62987.
OMA	YNCEKMI.
OrthoDB	EOG4V1726.
PhylomeDB	P62987.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_11123. Membrane Trafficking. REACT_13505. Proteasome mediated degradation of PAK-2p34. REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. REACT_15380. Diabetes pathways. REACT_17015. Metabolism of proteins. REACT_1762. 3' -UTR-mediated translational regulation. REACT_216. DNA Repair. REACT_24941. Circadian Clock. REACT_25177. RNF125 mediated ubiquitination of RIG-I, MDA5 and IPS-1. REACT_383. DNA Replication. REACT_578. Apoptosis. REACT_6167. Influenza Infection. REACT_6185. HIV Infection. REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A. REACT_6900. Immune System. REACT_71. Gene Expression. REACT_8017. APC-Cdc20 mediated degradation of Nek2A.
Gene expression databases
ArrayExpress	P62987.
Bgee	P62987.
CleanEx	HS_UBA52.
Genevestigator	P62987.
GermOnline	ENSG00000196084. Homo sapiens.
Family and domain databases
InterPro	IPR001975. Ribosomal_L40e. IPR000626. Ubiquitin. IPR019954. Ubiquitin_CS. IPR019956. Ubiquitin_subgr. IPR019955. Ubiquitin_supergroup. [Graphical view]
KO	K02927.
Pfam	PF01020. Ribosomal_L40e. 1 hit. PF00240. ubiquitin. 1 hit. [Graphical view]
PRINTS	PR00348. UBIQUITIN.
SMART	SM00213. UBQ. 1 hit. [Graphical view]
PROSITE	PS00299. UBIQUITIN_1. 1 hit. PS50053. UBIQUITIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

RL40_HUMAN

Accession

Primary (citable) accession number: P62987
Secondary accession number(s): P02248 , P02249, P02250, P14793, P62988, Q29120, Q6LBL4, Q6LDU5, Q8WYN8, Q91887, Q91888, Q9BWD6, Q9BX98, Q9UEF2, Q9UEG1, Q9UEK8, Q9UPK7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	August 10, 2010
Last modified:	January 25, 2012
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.