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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.12 Ribosomal protein L40 is a component of the 60S subunit of the ribosome. Ref.8 Ref.12
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	3D-structure 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 phase of mitotic cell cycle 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 Notch receptor processing Traceable author statement. Source: Reactome Notch signaling pathway Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome SRP-dependent cotranslational protein targeting to membrane Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like 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 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome cellular membrane organization Traceable author statement. Source: Reactome cytokine-mediated signaling pathway Traceable author statement. Source: Reactome egress of virus within host cell Traceable author statement. Source: Reactome endosomal transport Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome negative regulation of epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: Reactome negative regulation of transforming growth factor beta 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 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay 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 transcription from RNA polymerase II promoter 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 regulation of apoptotic process Traceable author statement. Source: Reactome regulation of transcription from RNA polymerase II promoter in response to hypoxia 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 transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome translation Non-traceable author statement PubMed 12962325. Source: UniProtKB translational elongation Traceable author statement. Source: Reactome translational initiation 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 PubMed 12962325. 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	structural constituent of ribosome Inferred from electronic annotation. Source: InterPro
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; alternate By similarity

Modified residue

48

1

N6-acetyllysine; alternate By similarity

Modified residue

57

1

Phosphoserine By similarity

Modified residue

65

1

Phosphoserine By similarity

Modified residue

88

1

N6-acetyllysine Ref.13

Modified residue

98

1

N6,N6,N6-trimethyllysine By similarity

Cross-link

6

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate 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); alternate Ref.6 Ref.8 Ref.10

Cross-link

63

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.8 Ref.11

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.11

Mutagenesis

63

1

K → R: Abolishes HLTF-mediated polyubiquitination of PCNA. Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

128

Helix Strand Turn

Details...

Beta strand

1 – 8

8

Beta strand

11 – 17

7

Helix

23 – 34

12

Helix

38 – 40

3

Beta strand

41 – 45

5

Helix

57 – 59

3

Beta strand

66 – 74

9

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-27.
[10]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-48, MASS SPECTROMETRY. Tissue: Lung adenocarcinoma.
[11]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-63, MUTAGENESIS OF LYS-48 AND LYS-63.
[12]	"The emerging complexity of protein ubiquitination." Komander D. Biochem. Soc. Trans. 37:937-953(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW, FUNCTION.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-88, MASS SPECTROMETRY.
[14]	"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] [Europe PMC] [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

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LJ5	NMR	-	A	1-76	[»]
4HJK	X-ray	1.78	A	1-76	[»]

ProteinModelPortal

P62987.

SMR

P62987. Positions 1-76, 89-128.

ModBase

Search...

Protein-protein interaction databases

IntAct

P62987. 3 interactions.

MINT

MINT-1137632.

STRING

9606.ENSP00000388107.

PTM databases

PhosphoSite

P62987.

Polymorphism databases

DMDM

302393718.

Proteomic databases

PaxDb

P62987.

PRIDE

P62987.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000430157; ENSP00000396910; ENSG00000221983.
ENST00000442744; ENSP00000388107; ENSG00000221983.
ENST00000595158; ENSP00000471622; ENSG00000221983.
ENST00000595683; ENSP00000470419; ENSG00000221983.
ENST00000596273; ENSP00000471062; ENSG00000221983.
ENST00000596304; ENSP00000472264; ENSG00000221983.
ENST00000597451; ENSP00000473048; ENSG00000221983.
ENST00000598780; ENSP00000472545; ENSG00000221983.
ENST00000599551; ENSP00000470507; ENSG00000221983.
ENST00000599595; ENSP00000471464; ENSG00000221983.

GeneID

7311.

KEGG

hsa:7311.

UCSC

uc002njr.3. human.

Organism-specific databases

CTD

7311.

GeneCards

GC19P018682.

HGNC

HGNC:12458. UBA52.

HPA

HPA041344.

MIM

191321. gene.

neXtProt

NX_P62987.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5272.

HOVERGEN

HBG079132.

InParanoid

P62987.

KO

K02927.

OMA

QKYNCEK.

OrthoDB

EOG4V1726.

Enzyme and pathway databases

Reactome

REACT_107772. Immune System.
REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.
REACT_115202. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_120956. Cellular responses to stress.
REACT_13505. Proteasome mediated degradation of PAK-2p34.
REACT_17015. Metabolism of proteins.
REACT_1762. 3' -UTR-mediated translational regulation.
REACT_2001. Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor.
REACT_21257. Metabolism of RNA.
REACT_21300. Mitotic M-M/G1 phases.
REACT_216. DNA Repair.
REACT_24941. Circadian Clock.
REACT_383. DNA Replication.
REACT_578. Apoptosis.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
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.
REACT_81380. Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor.
REACT_97910. Signal Transduction.

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]

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

ChiTaRS

UBA52. human.

GenomeRNAi

7311.

NextBio

28582.

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:	May 1, 2013
This is version 84 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.