P0CG47 (UBB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Polyubiquitin-B

Cleaved into the following chain:

1. Ubiquitin

Gene names

Name:

UBB

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	229 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
Subcellular location	Ubiquitin: Cytoplasm By similarity. Nucleus 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. The mRNA encoding variant UBB(+1) is produced by an unknown mechanism involving the deletion of a GT dinucleotide in the close proximity of a GAGAG motif (Ref.14). This variant mRNA is found in normal brain, but the encoded protein accumulates only in brain neurofibrillary tangles and neuritic plaques in Alzheimer disease and other tauopathies, as well as polyglutaminopathies (Ref.15). UBB(+1) variant cannot be used for polyubiquitination, is not effectively degraded by the proteasome when ubiquitinated and ubiquitinated UBB(+1) is refractory to disassembly by deubiquitinating enzymes (DUBs). In healthy brain, UBB(+1) C-terminus can be cleaved by UCHL3 (Ref.13). For a better understanding, features related to ubiquitin are only indicated for the first chain.
Sequence similarities	Belongs to the ubiquitin family. Contains 3 ubiquitin-like domains.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Domain	Repeat
PTM	Isopeptide bond 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 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 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 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 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 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
Cellular_component	cytosol Traceable author statement. Source: Reactome 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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCDC50	Q8IVM0	2	EBI-413034,EBI-723996
DUSP1	P28562	2	EBI-413034,EBI-975493
GGA1	Q9UJY5	3	EBI-413034,EBI-447141
GGA3	Q9NZ52	2	EBI-413034,EBI-447404
Mast2	Q60592	2	EBI-413034,EBI-493888	From a different organism.
MCM7	P33993	2	EBI-413034,EBI-355924
Pax3	P24610	2	EBI-413034,EBI-1208116	From a different organism.
RABGEF1	Q9UJ41	6	EBI-413034,EBI-913954
RNF11	Q9Y3C5	2	EBI-413034,EBI-396669
RNF43	Q68DV7	2	EBI-413034,EBI-1647060
SMURF2	Q9HAU4	4	EBI-413034,EBI-396727

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 76	76	Ubiquitin		PRO_0000396174
	Chain	77 – 152	76	Ubiquitin		PRO_0000396175
	Chain	153 – 228	76	Ubiquitin		PRO_0000396176
	Propeptide	229	1			PRO_0000396177
Regions
	Domain	1 – 76	76	Ubiquitin-like 1
	Domain	77 – 152	76	Ubiquitin-like 2
	Domain	153 – 228	76	Ubiquitin-like 3
Sites
	Binding site	54	1	Activating enzyme
	Binding site	72	1	Activating enzyme
	Site	68	1	Essential for function
Amino acid modifications
	Cross-link	6		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.7
	Cross-link	11		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.7 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.7 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)
Natural variations
	Natural variant	76 – 229	154	GMQIF…LRGGC → YADLREDPDRQDHHPGSGAQ in UBB(+1); loss of polyubiquitination; impairs the ubiquitin-proteasome pathway; refractory to disassembly by DUBs; slow degradation by UCHL3.		VAR_066248
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

Sequences

	Sequence		Length	Mass (Da)
	P0CG47 [UniParc]. Last modified August 10, 2010. Version 1. Checksum: 33011162F1C48BB1	FASTA	229	25,762
	10 20 30 40 50 60 MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN 70 80 90 100 110 120 IQKESTLHLV LRLRGGMQIF VKTLTGKTIT LEVEPSDTIE NVKAKIQDKE GIPPDQQRLI 130 140 150 160 170 180 FAGKQLEDGR TLSDYNIQKE STLHLVLRLR GGMQIFVKTL TGKTITLEVE PSDTIENVKA 190 200 210 220 KIQDKEGIPP DQQRLIFAGK QLEDGRTLSD YNIQKESTLH LVLRLRGGC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human ubiquitin gene family: structure of a gene and pseudogenes from the Ub B subfamily." Baker R.T., Board P.G. Nucleic Acids Res. 15:443-463(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[2]	"Lineage-specific homogenization of the polyubiquitin gene among human and great apes." Tachikui H., Saitou N., Nakajima T., Hayasaka I., Ishida T., Inoue I. J. Mol. Evol. 57:737-744(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Liver and Lung.
[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]	"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.
[7]	"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.
[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]	"Mutant ubiquitin (UBB(+1)) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3)." Dennissen F.J., Kholod N., Hermes D.J., Kemmerling N., Steinbusch H.W., Dantuma N.P., van Leeuwen F.W. FEBS Lett. 585:2568-2574(2011) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE BY UCHL3 (VARIANT UBB(+1)).
[14]	"Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients." van Leeuwen F.W., de Kleijn D.P., van den Hurk H.H., Neubauer A., Sonnemans M.A., Sluijs J.A., Koycu S., Ramdjielal R.D., Salehi A., Martens G.J., Grosveld F.G., Peter J., Burbach H., Hol E.M. Science 279:242-247(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF VARIANT UBB(+1).
[15]	"Disease-specific accumulation of mutant ubiquitin as a marker for proteasomal dysfunction in the brain." Fischer D.F., De Vos R.A., Van Dijk R., De Vrij F.M., Proper E.A., Sonnemans M.A., Verhage M.C., Sluijs J.A., Hobo B., Zouambia M., Steur E.N., Kamphorst W., Hol E.M., Van Leeuwen F.W. FASEB J. 17:2014-2024(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY (VARIANT UBB(+1)).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04803 Genomic DNA. Translation: CAA28495.1. AB089617 Genomic DNA. Translation: BAC56955.1. AC093484 Genomic DNA. No translation available. BC000379 mRNA. Translation: AAH00379.1. BC009301 mRNA. Translation: AAH09301.1. BC015127 mRNA. Translation: AAH15127.1. BC026301 mRNA. Translation: AAH26301.1. BC031027 mRNA. Translation: AAH31027.1. BC046123 mRNA. Translation: AAH46123.1.
IPI	IPI00719280.
PIR	UQHUB. A26437.
RefSeq	NP_061828.1. NM_018955.2.
UniGene	Hs.356190. Hs.740365.
3D structure databases
ProteinModelPortal	P0CG47.
SMR	P0CG47. Positions 1-227.
ModBase	Search...
Protein-protein interaction databases
IntAct	P0CG47. 63 interactions.
PTM databases
PhosphoSite	P0CG47.
Polymorphism databases
DMDM	302595875.
Proteomic databases
PRIDE	P0CG47.
Protocols and materials databases
DNASU	7314.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000302182; ENSP00000304697; ENSG00000170315. ENST00000395837; ENSP00000379178; ENSG00000170315. ENST00000395839; ENSP00000379180; ENSG00000170315.
GeneID	7314.
KEGG	hsa:7314.
UCSC	uc001ugw.3. human.
Organism-specific databases
CTD	7314.
GeneCards	GC17P016301.
HGNC	HGNC:12463. UBB.
HPA	CAB013048. HPA041344. HPA049132.
MIM	191339. gene.
neXtProt	NX_P0CG47.
GenAtlas	Search...
Phylogenomic databases
KO	K04551.
OMA	TIGCVNI.
OrthoDB	EOG4WDDB6.
PhylomeDB	P0CG47.
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_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	P0CG47.
Bgee	P0CG47.
GermOnline	ENSG00000170315. Homo sapiens.
Family and domain databases
InterPro	IPR000626. Ubiquitin. IPR019954. Ubiquitin_CS. IPR019956. Ubiquitin_subgr. IPR019955. Ubiquitin_supergroup. [Graphical view]
Pfam	PF00240. ubiquitin. 3 hits. [Graphical view]
PRINTS	PR00348. UBIQUITIN.
SMART	SM00213. UBQ. 3 hits. [Graphical view]
PROSITE	PS00299. UBIQUITIN_1. 3 hits. PS50053. UBIQUITIN_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	UBB. human.
GenomeRNAi	7314.
NextBio	28592.
SOURCE	Search...

Entry information

Entry name

UBB_HUMAN

Accession

Primary (citable) accession number: P0CG47
Secondary accession number(s): P02248 , P02249, P02250, P62988, Q29120, Q6LBL4, Q6LDU5, Q8WYN8, Q91887, Q91888, Q9BWD6, Q9BX98, Q9UEF2, Q9UEG1, Q9UEK8, Q9UPK7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 10, 2010
Last sequence update:	August 10, 2010
Last modified:	May 1, 2013
This is version 31 of the entry and version 1 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.