P51784 (UBP11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 11
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 11
Ubiquitin thiolesterase 11
Ubiquitin-specific-processing protease 11

Gene names

Name:	USP11
Synonyms:	UHX1

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	963 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains. Inhibits the degradation of target proteins by the proteasome. Plays a role in the regulation of pathways leading to NF-kappa-B activation. Plays a role in the regulation of DNA repair after double-stranded DNA breaks. Ref.5 Ref.6 Ref.7 Ref.10 Ref.11
Catalytic activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Ref.3
Subunit structure	Interacts with RANBP9/RANBPM. Interacts with BRCA2, CHUK/IKKA and NFKBIA. Interacts with papilloma virus protein 16E7. Ref.3 Ref.5 Ref.6 Ref.7 Ref.10
Subcellular location	Nucleus. Cytoplasm. Note: Predominantly nuclear. Associates with chromatin. Ref.3 Ref.5 Ref.11
Sequence similarities	Belongs to the peptidase C19 family. Contains 1 DUSP domain.
Caution	It is uncertain whether Met-1 or Met-44 is the initiator.
Sequence caution	The sequence AAC50450.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAC50450.1 differs from that shown. Reason: Frameshift at positions 65, 117, 134 and 146. The sequence BAC20463.1 differs from that shown. Reason: Erroneous initiation. The sequence CAD20056.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Molecular function	Hydrolase Protease Thiol protease
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein deubiquitination Inferred from direct assay Ref.5. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	cysteine-type endopeptidase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction Ref.5. Source: UniProtKB ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro ubiquitin-specific protease activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
E7	P03129	6	EBI-306876,EBI-866453	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 963	963	Ubiquitin carboxyl-terminal hydrolase 11		PRO_0000080632
Regions
	Domain	76 – 184	109	DUSP
Sites
	Active site	318	1	Nucleophile
	Active site	888	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	245	1	N6-acetyllysine Ref.9
	Modified residue	948	1	Phosphoserine Ref.8
	Modified residue	953	1	Phosphoserine Ref.8
Experimental info
	Mutagenesis	318	1	C → S: Loss of deubiquitinase activity. Ref.5
	Sequence conflict	52	1	A → AT in BAC20463. Ref.3
	Sequence conflict	58	1	V → M in AAC50450. Ref.4
	Sequence conflict	62	1	A → R in AAC50450. Ref.4
	Sequence conflict	82 – 83	2	WR → CG in AAC50450. Ref.4
	Sequence conflict	160	1	A → R in BAC20463. Ref.3
	Sequence conflict	161	1	A → R in BAC20463. Ref.3
	Sequence conflict	161	1	A → R in AAC50450. Ref.4
	Sequence conflict	489	1	P → L in AAH00350. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P51784 [UniParc]. Last modified July 7, 2009. Version 3. Checksum: 876FDC41945AFD9B	FASTA	963	109,817
	10 20 30 40 50 60 MAVAPRLFGG LCFRFRDQNP EVAVEGRLPI SHSCVGCRRE RTAMATVAAN PAAAAAAVAA 70 80 90 100 110 120 AAAVTEDREP QHEELPGLDS QWRQIENGES GRERPLRAGE SWFLVEKHWY KQWEAYVQGG 130 140 150 160 170 180 DQDSSTFPGC INNATLFQDE INWRLKEGLV EGEDYVLLPA AAWHYLVSWY GLEHGQPPIE 190 200 210 220 230 240 RKVIELPNIQ KVEVYPVELL LVRHNDLGKS HTVQFSHTDS IGLVLRTARE RFLVEPQEDT 250 260 270 280 290 300 RLWAKNSEGS LDRLYDTHIT VLDAALETGQ LIIMETRKKD GTWPSAQLHV MNNNMSEEDE 310 320 330 340 350 360 DFKGQPGICG LTNLGNTCFM NSALQCLSNV PQLTEYFLNN CYLEELNFRN PLGMKGEIAE 370 380 390 400 410 420 AYADLVKQAW SGHHRSIVPH VFKNKVGHFA SQFLGYQQHD SQELLSFLLD GLHEDLNRVK 430 440 450 460 470 480 KKEYVELCDA AGRPDQEVAQ EAWQNHKRRN DSVIVDTFHG LFKSTLVCPD CGNVSVTFDP 490 500 510 520 530 540 FCYLSVPLPI SHKRVLEVFF IPMDPRRKPE QHRLVVPKKG KISDLCVALS KHTGISPERM 550 560 570 580 590 600 MVADVFSHRF YKLYQLEEPL SSILDRDDIF VYEVSGRIEA IEGSREDIVV PVYLRERTPA 610 620 630 640 650 660 RDYNNSYYGL MLFGHPLLVS VPRDRFTWEG LYNVLMYRLS RYVTKPNSDD EDDGDEKEDD 670 680 690 700 710 720 EEDKDDVPGP STGGSLRDPE PEQAGPSSGV TNRCPFLLDN CLGTSQWPPR RRRKQLFTLQ 730 740 750 760 770 780 TVNSNGTSDR TTSPEEVHAQ PYIAIDWEPE MKKRYYDEVE AEGYVKHDCV GYVMKKAPVR 790 800 810 820 830 840 LQECIELFTT VETLEKENPW YCPSCKQHQL ATKKLDLWML PEILIIHLKR FSYTKFSREK 850 860 870 880 890 900 LDTLVEFPIR DLDFSEFVIQ PQNESNPELY KYDLIAVSNH YGGMRDGHYT TFACNKDSGQ 910 920 930 940 950 960 WHYFDDNSVS PVNENQIESK AAYVLFYQRQ DVARRLLSPA GSSGAPASPA CSSPPSSEFM DVN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[3]	"Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM." Ideguchi H., Ueda A., Tanaka M., Yang J., Tsuji T., Ohno S., Hagiwara E., Aoki A., Ishigatsubo Y. Biochem. J. 367:87-95(2002) [PubMed: 12084015] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 41-963, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH RANBP9. Tissue: Fetal brain.
[4]	"A ubiquitin C-terminal hydrolase gene on the proximal short arm of the X chromosome: implications for X-linked retinal disorders." Swanson D.A., Freund C.L., Ploder L., McInnes R.R., Valle D. Hum. Mol. Genet. 5:533-538(1996) [PubMed: 8845848] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 52-963. Tissue: Retina.
[5]	"BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage." Schoenfeld A.R., Apgar S., Dolios G., Wang R., Aaronson S.A. Mol. Cell. Biol. 24:7444-7455(2004) [PubMed: 15314155] [Abstract] Cited for: FUNCTION, INTERACTION WITH BRCA2, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-318, MASS SPECTROMETRY.
[6]	"The deubiquitinating enzyme USP11 controls an IkappaB kinase alpha (IKKalpha)-p53 signaling pathway in response to tumor necrosis factor alpha (TNFalpha)." Yamaguchi T., Kimura J., Miki Y., Yoshida K. J. Biol. Chem. 282:33943-33948(2007) [PubMed: 17897950] [Abstract] Cited for: FUNCTION, INTERACTION WITH CHUK.
[7]	"USP11 stabilizes HPV-16E7 and further modulates the E7 biological activity." Lin C.H., Chang H.S., Yu W.C. J. Biol. Chem. 283:15681-15688(2008) [PubMed: 18408009] [Abstract] Cited for: FUNCTION, INTERACTION WITH HUMAN PAPILLOMA VIRUS 16E7.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-948 AND SER-953, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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-245, MASS SPECTROMETRY.
[10]	"USP11 negatively regulates TNFalpha-induced NF-kappaB activation by targeting on IkappaBalpha." Sun W., Tan X., Shi Y., Xu G., Mao R., Gu X., Fan Y., Yu Y., Burlingame S., Zhang H., Rednam S.P., Lu X., Zhang T., Fu S., Cao G., Qin J., Yang J. Cell. Signal. 22:386-394(2010) [PubMed: 19874889] [Abstract] Cited for: FUNCTION, INTERACTION WITH NFKBIA, MASS SPECTROMETRY.
[11]	"Sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition identifies ubiquitin-specific peptidase 11 (USP11) as a regulator of DNA double-strand break repair." Wiltshire T.D., Lovejoy C.A., Wang T., Xia F., O'Connor M.J., Cortez D. J. Biol. Chem. 285:14565-14571(2010) [PubMed: 20233726] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]	"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	AL096791 Genomic DNA. Translation: CAD20056.1. Sequence problems. BC140849 mRNA. Translation: AAI40850.1. BC000350 mRNA. Translation: AAH00350.4. AB073597 mRNA. Translation: BAC20463.1. Different initiation. U44839 mRNA. Translation: AAC50450.1. Sequence problems.
IPI	IPI00184533.
RefSeq	NP_004642.2. NM_004651.3.
UniGene	Hs.171501.
3D structure databases
ProteinModelPortal	P51784.
SMR	P51784. Positions 73-289, 305-931.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27567N.
IntAct	P51784. 58 interactions.
MINT	MINT-1147600.
STRING	P51784.
Protein family/group databases
MEROPS	C19.014.
PTM databases
PhosphoSite	P51784.
Polymorphism databases
DMDM	251757432.
Proteomic databases
PRIDE	P51784.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000218348; ENSP00000218348; ENSG00000102226.
GeneID	8237.
KEGG	hsa:8237.
UCSC	uc004dhp.1. human.
Organism-specific databases
CTD	8237.
GeneCards	GC0XP047093.
H-InvDB	HIX0203281.
HGNC	HGNC:12609. USP11.
HPA	HPA003103. HPA037536.
MIM	300050. gene.
neXtProt	NX_P51784.
PharmGKB	PA37235.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11238.
HOGENOM	HBG318284.
HOVERGEN	HBG000864.
InParanoid	P51784.
OMA	KHDCVGY.
PhylomeDB	P51784.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins.
Gene expression databases
ArrayExpress	P51784.
Bgee	P51784.
CleanEx	HS_USP11.
Genevestigator	P51784.
GermOnline	ENSG00000102226. Homo sapiens.
Family and domain databases
InterPro	IPR006615. Pept_C19_DUSP. IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. [Graphical view]
KO	K11835.
Pfam	PF06337. DUSP. 1 hit. PF00443. UCH. 1 hit. [Graphical view]
SMART	SM00695. DUSP. 1 hit. [Graphical view]
PROSITE	PS51283. DUSP. 1 hit. PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

UBP11_HUMAN

Accession

Primary (citable) accession number: P51784
Secondary accession number(s): B2RTX1, Q8IUG6, Q9BWE1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 7, 2009
Last modified:	January 25, 2012
This is version 118 of the entry and version 3 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.