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Protein

Ubiquitin carboxyl-terminal hydrolase 49

Gene

USP49

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Specifically deubiquitinates histone H2B at 'Lys-120' (H2BK120Ub). H2BK120Ub is a specific tag for epigenetic transcriptional activation and acts as a regulator of mRNA splicing. Deubiquitination is required for efficient cotranscriptional splicing of a large set of exons.1 Publication

Catalytic activityi

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).2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei262 – 2621NucleophileCurated
Active sitei615 – 6151Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri24 – 8562UBP-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: UniProtKB
  2. histone binding Source: UniProtKB
  3. ubiquitin-specific protease activity Source: UniProtKB
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. histone H2B conserved C-terminal lysine deubiquitination Source: UniProtKB
  2. mRNA splicing, via spliceosome Source: UniProtKB
  3. proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  4. protein deubiquitination Source: FlyBase
  5. regulation of proteasomal protein catabolic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Protease, Thiol protease

Keywords - Biological processi

mRNA processing, mRNA splicing, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiC19.073.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 49 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 49
Ubiquitin thioesterase 49
Ubiquitin-specific-processing protease 49
Gene namesi
Name:USP49
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:20078. USP49.

Subcellular locationi

  1. Nucleus 1 Publication

GO - Cellular componenti

  1. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi262 – 2621C → A: Loss of deubiquitinase activity. 1 Publication

Organism-specific databases

PharmGKBiPA134954570.

Polymorphism and mutation databases

BioMutaiUSP49.
DMDMi52000871.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 688688Ubiquitin carboxyl-terminal hydrolase 49PRO_0000080678Add
BLAST

Proteomic databases

PaxDbiQ70CQ1.
PRIDEiQ70CQ1.

PTM databases

PhosphoSiteiQ70CQ1.

Expressioni

Gene expression databases

BgeeiQ70CQ1.
CleanExiHS_USP49.
ExpressionAtlasiQ70CQ1. baseline and differential.
GenevestigatoriQ70CQ1.

Organism-specific databases

HPAiHPA030254.
HPA030255.

Interactioni

Subunit structurei

Component of a complex with RUVBL1 and PSMC5.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FKBP5Q134512EBI-2511022,EBI-306914

Protein-protein interaction databases

BioGridi117382. 39 interactions.
IntActiQ70CQ1. 47 interactions.
STRINGi9606.ENSP00000297229.

Structurei

3D structure databases

ProteinModelPortaliQ70CQ1.
SMRiQ70CQ1. Positions 26-83, 246-655.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini253 – 657405USPAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 1 UBP-type zinc finger.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri24 – 8562UBP-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG5077.
GeneTreeiENSGT00780000121880.
HOGENOMiHOG000015084.
HOVERGENiHBG018027.
InParanoidiQ70CQ1.
KOiK11834.
OMAiCLECATT.
OrthoDBiEOG7JX33S.
PhylomeDBiQ70CQ1.
TreeFamiTF315281.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
SMARTiSM00290. ZnF_UBP. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q70CQ1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDRCKHVGRL RLAQDHSILN PQKWCCLECA TTESVWACLK CSHVACGRYI
60 70 80 90 100
EDHALKHFEE TGHPLAMEVR DLYVFCYLCK DYVLNDNPEG DLKLLRSSLL
110 120 130 140 150
AVRGQKQDTP VRRGRTLRSM ASGEDVVLPQ RAPQGQPQML TALWYRRQRL
160 170 180 190 200
LARTLRLWFE KSSRGQAKLE QRRQEEALER KKEEARRRRR EVKRRLLEEL
210 220 230 240 250
ASTPPRKSAR LLLHTPRDAG PAASRPAALP TSRRVPAATL KLRRQPAMAP
260 270 280 290 300
GVTGLRNLGN TCYMNSILQV LSHLQKFREC FLNLDPSKTE HLFPKATNGK
310 320 330 340 350
TQLSGKPTNS SATELSLRND RAEACEREGF CWNGRASISR SLELIQNKEP
360 370 380 390 400
SSKHISLCRE LHTLFRVMWS GKWALVSPFA MLHSVWSLIP AFRGYDQQDA
410 420 430 440 450
QEFLCELLHK VQQELESEGT TRRILIPFSQ RKLTKQVLKV VNTIFHGQLL
460 470 480 490 500
SQVTCISCNY KSNTIEPFWD LSLEFPERYH CIEKGFVPLN QTECLLTEML
510 520 530 540 550
AKFTETEALE GRIYACDQCN SKRRKSNPKP LVLSEARKQL MIYRLPQVLR
560 570 580 590 600
LHLKRFRWSG RNHREKIGVH VVFDQVLTME PYCCRDMLSS LDKETFAYDL
610 620 630 640 650
SAVVMHHGKG FGSGHYTAYC YNTEGGFWVH CNDSKLNVCS VEEVCKTQAY
660 670 680
ILFYTQRTVQ GNARISETHL QAQVQSSNND EGRPQTFS
Length:688
Mass (Da):79,198
Last modified:July 5, 2004 - v1
Checksum:i1DE97A430A636B0B
GO
Isoform 2 (identifier: Q70CQ1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     627-688: FWVHCNDSKL...NDEGRPQTFS → ACALLCGVGDTERG

Note: No experimental confirmation available.

Show »
Length:640
Mass (Da):73,455
Checksum:i2476376554DA939E
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei627 – 68862FWVHC…PQTFS → ACALLCGVGDTERG in isoform 2. 1 PublicationVSP_011556Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ586139 mRNA. Translation: CAE51939.1.
AL365205 Genomic DNA. Translation: CAI13187.1.
AL365205 Genomic DNA. Translation: CAI13188.1.
CH471081 Genomic DNA. Translation: EAX04065.1.
BC014176 mRNA. Translation: AAH14176.1.
CCDSiCCDS4861.1. [Q70CQ1-2]
CCDS69111.1. [Q70CQ1-1]
RefSeqiNP_001273483.1. NM_001286554.1. [Q70CQ1-1]
NP_061031.2. NM_018561.4. [Q70CQ1-2]
UniGeneiHs.593575.
Hs.665742.

Genome annotation databases

EnsembliENST00000373006; ENSP00000362097; ENSG00000164663. [Q70CQ1-2]
ENST00000373009; ENSP00000362100; ENSG00000164663. [Q70CQ1-1]
ENST00000394253; ENSP00000377797; ENSG00000164663. [Q70CQ1-1]
GeneIDi25862.
KEGGihsa:25862.
UCSCiuc003ori.3. human. [Q70CQ1-2]

Polymorphism and mutation databases

BioMutaiUSP49.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ586139 mRNA. Translation: CAE51939.1.
AL365205 Genomic DNA. Translation: CAI13187.1.
AL365205 Genomic DNA. Translation: CAI13188.1.
CH471081 Genomic DNA. Translation: EAX04065.1.
BC014176 mRNA. Translation: AAH14176.1.
CCDSiCCDS4861.1. [Q70CQ1-2]
CCDS69111.1. [Q70CQ1-1]
RefSeqiNP_001273483.1. NM_001286554.1. [Q70CQ1-1]
NP_061031.2. NM_018561.4. [Q70CQ1-2]
UniGeneiHs.593575.
Hs.665742.

3D structure databases

ProteinModelPortaliQ70CQ1.
SMRiQ70CQ1. Positions 26-83, 246-655.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117382. 39 interactions.
IntActiQ70CQ1. 47 interactions.
STRINGi9606.ENSP00000297229.

Protein family/group databases

MEROPSiC19.073.

PTM databases

PhosphoSiteiQ70CQ1.

Polymorphism and mutation databases

BioMutaiUSP49.
DMDMi52000871.

Proteomic databases

PaxDbiQ70CQ1.
PRIDEiQ70CQ1.

Protocols and materials databases

DNASUi25862.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373006; ENSP00000362097; ENSG00000164663. [Q70CQ1-2]
ENST00000373009; ENSP00000362100; ENSG00000164663. [Q70CQ1-1]
ENST00000394253; ENSP00000377797; ENSG00000164663. [Q70CQ1-1]
GeneIDi25862.
KEGGihsa:25862.
UCSCiuc003ori.3. human. [Q70CQ1-2]

Organism-specific databases

CTDi25862.
GeneCardsiGC06M041795.
H-InvDBHIX0164985.
HGNCiHGNC:20078. USP49.
HPAiHPA030254.
HPA030255.
neXtProtiNX_Q70CQ1.
PharmGKBiPA134954570.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5077.
GeneTreeiENSGT00780000121880.
HOGENOMiHOG000015084.
HOVERGENiHBG018027.
InParanoidiQ70CQ1.
KOiK11834.
OMAiCLECATT.
OrthoDBiEOG7JX33S.
PhylomeDBiQ70CQ1.
TreeFamiTF315281.

Miscellaneous databases

GenomeRNAii25862.
NextBioi47231.
PROiQ70CQ1.

Gene expression databases

BgeeiQ70CQ1.
CleanExiHS_USP49.
ExpressionAtlasiQ70CQ1. baseline and differential.
GenevestigatoriQ70CQ1.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
SMARTiSM00290. ZnF_UBP. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases."
    Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S., Lopez-Otin C.
    Biochem. Biophys. Res. Commun. 314:54-62(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY.
  2. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. 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] (ISOFORM 2).
    Tissue: Eye.
  5. "USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA splicing."
    Zhang Z., Jones A., Joo H.Y., Zhou D., Cao Y., Chen S., Erdjument-Bromage H., Renfrow M., He H., Tempst P., Townes T.M., Giles K.E., Ma L., Wang H.
    Genes Dev. 27:1581-1595(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH RUVBL1 AND PSMC5, MUTAGENESIS OF CYS-262.

Entry informationi

Entry nameiUBP49_HUMAN
AccessioniPrimary (citable) accession number: Q70CQ1
Secondary accession number(s): Q5T3D9, Q5T3E0, Q96CK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: July 5, 2004
Last modified: April 29, 2015
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.