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P62068 (UBP46_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin carboxyl-terminal hydrolase 46

EC=3.4.19.12
Alternative name(s):
Deubiquitinating enzyme 46
Ubiquitin thioesterase 46
Ubiquitin-specific-processing protease 46
Gene names
Name:USP46
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length366 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2. Ref.6

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.5 Ref.6

Subunit structure

Interacts with WDR48. Ref.6

Tissue specificity

Broadly expressed. Ref.5

Sequence similarities

Belongs to the peptidase C19 family. USP12/USP46 subfamily.

Contains 1 USP domain.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P62068-1)

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.
Isoform 2 (identifier: P62068-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-116: Missing.
     334-366: KIDAQAIEEFYGLTSDISKNSESGYILFYQSRE → VGLQIILQ
Note: No experimental confirmation available.
Isoform 3 (identifier: P62068-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MTVRNIASICNM → MNCFQ
Note: No experimental confirmation available.
Isoform 4 (identifier: P62068-4)

The sequence of this isoform differs from the canonical sequence as follows:
     40-51: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 366366Ubiquitin carboxyl-terminal hydrolase 46
PRO_0000080674

Regions

Domain35 – 365331USP

Sites

Active site441Nucleophile By similarity
Active site3131Proton acceptor By similarity

Natural variations

Alternative sequence1 – 116116Missing in isoform 2.
VSP_037618
Alternative sequence1 – 1212MTVRN…SICNM → MNCFQ in isoform 3.
VSP_037619
Alternative sequence40 – 5112Missing in isoform 4.
VSP_037620
Alternative sequence334 – 36633KIDAQ…YQSRE → VGLQIILQ in isoform 2.
VSP_037621
Natural variant811A → V.
Corresponds to variant rs17475800 [ dbSNP | Ensembl ].
VAR_051540

Experimental info

Sequence conflict1771T → A in BAH13161. Ref.2
Sequence conflict2501I → V in BAB14133. Ref.2
Sequence conflict2651H → R in BAB14133. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 21, 2004. Version 1.
Checksum: 67BB113FC4081C46

FASTA36642,442
        10         20         30         40         50         60 
MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNF GNTCYCNSVL QALYFCRPFR 

        70         80         90        100        110        120 
ENVLAYKAQQ KKKENLLTCL ADLFHSIATQ KKKVGVIPPK KFISRLRKEN DLFDNYMQQD 

       130        140        150        160        170        180 
AHEFLNYLLN TIADILQEEK KQEKQNGKLK NGNMNEPAEN NKPELTWVHE IFQGTLTNET 

       190        200        210        220        230        240 
RCLNCETVSS KDEDFLDLSV DVEQNTSITH CLRDFSNTET LCSEQKYYCE TCCSKQEAQK 

       250        260        270        280        290        300 
RMRVKKLPMI LALHLKRFKY MEQLHRYTKL SYRVVFPLEL RLFNTSSDAV NLDRMYDLVA 

       310        320        330        340        350        360 
VVVHCGSGPN RGHYITIVKS HGFWLLFDDD IVEKIDAQAI EEFYGLTSDI SKNSESGYIL 


FYQSRE 

« Hide

Isoform 2 [UniParc].

Checksum: 1460D49881E7AFBF
Show »

FASTA22526,243
Isoform 3 [UniParc].

Checksum: 724DEC421BEC14AC
Show »

FASTA35941,732
Isoform 4 [UniParc].

Checksum: 0018B82362D8A874
Show »

FASTA35441,112

References

« Hide 'large scale' references
[1]"Lysine 92 amino acid residue of USP46, a gene associated with 'behavioral despair' in mice, influences the deubiquitinating enzyme activity."
Zhang W., Tian Q.B., Li Q.K., Wang J.M., Wang C.N., Liu T., Liu D.W., Wang M.W.
PLoS ONE 6:E26297-E26297(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
Tissue: Brain, Placenta, Teratocarcinoma, Testis and Thalamus.
[3]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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 1).
Tissue: Uterus.
[5]"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: TISSUE SPECIFICITY, ENZYME ACTIVITY.
[6]"UAF1 is a subunit of multiple deubiquitinating enzyme complexes."
Cohn M.A., Kee Y., Haas W., Gygi S.P., D'Andrea A.D.
J. Biol. Chem. 284:5343-5351(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH WDR48.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
GU455414 mRNA. Translation: ADV57651.1.
AK022614 mRNA. Translation: BAB14133.1.
AK024318 mRNA. Translation: BAB14881.1.
AK296493 mRNA. Translation: BAH12373.1.
AK299883 mRNA. Translation: BAH13161.1.
AK302438 mRNA. Translation: BAH13709.1.
CH471057 Genomic DNA. Translation: EAX05435.1.
BC037574 mRNA. Translation: AAH37574.1.
RefSeqNP_001127695.1. NM_001134223.1.
NP_001273696.1. NM_001286767.1.
NP_001273697.1. NM_001286768.1.
NP_073743.2. NM_022832.3.
UniGeneHs.7966.

3D structure databases

ProteinModelPortalP62068.
SMRP62068. Positions 36-366.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122327. 21 interactions.
IntActP62068. 17 interactions.
STRING9606.ENSP00000407818.

Protein family/group databases

MEROPSC19.052.

Polymorphism databases

DMDM49065850.

Proteomic databases

PaxDbP62068.
PRIDEP62068.

Protocols and materials databases

DNASU64854.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000441222; ENSP00000407818; ENSG00000109189. [P62068-1]
ENST00000508499; ENSP00000423244; ENSG00000109189. [P62068-3]
GeneID64854.
KEGGhsa:64854.
UCSCuc003gzm.4. human. [P62068-3]
uc003gzn.3. human. [P62068-1]
uc011bzr.2. human. [P62068-4]
uc011bzs.2. human. [P62068-2]

Organism-specific databases

CTD64854.
GeneCardsGC04M053376.
HGNCHGNC:20075. USP46.
HPAHPA007288.
MIM612849. gene.
neXtProtNX_P62068.
PharmGKBPA134922048.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5077.
HOVERGENHBG054038.
InParanoidP62068.
KOK11842.
OMAQFNRHIK.
OrthoDBEOG7RBZ8G.
PhylomeDBP62068.
TreeFamTF314144.

Gene expression databases

ArrayExpressP62068.
BgeeP62068.
CleanExHS_USP46.
GenevestigatorP62068.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
[Graphical view]
PROSITEPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi64854.
NextBio66987.
PROP62068.
SOURCESearch...

Entry information

Entry nameUBP46_HUMAN
AccessionPrimary (citable) accession number: P62068
Secondary accession number(s): B7Z3Y7 expand/collapse secondary AC list , B7Z675, B7Z7S3, G8ACC7, Q80V95, Q9H7U4, Q9H9T8
Entry history
Integrated into UniProtKB/Swiss-Prot: June 21, 2004
Last sequence update: June 21, 2004
Last modified: April 16, 2014
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM