P62068 (UBP46_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	366 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Behavior Ubl conjugation pathway
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Protease Thiol protease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavior Inferred from sequence or structural similarity. Source: UniProtKB protein deubiquitination Inferred from direct assay Ref.6. Source: UniProtKB regulation of synaptic transmission, GABAergic Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Molecular_function	ubiquitin thiolesterase activity Inferred from direct assay Ref.6. Source: UniProtKB ubiquitin-specific protease activity Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 366	366	Ubiquitin carboxyl-terminal hydrolase 46		PRO_0000080674
Sites
	Active site	44	1	Nucleophile By similarity
	Active site	313	1	Proton acceptor By similarity
Natural variations
	Alternative sequence	1 – 116	116	Missing in isoform 2.		VSP_037618
	Alternative sequence	1 – 12	12	MTVRN…SICNM → MNCFQ in isoform 3.		VSP_037619
	Alternative sequence	40 – 51	12	Missing in isoform 4.		VSP_037620
	Alternative sequence	334 – 366	33	KIDAQ…YQSRE → VGLQIILQ in isoform 2.		VSP_037621
	Natural variant	81	1	A → V. Corresponds to variant rs17475800 [ dbSNP | Ensembl ].		VAR_051540
Experimental info
	Sequence conflict	177	1	T → A in BAH13161. Ref.2
	Sequence conflict	250	1	I → V in BAB14133. Ref.2
	Sequence conflict	265	1	H → R in BAB14133. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 21, 2004. Version 1. Checksum: 67BB113FC4081C46	FASTA	366	42,442
	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
	Isoform 2 [UniParc]. Checksum: 1460D49881E7AFBF	FASTA	225	26,243
	10 20 30 40 50 60 MQQDAHEFLN YLLNTIADIL QEEKKQEKQN GKLKNGNMNE PAENNKPELT WVHEIFQGTL 70 80 90 100 110 120 TNETRCLNCE TVSSKDEDFL DLSVDVEQNT SITHCLRDFS NTETLCSEQK YYCETCCSKQ 130 140 150 160 170 180 EAQKRMRVKK LPMILALHLK RFKYMEQLHR YTKLSYRVVF PLELRLFNTS SDAVNLDRMY 190 200 210 220 DLVAVVVHCG SGPNRGHYIT IVKSHGFWLL FDDDIVEVGL QIILQ
	Isoform 3 [UniParc]. Checksum: 724DEC421BEC14AC	FASTA	359	41,732
	10 20 30 40 50 60 MNCFQGTNAS ALEKDIGPEQ FPINEHYFGL VNFGNTCYCN SVLQALYFCR PFRENVLAYK 70 80 90 100 110 120 AQQKKKENLL TCLADLFHSI ATQKKKVGVI PPKKFISRLR KENDLFDNYM QQDAHEFLNY 130 140 150 160 170 180 LLNTIADILQ EEKKQEKQNG KLKNGNMNEP AENNKPELTW VHEIFQGTLT NETRCLNCET 190 200 210 220 230 240 VSSKDEDFLD LSVDVEQNTS ITHCLRDFSN TETLCSEQKY YCETCCSKQE AQKRMRVKKL 250 260 270 280 290 300 PMILALHLKR FKYMEQLHRY TKLSYRVVFP LELRLFNTSS DAVNLDRMYD LVAVVVHCGS 310 320 330 340 350 GPNRGHYITI VKSHGFWLLF DDDIVEKIDA QAIEEFYGLT SDISKNSESG YILFYQSRE
	Isoform 4 [UniParc]. Checksum: 0018B82362D8A874	FASTA	354	41,112
	10 20 30 40 50 60 MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNA LYFCRPFREN VLAYKAQQKK 70 80 90 100 110 120 KENLLTCLAD LFHSIATQKK KVGVIPPKKF ISRLRKENDL FDNYMQQDAH EFLNYLLNTI 130 140 150 160 170 180 ADILQEEKKQ EKQNGKLKNG NMNEPAENNK PELTWVHEIF QGTLTNETRC LNCETVSSKD 190 200 210 220 230 240 EDFLDLSVDV EQNTSITHCL RDFSNTETLC SEQKYYCETC CSKQEAQKRM RVKKLPMILA 250 260 270 280 290 300 LHLKRFKYME QLHRYTKLSY RVVFPLELRL FNTSSDAVNL DRMYDLVAVV VHCGSGPNRG 310 320 330 340 350 HYITIVKSHG FWLLFDDDIV EKIDAQAIEE FYGLTSDISK NSESGYILFY QSRE

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00303458. IPI00909695. IPI00935919. IPI00936274.
RefSeq	NP_001127695.1. NM_001134223.1. NP_073743.2. NM_022832.3.
UniGene	Hs.7966.
3D structure databases
ProteinModelPortal	P62068.
ModBase	Search...
Protein-protein interaction databases
IntAct	P62068. 17 interactions.
STRING	9606.ENSP00000407818.
Protein family/group databases
MEROPS	C19.052.
Polymorphism databases
DMDM	49065850.
Proteomic databases
PaxDb	P62068.
PRIDE	P62068.
Protocols and materials databases
DNASU	64854.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000441222; ENSP00000407818; ENSG00000109189. ENST00000508499; ENSP00000423244; ENSG00000109189.
GeneID	64854.
KEGG	hsa:64854.
UCSC	uc003gzm.4. human. uc003gzn.3. human. uc011bzr.2. human. uc011bzs.2. human.
Organism-specific databases
CTD	64854.
GeneCards	GC04M053376.
HGNC	HGNC:20075. USP46.
HPA	HPA007288.
MIM	612849. gene.
neXtProt	NX_P62068.
PharmGKB	PA134922048.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5077.
HOVERGEN	HBG054038.
InParanoid	P62068.
KO	K11842.
OMA	TEPTWVH.
OrthoDB	EOG42Z4Q8.
Gene expression databases
ArrayExpress	P62068.
Bgee	P62068.
CleanEx	HS_USP46.
Genevestigator	P62068.
GermOnline	ENSG00000109189. Homo sapiens.
Family and domain databases
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. [Graphical view]
Pfam	PF00443. UCH. 1 hit. [Graphical view]
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	64854.
NextBio	66987.
SOURCE	Search...

Entry information

Entry name

UBP46_HUMAN

Accession

Primary (citable) accession number: P62068
Secondary accession number(s): B7Z3Y7 , B7Z675, B7Z7S3, G8ACC7, Q80V95, Q9H7U4, Q9H9T8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2004
Last sequence update:	June 21, 2004
Last modified:	May 1, 2013
This is version 77 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.