Reviewed, UniProtKB/Swiss-Prot Q9Y5K5 (UCHL5_HUMAN)

Names and origin

Protein names

Recommended name:
    Ubiquitin carboxyl-terminal hydrolase isozyme L5
      Short name=UCH-L5
    EC=3.4.19.12
Alternative name(s):
    Ubiquitin thioesterase L5
    Ubiquitin C-terminal hydrolase UCH37

Gene names

Name:	UCHL5
Synonyms:	UCH37
ORF Names:	AD-019, CGI-70

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	329 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Deubiquitinating enzyme associated with the proteasome. Ref.1
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).
Enzyme regulation	Activated by ADRM1. Ref.1 Ref.8
Subunit structure	Component of the 19S (PA700) regulatory complex of the 26S proteasome. Interacts with ADRM1. Ref.1 Ref.8 Ref.7 Ref.9
Sequence similarities	Belongs to the peptidase C12 family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Proteasome
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Protease Thiol protease
Gene Ontology (GO)
Biological process	ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-KW protein complex Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q9Y5K5-1)

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: Q9Y5K5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     246-246: Missing.
     316-329: AKEKQNAKKAQETK → GK

Isoform 3 (identifier: Q9Y5K5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     246-246: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q9Y5K5-4)

The sequence of this isoform differs from the canonical sequence as follows:
     246-246: Missing.
     316-329: AKEKQNAKKAQETK → FEKHFEKTLLGK

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 329	329	Ubiquitin carboxyl-terminal hydrolase isozyme L5		PRO_0000211066
Regions
	Region	313 – 329	17	Interaction with ADRM1
Sites
	Active site	88	1
	Active site	164	1	By similarity
	Active site	179	1	By similarity
Natural variations
	Alternative sequence	246	1	Missing in isoform 2, isoform 3 and isoform 4.		VSP_005253
	Alternative sequence	316 – 329	14	AKEKQ…AQETK → GK in isoform 2.		VSP_005254
	Alternative sequence	316 – 329	14	AKEKQ…AQETK → FEKHFEKTLLGK in isoform 4.		VSP_017062
	Natural variant	197	1	I → F Ref.2 Ref.3		VAR_011613
Experimental info
	Mutagenesis	88	1	C → A: Abolishes enzymatic activity. Ref.1
	Sequence conflict	6	1	G → V in AAD34065. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2006. Version 3. Checksum: DF307347D48C9D0F	FASTA	329	37,607
	10 20 30 40 50 60 MTGNAGEWCL MESDPGVFTE LIKGFGCRGA QVEEIWSLEP ENFEKLKPVH GLIFLFKWQP 70 80 90 100 110 120 GEEPAGSVVQ DSRLDTIFFA KQVINNACAT QAIVSVLLNC THQDVHLGET LSEFKEFSQS 130 140 150 160 170 180 FDAAMKGLAL SNSDVIRQVH NSFARQQMFE FDTKTSAKEE DAFHFVSYVP VNGRLYELDG 190 200 210 220 230 240 LREGPIDLGA CNQDDWISAV RPVIEKRIQK YSEGEIRFNL MAIVSDRKMI YEQKIAELQR 250 260 270 280 290 300 QLAEEEPMDT DQGNSMLSAI QSEVAKNQML IEEEVQKLKR YKIENIRRKH NYLPFIMELL 310 320 KTLAEHQQLI PLVEKAKEKQ NAKKAQETK
	Isoform 2. Checksum: 2552C52F2CFC1E9C	FASTA	316	36,079
	10 20 30 40 50 60 MTGNAGEWCL MESDPGVFTE LIKGFGCRGA QVEEIWSLEP ENFEKLKPVH GLIFLFKWQP 70 80 90 100 110 120 GEEPAGSVVQ DSRLDTIFFA KQVINNACAT QAIVSVLLNC THQDVHLGET LSEFKEFSQS 130 140 150 160 170 180 FDAAMKGLAL SNSDVIRQVH NSFARQQMFE FDTKTSAKEE DAFHFVSYVP VNGRLYELDG 190 200 210 220 230 240 LREGPIDLGA CNQDDWISAV RPVIEKRIQK YSEGEIRFNL MAIVSDRKMI YEQKIAELQR 250 260 270 280 290 300 QLAEEPMDTD QGNSMLSAIQ SEVAKNQMLI EEEVQKLKRY KIENIRRKHN YLPFIMELLK 310 TLAEHQQLIP LVEKGK
	Isoform 3. Checksum: 2ECFB3AB11D07E72	FASTA	328	37,478
	10 20 30 40 50 60 MTGNAGEWCL MESDPGVFTE LIKGFGCRGA QVEEIWSLEP ENFEKLKPVH GLIFLFKWQP 70 80 90 100 110 120 GEEPAGSVVQ DSRLDTIFFA KQVINNACAT QAIVSVLLNC THQDVHLGET LSEFKEFSQS 130 140 150 160 170 180 FDAAMKGLAL SNSDVIRQVH NSFARQQMFE FDTKTSAKEE DAFHFVSYVP VNGRLYELDG 190 200 210 220 230 240 LREGPIDLGA CNQDDWISAV RPVIEKRIQK YSEGEIRFNL MAIVSDRKMI YEQKIAELQR 250 260 270 280 290 300 QLAEEPMDTD QGNSMLSAIQ SEVAKNQMLI EEEVQKLKRY KIENIRRKHN YLPFIMELLK 310 320 TLAEHQQLIP LVEKAKEKQN AKKAQETK
	Isoform 4. Checksum: A3570094A7EC96CB	FASTA	326	37,353
	10 20 30 40 50 60 MTGNAGEWCL MESDPGVFTE LIKGFGCRGA QVEEIWSLEP ENFEKLKPVH GLIFLFKWQP 70 80 90 100 110 120 GEEPAGSVVQ DSRLDTIFFA KQVINNACAT QAIVSVLLNC THQDVHLGET LSEFKEFSQS 130 140 150 160 170 180 FDAAMKGLAL SNSDVIRQVH NSFARQQMFE FDTKTSAKEE DAFHFVSYVP VNGRLYELDG 190 200 210 220 230 240 LREGPIDLGA CNQDDWISAV RPVIEKRIQK YSEGEIRFNL MAIVSDRKMI YEQKIAELQR 250 260 270 280 290 300 QLAEEPMDTD QGNSMLSAIQ SEVAKNQMLI EEEVQKLKRY KIENIRRKHN YLPFIMELLK 310 320 TLAEHQQLIP LVEKFEKHFE KTLLGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1." Yao T., Song L., Xu W., DeMartino G.N., Florens L., Swanson S.K., Washburn M.P., Conaway R.C., Conaway J.W., Cohen R.E. Nat. Cell Biol. 8:994-1002(2006) [PubMed: 16906146] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, MUTAGENESIS OF CYS-88, INTERACTION WITH ADRM1.
[2]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed: 10810093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT PHE-197.
[3]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed: 10931946] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT PHE-197. Tissue: Adrenal gland.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 3 AND 4). Tissue: Lung and Uterus.
[7]	"A novel proteasome-interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes." Hamazaki J., Iemura S., Natsume T., Yashiroda H., Tanaka K., Murata S. EMBO J. 25:4524-4536(2006) [PubMed: 16990800] [Abstract] Cited for: INTERACTION WITH ADRM1, MASS SPECTROMETRY.
[8]	"hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37." Qiu X.-B., Ouyang S.-Y., Li C.-J., Miao S., Wang L., Goldberg A.L. EMBO J. 25:5742-5753(2006) [PubMed: 17139257] [Abstract] Cited for: INTERACTION WITH ADRM1, ENZYME REGULATION, MASS SPECTROMETRY.
[9]	"Mass spectrometric characterization of the affinity-purified human 26S proteasome complex." Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L. Biochemistry 46:3553-3565(2007) [PubMed: 17323924] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], INTERACTION WITH PROTEASOME.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF147717 mRNA. Translation: AAD31528.1. AF151828 mRNA. Translation: AAD34065.1. AF157320 mRNA. Translation: AAF67486.1. BT006790 mRNA. Translation: AAP35436.1. AL136370 Genomic DNA. Translation: CAI10829.1. AL136370 Genomic DNA. Translation: CAI10830.1. AL136370 Genomic DNA. Translation: CAI10831.1. AL136370 Genomic DNA. Translation: CAI10833.1. BC015521 mRNA. Translation: AAH15521.1. BC025369 mRNA. Translation: AAH25369.1.
IPI	IPI00219512. IPI00219513. IPI00299313. IPI00549820.
RefSeq	NP_057068.1.
UniGene	Hs.591458
3D structure databases
HSSP	HSSP built from PDB template 1CMX based on UniProtKB P35127.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y5K5. 1 interaction.
Protein family/group databases
MEROPS	C12.005.
PTM databases
PhosphoSite	Q9Y5K5.
Proteomic databases
PRIDE	Q9Y5K5.
Genome annotation databases
Ensembl	ENSG00000116750. Homo sapiens. [Contig view]
GeneID	51377.
KEGG	hsa:51377.
Organism-specific databases
GeneCards	GC01M191251.
HGNC	HGNC:19678. UCHL5.
MIM	610667. gene.
PharmGKB	PA134916228.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9Y5K5.
Enzyme and pathway databases
BRENDA	3.4.19.12. 247.
Gene expression databases
ArrayExpress	Q9Y5K5.
Bgee	Q9Y5K5.
CleanEx	HS_UCHL5.
GermOnline	ENSG00000116750. Homo sapiens.
Family and domain databases
InterPro	IPR001578. Peptidase_C12. IPR017390. Ubiquitinyl_hydrolase_UCH37. [Graphical view]
Gene3D	G3DSA:3.40.532.10. Peptidase_C12. 1 hit.
PANTHER	PTHR10589. Peptidase_C12. 1 hit.
Pfam	PF01088. Peptidase_C12. 1 hit. [Graphical view]
PIRSF	PIRSF038120. Ubiquitinyl_hydrolase_UCH37. 1 hit.
PRINTS	PR00707. UBCTHYDRLASE.
ProDom	PD350662. Peptidase_C12. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00140. UCH_1. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	54875.
SOURCE	Search...

Entry information

Entry name

UCHL5_HUMAN

Accession

Primary (citable) accession number: Q9Y5K5
Secondary accession number(s): Q5LJA6 , Q5LJA7, Q8TBS4, Q96BJ9, Q9H1W5, Q9P0I3, Q9UQN2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	May 30, 2006
Last modified:	June 16, 2009
This is version 74 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)