Reviewed, UniProtKB/Swiss-Prot P45974 (UBP5_HUMAN)

Names and origin

Protein names

Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 5
    EC=3.1.2.15
Alternative name(s):
    Ubiquitin thioesterase 5
    Ubiquitin-specific-processing protease 5
    Deubiquitinating enzyme 5
    Isopeptidase T

Gene names

Name:	USP5
Synonyms:	ISOT

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

General annotation (Comments)

Function	Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers.
Catalytic activity	Ubiquitin C-terminal thioester + H2O = ubiquitin + a thiol.
Cofactor	Zinc.
Post-translational modification	The N-terminus is blocked.
Sequence similarities	Belongs to the peptidase C19 family. Contains 2 UBA domains. Contains 1 UBP-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	lysosome Traceable author statement. Source: ProtInc nucleus Inferred from direct assay. Source: HPA
Molecular function	cysteine-type endopeptidase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct ubiquitin thiolesterase activity Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TADA3L	O75528	1	EBI-741277,EBI-473249

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P45974-1)

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 Short (identifier: P45974-2)

The sequence of this isoform differs from the canonical sequence as follows:
     629-652: GSLGFYGNEDEDSFCSPHFSSPTS → A

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 858

858

Ubiquitin carboxyl-terminal hydrolase 5

PRO_0000080623

Regions

Domain

654 – 695

42

UBA 1

Domain

722 – 762

41

UBA 2

Zinc finger

197 – 269

73

UBP-type

Sites

Active site

335

1

By similarity

Active site

809

1

By similarity

Active site

818

1

By similarity

Amino acid modifications

Modified residue

623

1

Phosphothreonine Ref.7

Modified residue

783

1

Phosphoserine Ref.8

Natural variations

Alternative sequence

629 – 652

24

GSLGF…SSPTS → A in isoform Short.

VSP_005259

Experimental info

Sequence conflict

3 – 4

2

EL → DV in CAA62690. Ref.1

Sequence conflict

45

1

I → V in CAA62690. Ref.1

Sequence conflict

468

1

K → R in AAA78934. Ref.4

Sequence conflict

681

1

G → D in AAA78934. Ref.4

Secondary structure

1

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858

Helix Strand Turn

Details...

Beta strand

200 – 203

4

Beta strand

206 – 211

6

Turn

212 – 214

3

Beta strand

217 – 219

3

Helix

232 – 240

9

Beta strand

244 – 247

4

Beta strand

258 – 260

3

Turn

261 – 264

4

Beta strand

265 – 268

4

Helix

272 – 277

6

Turn

278 – 280

3

Helix

657 – 666

10

Helix

670 – 680

11

Helix

685 – 695

11

Beta strand

701 – 703

3

Helix

725 – 734

10

Helix

738 – 747

10

Helix

753 – 764

12

Beta strand

768 – 770

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified October 1, 1996. Version 2. Checksum: E99CB7CDFA682C65	FASTA	858	95,786
	10 20 30 40 50 60 MAELSEEALL SVLPTIRVPK AGDRVHKDEC AFSFDTPESE GGLYICMNTF LGFGKQYVER 70 80 90 100 110 120 HFNKTGQRVY LHLRRTRRPK EEDPATGTGD PPRKKPTRLA IGVEGGFDLS EEKFELDEDV 130 140 150 160 170 180 KIVILPDYLE IARDGLGGLP DIVRDRVTSA VEALLSADSA SRKQEVQAWD GEVRQVSKHA 190 200 210 220 230 240 FSLKQLDNPA RIPPCGWKCS KCDMRENLWL NLTDGSILCG RRYFDGSGGN NHAVEHYRET 250 260 270 280 290 300 GYPLAVKLGT ITPDGADVYS YDEDDMVLDP SLAEHLSHFG IDMLKMQKTD KTMTELEIDM 310 320 330 340 350 360 NQRIGEWELI QESGVPLKPL FGPGYTGIRN LGNSCYLNSV VQVLFSIPDF QRKYVDKLEK 370 380 390 400 410 420 IFQNAPTDPT QDFSTQVAKL GHGLLSGEYS KPVPESGDGE RVPEQKEVQD GIAPRMFKAL 430 440 450 460 470 480 IGKGHPEFST NRQQDAQEFF LHLINMVERN CRSSENPNEV FRFLVEEKIK CLATEKVKYT 490 500 510 520 530 540 QRVDYIMQLP VPMDAALNKE ELLEYEEKKR QAEEEKMALP ELVRAQVPFS SCLEAYGAPE 550 560 570 580 590 600 QVDDFWSTAL QAKSVAVKTT RFASFPDYLV IQIKKFTFGL DWVPKKLDVS IEMPEELDIS 610 620 630 640 650 660 QLRGTGLQPG EEELPDIAPP LVTPDEPKGS LGFYGNEDED SFCSPHFSSP TSPMLDESVI 670 680 690 700 710 720 IQLVEMGFPM DACRKAVYYT GNSGAEAAMN WVMSHMDDPD FANPLILPGS SGPGSTSAAA 730 740 750 760 770 780 DPPPEDCVTT IVSMGFSRDQ ALKALRATNN SLERAVDWIF SHIDDLDAEA AMDISEGRSA 790 800 810 820 830 840 ADSISESVPV GPKVRDGPGK YQLFAFISHM GTSTMCGHYV CHIKKEGRWV IYNDQKVCAS 850 EKPPKDLGYI YFYQRVAS
	Isoform Short. Checksum: 227CB29B11C7DAEA	FASTA	835	93,308
	10 20 30 40 50 60 MAELSEEALL SVLPTIRVPK AGDRVHKDEC AFSFDTPESE GGLYICMNTF LGFGKQYVER 70 80 90 100 110 120 HFNKTGQRVY LHLRRTRRPK EEDPATGTGD PPRKKPTRLA IGVEGGFDLS EEKFELDEDV 130 140 150 160 170 180 KIVILPDYLE IARDGLGGLP DIVRDRVTSA VEALLSADSA SRKQEVQAWD GEVRQVSKHA 190 200 210 220 230 240 FSLKQLDNPA RIPPCGWKCS KCDMRENLWL NLTDGSILCG RRYFDGSGGN NHAVEHYRET 250 260 270 280 290 300 GYPLAVKLGT ITPDGADVYS YDEDDMVLDP SLAEHLSHFG IDMLKMQKTD KTMTELEIDM 310 320 330 340 350 360 NQRIGEWELI QESGVPLKPL FGPGYTGIRN LGNSCYLNSV VQVLFSIPDF QRKYVDKLEK 370 380 390 400 410 420 IFQNAPTDPT QDFSTQVAKL GHGLLSGEYS KPVPESGDGE RVPEQKEVQD GIAPRMFKAL 430 440 450 460 470 480 IGKGHPEFST NRQQDAQEFF LHLINMVERN CRSSENPNEV FRFLVEEKIK CLATEKVKYT 490 500 510 520 530 540 QRVDYIMQLP VPMDAALNKE ELLEYEEKKR QAEEEKMALP ELVRAQVPFS SCLEAYGAPE 550 560 570 580 590 600 QVDDFWSTAL QAKSVAVKTT RFASFPDYLV IQIKKFTFGL DWVPKKLDVS IEMPEELDIS 610 620 630 640 650 660 QLRGTGLQPG EEELPDIAPP LVTPDEPKAP MLDESVIIQL VEMGFPMDAC RKAVYYTGNS 670 680 690 700 710 720 GAEAAMNWVM SHMDDPDFAN PLILPGSSGP GSTSAAADPP PEDCVTTIVS MGFSRDQALK 730 740 750 760 770 780 ALRATNNSLE RAVDWIFSHI DDLDAEAAMD ISEGRSAADS ISESVPVGPK VRDGPGKYQL 790 800 810 820 830 FAFISHMGTS TMCGHYVCHI KKEGRWVIYN DQKVCASEKP PKDLGYIYFY QRVAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of a human 100 kDa de-ubiquitinating enzyme: the 100 kDa human de-ubiquitinase belongs to the ubiquitin C-terminal hydrolase family 2 (UCH2)." Falquet L., Paquet N., Frutiger S., Hughes G.J., Hoang-Van K., Jaton J.-C. FEBS Lett. 376:233-237(1995) [PubMed: 7498549] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13." Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S., Malley T., Gibbs R.A. Genome Res. 6:314-326(1996) [PubMed: 8723724] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination." Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A. Genome Res. 7:268-280(1997) [PubMed: 9074930] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	Tashayev V.L., O'Connor L.B., Larsen C.N., Kasperek E., Pickart C.M. Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"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 LONG AND SHORT). Tissue: Kidney and Lung.
[6]	"A human de-ubiquitinating enzyme with both isopeptidase and peptidase activities in vitro." Falquet L., Paquet N., Frutiger S., Hughes G.J., Hoang-Van K., Jaton J.-C. FEBS Lett. 359:73-77(1995) [PubMed: 7851534] [Abstract] Cited for: CHARACTERIZATION.
[7]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-623, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Solution structure of the first and second UBA domains in the human ubiquitin specific protease 5 (isopeptidase 5)." RIKEN structural genomics initiative (RSGI) Submitted (JUN-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 655-772.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X91349 mRNA. Translation: CAA62690.1.
U47927 mRNA. Translation: AAC50465.1.
U47924 Genomic DNA. Translation: AAB51314.1.
U47924 Genomic DNA. Translation: AAB51315.1.
U35116 mRNA. Translation: AAA78934.1.
BC004889 mRNA. Translation: AAH04889.1.
BC005139 mRNA. Translation: AAH05139.1.

IPI

IPI00024664.
IPI00375145.

PIR

S68227.

RefSeq

NP_001092006.1.
NP_003472.2.

UniGene

Hs.631661

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DAG	NMR	-	A	655-715	[»]
2DAK	NMR	-	A	723-772	[»]
2G43	X-ray	2.09	A/B	163-291	[»]
2G45	X-ray	1.99	A/D	163-291	[»]

SMR

P45974. Positions 649-707.

ModBase

Search...

Protein-protein interaction databases

IntAct

P45974. 4 interactions.

Protein family/group databases

MEROPS

C19.001.

PTM databases

PhosphoSite

P45974.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00375145.

Proteomic databases

PRIDE

P45974.

Genome annotation databases

Ensembl

ENSG00000111667. Homo sapiens. [Contig view]

GeneID

8078.

KEGG

hsa:8078.

Organism-specific databases

GeneCards

GC12P006831.

H-InvDB

HIX0010386.

HGNC

HGNC:12628. USP5.

HPA

HPA006756.

MIM

601447. gene.

PharmGKB

PA27528.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P45974.

HOVERGEN

P45974.

OMA

P45974. ERAVDWI.

Enzyme and pathway databases

BRENDA

3.1.2.15. 247.

Gene expression databases

ArrayExpress

P45974.

Bgee

P45974.

CleanEx

HS_USP5.

GermOnline

ENSG00000111667. Homo sapiens.

Family and domain databases

InterPro

IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19.
IPR000449. UBA/transl_elong_EF1B_N.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR016652. Ubiquitinyl_hydrolase.
IPR001607. Znf_UBP.
[Graphical view]

Pfam

PF00627. UBA. 2 hits.
PF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]

PIRSF

PIRSF016308. UBP. 1 hit.

SMART

SM00165. UBA. 2 hits.
SM00290. ZnF_UBP. 1 hit.
[Graphical view]

PROSITE

PS50030. UBA. 2 hits.
PS00972. UCH_2_1. 1 hit.
PS00973. UCH_2_2. 1 hit.
PS50235. UCH_2_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

30687.

PMAP-CutDB

P45974.

SOURCE

Search...

Entry information

Entry name

UBP5_HUMAN

Accession

Primary (citable) accession number: P45974
Secondary accession number(s): Q96J22

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)