Q9JMA1 (UBP14_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 14
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 14
Ubiquitin thioesterase 14
Ubiquitin-specific-processing protease 14

Gene names

Name:

Usp14

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	493 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Maintains the cellular levels of monomeric ubiquitin in cells. Indispensable for synaptic development and function at neuromuscular junctions (NMJs). Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor cxcr4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Ref.5 Ref.7
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).
Subunit structure	Homodimer Potential. Interacts with FANCC, CXCR4 and ERN1 By similarity. Associates with the 26S proteasome.
Subcellular location	Cytoplasm By similarity. Cell membrane; Peripheral membrane protein By similarity.
Sequence similarities	Belongs to the peptidase C19 family. USP14/UBP6 subfamily. Contains 1 ubiquitin-like domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cell membrane Cytoplasm Membrane Proteasome
Molecular function	Hydrolase Protease Thiol protease
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of chemotaxis Inferred from electronic annotation. Source: Compara regulation of proteasomal protein catabolic process Inferred from electronic annotation. Source: Compara synaptic transmission Inferred from mutant phenotype PubMed 12368914. Source: MGI ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell proteasome complex Inferred from electronic annotation. Source: UniProtKB-KW synapse Inferred from direct assay PubMed 12368914. Source: MGI
Molecular_function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW endopeptidase inhibitor activity Inferred from electronic annotation. Source: Compara ubiquitin thiolesterase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 493

493

Ubiquitin carboxyl-terminal hydrolase 14

PRO_0000080637

Regions

Domain

4 – 80

77

Ubiquitin-like

Sites

Active site

114

1

Nucleophile By similarity

Active site

434

1

Proton acceptor By similarity

Amino acid modifications

Modified residue

136

1

Phosphotyrosine Ref.6

Modified residue

143

1

Phosphoserine Ref.6

Modified residue

222

1

Phosphoserine Ref.6

Modified residue

235

1

Phosphothreonine By similarity

Modified residue

448

1

N6-acetyllysine By similarity

Experimental info

Sequence conflict

185

1

Q → R in BAA93551. Ref.1

Sequence conflict

310

1

L → S in BAA93551. Ref.1

Sequence conflict

385

1

Q → E in BAB27544. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

493

Helix Strand Turn

Details...

Beta strand

4 – 10

7

Beta strand

13 – 24

12

Helix

26 – 36

11

Turn

41 – 43

3

Beta strand

68 – 70

3

Sequences

	Sequence		Length	Mass (Da)
	Q9JMA1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 4E5F5DCB86057FF9	FASTA	493	56,002
	10 20 30 40 50 60 MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN 70 80 90 100 110 120 IKMKNGMTVL MMGSADALPE EPSAKTVFVE DMTEEQLATA MELPCGLTNL GNTCYMNATV 130 140 150 160 170 180 QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH 190 200 210 220 230 240 MAFPQFAEKG EQGQYLQQDA NECWIQMMRV LQQKLEAIED DSGRETDSSS APAVTPSKKK 250 260 270 280 290 300 SLIDQYFGVE FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK 310 320 330 340 350 360 QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDVYELCT 370 380 390 400 410 420 PELQEKMVSF RSKFKDLEDK KVNQQPNAND KNSPPKEIKY EPFSFADDIG SNNCGYYDLQ 430 440 450 460 470 480 AVLTHQGRSS SSGHYVSWVR RKQDEWIKFD DDKVSIVTPE DILRLSGGGD WHIAYVLLYG 490 PRRVEIMEEE SEQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse deubiquitinating enzyme-type TGT." Hidaka T., Morishita T. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Corpora quadrigemina, Embryo and Testis.
[3]	"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].
[4]	"A novel active site-directed probe specific for deubiquitylating enzymes reveals proteasome association of USP14." Borodovsky A., Kessler B.M., Casagrande R., Overkleeft H.S., Wilkinson K.D., Ploegh H.L. EMBO J. 20:5187-5196(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, ASSOCIATION WITH THE 26S PROTEASOME.
[5]	"Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice." Anderson C., Crimmins S., Wilson J.A., Korbel G.A., Ploegh H.L., Wilson S.M. J. Neurochem. 95:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ASSOCIATION WITH THE 26S PROTEASOME.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-136; SER-143 AND SER-222, MASS SPECTROMETRY. Tissue: Liver.
[7]	"The proteasome-associated deubiquitinating enzyme Usp14 is essential for the maintenance of synaptic ubiquitin levels and the development of neuromuscular junctions." Chen P.C., Qin L.N., Li X.M., Walters B.J., Wilson J.A., Mei L., Wilson S.M. J. Neurosci. 29:10909-10919(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Solution structure of the N-terminal ubiquitin-like domain of mouse ubiquitin specific protease 14 (usp14)." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 4-86.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB034633 mRNA. Translation: BAA93551.1.
AK011322 mRNA. Translation: BAB27544.1.
AK029977 mRNA. Translation: BAC26713.1.
AK045909 mRNA. Translation: BAC32528.1.
BC005571 mRNA. Translation: AAH05571.1.

IPI

IPI00270877.

RefSeq

NP_067497.2. NM_021522.4.

UniGene

Mm.219648.
Mm.329277.
Mm.447089.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WGG	NMR	-	A	4-85	[»]

ProteinModelPortal

Q9JMA1.

SMR

Q9JMA1. Positions 6-86, 98-482.

ModBase

Search...

Protein family/group databases

MEROPS

C19.015.

PTM databases

PhosphoSite

Q9JMA1.

Proteomic databases

PaxDb

Q9JMA1.

PRIDE

Q9JMA1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000092096; ENSMUSP00000089728; ENSMUSG00000047879.

GeneID

59025.

KEGG

mmu:59025.

UCSC

uc008ean.1. mouse.

Organism-specific databases

CTD

9097.

MGI

MGI:1928898. Usp14.

Phylogenomic databases

eggNOG

NOG286607.

GeneTree

ENSGT00390000009615.

HOGENOM

HOG000202292.

HOVERGEN

HBG054185.

KO

K11843.

OMA

YGPRRIE.

OrthoDB

EOG4JT05C.

Gene expression databases

ArrayExpress

Q9JMA1.

Bgee

Q9JMA1.

CleanEx

MM_USP14.

Genevestigator

Q9JMA1.

GermOnline

ENSMUSG00000047879. Mus musculus.

Family and domain databases

InterPro

IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19.
IPR000626. Ubiquitin.
IPR019954. Ubiquitin_CS.
IPR019955. Ubiquitin_supergroup.
[Graphical view]

Pfam

PF00443. UCH. 1 hit.
[Graphical view]

SMART

SM00213. UBQ. 1 hit.
[Graphical view]

PROSITE

PS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
PS00972. UCH_2_1. 1 hit.
PS00973. UCH_2_2. 1 hit.
PS50235. UCH_2_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9JMA1.

NextBio

314596.

SOURCE

Search...

Entry information

Entry name

UBP14_MOUSE

Accession

Primary (citable) accession number: Q9JMA1
Secondary accession number(s): Q543U5, Q923F2, Q9D0L0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program