Q5I043 (UBP28_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 28
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 28
Ubiquitin thioesterase 28
Ubiquitin-specific-processing protease 28

Gene names

Name:	Usp28
Synonyms:	Kiaa1515

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	1051 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBXW7) complex By similarity.
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	Interacts with FBXW7; following DNA damage, dissociates from FBXW7 leading to degradation of MYC.
Subcellular location	Nucleus › nucleoplasm By similarity.
Post-translational modification	Degradaded upon nickel ion level or hypoxia exposure By similarity. Phosphorylated upon DNA damage at Ser-67 and Ser-720, by ATM or ATR By similarity.
Sequence similarities	Belongs to the peptidase C19 family. USP28 subfamily. Contains 1 UIM (ubiquitin-interacting motif) repeat.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage checkpoint Inferred from sequence or structural similarity. Source: UniProtKB DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB cellular response to UV Inferred from electronic annotation. Source: Compara intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from sequence or structural similarity. Source: UniProtKB protein deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB response to ionizing radiation Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	nucleolus Inferred from electronic annotation. Source: Compara nucleoplasm Inferred from sequence or structural similarity. Source: UniProtKB protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	ubiquitin thiolesterase activity Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-specific protease activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q5I043-1)

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: Q5I043-2)

The sequence of this isoform differs from the canonical sequence as follows:
     429-453: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1051	1051	Ubiquitin carboxyl-terminal hydrolase 28		PRO_0000080658
Regions
	Repeat	97 – 116	20	UIM
Sites
	Active site	171	1	Nucleophile By similarity
	Active site	605	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	67	1	Phosphoserine By similarity
	Modified residue	720	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	429 – 453	25	Missing in isoform 2.		VSP_015581
Experimental info
	Sequence conflict	523	1	P → L in BAC98190. Ref.3
	Sequence conflict	617	1	T → I in BAC98190. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 15, 2005. Version 1. Checksum: 72623C4668860749	FASTA	1,051	119,318
	10 20 30 40 50 60 MTAELQQDDS AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD ITQAVSLLTD 70 80 90 100 110 120 QRVKEPSHDT TAAEPSEVEE SATSKDLLAK VIDLTHDNKD DLQAAIALSL LESPNIQADN 130 140 150 160 170 180 RDLNRAHEAN SAETKRSKRK RCEVWGENHN PNNWRRVDGW PVGLKNVGNT CWFSAVIQSL 190 200 210 220 230 240 FQLPEFRRLV LSYNLPQNIL ENCRSHTEKR NIMFMQELQY LFALLLGSNR KFVDPSAALD 250 260 270 280 290 300 LLKGAFRSSE EQQQDVSEFT HKLLDWLEDA FQLAVNVNSH LRNKSENPMV QLFYGTFLTE 310 320 330 340 350 360 GVREGKPFCN NETFGQYPLQ VNGYHNLDEC LEGAMVEGDI ALLPSDRSVK YGQERWFTKL 370 380 390 400 410 420 PPVLTFELSR FEFNQSLGQP EKIHNKLEFP QIIYMDRYMY KSKELIRSKR ESVRKLKEEI 430 440 450 460 470 480 QVLQQKLERY VKYGSGPSRF PLPDMLKYVI EFASTKPASE SCLSGSAEHV TLPLPSVHCP 490 500 510 520 530 540 ISDLTPKESS SPESCSQNAG STFSSPEDAL PSSEGMNGPF TSPHSSLETP APPAPRTVTD 550 560 570 580 590 600 EEMNFVKTCL QRWRSEIEQD IQDLKNCISS STKAIEQMYC DPLLRQVPYR LHAVLVHEGQ 610 620 630 640 650 660 ASAGHYWAYI YNQPRQTWLK YNDISVTESS WEELERDSYG GLRNVSAYCL MYINDNLPHF 670 680 690 700 710 720 SAEASSNESD ETAGEVEALS VELRQYIQED NWRFQQEVEE WEEEQSCKIP QMESSPNSSS 730 740 750 760 770 780 QDFSTSQESP AVSSHEVRCL SSEHAVIAKE QTAQAIANTA HAYEKSGVEA ALSEAFHEEY 790 800 810 820 830 840 SRLYQLAKET PTSHSDPRLQ HVLVYFFQNE APKRVVERTL LEQFADRNLS YDERSISIMK 850 860 870 880 890 900 VAQAKLMEIG PDDMNMEEYK RWHEDYSLFR KVSVYLLTGL ELFQKGKYQE ALSYLVYAYQ 910 920 930 940 950 960 SNAGLLVKGP RRGVKESVIA LYRRKCLLEL NAKAASLFET NDDHSVTEGI NVMNELIIPC 970 980 990 1000 1010 1020 IHLIINNDIS KDDLDAIEVM RNHWCSYLGK DIAENLQLCL GEFLPRLLDP SAEIIVLKEP 1030 1040 1050 PTIRPNSPYD LCNRFAAVME SIQGVSTVTV K
	Isoform 2 [UniParc]. Checksum: 4620DBD05FE6E55A	FASTA	1,026	116,402
	10 20 30 40 50 60 MTAELQQDDS AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD ITQAVSLLTD 70 80 90 100 110 120 QRVKEPSHDT TAAEPSEVEE SATSKDLLAK VIDLTHDNKD DLQAAIALSL LESPNIQADN 130 140 150 160 170 180 RDLNRAHEAN SAETKRSKRK RCEVWGENHN PNNWRRVDGW PVGLKNVGNT CWFSAVIQSL 190 200 210 220 230 240 FQLPEFRRLV LSYNLPQNIL ENCRSHTEKR NIMFMQELQY LFALLLGSNR KFVDPSAALD 250 260 270 280 290 300 LLKGAFRSSE EQQQDVSEFT HKLLDWLEDA FQLAVNVNSH LRNKSENPMV QLFYGTFLTE 310 320 330 340 350 360 GVREGKPFCN NETFGQYPLQ VNGYHNLDEC LEGAMVEGDI ALLPSDRSVK YGQERWFTKL 370 380 390 400 410 420 PPVLTFELSR FEFNQSLGQP EKIHNKLEFP QIIYMDRYMY KSKELIRSKR ESVRKLKEEI 430 440 450 460 470 480 QVLQQKLEST KPASESCLSG SAEHVTLPLP SVHCPISDLT PKESSSPESC SQNAGSTFSS 490 500 510 520 530 540 PEDALPSSEG MNGPFTSPHS SLETPAPPAP RTVTDEEMNF VKTCLQRWRS EIEQDIQDLK 550 560 570 580 590 600 NCISSSTKAI EQMYCDPLLR QVPYRLHAVL VHEGQASAGH YWAYIYNQPR QTWLKYNDIS 610 620 630 640 650 660 VTESSWEELE RDSYGGLRNV SAYCLMYIND NLPHFSAEAS SNESDETAGE VEALSVELRQ 670 680 690 700 710 720 YIQEDNWRFQ QEVEEWEEEQ SCKIPQMESS PNSSSQDFST SQESPAVSSH EVRCLSSEHA 730 740 750 760 770 780 VIAKEQTAQA IANTAHAYEK SGVEAALSEA FHEEYSRLYQ LAKETPTSHS DPRLQHVLVY 790 800 810 820 830 840 FFQNEAPKRV VERTLLEQFA DRNLSYDERS ISIMKVAQAK LMEIGPDDMN MEEYKRWHED 850 860 870 880 890 900 YSLFRKVSVY LLTGLELFQK GKYQEALSYL VYAYQSNAGL LVKGPRRGVK ESVIALYRRK 910 920 930 940 950 960 CLLELNAKAA SLFETNDDHS VTEGINVMNE LIIPCIHLII NNDISKDDLD AIEVMRNHWC 970 980 990 1000 1010 1020 SYLGKDIAEN LQLCLGEFLP RLLDPSAEII VLKEPPTIRP NSPYDLCNRF AAVMESIQGV STVTVK

References

[1]	"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] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Brain and Embryonic germ cell.
[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] OF 292-1051. Strain: C57BL/6J. Tissue: Lung.
[3]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 392-1051. Tissue: Embryonic tail.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC066033 mRNA. Translation: AAH66033.1. BC088733 mRNA. Translation: AAH88733.1. AK052442 mRNA. Translation: BAC34993.1. AK129380 mRNA. Translation: BAC98190.1.
IPI	IPI00283817. IPI00649320.
RefSeq	NP_780691.2. NM_175482.3.
UniGene	Mm.21630.
3D structure databases
ProteinModelPortal	Q5I043.
SMR	Q5I043. Positions 22-132, 162-402, 576-656.
ModBase	Search...
Protein family/group databases
MEROPS	C19.054.
PTM databases
PhosphoSite	Q5I043.
Proteomic databases
PaxDb	Q5I043.
PRIDE	Q5I043.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000047349; ENSMUSP00000047467; ENSMUSG00000032267.
GeneID	235323.
KEGG	mmu:235323.
UCSC	uc009pir.1. mouse. uc009pis.1. mouse.
Organism-specific databases
CTD	57646.
MGI	MGI:2442293. Usp28.
Rouge	Search...
Phylogenomic databases
eggNOG	COG5077.
GeneTree	ENSGT00390000016082.
HOGENOM	HOG000007956.
HOVERGEN	HBG056030.
InParanoid	Q5I043.
KO	K11849.
OMA	DLNRMHE.
OrthoDB	EOG4WM4T0.
Gene expression databases
ArrayExpress	Q5I043.
Bgee	Q5I043.
CleanEx	MM_USP28.
Genevestigator	Q5I043.
GermOnline	ENSMUSG00000032267. Mus musculus.
Family and domain databases
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR009060. UBA-like. IPR003903. Ubiquitin-int_motif. [Graphical view]
Pfam	PF00443. UCH. 1 hit. [Graphical view]
SMART	SM00726. UIM. 1 hit. [Graphical view]
SUPFAM	SSF46934. UBA_like. 1 hit.
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. PS50330. UIM. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	382599.
SOURCE	Search...

Entry information

Entry name

UBP28_MOUSE

Accession

Primary (citable) accession number: Q5I043
Secondary accession number(s): Q6NZP3, Q6ZPP1, Q8BWI1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	February 15, 2005
Last modified:	May 1, 2013
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program