Q9H4L4 (SENP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sentrin-specific protease 3
EC=3.4.22.68

Alternative name(s):
SUMO-1-specific protease 3
Sentrin/SUMO-specific protease SENP3

Gene names

Name:	SENP3
Synonyms:	SSP3, SUSP3

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	574 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates. Deconjugates SUMO2 from MEF2D, which increases its transcriptional activation capability. Deconjugates SUMO2 and SUMO3 from CDCA8. Redox sensor that, when redistributed into nucleoplasm, can act as an effector to enhance HIF1A transcriptional activity by desumoylating EP300. Required for rRNA processing through deconjugation of SUMO2 and SUMO3 from nucleophosmin, NPM1. Plays a role in the regulation of sumoylation status of ZNF148. Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Ref.7 Ref.9 Ref.10 Ref.11 Ref.15 Ref.16 Ref.21
Catalytic activity	Hydrolysis of the alpha-linked peptide bond in the sequence Gly-Gly-|-Ala-Thr-Tyr at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptide, Smt3, leading to the mature form of the protein. A second reaction involves the cleavage of an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein.
Enzyme regulation	On oxidative stress, SENP3 degradation is blocked by inhibition of its ubiquitination, which stabilizes it as it accumulates in the nucleoplasm. Ref.15
Subunit structure	Binds to SUMO1 and SUMO3 By similarity. Component of some MLL1/MLL complex, at least composed of the core components MLL, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with EP300, NPM1 and CDCA8. Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148. Interacts with NOL9. Ref.6 Ref.10 Ref.11 Ref.15 Ref.16 Ref.21
Subcellular location	Cytoplasm By similarity. Nucleus › nucleolus. Nucleus › nucleoplasm. Note: Mainly found in the nucleoplasm, with low levels detected in the cytoplasmic and chromatin fractions By similarity. Redistributes between the nucleolus and the nucleoplasm in response to mild oxidative stress. Ref.11 Ref.15
Sequence similarities	Belongs to the peptidase C48 family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	MLL1 complex Inferred from direct assay Ref.6. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from direct assay. Source: LIFEdb
Molecular_function	ubiquitin-specific protease 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 – 574	574	Sentrin-specific protease 3		PRO_0000101721
Regions
	Region	386 – 543	158	Protease
	Motif	125 – 128	4	Nuclear localization signal Potential
	Motif	153 – 159	7	Nuclear localization signal Potential
	Compositional bias	13 – 68	56	Pro-rich
	Compositional bias	76 – 92	17	Glu-rich
	Compositional bias	192 – 195	4	Poly-Pro
Sites
	Active site	465	1	By similarity
	Active site	482	1	By similarity
	Active site	532	1	By similarity
Amino acid modifications
	Modified residue	169	1	Phosphoserine Ref.12 Ref.13 Ref.18
	Modified residue	181	1	Phosphoserine Ref.12
	Modified residue	212	1	Phosphoserine Ref.14 Ref.17
	Modified residue	232	1	Phosphoserine Ref.8 Ref.13 Ref.20
	Modified residue	353	1	Phosphothreonine Ref.14
Natural variations
	Natural variant	515	1	W → R. Corresponds to variant rs9972914 [ dbSNP | Ensembl ].		VAR_051544
Experimental info
	Mutagenesis	532	1	C → S: Loss of enzymatic activity. Ref.10
	Sequence conflict	30 – 31	2	ER → DG in AAG33252. Ref.1
	Sequence conflict	60	1	A → T in AAG33252. Ref.1
	Sequence conflict	65	1	V → A in AAG33252. Ref.1
	Sequence conflict	113 – 114	2	PS → AL in AAG33252. Ref.1
	Sequence conflict	117	1	T → S in AAG33252. Ref.1
	Sequence conflict	134	1	R → Q in AAG33252. Ref.1
	Sequence conflict	161	1	L → S in AAH48306. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9H4L4 [UniParc]. Last modified December 12, 2006. Version 2. Checksum: E495137EE7500741	FASTA	574	65,010
	10 20 30 40 50 60 MKETIQGTGS WGPEPPGPGI PPAYSSPRRE RLRWPPPPKP RLKSGGGFGP DPGSGTTVPA 70 80 90 100 110 120 RRLPVPRPSF DASASEEEEE EEEEEDEDEE EEVAAWRLPP RWSQLGTSQR PRPSRPTHRK 130 140 150 160 170 180 TCSQRRRRAM RAFRMLLYSK STSLTFHWKL WGRHRGRRRG LAHPKNHLSP QQGGATPQVP 190 200 210 220 230 240 SPCCRFDSPR GPPPPRLGLL GALMAEDGVR GSPPVPSGPP MEEDGLRWTP KSPLDPDSGL 250 260 270 280 290 300 LSCTLPNGFG GQSGPEGERS LAPPDASILI SNVCSIGDHV AQELFQGSDL GMAEEAERPG 310 320 330 340 350 360 EKAGQHSPLR EEHVTCVQSI LDEFLQTYGS LIPLSTDEVV EKLEDIFQQE FSTPSRKGLV 370 380 390 400 410 420 LQLIQSYQRM PGNAMVRGFR VAYKRHVLTM DDLGTLYGQN WLNDQVMNMY GDLVMDTVPE 430 440 450 460 470 480 KVHFFNSFFY DKLRTKGYDG VKRWTKNVDI FNKELLLIPI HLEVHWSLIS VDVRRRTITY 490 500 510 520 530 540 FDSQRTLNRR CPKHIAKYLQ AEAVKKDRLD FHQGWKGYFK MNVARQNNDS DCGAFVLQYC 550 560 570 KHLALSQPFS FTQQDMPKLR RQIYKELCHC KLTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Ubiquitin-like proteins: new wines in new bottles." Yeh E.T.H., Gong L., Kamitani T. Gene 248:1-14(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Choi S.J., Jeon Y.-J., Kim K.I., Nishimori S., Suzuki T., Uchida S., Shimbara N., Tanaka K., Chung C.H. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Melanoma and Uterus.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph and Uterus.
[6]	"Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF." Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J., Allis C.D., Chait B.T., Hess J.L., Roeder R.G. Cell 121:873-885(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE MLL1/MLL COMPLEX.
[7]	"Association with class IIa histone deacetylases upregulates the sumoylation of MEF2 transcription factors." Gregoire S., Yang X.-J. Mol. Cell. Biol. 25:2273-2287(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3." Gong L., Yeh E.T.H. J. Biol. Chem. 281:15869-15877(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"The nucleolar SUMO-specific protease SENP3 reverses SUMO modification of nucleophosmin and is required for rRNA processing." Haindl M., Harasim T., Eick D., Muller S. EMBO Rep. 9:273-279(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-532, INTERACTION WITH NPM1.
[11]	"Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases." Yun C., Wang Y., Mukhopadhyay D., Backlund P., Kolli N., Yergey A., Wilkinson K.D., Dasso M. J. Cell Biol. 183:589-595(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH NPM1.
[12]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-169 AND SER-181, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-169 AND SER-232, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212 AND THR-353, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"SENP3 is responsible for HIF-1 transactivation under mild oxidative stress via p300 de-SUMOylation." Huang C., Han Y., Wang Y., Sun X., Yan S., Yeh E.T.H., Chen Y., Cang H., Li H., Shi G., Cheng J., Tang X., Yi J. EMBO J. 28:2748-2762(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH EP300.
[16]	"RanBP2 and SENP3 function in a mitotic SUMO2/3 conjugation-deconjugation cycle on Borealin." Klein U.R., Haindl M., Nigg E.A., Muller S. Mol. Biol. Cell 20:410-418(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDCA8.
[17]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[18]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-169, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, MASS SPECTROMETRY.
[21]	"Five Friends of Methylated Chtop, a complex linking arginine methylation to desumoylation." Fanis P., Gillemans N., Aghajanirefah A., Pourfarzad F., Demmers J., Esteghamat F., Vadlamudi R.K., Grosveld F., Philipsen S., van Dijk T.B. Mol. Cell. Proteomics 11:1263-1273(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE 5FMC COMPLEX.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY008763 mRNA. Translation: AAG33252.1. AF199459 mRNA. Translation: AAL25652.1. AL050283 mRNA. Translation: CAB43384.2. AL834294 mRNA. Translation: CAD38967.1. BC048306 mRNA. Translation: AAH48306.1. BC080658 mRNA. Translation: AAH80658.1.
IPI	IPI00171525.
PIR	T08759.
RefSeq	NP_056485.2. NM_015670.5.
UniGene	Hs.513926. Hs.733104.
3D structure databases
ProteinModelPortal	Q9H4L4.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-47511N.
IntAct	Q9H4L4. 4 interactions.
MINT	MINT-1200849.
STRING	9606.ENSP00000314029.
Protein family/group databases
MEROPS	C48.003.
PTM databases
PhosphoSite	Q9H4L4.
Polymorphism databases
DMDM	119370525.
Proteomic databases
PaxDb	Q9H4L4.
PRIDE	Q9H4L4.
Protocols and materials databases
DNASU	26168.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000429205; ENSP00000403712; ENSG00000161956.
GeneID	26168.
KEGG	hsa:26168.
UCSC	uc002ghm.3. human.
Organism-specific databases
CTD	26168.
GeneCards	GC17P007467.
H-InvDB	HIX0013501.
HGNC	HGNC:17862. SENP3.
MIM	612844. gene.
neXtProt	NX_Q9H4L4.
PharmGKB	PA134933213.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5160.
HOGENOM	HOG000154287.
HOVERGEN	HBG059450.
InParanoid	Q9H4L4.
KO	K08593.
OMA	VPRPSFD.
OrthoDB	EOG4RXXZX.
Enzyme and pathway databases
BRENDA	3.4.22.68. 2681.
Gene expression databases
Bgee	Q9H4L4.
CleanEx	HS_SENP3.
Genevestigator	Q9H4L4.
GermOnline	ENSG00000161956. Homo sapiens.
Family and domain databases
InterPro	IPR003653. Peptidase_C48. [Graphical view]
Pfam	PF02902. Peptidase_C48. 1 hit. [Graphical view]
PROSITE	PS50600. ULP_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SENP3. human.
GenomeRNAi	26168.
NextBio	48279.
SOURCE	Search...

Entry information

Entry name

SENP3_HUMAN

Accession

Primary (citable) accession number: Q9H4L4
Secondary accession number(s): Q66K15 , Q86VS7, Q96PS4, Q9Y3W9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2002
Last sequence update:	December 12, 2006
Last modified:	May 1, 2013
This is version 104 of the entry and version 2 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.