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Q9H4L4 (SENP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length574 AA.
Sequence statusComplete.
Protein existenceEvidence 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 KMT2A/MLL1, 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. Nucleusnucleolus. Nucleusnucleoplasm. 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 processUbl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   Molecular functionHydrolase
Protease
Thiol protease
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentMLL1 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_functionprotein binding

Inferred from physical interaction Ref.10Ref.15PubMed 21326211. Source: IntAct

ubiquitin-specific protease activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 574574Sentrin-specific protease 3
PRO_0000101721

Regions

Region386 – 543158Protease
Motif125 – 1284Nuclear localization signal Potential
Motif153 – 1597Nuclear localization signal Potential
Compositional bias13 – 6856Pro-rich
Compositional bias76 – 9217Glu-rich
Compositional bias192 – 1954Poly-Pro

Sites

Active site4651 By similarity
Active site4821 By similarity
Active site5321 By similarity

Amino acid modifications

Modified residue1691Phosphoserine Ref.12 Ref.13 Ref.18
Modified residue1811Phosphoserine Ref.12
Modified residue2121Phosphoserine Ref.14 Ref.17
Modified residue2321Phosphoserine Ref.8 Ref.13 Ref.20
Modified residue3531Phosphothreonine Ref.14

Natural variations

Natural variant5151W → R.
Corresponds to variant rs9972914 [ dbSNP | Ensembl ].
VAR_051544

Experimental info

Mutagenesis5321C → S: Loss of enzymatic activity. Ref.10
Sequence conflict30 – 312ER → DG in AAG33252. Ref.1
Sequence conflict601A → T in AAG33252. Ref.1
Sequence conflict651V → A in AAG33252. Ref.1
Sequence conflict113 – 1142PS → AL in AAG33252. Ref.1
Sequence conflict1171T → S in AAG33252. Ref.1
Sequence conflict1341R → Q in AAG33252. Ref.1
Sequence conflict1611L → S in AAH48306. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q9H4L4 [UniParc].

Last modified December 12, 2006. Version 2.
Checksum: E495137EE7500741

FASTA57465,010
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Five friends of methylated chromatin target of protein-arginine-methyltransferase[prmt]-1 (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.
PIRT08759.
RefSeqNP_056485.2. NM_015670.5.
UniGeneHs.513926.
Hs.733104.

3D structure databases

ProteinModelPortalQ9H4L4.
SMRQ9H4L4. Positions 385-572.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117594. 36 interactions.
DIPDIP-47511N.
IntActQ9H4L4. 21 interactions.
MINTMINT-1200849.
STRING9606.ENSP00000314029.

Protein family/group databases

MEROPSC48.003.

PTM databases

PhosphoSiteQ9H4L4.

Polymorphism databases

DMDM119370525.

Proteomic databases

MaxQBQ9H4L4.
PaxDbQ9H4L4.
PRIDEQ9H4L4.

Protocols and materials databases

DNASU26168.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000429205; ENSP00000403712; ENSG00000161956.
GeneID26168.
KEGGhsa:26168.
UCSCuc002ghm.3. human.

Organism-specific databases

CTD26168.
GeneCardsGC17P007467.
H-InvDBHIX0013501.
HGNCHGNC:17862. SENP3.
HPAHPA060290.
MIM612844. gene.
neXtProtNX_Q9H4L4.
PharmGKBPA134933213.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5160.
HOGENOMHOG000154287.
HOVERGENHBG059450.
InParanoidQ9H4L4.
KOK08593.
OMARLPPRWG.
PhylomeDBQ9H4L4.
TreeFamTF316289.

Enzyme and pathway databases

BRENDA3.4.22.68. 2681.

Gene expression databases

ArrayExpressQ9H4L4.
BgeeQ9H4L4.
CleanExHS_SENP3.
GenevestigatorQ9H4L4.

Family and domain databases

InterProIPR003653. Peptidase_C48.
[Graphical view]
PfamPF02902. Peptidase_C48. 1 hit.
[Graphical view]
PROSITEPS50600. ULP_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSENP3. human.
GeneWikiSENP3.
GenomeRNAi26168.
NextBio48279.
PROQ9H4L4.
SOURCESearch...

Entry information

Entry nameSENP3_HUMAN
AccessionPrimary (citable) accession number: Q9H4L4
Secondary accession number(s): Q66K15 expand/collapse secondary AC list , Q86VS7, Q96PS4, Q9Y3W9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: December 12, 2006
Last modified: June 11, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM