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Protein

Sentrin-specific protease 2

Gene

SENP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protease that catalyzes two essential functions in the SUMO pathway: processing of full-length SUMO1, SUMO2 and SUMO3 to their mature forms and deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins. May down-regulate CTNNB1 levels and thereby modulate the Wnt pathway. Deconjugates SUMO2 from MTA1. Plays a dynamic role in adipogenesis by desumoylating and promoting the stabilization of CEBPB (PubMed:20194620).By similarity4 Publications

Catalytic activityi

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei4781
Active sitei4951
Active sitei548Nucleophile1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

mRNA transport, Protein transport, Translocation, Transport, Ubl conjugation pathway, Wnt signaling pathway

Enzyme and pathway databases

BRENDAi3.4.22.B71. 2681.
ReactomeiR-HSA-3065679. SUMO is proteolytically processed.

Protein family/group databases

MEROPSiC48.007.
TCDBi1.I.1.1.3. the nuclear pore complex (npc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sentrin-specific protease 2 (EC:3.4.22.68)
Alternative name(s):
Axam2
SMT3-specific isopeptidase 2
Short name:
Smt3ip2
Sentrin/SUMO-specific protease SENP2
Gene namesi
Name:SENP2
Synonyms:KIAA1331
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:23116. SENP2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasmic vesicle Source: Ensembl
  • nuclear membrane Source: UniProtKB-SubCell
  • nuclear pore Source: UniProtKB
  • nucleoplasm Source: Reactome
  • PML body Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nuclear pore complex, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi548C → S: Does not desumoylate CEBPB. 1 Publication1
Mutagenesisi576 – 577RK → LM: Does not desumoylate CEBPB. 1 Publication2

Organism-specific databases

DisGeNETi59343.
OpenTargetsiENSG00000163904.
PharmGKBiPA134955185.

Chemistry databases

ChEMBLiCHEMBL2176776.

Polymorphism and mutation databases

BioMutaiSENP2.
DMDMi143811458.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001017181 – 589Sentrin-specific protease 2Add BLAST589

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei32PhosphoserineCombined sources1
Modified residuei333PhosphoserineCombined sources1
Modified residuei344PhosphoserineCombined sources1

Post-translational modificationi

Polyubiquitinated; which leads to proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9HC62.
MaxQBiQ9HC62.
PaxDbiQ9HC62.
PeptideAtlasiQ9HC62.
PRIDEiQ9HC62.

PTM databases

iPTMnetiQ9HC62.
PhosphoSitePlusiQ9HC62.

Expressioni

Gene expression databases

BgeeiENSG00000163904.
CleanExiHS_SENP2.
ExpressionAtlasiQ9HC62. baseline and differential.
GenevisibleiQ9HC62. HS.

Organism-specific databases

HPAiHPA029247.
HPA029248.

Interactioni

Subunit structurei

Binds to SUMO2 and SUMO3 (By similarity). Interacts with the C-terminal domain of NUP153 via its N-terminus. Interacts with MTA1.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGTRAPQ6RW133EBI-714881,EBI-741181
ARL6IP1Q150413EBI-714881,EBI-714543
CCDC155Q8N6L05EBI-714881,EBI-749265
FUNDC1Q8IVP53EBI-714881,EBI-3059266
IKBKGQ9Y6K93EBI-714881,EBI-81279
SUMO2P619563EBI-714881,EBI-473220
SUMO3P558546EBI-714881,EBI-474067
SYNE4Q8N2053EBI-714881,EBI-7131783
TMEM239Q8WW343EBI-714881,EBI-9675724

Protein-protein interaction databases

BioGridi121885. 37 interactors.
DIPiDIP-29254N.
IntActiQ9HC62. 25 interactors.
MINTiMINT-1389034.
STRINGi9606.ENSP00000296257.

Chemistry databases

BindingDBiQ9HC62.

Structurei

Secondary structure

1589
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi370 – 380Combined sources11
Beta strandi381 – 383Combined sources3
Beta strandi388 – 392Combined sources5
Beta strandi395 – 398Combined sources4
Helixi399 – 402Combined sources4
Helixi403 – 405Combined sources3
Helixi413 – 430Combined sources18
Beta strandi435 – 437Combined sources3
Helixi442 – 454Combined sources13
Helixi455 – 458Combined sources4
Helixi463 – 465Combined sources3
Beta strandi466 – 474Combined sources9
Beta strandi479 – 485Combined sources7
Turni486 – 489Combined sources4
Beta strandi490 – 494Combined sources5
Beta strandi496 – 498Combined sources3
Helixi502 – 520Combined sources19
Helixi526 – 528Combined sources3
Beta strandi530 – 533Combined sources4
Turni536 – 538Combined sources3
Turni543 – 546Combined sources4
Helixi548 – 560Combined sources13
Helixi569 – 571Combined sources3
Helixi572 – 585Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TGZX-ray2.80A364-589[»]
1TH0X-ray2.20A/B364-589[»]
2IO0X-ray2.30A364-589[»]
2IO1X-ray2.60A/C/E364-589[»]
2IO2X-ray2.90A364-589[»]
2IO3X-ray3.20A364-589[»]
3ZO5X-ray2.15A363-589[»]
5AEKX-ray3.00A/C/E/G/I/K/M/O/Q/S/U/W366-589[»]
ProteinModelPortaliQ9HC62.
SMRiQ9HC62.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HC62.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni396 – 560ProteaseAdd BLAST165

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi28 – 31Nuclear localization signal1 Publication4
Motifi46 – 51Nuclear localization signal1 Publication6
Motifi317 – 332Nuclear export signalAdd BLAST16

Domaini

The N-terminus is necessary and sufficient for nuclear envelope targeting.

Sequence similaritiesi

Belongs to the peptidase C48 family.Curated

Phylogenomic databases

eggNOGiKOG0778. Eukaryota.
COG5160. LUCA.
GeneTreeiENSGT00530000062941.
HOGENOMiHOG000070234.
HOVERGENiHBG054228.
InParanoidiQ9HC62.
KOiK03345.
OMAiRRGYQLE.
OrthoDBiEOG091G092N.
PhylomeDBiQ9HC62.
TreeFamiTF316289.

Family and domain databases

InterProiIPR003653. Peptidase_C48_C.
[Graphical view]
PfamiPF02902. Peptidase_C48. 1 hit.
[Graphical view]
PROSITEiPS50600. ULP_PROTEASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9HC62-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MYRWLVRILG TIFRFCDRSV PPARALLKRR RSDSTLFSTV DTDEIPAKRP
60 70 80 90 100
RLDCFIHQVK NSLYNAASLF GFPFQLTTKP MVTSACNGTR NVAPSGEVFS
110 120 130 140 150
NSSSCELTGS GSWNNMLKLG NKSPNGISDY PKIRVTVTRD QPRRVLPSFG
160 170 180 190 200
FTLNSEGCNR RPGGRRHSKG NPESSLMWKP QEQAVTEMIS EESGKGLRRP
210 220 230 240 250
HCTVEEGVQK EEREKYRKLL ERLKESGHGN SVCPVTSNYH SSQRSQMDTL
260 270 280 290 300
KTKGWGEEQN HGVKTTQFVP KQYRLVETRG PLCSLRSEKR CSKGKITDTE
310 320 330 340 350
TMVGIRFENE SRRGYQLEPD LSEEVSARLR LGSGSNGLLR RKVSIIETKE
360 370 380 390 400
KNCSGKERDR RTDDLLELTE DMEKEISNAL GHGPQDEILS SAFKLRITRG
410 420 430 440 450
DIQTLKNYHW LNDEVINFYM NLLVERNKKQ GYPALHVFST FFYPKLKSGG
460 470 480 490 500
YQAVKRWTKG VNLFEQEIIL VPIHRKVHWS LVVIDLRKKC LKYLDSMGQK
510 520 530 540 550
GHRICEILLQ YLQDESKTKR NSDLNLLEWT HHSMKPHEIP QQLNGSDCGM
560 570 580
FTCKYADYIS RDKPITFTQH QMPLFRKKMV WEILHQQLL
Length:589
Mass (Da):67,855
Last modified:April 3, 2007 - v3
Checksum:i712707DCC2C5431C
GO
Isoform 2 (identifier: Q9HC62-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: MYRWLVRILGTIFRFCDRSVPPARALLKRRRSD → MDSHPCLYCGPQDSEGTNWQTSP

Note: No experimental confirmation available.
Show »
Length:579
Mass (Da):66,358
Checksum:i06C0D0649B5BCFC7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39T → TA in AAG15309 (Ref. 1) Curated1
Sequence conflicti403Q → H in BAB55222 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029650301T → K.4 PublicationsCorresponds to variant rs6762208dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0566971 – 33MYRWL…RRRSD → MDSHPCLYCGPQDSEGTNWQ TSP in isoform 2. 1 PublicationAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151697 mRNA. Translation: AAG15309.2.
AB037752 mRNA. Translation: BAA92569.2.
AK027599 mRNA. Translation: BAB55222.1.
AK298628 mRNA. Translation: BAG60804.1.
AC016961 Genomic DNA. No translation available.
AC133473 Genomic DNA. No translation available.
BC040609 mRNA. Translation: AAH40609.1.
AL834380 mRNA. Translation: CAD39043.1.
CCDSiCCDS33902.1. [Q9HC62-1]
RefSeqiNP_067640.2. NM_021627.2. [Q9HC62-1]
UniGeneiHs.401388.

Genome annotation databases

EnsembliENST00000296257; ENSP00000296257; ENSG00000163904. [Q9HC62-1]
GeneIDi59343.
KEGGihsa:59343.
UCSCiuc003fpn.4. human. [Q9HC62-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151697 mRNA. Translation: AAG15309.2.
AB037752 mRNA. Translation: BAA92569.2.
AK027599 mRNA. Translation: BAB55222.1.
AK298628 mRNA. Translation: BAG60804.1.
AC016961 Genomic DNA. No translation available.
AC133473 Genomic DNA. No translation available.
BC040609 mRNA. Translation: AAH40609.1.
AL834380 mRNA. Translation: CAD39043.1.
CCDSiCCDS33902.1. [Q9HC62-1]
RefSeqiNP_067640.2. NM_021627.2. [Q9HC62-1]
UniGeneiHs.401388.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TGZX-ray2.80A364-589[»]
1TH0X-ray2.20A/B364-589[»]
2IO0X-ray2.30A364-589[»]
2IO1X-ray2.60A/C/E364-589[»]
2IO2X-ray2.90A364-589[»]
2IO3X-ray3.20A364-589[»]
3ZO5X-ray2.15A363-589[»]
5AEKX-ray3.00A/C/E/G/I/K/M/O/Q/S/U/W366-589[»]
ProteinModelPortaliQ9HC62.
SMRiQ9HC62.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121885. 37 interactors.
DIPiDIP-29254N.
IntActiQ9HC62. 25 interactors.
MINTiMINT-1389034.
STRINGi9606.ENSP00000296257.

Chemistry databases

BindingDBiQ9HC62.
ChEMBLiCHEMBL2176776.

Protein family/group databases

MEROPSiC48.007.
TCDBi1.I.1.1.3. the nuclear pore complex (npc) family.

PTM databases

iPTMnetiQ9HC62.
PhosphoSitePlusiQ9HC62.

Polymorphism and mutation databases

BioMutaiSENP2.
DMDMi143811458.

Proteomic databases

EPDiQ9HC62.
MaxQBiQ9HC62.
PaxDbiQ9HC62.
PeptideAtlasiQ9HC62.
PRIDEiQ9HC62.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296257; ENSP00000296257; ENSG00000163904. [Q9HC62-1]
GeneIDi59343.
KEGGihsa:59343.
UCSCiuc003fpn.4. human. [Q9HC62-1]

Organism-specific databases

CTDi59343.
DisGeNETi59343.
GeneCardsiSENP2.
HGNCiHGNC:23116. SENP2.
HPAiHPA029247.
HPA029248.
MIMi608261. gene.
neXtProtiNX_Q9HC62.
OpenTargetsiENSG00000163904.
PharmGKBiPA134955185.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0778. Eukaryota.
COG5160. LUCA.
GeneTreeiENSGT00530000062941.
HOGENOMiHOG000070234.
HOVERGENiHBG054228.
InParanoidiQ9HC62.
KOiK03345.
OMAiRRGYQLE.
OrthoDBiEOG091G092N.
PhylomeDBiQ9HC62.
TreeFamiTF316289.

Enzyme and pathway databases

BRENDAi3.4.22.B71. 2681.
ReactomeiR-HSA-3065679. SUMO is proteolytically processed.

Miscellaneous databases

ChiTaRSiSENP2. human.
EvolutionaryTraceiQ9HC62.
GeneWikiiSENP2.
GenomeRNAii59343.
PROiQ9HC62.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163904.
CleanExiHS_SENP2.
ExpressionAtlasiQ9HC62. baseline and differential.
GenevisibleiQ9HC62. HS.

Family and domain databases

InterProiIPR003653. Peptidase_C48_C.
[Graphical view]
PfamiPF02902. Peptidase_C48. 1 hit.
[Graphical view]
PROSITEiPS50600. ULP_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSENP2_HUMAN
AccessioniPrimary (citable) accession number: Q9HC62
Secondary accession number(s): B4DQ42
, Q8IW97, Q96SR2, Q9P2L5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: April 3, 2007
Last modified: November 30, 2016
This is version 150 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.