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Protein

Sentrin-specific protease 6

Gene

SENP6

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

Functioni

Protease that deconjugates SUMO1, SUMO2 and SUMO3 from targeted proteins. Processes preferentially poly-SUMO2 and poly-SUMO3 chains, but does not efficiently process SUMO1, SUMO2 and SUMO3 precursors. Deconjugates SUMO1 from RXRA, leading to transcriptional activation. Involved in chromosome alignment and spindle assembly, by regulating the kinetochore CENPH-CENPI-CENPK complex. Desumoylates PML and CENPI, protecting them from degradation by the ubiquitin ligase RNF4, which targets polysumoylated proteins for proteasomal degradation. Desumoylates also RPA1, thus preventing recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination.6 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.1 Publication

Pathwayi: protein sumoylation

This protein is involved in the pathway protein sumoylation, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein sumoylation and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei765By similarity1
Active sitei917By similarity1
Active sitei1030By similarity1

GO - Molecular functioni

  • SUMO-specific protease activity Source: UniProtKB

GO - Biological processi

  • protein desumoylation Source: UniProtKB
  • protein modification by small protein removal Source: UniProtKB
  • protein sumoylation Source: UniProtKB-UniPathway
  • regulation of kinetochore assembly Source: UniProtKB
  • regulation of spindle assembly Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000112701-MONOMER.
BRENDAi3.4.22.B74. 2681.
UniPathwayiUPA00886.

Protein family/group databases

MEROPSiC48.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Sentrin-specific protease 6 (EC:3.4.22.681 Publication)
Alternative name(s):
SUMO-1-specific protease 1
Sentrin/SUMO-specific protease SENP6
Gene namesi
Name:SENP6
Synonyms:KIAA0797, SSP1, SUSP1
ORF Names:FKSG6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:20944. SENP6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1030C → S: Abolishes enzymatic activity. 1 Publication1

Organism-specific databases

DisGeNETi26054.
OpenTargetsiENSG00000112701.
PharmGKBiPA134893291.

Chemistry databases

ChEMBLiCHEMBL1741215.

Polymorphism and mutation databases

BioMutaiSENP6.
DMDMi119370526.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001017251 – 1112Sentrin-specific protease 6Add BLAST1112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42PhosphoserineCombined sources1
Modified residuei335PhosphoserineCombined sources1
Modified residuei336PhosphoserineCombined sources1
Modified residuei350PhosphoserineCombined sources1
Modified residuei352PhosphoserineCombined sources1
Modified residuei416PhosphothreonineCombined sources1
Modified residuei919PhosphoserineCombined sources1
Modified residuei1111PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9GZR1.
PaxDbiQ9GZR1.
PeptideAtlasiQ9GZR1.
PRIDEiQ9GZR1.

PTM databases

iPTMnetiQ9GZR1.
PhosphoSitePlusiQ9GZR1.

Expressioni

Tissue specificityi

Highly expressed in reproductive organs, such as testis, ovary and prostate.

Gene expression databases

BgeeiENSG00000112701.
CleanExiHS_SENP6.
ExpressionAtlasiQ9GZR1. baseline and differential.
GenevisibleiQ9GZR1. HS.

Organism-specific databases

HPAiHPA024376.

Interactioni

Subunit structurei

Interacts with RXRA. Forms a complex with KAT5-TIP60 and UBE2I in response to UV irradiation. Interacts with RPA1 to maintain it in hyposumoylated state during S phase preventing DNA repair initiation.2 Publications

Protein-protein interaction databases

BioGridi117517. 13 interactors.
IntActiQ9GZR1. 5 interactors.
STRINGi9606.ENSP00000402527.

Chemistry databases

BindingDBiQ9GZR1.

Structurei

3D structure databases

ProteinModelPortaliQ9GZR1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni666 – 1112ProteaseAdd BLAST447

Sequence similaritiesi

Belongs to the peptidase C48 family.Curated

Phylogenomic databases

eggNOGiKOG0779. Eukaryota.
COG5160. LUCA.
GeneTreeiENSGT00530000063531.
HOVERGENiHBG059746.
InParanoidiQ9GZR1.
KOiK08595.
OMAiRKEYPPH.
OrthoDBiEOG091G012K.
PhylomeDBiQ9GZR1.
TreeFamiTF350136.

Family and domain databases

InterProiIPR003653. Peptidase_C48_C.
[Graphical view]
PfamiPF02902. Peptidase_C48. 2 hits.
[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: Q9GZR1-1) [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
MAAGKSGGSA GEITFLEALA RSESKRDGGF KNNWSFDHEE ESEGDTDKDG
60 70 80 90 100
TNLLSVDEDE DSETSKGKKL NRRSEIVANS SGEFILKTYV RRNKSESFKT
110 120 130 140 150
LKGNPIGLNM LSNNKKLSEN TQNTSLCSGT VVHGRRFHHA HAQIPVVKTA
160 170 180 190 200
AQSSLDRKER KEYPPHVQKV EINPVRLSRL QGVERIMKKT EESESQVEPE
210 220 230 240 250
IKRKVQQKRH CSTYQPTPPL SPASKKCLTH LEDLQRNCRQ AITLNESTGP
260 270 280 290 300
LLRTSIHQNS GGQKSQNTGL TTKKFYGNNV EKVPIDIIVN CDDSKHTYLQ
310 320 330 340 350
TNGKVILPGA KIPKITNLKE RKTSLSDLND PIILSSDDDD DNDRTNRRES
360 370 380 390 400
ISPQPADSAC SSPAPSTGKV EAALNENTCR AERELRSIPE DSELNTVTLP
410 420 430 440 450
RKARMKDQFG NSIINTPLKR RKVFSQEPPD ALALSCQSSF DSVILNCRSI
460 470 480 490 500
RVGTLFRLLI EPVIFCLDFI KIQLDEPDHD PVEIILNTSD LTKCEWCNVR
510 520 530 540 550
KLPVVFLQAI PAVYQKLSIQ LQMNKEDKVW NDCKGVNKLT NLEEQYIILI
560 570 580 590 600
FQNGLDPPAN MVFESIINEI GIKNNISNFF AKIPFEEANG RLVACTRTYE
610 620 630 640 650
ESIKGSCGQK ENKIKTVSFE SKIQLRSKQE FQFFDEEEET GENHTIFIGP
660 670 680 690 700
VEKLIVYPPP PAKGGISVTN EDLHCLNEGE FLNDVIIDFY LKYLVLEKLK
710 720 730 740 750
KEDADRIHIF SSFFYKRLNQ RERRNHETTN LSIQQKRHGR VKTWTRHVDI
760 770 780 790 800
FEKDFIFVPL NEAAHWFLAV VCFPGLEKPK YEPNPHYHEN AVIQKCSTVE
810 820 830 840 850
DSCISSSASE MESCSQNSSA KPVIKKMLNK KHCIAVIDSN PGQEESDPRY
860 870 880 890 900
KRNICSVKYS VKKINHTASE NEEFNKGEST SQKVADRTKS ENGLQNESLS
910 920 930 940 950
STHHTDGLSK IRLNYSDESP EAGKMLEDEL VDFSEDQDNQ DDSSDDGFLA
960 970 980 990 1000
DDNCSSEIGQ WHLKPTICKQ PCILLMDSLR GPSRSNVVKI LREYLEVEWE
1010 1020 1030 1040 1050
VKKGSKRSFS KDVMKGSNPK VPQQNNFSDC GVYVLQYVES FFENPILSFE
1060 1070 1080 1090 1100
LPMNLANWFP PPRMRTKREE IRNIILKLQE DQSKEKRKHK DTYSTEAPLG
1110
EGTEQYVNSI SD
Length:1,112
Mass (Da):126,146
Last modified:December 12, 2006 - v2
Checksum:iA7B07C75C39EE786
GO
Isoform 2 (identifier: Q9GZR1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     153-159: Missing.

Note: No experimental confirmation available.
Show »
Length:1,105
Mass (Da):125,330
Checksum:i7C0F2FF3E8BE3D46
GO

Sequence cautioni

The sequence BAA34517 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAH72480 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAH72481 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAH74168 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAH74170 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI19523 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI23575 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI23576 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti293D → V in BAC04794 (PubMed:14702039).Curated1
Sequence conflicti1043E → Q in AAG29831 (PubMed:10806345).Curated1
Sequence conflicti1043E → Q in AAG30253 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029653121T → M.2 PublicationsCorresponds to variant rs17414086dbSNPEnsembl.1
Natural variantiVAR_029654637E → K.Corresponds to variant rs1061347dbSNPEnsembl.1
Natural variantiVAR_029655717R → P.Corresponds to variant rs12195603dbSNPEnsembl.1
Natural variantiVAR_051545820A → V.Corresponds to variant rs34045941dbSNPEnsembl.1
Natural variantiVAR_0160961106Y → C.2 PublicationsCorresponds to variant rs9250dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005274153 – 159Missing in isoform 2. 2 Publications7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF196304 mRNA. Translation: AAF04852.1.
AF307849 mRNA. Translation: AAG29831.1.
AF306508 mRNA. Translation: AAG30253.1.
AB018340 mRNA. Translation: BAA34517.2. Different initiation.
AL589656
, AL109897, AL355797, AL356057 Genomic DNA. Translation: CAH72480.1. Sequence problems.
AL589656, AL355797, AL356057 Genomic DNA. Translation: CAH72481.1. Sequence problems.
AL356057
, AL109897, AL355797, AL589656 Genomic DNA. Translation: CAH74168.1. Sequence problems.
AL356057, AL355797, AL589656 Genomic DNA. Translation: CAH74170.1. Sequence problems.
AL109897
, AL355797, AL356057, AL589656 Genomic DNA. Translation: CAI19523.1. Sequence problems.
AL355797
, AL109897, AL356057, AL589656 Genomic DNA. Translation: CAI23575.1. Sequence problems.
AL355797, AL356057, AL589656 Genomic DNA. Translation: CAI23576.1. Sequence problems.
CH471051 Genomic DNA. Translation: EAW48734.1.
BC028583 mRNA. Translation: AAH28583.1.
AK096455 mRNA. Translation: BAC04794.1.
CCDSiCCDS43483.1. [Q9GZR1-2]
CCDS47454.1. [Q9GZR1-1]
RefSeqiNP_001093879.1. NM_001100409.2. [Q9GZR1-2]
NP_001291721.1. NM_001304792.1.
NP_056386.2. NM_015571.3. [Q9GZR1-1]
UniGeneiHs.485784.

Genome annotation databases

EnsembliENST00000370010; ENSP00000359027; ENSG00000112701. [Q9GZR1-2]
ENST00000447266; ENSP00000402527; ENSG00000112701. [Q9GZR1-1]
GeneIDi26054.
KEGGihsa:26054.
UCSCiuc003pid.5. human. [Q9GZR1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF196304 mRNA. Translation: AAF04852.1.
AF307849 mRNA. Translation: AAG29831.1.
AF306508 mRNA. Translation: AAG30253.1.
AB018340 mRNA. Translation: BAA34517.2. Different initiation.
AL589656
, AL109897, AL355797, AL356057 Genomic DNA. Translation: CAH72480.1. Sequence problems.
AL589656, AL355797, AL356057 Genomic DNA. Translation: CAH72481.1. Sequence problems.
AL356057
, AL109897, AL355797, AL589656 Genomic DNA. Translation: CAH74168.1. Sequence problems.
AL356057, AL355797, AL589656 Genomic DNA. Translation: CAH74170.1. Sequence problems.
AL109897
, AL355797, AL356057, AL589656 Genomic DNA. Translation: CAI19523.1. Sequence problems.
AL355797
, AL109897, AL356057, AL589656 Genomic DNA. Translation: CAI23575.1. Sequence problems.
AL355797, AL356057, AL589656 Genomic DNA. Translation: CAI23576.1. Sequence problems.
CH471051 Genomic DNA. Translation: EAW48734.1.
BC028583 mRNA. Translation: AAH28583.1.
AK096455 mRNA. Translation: BAC04794.1.
CCDSiCCDS43483.1. [Q9GZR1-2]
CCDS47454.1. [Q9GZR1-1]
RefSeqiNP_001093879.1. NM_001100409.2. [Q9GZR1-2]
NP_001291721.1. NM_001304792.1.
NP_056386.2. NM_015571.3. [Q9GZR1-1]
UniGeneiHs.485784.

3D structure databases

ProteinModelPortaliQ9GZR1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117517. 13 interactors.
IntActiQ9GZR1. 5 interactors.
STRINGi9606.ENSP00000402527.

Chemistry databases

BindingDBiQ9GZR1.
ChEMBLiCHEMBL1741215.

Protein family/group databases

MEROPSiC48.004.

PTM databases

iPTMnetiQ9GZR1.
PhosphoSitePlusiQ9GZR1.

Polymorphism and mutation databases

BioMutaiSENP6.
DMDMi119370526.

Proteomic databases

MaxQBiQ9GZR1.
PaxDbiQ9GZR1.
PeptideAtlasiQ9GZR1.
PRIDEiQ9GZR1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370010; ENSP00000359027; ENSG00000112701. [Q9GZR1-2]
ENST00000447266; ENSP00000402527; ENSG00000112701. [Q9GZR1-1]
GeneIDi26054.
KEGGihsa:26054.
UCSCiuc003pid.5. human. [Q9GZR1-1]

Organism-specific databases

CTDi26054.
DisGeNETi26054.
GeneCardsiSENP6.
HGNCiHGNC:20944. SENP6.
HPAiHPA024376.
MIMi605003. gene.
neXtProtiNX_Q9GZR1.
OpenTargetsiENSG00000112701.
PharmGKBiPA134893291.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0779. Eukaryota.
COG5160. LUCA.
GeneTreeiENSGT00530000063531.
HOVERGENiHBG059746.
InParanoidiQ9GZR1.
KOiK08595.
OMAiRKEYPPH.
OrthoDBiEOG091G012K.
PhylomeDBiQ9GZR1.
TreeFamiTF350136.

Enzyme and pathway databases

UniPathwayiUPA00886.
BioCyciZFISH:ENSG00000112701-MONOMER.
BRENDAi3.4.22.B74. 2681.

Miscellaneous databases

ChiTaRSiSENP6. human.
GeneWikiiSENP6.
GenomeRNAii26054.
PROiQ9GZR1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112701.
CleanExiHS_SENP6.
ExpressionAtlasiQ9GZR1. baseline and differential.
GenevisibleiQ9GZR1. HS.

Family and domain databases

InterProiIPR003653. Peptidase_C48_C.
[Graphical view]
PfamiPF02902. Peptidase_C48. 2 hits.
[Graphical view]
PROSITEiPS50600. ULP_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSENP6_HUMAN
AccessioniPrimary (citable) accession number: Q9GZR1
Secondary accession number(s): A6NNY9
, O94891, Q5VUL3, Q5VUL4, Q8TBY4, Q9UJV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: December 12, 2006
Last modified: November 2, 2016
This is version 145 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  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.