Reviewed, UniProtKB/Swiss-Prot Q9HC62 (SENP2_HUMAN)

Names and origin

Protein names

Recommended name:
    Sentrin-specific protease 2
    EC=3.4.22.-
Alternative name(s):
    Sentrin/SUMO-specific protease SENP2
    SMT3-specific isopeptidase 2
      Short name=Smt3ip2
    Axam2

Gene names

Name:	SENP2
Synonyms:	KIAA1331

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	589 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 By similarity. Ref.7 Ref.8
Subunit structure	Binds to SUMO2 and SUMO3 By similarity. Interacts with the C-terminal domain of NUP153 via its N-terminus. Ref.7 Ref.8
Subcellular location	Nucleus › nuclear pore complex. Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side. Cytoplasm. Note: Shuttles between cytoplasm and nucleus. Ref.7 Ref.8 Ref.9
Domain	The N-terminus is necessary and sufficient for nuclear envelope targeting.
Post-translational modification	Polyubiquitinated; which leads to proteasomal degradation.
Sequence similarities	Belongs to the peptidase C48 family.

Ontologies

Keywords
Biological process	Protein transport Translocation Transport Ubl conjugation pathway Wnt signaling pathway mRNA transport
Cellular component	Cytoplasm Membrane Nuclear pore complex Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of Wnt receptor signaling pathway Ref.8 Non-traceable author statement. Source: UniProtKB transmembrane transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear pore Ref.7 Inferred from direct assay. Source: UniProtKB
Molecular function	SUMO-specific protease activity Ref.8 Inferred from direct assay. Source: UniProtKB protein binding Ref.8 Ref.13 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SUMO1	P63165	1	EBI-714881,EBI-80140

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 589

589

Sentrin-specific protease 2

PRO_0000101718

Regions

Region

396 – 560

165

Protease

Motif

28 – 31

4

Nuclear localization signal Ref.9

Motif

46 – 51

6

Nuclear localization signal Ref.9

Motif

317 – 332

16

Nuclear export signal

Sites

Active site

478

1

Active site

495

1

Active site

548

1

Nucleophile

Amino acid modifications

Modified residue

216

1

Phosphotyrosine Ref.10

Modified residue

333

1

Phosphoserine Ref.11 Ref.12

Natural variations

Natural variant

301

1

T → K: dbSNP rs6762208. Ref.1 Ref.2 Ref.4 Ref.6

VAR_029650

Experimental info

Sequence conflict

39

1

T → TA in AAG15309. Ref.1

Sequence conflict

403

1

Q → H in BAB55222. Ref.4

Secondary structure

1

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589

Helix Strand Turn

Details...

Helix

370 – 380

11

Beta strand

381 – 383

3

Beta strand

388 – 392

5

Beta strand

395 – 398

4

Helix

399 – 402

4

Helix

403 – 405

3

Helix

413 – 430

18

Beta strand

435 – 437

3

Helix

442 – 449

8

Helix

451 – 453

3

Helix

455 – 458

4

Helix

463 – 465

3

Beta strand

466 – 475

10

Beta strand

478 – 485

8

Turn

486 – 489

4

Beta strand

490 – 494

5

Helix

502 – 519

18

Helix

526 – 528

3

Beta strand

530 – 533

4

Turn

536 – 538

3

Beta strand

544 – 546

3

Helix

548 – 559

12

Turn

560 – 562

3

Helix

569 – 571

3

Helix

572 – 585

14

Sequences

	Sequence		Length	Mass (Da)
	Q9HC62-1 [UniParc]. Last modified April 3, 2007. Version 3. Checksum: 712707DCC2C5431C	FASTA	589	67,855
	10 20 30 40 50 60 MYRWLVRILG TIFRFCDRSV PPARALLKRR RSDSTLFSTV DTDEIPAKRP RLDCFIHQVK 70 80 90 100 110 120 NSLYNAASLF GFPFQLTTKP MVTSACNGTR NVAPSGEVFS NSSSCELTGS GSWNNMLKLG 130 140 150 160 170 180 NKSPNGISDY PKIRVTVTRD QPRRVLPSFG FTLNSEGCNR RPGGRRHSKG NPESSLMWKP 190 200 210 220 230 240 QEQAVTEMIS EESGKGLRRP HCTVEEGVQK EEREKYRKLL ERLKESGHGN SVCPVTSNYH 250 260 270 280 290 300 SSQRSQMDTL KTKGWGEEQN HGVKTTQFVP KQYRLVETRG PLCSLRSEKR CSKGKITDTE 310 320 330 340 350 360 TMVGIRFENE SRRGYQLEPD LSEEVSARLR LGSGSNGLLR RKVSIIETKE KNCSGKERDR 370 380 390 400 410 420 RTDDLLELTE DMEKEISNAL GHGPQDEILS SAFKLRITRG DIQTLKNYHW LNDEVINFYM 430 440 450 460 470 480 NLLVERNKKQ GYPALHVFST FFYPKLKSGG YQAVKRWTKG VNLFEQEIIL VPIHRKVHWS 490 500 510 520 530 540 LVVIDLRKKC LKYLDSMGQK GHRICEILLQ YLQDESKTKR NSDLNLLEWT HHSMKPHEIP 550 560 570 580 QQLNGSDCGM FTCKYADYIS RDKPITFTQH QMPLFRKKMV WEILHQQLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of SENP2, a novel member of sentrin-specific protease family." Gong L., Yeh E.T.H. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-301.
[2]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed: 10718198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-301. Tissue: Brain.
[3]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-301. Tissue: Teratocarcinoma.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-589, VARIANT LYS-301. Tissue: Melanoma.
[7]	"Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex." Zhang H., Saitoh H., Matunis M.J. Mol. Cell. Biol. 22:6498-6508(2002) [PubMed: 12192048] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NUP153. Tissue: Fetal brain.
[8]	"Association of the human SUMO-1 protease SENP2 with the nuclear pore." Hang J., Dasso M. J. Biol. Chem. 277:19961-19966(2002) [PubMed: 11896061] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NUP153.
[9]	"Nucleocytoplasmic shuttling modulates activity and ubiquitination-dependent turnover of SUMO-specific protease 2." Itahana Y., Yeh E.T.H., Zhang Y. Mol. Cell. Biol. 26:4675-4689(2006) [PubMed: 16738331] [Abstract] Cited for: NUCLEAR LOCALIZATION SIGNAL, NUCLEAR EXPORT SIGNAL, SUBCELLULAR LOCATION, UBIQUITINATION.
[10]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216, MASS SPECTROMETRY.
[11]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, MASS SPECTROMETRY.
[12]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, MASS SPECTROMETRY. Tissue: T-cell.
[13]	"A basis for SUMO protease specificity provided by analysis of human Senp2 and a Senp2-SUMO complex." Reverter D., Lima C.D. Structure 12:1519-1531(2004) [PubMed: 15296745] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 364-589, X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 364-589 IN COMPLEX WITH SUMO1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF151697 mRNA. Translation: AAG15309.2.
AB037752 mRNA. Translation: BAA92569.2.
AK027599 mRNA. Translation: BAB55222.1.
BC040609 mRNA. Translation: AAH40609.1.
AL834380 mRNA. Translation: CAD39043.1.

IPI

IPI00939143.

RefSeq

NP_067640.2.

UniGene

Hs.401388

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TGZ	X-ray	2.80	A	364-589	[»]
1TH0	X-ray	2.20	A/B	364-589	[»]
2IO0	X-ray	2.30	A	364-589	[»]
2IO1	X-ray	2.60	A/C/E	364-589	[»]
2IO2	X-ray	2.90	A	364-589	[»]
2IO3	X-ray	3.20	A	364-589	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29254N.

IntAct

Q9HC62. 2 interactions.

STRING

Q9HC62.

PTM databases

PhosphoSite

Q9HC62.

Proteomic databases

PRIDE

Q9HC62.

Genome annotation databases

Ensembl

ENST00000296257; ENSP00000296257; ENSG00000163904; Homo sapiens. [Genome view]
ENST00000427465; ENSP00000394562; ENSG00000163904; Homo sapiens. [Genome view]

GeneID

59343.

KEGG

hsa:59343.

UCSC

uc003fpn.1. human.

Organism-specific databases

CTD

59343.

GeneCards

GC03P186786.

H-InvDB

HIX0018164.

HGNC

HGNC:23116. SENP2.

MIM

608261. gene.

PharmGKB

PA134955185.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05449.

HOVERGEN

Q9HC62.

InParanoid

Q9HC62.

PhylomeDB

Q9HC62.

Gene expression databases

ArrayExpress

Q9HC62.

Bgee

Q9HC62.

CleanEx

HS_SENP2.

Genevestigator

Q9HC62.

GermOnline

ENSG00000163904. 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 Resources

NextBio

65238.

SOURCE

Search...

Entry information

Entry name

SENP2_HUMAN

Accession

Primary (citable) accession number: Q9HC62
Secondary accession number(s): Q8IW97, Q96SR2, Q9P2L5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2002
Last sequence update:	April 3, 2007
Last modified:	February 9, 2010
This is version 82 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.