Q03018 (ESP1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Separin
EC=3.4.22.49

Alternative name(s):
Separase

Gene names

Name:	ESP1
Ordered Locus Names:	YGR098C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	1630 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the MCD1/SCC1 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by securin/PDS1 protein. It also promotes anaphase spindle elongation. A component of the FEAR (CDC14 early anaphase release) network which promotes CDC14 release from the nucleolus during early anaphase. Cleaves SLK19. Ref.4 Ref.5 Ref.6 Ref.7
Catalytic activity	All bonds known to be hydrolyzed by this endopeptidase have arginine in P1 and an acidic residue in P4. P6 is often occupied by an acidic residue or by a hydroxy-amino-acid residue, the phosphorylation of which enhances cleavage.
Enzyme regulation	It is inactivated via its interaction with PDS1, which probably covers its active site. PDS1 degradation at anaphase, liberates it and triggers MCD1 cleavage.
Subunit structure	May bind calcium. Interacts with PDS1. Interacts with MCD1. Ref.4
Subcellular location	Nucleus. Cytoplasm › cytoskeleton › spindle pole body. Cytoplasm. Note: Accumulates in the nucleus in G2 and is mobilized onto the spindle pole bodies and spindle midzone at anaphase onset, where it persists into midanaphase. The association with MCD1 may be important for its nuclear targeting. Ref.6
Sequence similarities	Belongs to the peptidase C50 family.

Ontologies

Keywords
Biological process	Chromosome partition
Cellular component	Cytoplasm Cytoskeleton Nucleus
Ligand	Calcium
Molecular function	Hydrolase Protease Thiol protease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from mutant phenotype PubMed 18321989. Source: SGD mitotic sister chromatid segregation Inferred from mutant phenotype Ref.4. Source: SGD negative regulation of protein phosphatase type 2A activity Inferred from mutant phenotype PubMed 16713564. Source: SGD proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of exit from mitosis Inferred from genetic interaction PubMed 12598903. Source: SGD regulation of mitotic spindle elongation Inferred from mutant phenotype PubMed 18430955. Source: SGD
Cellular_component	mitochondrion Inferred from direct assay PubMed 14576278PubMed 16823961. Source: SGD nucleus Inferred from direct assay Ref.6PubMed 22842922. Source: SGD spindle Inferred from direct assay Ref.6. Source: SGD spindle pole body Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type endopeptidase activity Inferred from direct assay PubMed 11081625. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC55	Q00362	2	EBI-6657,EBI-1942

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1630	1630	Separin		PRO_0000205904
Sites
	Active site	1531	1	By similarity
Experimental info
	Mutagenesis	1568 – 1570	3	DKD → AKA: Reduces function. Loss of function. Ref.6
	Sequence conflict	136	1	F → S in AAB03897. Ref.1
	Sequence conflict	250 – 253	4	TVEC → IRRV in AAB03897. Ref.1
	Sequence conflict	540	1	V → L in AAB03897. Ref.1
	Sequence conflict	636	1	S → Y in AAB03897. Ref.1
	Sequence conflict	782	1	K → E in AAB03897. Ref.1
	Sequence conflict	800	1	A → E in AAB03897. Ref.1
	Sequence conflict	1146	1	I → T in AAB03897. Ref.1
	Sequence conflict	1295	1	K → R in AAB03897. Ref.1
	Sequence conflict	1333 – 1336	4	QEID → ARKSI in AAB03897. Ref.1
	Sequence conflict	1443	1	E → Q in AAB03897. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q03018 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: FBAFD33FF706C6BA	FASTA	1,630	187,447
	10 20 30 40 50 60 MMVKQEEPLN EISPNTPMTS KSYLLNDTLS KVHHSGQTRP LTSVLSGDAS SNSIGILAMH 70 80 90 100 110 120 NNIIRDFTKI ASNNIDLAIE DITTVDHSLN SIYSLLKSHH MWGHINSTVK QHLMIIVKLI 130 140 150 160 170 180 NNNALGLASS EIIFLFNETN LFQAHSLKNI LLADFSTWND YYLSNLKILA LQIILKRKLV 190 200 210 220 230 240 DEYLPHILEL FSHDKRYLLK DPNLKAHALT KIVLSFFSVT TSCKVLFGLK FLQYIKQFKL 250 260 270 280 290 300 PFKKFISNIT VECFSKNLLH KNYLEMGPNK IYLNSFYLSY SMLYDGLDKI MLLDILSYEE 310 320 330 340 350 360 TTEVQRAIKS KKEFNEYCNM SENRLLWSCI SVDDLNVILE NATNFLQNKG KHISATLKCL 370 380 390 400 410 420 VCLWSTIRLE GLPKNKDILR QFDCTVIYIN SNIKSINDES AAALLSELLG VLSEICIDYK 430 440 450 460 470 480 EPKRLSNIIS VLFNASVLFK SHSFLLKTAN LEISNVLISN DSKTSHRTIL KFEKFISSAQ 490 500 510 520 530 540 SAQKKIEIFS CLFNVYCMLR NDTLSFVFDF CQNAFIHCFT RLKITKFIEF SNSSEIMLSV 550 560 570 580 590 600 LYGNSSIENI PSENWSQLSR MIFCSLRGIF DLDPLELNNT FDKLHLLNKY ELLIRIVYLL 610 620 630 640 650 660 NLDMSKHLTT NLSKITKLYI NKWLQKSDEK AERISSFEMD FVKMLLCYLN FNNFDKLSIE 670 680 690 700 710 720 LSLCIKSKEK YYSSIVPYAD NYLLEAYLSL YMIDDALMMK NQLQKTMNLS TAKIEQALLH 730 740 750 760 770 780 ASSLINVHLW DSDLTAFQIY FGKTLPAMKP ELFDINNDHN LPMSLYIKVI LLNIKIFNES 790 800 810 820 830 840 AKLNIKAGNV ISAVIDCRKA QNLALSLLKK KNKLSQGSRL ALLKSLSFSF FQLIKIHIRI 850 860 870 880 890 900 GSARDCEFYS KELSRIISDL EEPIIVYRCL HFLHRYYMIT EQTCLQNITL GKANKAFDYL 910 920 930 940 950 960 DAEADITSLT MFLYDNKEFV KLEQSLVLYF GDQLEKTFLP NLWKLHLGKD IDDSICLSEY 970 980 990 1000 1010 1020 MPKNVINRVH NMWQKVMSQL EEDPFFKGMF ESTLGIPSSL PVIPSTMPNN ILKTPSKHST 1030 1040 1050 1060 1070 1080 GLKLCDSPRS SSMTPRGKNI RQKFDRIAAI SKLKQMKELL ESLKLDTLDN HELSKISSLS 1090 1100 1110 1120 1130 1140 SLTLTILSNI TSIHNAESSL ITNFSLTDLP RHMPLLFDKV LNNIDNKNYR EFRVSSLIAP 1150 1160 1170 1180 1190 1200 NNISTITESI RVSAAQKDLM ESNLNINVIT IDFCPITGNL LLSKLEPRRK RRTHLRLPLI 1210 1220 1230 1240 1250 1260 RSNSRDLDEV HLSFPEATKK LLSIINESNQ TTSVEVTNKI KTREERKSWW TTRYDLDKRM 1270 1280 1290 1300 1310 1320 QQLLNNIENS WFNGVQGFFS PEVVDNSLFE KFKDKFYEIL HQNLPSRKLY GNPAMFIKVE 1330 1340 1350 1360 1370 1380 DWVIELFLKL NPQEIDFLSK MEDLIYFVLD ILLFHGEENA YDEIDFSMLH VQLEEQIKKY 1390 1400 1410 1420 1430 1440 RATMTTNSIF HTFLVVSSSC HLFPWECLSF LKDLSITRVP SYVCLNKLLS RFHYQLPLQV 1450 1460 1470 1480 1490 1500 TIEDNISMIL NPNGDLSRTE SKFKGMFQKI IDAKPSSQLV MNEKPEEETL LKMLQNSNLF 1510 1520 1530 1540 1550 1560 VYIGHGGGEQ YVRSKEIKKC TKIAPSFLLG CSSAAMKYYG KLEPTGTIYT YLLGGCPMVL 1570 1580 1590 1600 1610 1620 GNLWDVTDKD IDKFSEELFE KMGFRCNTDD LNGNSLSVSY AVSKSRGVCH LRYLNGAAPV 1630 IYGLPIKFVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Requirement for ESP1 in the nuclear division of Saccharomyces cerevisiae." McGrew J.T., Goetsch L., Byers B.E., Baum P. Mol. Biol. Cell 3:1443-1454(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 59-1630.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome VII." Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E. , Defoor E., Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., Zollner A., Kleine K. Nature 387:81-84(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast." Ciosk R., Zachariae W., Michaelis C., Shevchenko A., Mann M., Nasmyth K. Cell 93:1067-1076(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PDS1.
[5]	"Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1." Uhlmann F., Lottspeich F., Nasmyth K. Nature 400:37-42(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE OF MCD1, FUNCTION.
[6]	"A novel role of the budding yeast separin Esp1 in anaphase spindle elongation: evidence that proper spindle association of Esp1 is regulated by Pds1." Jensen S., Segal M., Clarke D.J., Reed S.I. J. Cell Biol. 152:27-40(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 1568-ASP--ASP-1570.
[7]	"Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase." Stegmeier F., Visintin R., Amon A. Cell 108:207-220(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A COMPONENT OF THE FEAR NETWORK.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L07289 Genomic DNA. Translation: AAB03897.1. Z72883 Genomic DNA. Translation: CAA97101.1. BK006941 Genomic DNA. Translation: DAA08191.1.
PIR	S64403.
RefSeq	NP_011612.3. NM_001181227.3.
3D structure databases
ProteinModelPortal	Q03018.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2933N.
IntAct	Q03018. 6 interactions.
MINT	MINT-614508.
STRING	4932.YGR098C.
Protein family/group databases
MEROPS	C50.001.
Proteomic databases
PaxDb	Q03018.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YGR098C; YGR098C; YGR098C.
GeneID	852990.
KEGG	sce:YGR098C. sce:YGR104C.
Organism-specific databases
CYGD	YGR098c.
SGD	S000003330. ESP1.
Phylogenomic databases
eggNOG	COG5155.
GeneTree	ENSGT00390000004990.
HOGENOM	HOG000065988.
KO	K02365. K15136.
OMA	FDILLFH.
OrthoDB	EOG47Q1F3.
Gene expression databases
Genevestigator	Q03018.
GermOnline	YGR098C. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR005314. Peptidase_C50. [Graphical view]
PANTHER	PTHR12792. PTHR12792. 1 hit.
Pfam	PF03568. Peptidase_C50. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	972815.

Entry information

Entry name

ESP1_YEAST

Accession

Primary (citable) accession number: Q03018
Secondary accession number(s): D6VUN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program