Q96AY2 (EME1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Crossover junction endonuclease EME1
EC=3.1.22.-

Alternative name(s):
MMS4 homolog
Short name=hMMS4

Gene names

Name:	EME1
Synonyms:	MMS4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	570 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks. Ref.3 Ref.4 Ref.5 Ref.7
Cofactor	Magnesium.
Subunit structure	May self-associate. Interacts with MUS81. Interacts with ERCC4 and FANCM. Ref.3 Ref.4 Ref.5 Ref.7
Subcellular location	Nucleus › nucleolus. Note: Recruited to regions of DNA damage in S-phase cells. Ref.5
Sequence similarities	Belongs to the EME1/MMS4 family.

Ontologies

Keywords
Biological process	DNA damage DNA recombination DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW DNA repair Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC
Cellular_component	nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: InterPro endonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MUS81	Q96NY9	4	EBI-2370825,EBI-2370806
SLX4	Q8IY92	4	EBI-2370825,EBI-2370740

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96AY2-1)

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.

Isoform 2 (identifier: Q96AY2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     370-370: F → FSLELLFFDFLPCT

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 570

570

Crossover junction endonuclease EME1

PRO_0000223630

Amino acid modifications

Modified residue

12

1

Phosphoserine Ref.9

Modified residue

15

1

Phosphoserine Ref.9

Modified residue

84

1

Phosphoserine Ref.6 Ref.10 Ref.11 Ref.12

Modified residue

85

1

Phosphoserine Ref.6 Ref.10 Ref.11 Ref.12

Modified residue

87

1

Phosphoserine Ref.6 Ref.10 Ref.11 Ref.12

Modified residue

111

1

Phosphoserine Ref.11

Modified residue

117

1

Phosphoserine Ref.11

Modified residue

150

1

Phosphothreonine Ref.8 Ref.11

Natural variations

Alternative sequence

370

1

F → FSLELLFFDFLPCT in isoform 2.

VSP_017284

Natural variant

5

1

K → N.
Corresponds to variant rs35248609 [ dbSNP | Ensembl ].

VAR_055708

Natural variant

49

1

I → V.
Corresponds to variant rs9896405 [ dbSNP | Ensembl ].

VAR_025337

Natural variant

63

1

F → L.
Corresponds to variant rs17714854 [ dbSNP | Ensembl ].

VAR_055709

Natural variant

69

1

E → D. Ref.1 Ref.2
Corresponds to variant rs3760413 [ dbSNP | Ensembl ].

VAR_025338

Natural variant

347

1

V → I.
Corresponds to variant rs7222520 [ dbSNP | Ensembl ].

VAR_055710

Natural variant

350

1

I → T.
Corresponds to variant rs12450550 [ dbSNP | Ensembl ].

VAR_025339

Experimental info

Sequence conflict

214

1

R → Q in BAB71047. Ref.1

Secondary structure

1

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570

Helix Strand Turn

Details...

Helix

249 – 251

3

Beta strand

253 – 256

4

Helix

258 – 261

4

Helix

266 – 275

10

Beta strand

279 – 282

4

Beta strand

290 – 294

5

Beta strand

312 – 317

6

Helix

318 – 326

9

Helix

345 – 354

10

Beta strand

359 – 364

6

Helix

405 – 418

14

Beta strand

425 – 428

4

Helix

429 – 444

16

Helix

456 – 460

5

Turn

473 – 475

3

Helix

478 – 486

9

Beta strand

487 – 491

5

Helix

494 – 503

10

Helix

507 – 515

9

Helix

520 – 523

4

Turn

524 – 529

6

Turn

532 – 535

4

Helix

547 – 558

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 21, 2006. Version 2. Checksum: BA08F5655761AF85	FASTA	570	63,252
	10 20 30 40 50 60 MALKKSSPSL DSGDSDSEEL PTFAFLKKEP SSTKRRQPER EEKIVVVDIS DCEASCPPAP 70 80 90 100 110 120 ELFSPPVPEI AETVTQTQPV RLLSSESEDE EEFIPLAQRL TCKFLTHKQL SPEDSSSPVK 130 140 150 160 170 180 SVLDHQNNEG ASCDWKKPFP KIPEVPLHDT PERSAADNKD LILDPCCQLP AYLSTCPGQS 190 200 210 220 230 240 SSLAVTKTNS DILPPQKKTK PSQKVQGRGS HGCRQQRQAR QKESTLRRQE RKNAALVTRM 250 260 270 280 290 300 KAQRPEECLK HIIVVLDPVL LQMEGGGQLL GALQTMECRC VIEAQAVPCS VTWRRRAGPS 310 320 330 340 350 360 EDREDWVEEP TVLVLLRAEA FVSMIDNGKQ GSLDSTMKGK ETLQGFVTDI TAKTAGKALS 370 380 390 400 410 420 LVIVDQEKCF SAQNPPRRGK QGANKQTKKQ QQRQPEASIG SMVSRVDAEE ALVDLQLHTE 430 440 450 460 470 480 AQAQIVQSWK ELADFTCAFT KAVAEAPFKK LRDETTFSFC LESDWAGGVK VDLAGRGLAL 490 500 510 520 530 540 VWRRQIQQLN RVSLEMASAV VNAYPSPQLL VQAYQQCFSD KERQNLLADI QVRRGEGVTS 550 560 570 TSRRIGPELS RRIYLQMTTL QPHLSLDSAD
	Isoform 2 [UniParc]. Checksum: B3A20963049D2F42	FASTA	583	64,779
	10 20 30 40 50 60 MALKKSSPSL DSGDSDSEEL PTFAFLKKEP SSTKRRQPER EEKIVVVDIS DCEASCPPAP 70 80 90 100 110 120 ELFSPPVPEI AETVTQTQPV RLLSSESEDE EEFIPLAQRL TCKFLTHKQL SPEDSSSPVK 130 140 150 160 170 180 SVLDHQNNEG ASCDWKKPFP KIPEVPLHDT PERSAADNKD LILDPCCQLP AYLSTCPGQS 190 200 210 220 230 240 SSLAVTKTNS DILPPQKKTK PSQKVQGRGS HGCRQQRQAR QKESTLRRQE RKNAALVTRM 250 260 270 280 290 300 KAQRPEECLK HIIVVLDPVL LQMEGGGQLL GALQTMECRC VIEAQAVPCS VTWRRRAGPS 310 320 330 340 350 360 EDREDWVEEP TVLVLLRAEA FVSMIDNGKQ GSLDSTMKGK ETLQGFVTDI TAKTAGKALS 370 380 390 400 410 420 LVIVDQEKCF SLELLFFDFL PCTSAQNPPR RGKQGANKQT KKQQQRQPEA SIGSMVSRVD 430 440 450 460 470 480 AEEALVDLQL HTEAQAQIVQ SWKELADFTC AFTKAVAEAP FKKLRDETTF SFCLESDWAG 490 500 510 520 530 540 GVKVDLAGRG LALVWRRQIQ QLNRVSLEMA SAVVNAYPSP QLLVQAYQQC FSDKERQNLL 550 560 570 580 ADIQVRRGEG VTSTSRRIGP ELSRRIYLQM TTLQPHLSLD SAD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASP-69.
[2]	"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] (ISOFORM 2), VARIANT ASP-69. Tissue: Placenta.
[3]	"Identification and characterization of human MUS81-MMS4 structure-specific endonuclease." Oegruenc M., Sancar A. J. Biol. Chem. 278:21715-21720(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MUS81.
[4]	"Identification and characterization of the human mus81-eme1 endonuclease." Ciccia A., Constantinou A., West S.C. J. Biol. Chem. 278:25172-25178(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MUS81.
[5]	"RNA interference inhibition of Mus81 reduces mitotic recombination in human cells." Blais V., Gao H., Elwell C.A., Boddy M.N., Gaillard P.-H.L., Russell P., McGowan C.H. Mol. Biol. Cell 15:552-562(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SELF-ASSOCIATION, INTERACTION WITH MUS81, SUBCELLULAR LOCATION.
[6]	"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-84; SER-85 AND SER-87, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM." Ciccia A., Ling C., Coulthard R., Yan Z., Xue Y., Meetei A.R., Laghmani el H., Joenje H., McDonald N., de Winter J.P., Wang W., West S.C. Mol. Cell 25:331-343(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ERCC4; FANCM AND MUS81.
[8]	"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 THR-150, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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-12 AND SER-15, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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-84; SER-85 AND SER-87, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"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-84; SER-85; SER-87; SER-111; SER-117 AND THR-150, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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-84; SER-85 AND SER-87, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK055926 mRNA. Translation: BAB71047.1.
BC016470 mRNA. Translation: AAH16470.1.

IPI

IPI00073193.
IPI00718899.

RefSeq

NP_001159603.1. NM_001166131.1.
NP_689676.2. NM_152463.2.

UniGene

Hs.514330.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZIU	X-ray	2.70	B	246-570	[»]
2ZIV	X-ray	2.70	B	246-570	[»]
2ZIW	X-ray	2.80	B	246-570	[»]
2ZIX	X-ray	3.50	B	246-570	[»]

ProteinModelPortal

Q96AY2.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48629N.

IntAct

Q96AY2. 3 interactions.

STRING

9606.ENSP00000339897.

PTM databases

PhosphoSite

Q96AY2.

Polymorphism databases

DMDM

88909612.

Proteomic databases

PaxDb

Q96AY2.

PRIDE

Q96AY2.

Protocols and materials databases

DNASU

146956.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338165; ENSP00000339897; ENSG00000154920.
ENST00000393271; ENSP00000376952; ENSG00000154920.
ENST00000511648; ENSP00000421700; ENSG00000154920.

GeneID

146956.

KEGG

hsa:146956.

UCSC

uc002iqs.2. human.
uc010dbp.2. human.

Organism-specific databases

CTD

146956.

GeneCards

GC17P048450.

HGNC

HGNC:24965. EME1.

HPA

CAB016127.

MIM

610885. gene.

neXtProt

NX_Q96AY2.

PharmGKB

PA134904115.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG85607.

HOGENOM

HOG000112362.

HOVERGEN

HBG081476.

KO

K10882.

OMA

LQMEGGG.

OrthoDB

EOG4SQWWH.

PhylomeDB

Q96AY2.

Gene expression databases

ArrayExpress

Q96AY2.

Bgee

Q96AY2.

CleanEx

HS_EME1.

Genevestigator

Q96AY2.

GermOnline

ENSG00000154920. Homo sapiens.

Family and domain databases

InterPro

IPR006166. ERCC4_domain.
[Graphical view]

Pfam

PF02732. ERCC4. 1 hit.
[Graphical view]

SMART

SM00891. ERCC4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q96AY2.

GenomeRNAi

146956.

NextBio

85519.

SOURCE

Search...

Entry information

Entry name

EME1_HUMAN

Accession

Primary (citable) accession number: Q96AY2
Secondary accession number(s): Q96N62

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2006
Last sequence update:	February 21, 2006
Last modified:	May 1, 2013
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.