P07992 (ERCC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA excision repair protein ERCC-1

Gene names

Name:

ERCC1

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	297 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair.
Subunit structure	Heterodimer composed of ERCC1 and XPF/ERRC4.
Subcellular location	Nucleus.
Involvement in disease	Cerebro-oculo-facio-skeletal syndrome 4 (COFS4) [MIM:610758]: A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Belongs to the ERCC1/RAD10/SWI10 family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cataract
Ligand	DNA-binding
Molecular function	Endonuclease Hydrolase Nuclease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	UV protection Inferred from electronic annotation. Source: Compara cell proliferation Inferred from electronic annotation. Source: Compara chromosome organization Inferred from electronic annotation. Source: Compara double-strand break repair Inferred from electronic annotation. Source: Compara embryonic organ development Inferred from electronic annotation. Source: Compara germ cell development Inferred from electronic annotation. Source: Compara isotype switching Inferred from electronic annotation. Source: Compara male gonad development Inferred from electronic annotation. Source: Compara mitotic recombination Inferred from mutant phenotype PubMed 8811092. Source: UniProtKB multicellular organism growth Inferred from electronic annotation. Source: Compara multicellular organismal aging Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of telomere maintenance Inferred from mutant phenotype PubMed 17055345. Source: UniProtKB nucleotide-excision repair, DNA damage removal Traceable author statement. Source: Reactome nucleotide-excision repair, DNA incision, 3'-to lesion Inferred from mutant phenotype PubMed 7657672. Source: UniProtKB nucleotide-excision repair, DNA incision, 5'-to lesion Inferred from mutant phenotype PubMed 7657672. Source: UniProtKB oogenesis Inferred from electronic annotation. Source: Compara post-embryonic hemopoiesis Inferred from electronic annotation. Source: Compara pyrimidine dimer repair by nucleotide-excision repair Inferred from electronic annotation. Source: Compara replicative cell aging Inferred from electronic annotation. Source: Compara response to X-ray Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to oxidative stress Inferred from mutant phenotype PubMed 17614221PubMed 9256505. Source: UniProtKB response to sucrose stimulus Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara syncytium formation Inferred from electronic annotation. Source: Compara transcription-coupled nucleotide-excision repair Traceable author statement. Source: Reactome
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nuclear chromosome, telomeric region Inferred from direct assay PubMed 14690602. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome nucleotide-excision repair complex Inferred from direct assay PubMed 7559382PubMed 8197175. Source: UniProtKB
Molecular_function	damaged DNA binding Inferred from direct assay PubMed 17720715. Source: UniProtKB endonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW single-stranded DNA binding Inferred from direct assay PubMed 16076955PubMed 17720715. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SLX4	Q8IY92	6	EBI-750962,EBI-2370740

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P07992-1)

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: P07992-2)

The sequence of this isoform differs from the canonical sequence as follows:
     235-258: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: P07992-3)

The sequence of this isoform differs from the canonical sequence as follows:
     282-297: ARRLFDVLHEPFLKVP → VRALGKNPRSWGKERAPNKHNLRPQSFKVKKEPKTRHSGFRL

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 297

297

DNA excision repair protein ERCC-1

PRO_0000087006

Regions

DNA binding

134 – 156

23

Potential

Motif

17 – 23

7

Nuclear localization signal Potential

Natural variations

Alternative sequence

235 – 258

24

Missing in isoform 2.

VSP_042727

Alternative sequence

282 – 297

16

ARRLF…FLKVP → VRALGKNPRSWGKERAPNKH NLRPQSFKVKKEPKTRHSGF RL in isoform 3.

VSP_043455

Natural variant

231

1

F → L in COFS4. Ref.10

VAR_032776

Natural variant

266

1

A → T. Ref.8
Corresponds to variant rs3212977 [ dbSNP | Ensembl ].

VAR_019167

Secondary structure

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297

Helix Strand Turn

Details...

Beta strand

101 – 103

3

Helix

105 – 107

3

Helix

111 – 115

5

Beta strand

121 – 123

3

Beta strand

127 – 133

7

Beta strand

136 – 142

7

Helix

143 – 148

6

Helix

152 – 160

9

Beta strand

163 – 172

10

Beta strand

175 – 177

3

Helix

179 – 192

14

Beta strand

195 – 201

7

Helix

202 – 213

12

Helix

222 – 226

5

Beta strand

242 – 244

3

Helix

247 – 257

11

Helix

260 – 264

5

Helix

268 – 272

5

Beta strand

274 – 276

3

Helix

280 – 290

11

Beta strand

293 – 295

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: 6FCE3615732349E5	FASTA	297	32,562
	10 20 30 40 50 60 MDPGKDKEGV PQPSGPPARK KFVIPLDEDE VPPGVAKPLF RSTQSLPTVD TSAQAAPQTY 70 80 90 100 110 120 AEYAISQPLE GAGATCPTGS EPLAGETPNQ ALKPGAKSNS IIVSPRQRGN PVLKFVRNVP 130 140 150 160 170 180 WEFGDVIPDY VLGQSTCALF LSLRYHNLHP DYIHGRLQSL GKNFALRVLL VQVDVKDPQQ 190 200 210 220 230 240 ALKELAKMCI LADCTLILAW SPEEAGRYLE TYKAYEQKPA DLLMEKLEQD FVSRVTECLT 250 260 270 280 290 TVKSVNKTDS QTLLTTFGSL EQLIAASRED LALCPGLGPQ KARRLFDVLH EPFLKVP
	Isoform 2 [UniParc]. Checksum: 04DA21E774A33524	FASTA	273	29,993
	10 20 30 40 50 60 MDPGKDKEGV PQPSGPPARK KFVIPLDEDE VPPGVAKPLF RSTQSLPTVD TSAQAAPQTY 70 80 90 100 110 120 AEYAISQPLE GAGATCPTGS EPLAGETPNQ ALKPGAKSNS IIVSPRQRGN PVLKFVRNVP 130 140 150 160 170 180 WEFGDVIPDY VLGQSTCALF LSLRYHNLHP DYIHGRLQSL GKNFALRVLL VQVDVKDPQQ 190 200 210 220 230 240 ALKELAKMCI LADCTLILAW SPEEAGRYLE TYKAYEQKPA DLLMEKLEQD FVSRSLEQLI 250 260 270 AASREDLALC PGLGPQKARR LFDVLHEPFL KVP
	Isoform 3 [UniParc]. Checksum: D99BFAC9CE8E912E	FASTA	323	35,563
	10 20 30 40 50 60 MDPGKDKEGV PQPSGPPARK KFVIPLDEDE VPPGVAKPLF RSTQSLPTVD TSAQAAPQTY 70 80 90 100 110 120 AEYAISQPLE GAGATCPTGS EPLAGETPNQ ALKPGAKSNS IIVSPRQRGN PVLKFVRNVP 130 140 150 160 170 180 WEFGDVIPDY VLGQSTCALF LSLRYHNLHP DYIHGRLQSL GKNFALRVLL VQVDVKDPQQ 190 200 210 220 230 240 ALKELAKMCI LADCTLILAW SPEEAGRYLE TYKAYEQKPA DLLMEKLEQD FVSRVTECLT 250 260 270 280 290 300 TVKSVNKTDS QTLLTTFGSL EQLIAASRED LALCPGLGPQ KVRALGKNPR SWGKERAPNK 310 320 HNLRPQSFKV KKEPKTRHSG FRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of the human excision repair gene ERCC-1: cDNA cloning and amino acid homology with the yeast DNA repair gene RAD10." van Duin M., de Wit J., Odijk H., Westerveld A., Yasui A., Koken M.H.M., Hoeijmakers J.H.J., Bootsma D. Cell 44:913-923(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Identification of DNA repair genes in the human genome." Hoeijmakers J.H.J., van Duin M., Westerveld A., Yasui A., Bootsma D. Cold Spring Harb. Symp. Quant. Biol. 51:91-101(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"A nucleotide polymorphism in ERCC1 in human ovarian cancer cell lines and tumor tissues." Yu J.J., Mu C.J., Lee K.B., Okamoto A., Reed E.L., Bostick-Bruton F., Mitchell K.C., Reed E. Mutat. Res. 382:13-20(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Human excision repair protein 1, transcript variant, mRNA." Hisatomi H., Nagao K., Ishikawa H., Yokoyama Y., Ishihara Y., Hikiji K., Iizuka T. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	NIEHS SNPs program Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-266.
[9]	"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] (ISOFORMS 1 AND 3). Tissue: Lung and Uterus.
[10]	"First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure." Jaspers N.G.J., Raams A., Silengo M.C., Wijgers N., Niedernhofer L.J., Robinson A.R., Giglia-Mari G., Hoogstraten D., Kleijer W.J., Hoeijmakers J.H.J., Vermeulen W. Am. J. Hum. Genet. 80:457-466(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT COFS4 LEU-231.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13194 mRNA. Translation: AAA52394.1.
M26163 Genomic DNA. Translation: AAA52395.1.
M28650 mRNA. Translation: AAA35810.1.
AF001925 mRNA. Translation: AAC16253.1.
AB069681 mRNA. Translation: BAB62810.1.
BT019806 mRNA. Translation: AAV38609.1.
AF512555 Genomic DNA. Translation: AAM34796.1.
AC092309 Genomic DNA. No translation available.
AC138128 Genomic DNA. No translation available.
AC138534 Genomic DNA. No translation available.
AC139353 Genomic DNA. No translation available.
CH471126 Genomic DNA. Translation: EAW57349.1.
BC008930 mRNA. Translation: AAH08930.1.
BC052813 mRNA. Translation: AAH52813.1.

IPI

IPI00014040.
IPI00045494.
IPI00401902.

PIR

A24781. A32875.

RefSeq

NP_001159521.1. NM_001166049.1.
NP_001974.1. NM_001983.3.
NP_973730.1. NM_202001.2.

UniGene

Hs.435981.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z00	NMR	-	A	220-297	[»]
2A1I	X-ray	1.90	A	96-227	[»]
2A1J	X-ray	2.70	B	220-296	[»]
2JNW	NMR	-	A	96-214	[»]
2JPD	NMR	-	A	96-219	[»]

ProteinModelPortal

P07992.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24235N.

IntAct

P07992. 4 interactions.

MINT

MINT-1457664.

STRING

9606.ENSP00000013807.

PTM databases

PhosphoSite

P07992.

Polymorphism databases

DMDM

119538.

Proteomic databases

PaxDb

P07992.

PRIDE

P07992.

Protocols and materials databases

DNASU

2067.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000013807; ENSP00000013807; ENSG00000012061.
ENST00000300853; ENSP00000300853; ENSG00000012061.
ENST00000340192; ENSP00000345203; ENSG00000012061.
ENST00000589165; ENSP00000468035; ENSG00000012061.

GeneID

2067.

KEGG

hsa:2067.

UCSC

uc002pbs.2. human.
uc002pbt.2. human.
uc002pbv.3. human.

Organism-specific databases

CTD

2067.

GeneCards

GC19M045912.

HGNC

HGNC:3433. ERCC1.

HPA

CAB004390.
HPA029773.

MIM

126380. gene.
610758. phenotype.

neXtProt

NX_P07992.

Orphanet

1466. COFS syndrome.

PharmGKB

PA155.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5241.

HOGENOM

HOG000037440.

HOVERGEN

HBG051497.

KO

K10849.

OMA

HPDYIHQ.

OrthoDB

EOG4R23VJ.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

P07992.

Bgee

P07992.

CleanEx

HS_ERCC1.

Genevestigator

P07992.

GermOnline

ENSG00000012061. Homo sapiens.

Family and domain databases

InterPro

IPR004579. DNA_repair_Rad10.
IPR000445. HhH_motif.
IPR003583. Hlx-hairpin-Hlx_DNA-bd_motif.
IPR011335. Restrct_endonuc-II-like.
IPR010994. RuvA_2-like.
[Graphical view]

Pfam

PF00633. HHH. 1 hit.
PF03834. Rad10. 1 hit.
[Graphical view]

ProDom

PD013585. DNA_repair_Rad10. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00278. HhH1. 1 hit.
[Graphical view]

SUPFAM

SSF52980. Restrict_endonuc_II-like_core. 1 hit.
SSF47781. RuvA_2_like. 1 hit.

TIGRFAMs

TIGR00597. rad10. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

ERCC1. human.

EvolutionaryTrace

P07992.

GenomeRNAi

2067.

NextBio

8403.

SOURCE

Search...

Entry information

Entry name

ERCC1_HUMAN

Accession

Primary (citable) accession number: P07992
Secondary accession number(s): Q7Z7F5, Q96S40

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	August 1, 1988
Last modified:	May 29, 2013
This is version 137 of the entry and version 1 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.