UniProtKB - P18074 (ERCC2_HUMAN)
General transcription and DNA repair factor IIH helicase subunit XPD
ERCC2
Functioni
ATP-dependent 5'-3' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATP-dependent helicase activity of XPD/ERCC2 is required for DNA opening. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. XPD/ERCC2 acts by forming a bridge between CAK and the core-TFIIH complex. Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers.
4 PublicationsCatalytic activityi
- EC:3.6.4.12
Cofactori
Protein has several cofactor binding sites:- Mg2+1 Publication
- [4Fe-4S] cluster1 PublicationNote: Binds 1 [4Fe-4S] cluster.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 116 | Iron-sulfur (4Fe-4S)By similarity | 1 | |
Metal bindingi | 134 | Iron-sulfur (4Fe-4S)By similarity | 1 | |
Metal bindingi | 155 | Iron-sulfur (4Fe-4S)By similarity | 1 | |
Metal bindingi | 190 | Iron-sulfur (4Fe-4S)Curated | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 42 – 49 | ATPPROSITE-ProRule annotation | 8 |
GO - Molecular functioni
- 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
- 5'-3' DNA helicase activity Source: UniProtKB
- ATP binding Source: UniProtKB-KW
- ATP hydrolysis activity Source: RHEA
- damaged DNA binding Source: GO_Central
- DNA helicase activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- protein C-terminus binding Source: UniProtKB
- protein-macromolecule adaptor activity Source: UniProtKB
- protein N-terminus binding Source: UniProtKB
GO - Biological processi
- aging Source: Ensembl
- apoptotic process Source: UniProtKB
- bone mineralization Source: Ensembl
- cell population proliferation Source: Ensembl
- central nervous system myelin formation Source: Ensembl
- chromosome segregation Source: UniProtKB
- embryonic cleavage Source: Ensembl
- erythrocyte maturation Source: Ensembl
- extracellular matrix organization Source: Ensembl
- hair cell differentiation Source: UniProtKB
- hair follicle maturation Source: Ensembl
- hematopoietic stem cell differentiation Source: Ensembl
- in utero embryonic development Source: Ensembl
- maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) Source: Ensembl
- multicellular organism growth Source: Ensembl
- nucleotide-excision repair Source: MGI
- nucleotide-excision repair, DNA duplex unwinding Source: GO_Central
- nucleotide-excision repair, DNA incision Source: UniProtKB
- positive regulation of DNA binding Source: Ensembl
- positive regulation of mitotic recombination Source: GO_Central
- post-embryonic development Source: Ensembl
- regulation of mitotic cell cycle phase transition Source: UniProtKB
- response to oxidative stress Source: UniProtKB
- response to UV Source: GO_Central
- spinal cord development Source: Ensembl
- transcription by RNA polymerase II Source: UniProtKB
- transcription-coupled nucleotide-excision repair Source: UniProtKB
- transcription elongation from RNA polymerase I promoter Source: Ensembl
- UV protection Source: MGI
Keywordsi
Molecular function | DNA-binding, Helicase, Hydrolase |
Biological process | Chromosome partition, DNA damage, DNA repair, Host-virus interaction, Transcription, Transcription regulation |
Ligand | 4Fe-4S, ATP-binding, Iron, Iron-sulfur, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 3.6.4.12, 2681 |
PathwayCommonsi | P18074 |
Reactomei | R-HSA-112382, Formation of RNA Pol II elongation complex R-HSA-113418, Formation of the Early Elongation Complex R-HSA-167152, Formation of HIV elongation complex in the absence of HIV Tat R-HSA-167158, Formation of the HIV-1 Early Elongation Complex R-HSA-167160, RNA Pol II CTD phosphorylation and interaction with CE during HIV infection R-HSA-167161, HIV Transcription Initiation R-HSA-167162, RNA Polymerase II HIV Promoter Escape R-HSA-167172, Transcription of the HIV genome R-HSA-167200, Formation of HIV-1 elongation complex containing HIV-1 Tat R-HSA-167246, Tat-mediated elongation of the HIV-1 transcript R-HSA-2564830, Cytosolic iron-sulfur cluster assembly R-HSA-427413, NoRC negatively regulates rRNA expression R-HSA-5696395, Formation of Incision Complex in GG-NER R-HSA-5696400, Dual Incision in GG-NER R-HSA-674695, RNA Polymerase II Pre-transcription Events R-HSA-6781823, Formation of TC-NER Pre-Incision Complex R-HSA-6781827, Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-6782135, Dual incision in TC-NER R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6796648, TP53 Regulates Transcription of DNA Repair Genes R-HSA-72086, mRNA Capping R-HSA-73762, RNA Polymerase I Transcription Initiation R-HSA-73772, RNA Polymerase I Promoter Escape R-HSA-73776, RNA Polymerase II Promoter Escape R-HSA-73779, RNA Polymerase II Transcription Pre-Initiation And Promoter Opening R-HSA-73863, RNA Polymerase I Transcription Termination R-HSA-75953, RNA Polymerase II Transcription Initiation R-HSA-75955, RNA Polymerase II Transcription Elongation R-HSA-76042, RNA Polymerase II Transcription Initiation And Promoter Clearance R-HSA-77075, RNA Pol II CTD phosphorylation and interaction with CE |
SignaLinki | P18074 |
SIGNORi | P18074 |
Names & Taxonomyi
Protein namesi | Recommended name: General transcription and DNA repair factor IIH helicase subunit XPD (EC:3.6.4.12)Short name: TFIIH subunit XPD Alternative name(s): Basic transcription factor 2 80 kDa subunit Short name: BTF2 p80 CXPD DNA excision repair protein ERCC-2 DNA repair protein complementing XP-D cells TFIIH basal transcription factor complex 80 kDa subunit Short name: TFIIH 80 kDa subunit Short name: TFIIH p80 Xeroderma pigmentosum group D-complementing protein |
Gene namesi | Name:ERCC2 Synonyms:XPD, XPDC |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3434, ERCC2 |
MIMi | 126340, gene |
neXtProti | NX_P18074 |
VEuPathDBi | HostDB:ENSG00000104884 |
Subcellular locationi
Cytoskeleton
- MMXD complex Source: UniProtKB
- spindle Source: UniProtKB
Cytosol
- cytosol Source: HPA
Nucleus
- CAK-ERCC2 complex Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
- transcription factor TFIID complex Source: UniProtKB
- transcription factor TFIIH core complex Source: UniProtKB
- transcription factor TFIIH holo complex Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, NucleusPathology & Biotechi
Involvement in diseasei
Xeroderma pigmentosum complementation group D (XP-D)7 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008187 | 47 | G → R in XP-D. Corresponds to variant dbSNP:rs1360631927Ensembl. | 1 | |
Natural variantiVAR_017282 | 76 | T → A in XP-D. | 1 | |
Natural variantiVAR_003622 | 112 | R → H in TTD1 and XP-D. 3 PublicationsCorresponds to variant dbSNP:rs121913020EnsemblClinVar. | 1 | |
Natural variantiVAR_008188 | 234 | D → N in XP-D. Corresponds to variant dbSNP:rs1340806384Ensembl. | 1 | |
Natural variantiVAR_003623 | 461 | L → V in XP-D and TTD1. 3 PublicationsCorresponds to variant dbSNP:rs121913016EnsemblClinVar. | 1 | |
Natural variantiVAR_017283 | 485 | L → P in XP-D; the corresponding mutation in fission yeast causes complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121913025EnsemblClinVar. | 1 | |
Natural variantiVAR_017285 | 511 | R → Q in XP-D. Corresponds to variant dbSNP:rs772572683Ensembl. | 1 | |
Natural variantiVAR_003625 | 541 | S → R in XP-D; mild. 1 PublicationCorresponds to variant dbSNP:rs121913019EnsemblClinVar. | 1 | |
Natural variantiVAR_008191 | 542 | Y → C in XP-D. | 1 | |
Natural variantiVAR_017286 | 582 – 583 | EK → VSE in XP-D. 1 Publication | 2 | |
Natural variantiVAR_008192 | 601 | R → L in XP-D. Corresponds to variant dbSNP:rs140522180Ensembl. | 1 | |
Natural variantiVAR_017289 | 601 | R → W in XP-D. Corresponds to variant dbSNP:rs753641926EnsemblClinVar. | 1 | |
Natural variantiVAR_003627 | 602 | G → D in XP-D; combined with features of Cockayne syndrome. Corresponds to variant dbSNP:rs771824813Ensembl. | 1 | |
Natural variantiVAR_003626 | 616 | R → P in XP-D and TTD1. 1 PublicationCorresponds to variant dbSNP:rs376556895EnsemblClinVar. | 1 | |
Natural variantiVAR_008193 | 616 | R → W in XP-D and COFS2. 1 PublicationCorresponds to variant dbSNP:rs121913024EnsemblClinVar. | 1 | |
Natural variantiVAR_017292 | 666 | R → W in XP-D. Corresponds to variant dbSNP:rs752510317Ensembl. | 1 | |
Natural variantiVAR_017293 | 681 | D → N in XP-D and COFS2. 1 PublicationCorresponds to variant dbSNP:rs121913023EnsemblClinVar. | 1 | |
Natural variantiVAR_008197 | 683 | R → Q in XP-D. Corresponds to variant dbSNP:rs758439420EnsemblClinVar. | 1 | |
Natural variantiVAR_008198 | 683 | R → W in XP-D; vitamin D-mediated activation of CYP24A1 is impaired in patient fibroblasts due to altered TFIIH-dependent phosphorylation of ETS1, subsequent impaired cooperation of ETS1 with VDR and altered VDR recruitment to CYP24A1 promoter. 1 PublicationCorresponds to variant dbSNP:rs41556519EnsemblClinVar. | 1 | |
Natural variantiVAR_003629 | 716 – 730 | Missing in XP-D and TTD1. 1 PublicationAdd BLAST | 15 |
Trichothiodystrophy 1, photosensitive (TTD1)6 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_003622 | 112 | R → H in TTD1 and XP-D. 3 PublicationsCorresponds to variant dbSNP:rs121913020EnsemblClinVar. | 1 | |
Natural variantiVAR_008189 | 259 | C → Y in TTD1. 1 PublicationCorresponds to variant dbSNP:rs370454709EnsemblClinVar. | 1 | |
Natural variantiVAR_003623 | 461 | L → V in XP-D and TTD1. 3 PublicationsCorresponds to variant dbSNP:rs121913016EnsemblClinVar. | 1 | |
Natural variantiVAR_008190 | 482 | Missing in TTD1. 1 Publication | 1 | |
Natural variantiVAR_017284 | 487 | R → G in TTD1. | 1 | |
Natural variantiVAR_003624 | 488 – 493 | Missing in TTD1; mild. 1 Publication | 6 | |
Natural variantiVAR_017287 | 592 | R → P in TTD1. | 1 | |
Natural variantiVAR_017288 | 594 | A → P in TTD1. | 1 | |
Natural variantiVAR_003626 | 616 | R → P in XP-D and TTD1. 1 PublicationCorresponds to variant dbSNP:rs376556895EnsemblClinVar. | 1 | |
Natural variantiVAR_008194 | 658 | R → C in TTD1. 2 PublicationsCorresponds to variant dbSNP:rs121913021EnsemblClinVar. | 1 | |
Natural variantiVAR_017290 | 658 | R → G in TTD1. | 1 | |
Natural variantiVAR_008195 | 658 | R → H in TTD1. Corresponds to variant dbSNP:rs762141272Ensembl. | 1 | |
Natural variantiVAR_017291 | 663 | C → R in TTD1. Corresponds to variant dbSNP:rs770367713Ensembl. | 1 | |
Natural variantiVAR_008196 | 673 | D → G in TTD1. 1 Publication | 1 | |
Natural variantiVAR_008199 | 713 | G → R in TTD1. 2 PublicationsCorresponds to variant dbSNP:rs121913022EnsemblClinVar. | 1 | |
Natural variantiVAR_003629 | 716 – 730 | Missing in XP-D and TTD1. 1 PublicationAdd BLAST | 15 | |
Natural variantiVAR_003630 | 722 | R → W in TTD1. 2 PublicationsCorresponds to variant dbSNP:rs121913026EnsemblClinVar. | 1 | |
Natural variantiVAR_003631 | 725 | A → P in TTD1. 1 PublicationCorresponds to variant dbSNP:rs121913018EnsemblClinVar. | 1 |
Cerebro-oculo-facio-skeletal syndrome 2 (COFS2)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008193 | 616 | R → W in XP-D and COFS2. 1 PublicationCorresponds to variant dbSNP:rs121913024EnsemblClinVar. | 1 | |
Natural variantiVAR_017293 | 681 | D → N in XP-D and COFS2. 1 PublicationCorresponds to variant dbSNP:rs121913023EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 48 | K → R: Decreased transcriptional activity of the reconstituted TFIIH complex. 1 Publication | 1 | |
Mutagenesisi | 190 | C → S: Reduced iron-sulfur-binding. Iron-sulfur-binding is further decreased in absence of MMS19. 1 Publication | 1 |
Keywords - Diseasei
Cataract, Cockayne syndrome, Deafness, Disease variant, Dwarfism, Ichthyosis, Xeroderma pigmentosumOrganism-specific databases
DisGeNETi | 2068 |
GeneReviewsi | ERCC2 |
MalaCardsi | ERCC2 |
MIMi | 278730, phenotype 601675, phenotype 610756, phenotype |
OpenTargetsi | ENSG00000104884 |
Orphaneti | 1466, COFS syndrome 33364, Trichothiodystrophy 910, Xeroderma pigmentosum 220295, Xeroderma pigmentosum-Cockayne syndrome complex |
PharmGKBi | PA27848 |
Miscellaneous databases
Pharosi | P18074, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4105743 |
Genetic variation databases
BioMutai | ERCC2 |
DMDMi | 119540 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000101980 | 1 – 760 | General transcription and DNA repair factor IIH helicase subunit XPDAdd BLAST | 760 |
Post-translational modificationi
Keywords - PTMi
Ubl conjugationProteomic databases
EPDi | P18074 |
jPOSTi | P18074 |
MassIVEi | P18074 |
MaxQBi | P18074 |
PaxDbi | P18074 |
PeptideAtlasi | P18074 |
PRIDEi | P18074 |
ProteomicsDBi | 53542 [P18074-1] 53543 [P18074-2] |
PTM databases
iPTMneti | P18074 |
PhosphoSitePlusi | P18074 |
Expressioni
Gene expression databases
Bgeei | ENSG00000104884, Expressed in stromal cell of endometrium and 146 other tissues |
ExpressionAtlasi | P18074, baseline and differential |
Genevisiblei | P18074, HS |
Organism-specific databases
HPAi | ENSG00000104884, Low tissue specificity |
Interactioni
Subunit structurei
Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. The interaction with GTF2H2 results in the stimulation of the 5'-->3' helicase activity (PubMed:9771713, PubMed:9852112).
Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5 (PubMed:20797633).
Interacts with CIAO1 and CIAO2B; the interaction WITH CIAO2B is direct (PubMed:23891004).
Interacts with ATF7IP (PubMed:19106100).
Interacts directly with MMS19 (PubMed:23585563).
6 Publications(Microbial infection) Interacts with Epstein-Barr virus EBNA2.
1 PublicationBinary interactionsi
P18074
With | #Exp. | IntAct |
---|---|---|
ERCC3 [P19447] | 5 | EBI-6380590,EBI-1183307 |
GTF2H2 [Q13888] | 9 | EBI-6380590,EBI-1565170 |
GTF2H2C_2 [Q6P1K8] | 3 | EBI-6380590,EBI-8469755 |
MMS19 [Q96T76] | 7 | EBI-6380590,EBI-1044169 |
GO - Molecular functioni
- protein C-terminus binding Source: UniProtKB
- protein N-terminus binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 108380, 60 interactors |
CORUMi | P18074 |
DIPi | DIP-644N |
IntActi | P18074, 51 interactors |
MINTi | P18074 |
STRINGi | 9606.ENSP00000375809 |
Miscellaneous databases
RNActi | P18074, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P18074 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 7 – 283 | Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST | 277 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 438 – 637 | Mediates interaction with MMS19Add BLAST | 200 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 234 – 237 | DEAH box | 4 | |
Motifi | 682 – 695 | Nuclear localization signalSequence analysisAdd BLAST | 14 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1131, Eukaryota |
GeneTreei | ENSGT00950000182970 |
HOGENOMi | CLU_045429_0_0_1 |
InParanoidi | P18074 |
OMAi | PYFTARR |
OrthoDBi | 186062at2759 |
PhylomeDBi | P18074 |
TreeFami | TF101232 |
Family and domain databases
Gene3Di | 3.40.50.300, 2 hits |
InterProi | View protein in InterPro IPR006555, ATP-dep_Helicase_C IPR010614, DEAD_2 IPR045028, DinG/Rad3-like IPR002464, DNA/RNA_helicase_DEAH_CS IPR010643, HBB IPR014013, Helic_SF1/SF2_ATP-bd_DinG/Rad3 IPR006554, Helicase-like_DEXD_c2 IPR027417, P-loop_NTPase IPR013020, Rad3/Chl1-like IPR001945, RAD3/XPD |
PANTHERi | PTHR11472, PTHR11472, 1 hit PTHR11472:SF1, PTHR11472:SF1, 1 hit |
Pfami | View protein in Pfam PF06733, DEAD_2, 1 hit PF06777, HBB, 1 hit PF13307, Helicase_C_2, 1 hit |
PRINTSi | PR00852, XRODRMPGMNTD |
SMARTi | View protein in SMART SM00488, DEXDc2, 1 hit SM00491, HELICc2, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR00604, rad3, 1 hit |
PROSITEi | View protein in PROSITE PS00690, DEAH_ATP_HELICASE, 1 hit PS51193, HELICASE_ATP_BIND_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKLNVDGLLV YFPYDYIYPE QFSYMRELKR TLDAKGHGVL EMPSGTGKTV
60 70 80 90 100
SLLALIMAYQ RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LNFYEKQEGE
110 120 130 140 150
KLPFLGLALS SRKNLCIHPE VTPLRFGKDV DGKCHSLTAS YVRAQYQHDT
160 170 180 190 200
SLPHCRFYEE FDAHGREVPL PAGIYNLDDL KALGRRQGWC PYFLARYSIL
210 220 230 240 250
HANVVVYSYH YLLDPKIADL VSKELARKAV VVFDEAHNID NVCIDSMSVN
260 270 280 290 300
LTRRTLDRCQ GNLETLQKTV LRIKETDEQR LRDEYRRLVE GLREASAARE
310 320 330 340 350
TDAHLANPVL PDEVLQEAVP GSIRTAEHFL GFLRRLLEYV KWRLRVQHVV
360 370 380 390 400
QESPPAFLSG LAQRVCIQRK PLRFCAERLR SLLHTLEITD LADFSPLTLL
410 420 430 440 450
ANFATLVSTY AKGFTIIIEP FDDRTPTIAN PILHFSCMDA SLAIKPVFER
460 470 480 490 500
FQSVIITSGT LSPLDIYPKI LDFHPVTMAT FTMTLARVCL CPMIIGRGND
510 520 530 540 550
QVAISSKFET REDIAVIRNY GNLLLEMSAV VPDGIVAFFT SYQYMESTVA
560 570 580 590 600
SWYEQGILEN IQRNKLLFIE TQDGAETSVA LEKYQEACEN GRGAILLSVA
610 620 630 640 650
RGKVSEGIDF VHHYGRAVIM FGVPYVYTQS RILKARLEYL RDQFQIREND
660 670 680 690 700
FLTFDAMRHA AQCVGRAIRG KTDYGLMVFA DKRFARGDKR GKLPRWIQEH
710 720 730 740 750
LTDANLNLTV DEGVQVAKYF LRQMAQPFHR EDQLGLSLLS LEQLESEETL
760
KRIEQIAQQL
Computationally mapped potential isoform sequencesi
There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA8MX75 | A8MX75_HUMAN | General transcription and DNA repai... | ERCC2 | 706 | Annotation score: | ||
K7EIT8 | K7EIT8_HUMAN | DNA helicase | ERCC2 | 292 | Annotation score: | ||
E7EVE9 | E7EVE9_HUMAN | General transcription and DNA repai... | ERCC2 | 829 | Annotation score: | ||
K7EKF3 | K7EKF3_HUMAN | DNA helicase | ERCC2 | 202 | Annotation score: | ||
A0A804HK53 | A0A804HK53_HUMAN | General transcription and DNA repai... | ERCC2 | 719 | Annotation score: | ||
K7ENL1 | K7ENL1_HUMAN | General transcription and DNA repai... | ERCC2 | 109 | Annotation score: | ||
B4E0F6 | B4E0F6_HUMAN | General transcription and DNA repai... | ERCC2 | 127 | Annotation score: | ||
A0A804HL97 | A0A804HL97_HUMAN | DNA helicase | ERCC2 | 459 | Annotation score: | ||
A0A804HK75 | A0A804HK75_HUMAN | General transcription and DNA repai... | ERCC2 | 205 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008187 | 47 | G → R in XP-D. Corresponds to variant dbSNP:rs1360631927Ensembl. | 1 | |
Natural variantiVAR_017282 | 76 | T → A in XP-D. | 1 | |
Natural variantiVAR_003622 | 112 | R → H in TTD1 and XP-D. 3 PublicationsCorresponds to variant dbSNP:rs121913020EnsemblClinVar. | 1 | |
Natural variantiVAR_011412 | 199 | I → M. Corresponds to variant dbSNP:rs1799791Ensembl. | 1 | |
Natural variantiVAR_011413 | 201 | H → Y. Corresponds to variant dbSNP:rs1799792EnsemblClinVar. | 1 | |
Natural variantiVAR_008188 | 234 | D → N in XP-D. Corresponds to variant dbSNP:rs1340806384Ensembl. | 1 | |
Natural variantiVAR_008189 | 259 | C → Y in TTD1. 1 PublicationCorresponds to variant dbSNP:rs370454709EnsemblClinVar. | 1 | |
Natural variantiVAR_011414 | 312 | D → N4 PublicationsCorresponds to variant dbSNP:rs1799793EnsemblClinVar. | 1 | |
Natural variantiVAR_003623 | 461 | L → V in XP-D and TTD1. 3 PublicationsCorresponds to variant dbSNP:rs121913016EnsemblClinVar. | 1 | |
Natural variantiVAR_008190 | 482 | Missing in TTD1. 1 Publication | 1 | |
Natural variantiVAR_017283 | 485 | L → P in XP-D; the corresponding mutation in fission yeast causes complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121913025EnsemblClinVar. | 1 | |
Natural variantiVAR_017284 | 487 | R → G in TTD1. | 1 | |
Natural variantiVAR_003624 | 488 – 493 | Missing in TTD1; mild. 1 Publication | 6 | |
Natural variantiVAR_017285 | 511 | R → Q in XP-D. Corresponds to variant dbSNP:rs772572683Ensembl. | 1 | |
Natural variantiVAR_003625 | 541 | S → R in XP-D; mild. 1 PublicationCorresponds to variant dbSNP:rs121913019EnsemblClinVar. | 1 | |
Natural variantiVAR_008191 | 542 | Y → C in XP-D. | 1 | |
Natural variantiVAR_017286 | 582 – 583 | EK → VSE in XP-D. 1 Publication | 2 | |
Natural variantiVAR_017287 | 592 | R → P in TTD1. | 1 | |
Natural variantiVAR_017288 | 594 | A → P in TTD1. | 1 | |
Natural variantiVAR_008192 | 601 | R → L in XP-D. Corresponds to variant dbSNP:rs140522180Ensembl. | 1 | |
Natural variantiVAR_017289 | 601 | R → W in XP-D. Corresponds to variant dbSNP:rs753641926EnsemblClinVar. | 1 | |
Natural variantiVAR_003627 | 602 | G → D in XP-D; combined with features of Cockayne syndrome. Corresponds to variant dbSNP:rs771824813Ensembl. | 1 | |
Natural variantiVAR_011415 | 616 | R → C1 Publication | 1 | |
Natural variantiVAR_003626 | 616 | R → P in XP-D and TTD1. 1 PublicationCorresponds to variant dbSNP:rs376556895EnsemblClinVar. | 1 | |
Natural variantiVAR_008193 | 616 | R → W in XP-D and COFS2. 1 PublicationCorresponds to variant dbSNP:rs121913024EnsemblClinVar. | 1 | |
Natural variantiVAR_008194 | 658 | R → C in TTD1. 2 PublicationsCorresponds to variant dbSNP:rs121913021EnsemblClinVar. | 1 | |
Natural variantiVAR_017290 | 658 | R → G in TTD1. | 1 | |
Natural variantiVAR_008195 | 658 | R → H in TTD1. Corresponds to variant dbSNP:rs762141272Ensembl. | 1 | |
Natural variantiVAR_017291 | 663 | C → R in TTD1. Corresponds to variant dbSNP:rs770367713Ensembl. | 1 | |
Natural variantiVAR_017292 | 666 | R → W in XP-D. Corresponds to variant dbSNP:rs752510317Ensembl. | 1 | |
Natural variantiVAR_008196 | 673 | D → G in TTD1. 1 Publication | 1 | |
Natural variantiVAR_003628 | 675 | G → R in XP-D/CS; severe form. 1 Publication | 1 | |
Natural variantiVAR_017293 | 681 | D → N in XP-D and COFS2. 1 PublicationCorresponds to variant dbSNP:rs121913023EnsemblClinVar. | 1 | |
Natural variantiVAR_008197 | 683 | R → Q in XP-D. Corresponds to variant dbSNP:rs758439420EnsemblClinVar. | 1 | |
Natural variantiVAR_008198 | 683 | R → W in XP-D; vitamin D-mediated activation of CYP24A1 is impaired in patient fibroblasts due to altered TFIIH-dependent phosphorylation of ETS1, subsequent impaired cooperation of ETS1 with VDR and altered VDR recruitment to CYP24A1 promoter. 1 PublicationCorresponds to variant dbSNP:rs41556519EnsemblClinVar. | 1 | |
Natural variantiVAR_008199 | 713 | G → R in TTD1. 2 PublicationsCorresponds to variant dbSNP:rs121913022EnsemblClinVar. | 1 | |
Natural variantiVAR_003629 | 716 – 730 | Missing in XP-D and TTD1. 1 PublicationAdd BLAST | 15 | |
Natural variantiVAR_003630 | 722 | R → W in TTD1. 2 PublicationsCorresponds to variant dbSNP:rs121913026EnsemblClinVar. | 1 | |
Natural variantiVAR_003631 | 725 | A → P in TTD1. 1 PublicationCorresponds to variant dbSNP:rs121913018EnsemblClinVar. | 1 | |
Natural variantiVAR_011416 | 751 | K → Q May be associated with increased susceptibility to DNA damage. 6 PublicationsCorresponds to variant dbSNP:rs13181EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_043132 | 1 – 24 | Missing in isoform 2. 1 PublicationAdd BLAST | 24 | |
Alternative sequenceiVSP_043133 | 414 – 429 | FTIII…TPTIA → QAQHCGSSRNQKRSHP in isoform 2. 1 PublicationAdd BLAST | 16 | |
Alternative sequenceiVSP_043134 | 430 – 760 | Missing in isoform 2. 1 PublicationAdd BLAST | 331 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X52221 mRNA Translation: CAA36463.1 X52222 mRNA Translation: CAA36464.1 L47234 Genomic DNA Translation: AAL48323.1 AY092780 Genomic DNA Translation: AAM45142.1 Sequence problems. BT006883 mRNA Translation: AAP35529.1 CH471126 Genomic DNA Translation: EAW57341.1 BC108255 mRNA Translation: AAI08256.1 BC110523 mRNA Translation: AAI10524.1 |
CCDSi | CCDS33049.1 [P18074-1] CCDS46112.1 [P18074-2] |
PIRi | S10888 |
RefSeqi | NP_000391.1, NM_000400.3 [P18074-1] NP_001124339.1, NM_001130867.1 [P18074-2] |
Genome annotation databases
Ensembli | ENST00000391945; ENSP00000375809; ENSG00000104884 ENST00000485403; ENSP00000431229; ENSG00000104884 [P18074-2] ENST00000682414; ENSP00000507019; ENSG00000104884 |
GeneIDi | 2068 |
KEGGi | hsa:2068 |
MANE-Selecti | ENST00000391945.10; ENSP00000375809.4; NM_000400.4; NP_000391.1 |
UCSCi | uc002pbj.3, human [P18074-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X52221 mRNA Translation: CAA36463.1 X52222 mRNA Translation: CAA36464.1 L47234 Genomic DNA Translation: AAL48323.1 AY092780 Genomic DNA Translation: AAM45142.1 Sequence problems. BT006883 mRNA Translation: AAP35529.1 CH471126 Genomic DNA Translation: EAW57341.1 BC108255 mRNA Translation: AAI08256.1 BC110523 mRNA Translation: AAI10524.1 |
CCDSi | CCDS33049.1 [P18074-1] CCDS46112.1 [P18074-2] |
PIRi | S10888 |
RefSeqi | NP_000391.1, NM_000400.3 [P18074-1] NP_001124339.1, NM_001130867.1 [P18074-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5IVW | electron microscopy | 10.00 | W | 1-760 | [»] | |
5IY6 | electron microscopy | 7.20 | W | 1-760 | [»] | |
5IY7 | electron microscopy | 8.60 | W | 1-760 | [»] | |
5IY8 | electron microscopy | 7.90 | W | 1-760 | [»] | |
5IY9 | electron microscopy | 6.30 | W | 1-760 | [»] | |
5OF4 | electron microscopy | 4.40 | B | 1-760 | [»] | |
6NMI | electron microscopy | 3.70 | B | 1-760 | [»] | |
6O9L | electron microscopy | 7.20 | 0 | 1-760 | [»] | |
6O9M | electron microscopy | 4.40 | 0 | 1-760 | [»] | |
6RO4 | electron microscopy | 3.50 | B | 1-760 | [»] | |
6TUN | X-ray | 2.07 | A/B | 245-439 | [»] | |
7AD8 | electron microscopy | 3.50 | B | 1-760 | [»] | |
7EGB | electron microscopy | 3.30 | 7 | 1-760 | [»] | |
7EGC | electron microscopy | 3.90 | 7 | 1-760 | [»] | |
7ENA | electron microscopy | 4.07 | 7 | 1-760 | [»] | |
7ENC | electron microscopy | 4.13 | 7 | 1-760 | [»] | |
7LBM | electron microscopy | 4.80 | X | 1-760 | [»] | |
7NVR | electron microscopy | 4.50 | 0 | 1-760 | [»] | |
7NVW | electron microscopy | 4.30 | 0 | 1-760 | [»] | |
7NVX | electron microscopy | 3.90 | 0 | 1-760 | [»] | |
7NVY | electron microscopy | 7.30 | 0 | 1-760 | [»] | |
7NVZ | electron microscopy | 7.20 | 0 | 1-760 | [»] | |
7NW0 | electron microscopy | 6.60 | 0 | 1-760 | [»] | |
SMRi | P18074 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108380, 60 interactors |
CORUMi | P18074 |
DIPi | DIP-644N |
IntActi | P18074, 51 interactors |
MINTi | P18074 |
STRINGi | 9606.ENSP00000375809 |
Chemistry databases
ChEMBLi | CHEMBL4105743 |
PTM databases
iPTMneti | P18074 |
PhosphoSitePlusi | P18074 |
Genetic variation databases
BioMutai | ERCC2 |
DMDMi | 119540 |
Proteomic databases
EPDi | P18074 |
jPOSTi | P18074 |
MassIVEi | P18074 |
MaxQBi | P18074 |
PaxDbi | P18074 |
PeptideAtlasi | P18074 |
PRIDEi | P18074 |
ProteomicsDBi | 53542 [P18074-1] 53543 [P18074-2] |
Protocols and materials databases
Antibodypediai | 17895, 278 antibodies from 37 providers |
CPTCi | P18074, 1 antibody |
DNASUi | 2068 |
Genome annotation databases
Ensembli | ENST00000391945; ENSP00000375809; ENSG00000104884 ENST00000485403; ENSP00000431229; ENSG00000104884 [P18074-2] ENST00000682414; ENSP00000507019; ENSG00000104884 |
GeneIDi | 2068 |
KEGGi | hsa:2068 |
MANE-Selecti | ENST00000391945.10; ENSP00000375809.4; NM_000400.4; NP_000391.1 |
UCSCi | uc002pbj.3, human [P18074-1] |
Organism-specific databases
CTDi | 2068 |
DisGeNETi | 2068 |
GeneCardsi | ERCC2 |
GeneReviewsi | ERCC2 |
HGNCi | HGNC:3434, ERCC2 |
HPAi | ENSG00000104884, Low tissue specificity |
MalaCardsi | ERCC2 |
MIMi | 126340, gene 278730, phenotype 601675, phenotype 610756, phenotype |
neXtProti | NX_P18074 |
OpenTargetsi | ENSG00000104884 |
Orphaneti | 1466, COFS syndrome 33364, Trichothiodystrophy 910, Xeroderma pigmentosum 220295, Xeroderma pigmentosum-Cockayne syndrome complex |
PharmGKBi | PA27848 |
VEuPathDBi | HostDB:ENSG00000104884 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1131, Eukaryota |
GeneTreei | ENSGT00950000182970 |
HOGENOMi | CLU_045429_0_0_1 |
InParanoidi | P18074 |
OMAi | PYFTARR |
OrthoDBi | 186062at2759 |
PhylomeDBi | P18074 |
TreeFami | TF101232 |
Enzyme and pathway databases
BRENDAi | 3.6.4.12, 2681 |
PathwayCommonsi | P18074 |
Reactomei | R-HSA-112382, Formation of RNA Pol II elongation complex R-HSA-113418, Formation of the Early Elongation Complex R-HSA-167152, Formation of HIV elongation complex in the absence of HIV Tat R-HSA-167158, Formation of the HIV-1 Early Elongation Complex R-HSA-167160, RNA Pol II CTD phosphorylation and interaction with CE during HIV infection R-HSA-167161, HIV Transcription Initiation R-HSA-167162, RNA Polymerase II HIV Promoter Escape R-HSA-167172, Transcription of the HIV genome R-HSA-167200, Formation of HIV-1 elongation complex containing HIV-1 Tat R-HSA-167246, Tat-mediated elongation of the HIV-1 transcript R-HSA-2564830, Cytosolic iron-sulfur cluster assembly R-HSA-427413, NoRC negatively regulates rRNA expression R-HSA-5696395, Formation of Incision Complex in GG-NER R-HSA-5696400, Dual Incision in GG-NER R-HSA-674695, RNA Polymerase II Pre-transcription Events R-HSA-6781823, Formation of TC-NER Pre-Incision Complex R-HSA-6781827, Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-6782135, Dual incision in TC-NER R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6796648, TP53 Regulates Transcription of DNA Repair Genes R-HSA-72086, mRNA Capping R-HSA-73762, RNA Polymerase I Transcription Initiation R-HSA-73772, RNA Polymerase I Promoter Escape R-HSA-73776, RNA Polymerase II Promoter Escape R-HSA-73779, RNA Polymerase II Transcription Pre-Initiation And Promoter Opening R-HSA-73863, RNA Polymerase I Transcription Termination R-HSA-75953, RNA Polymerase II Transcription Initiation R-HSA-75955, RNA Polymerase II Transcription Elongation R-HSA-76042, RNA Polymerase II Transcription Initiation And Promoter Clearance R-HSA-77075, RNA Pol II CTD phosphorylation and interaction with CE |
SignaLinki | P18074 |
SIGNORi | P18074 |
Miscellaneous databases
BioGRID-ORCSi | 2068, 724 hits in 1060 CRISPR screens |
ChiTaRSi | ERCC2, human |
GeneWikii | ERCC2 |
GenomeRNAii | 2068 |
Pharosi | P18074, Tbio |
PROi | PR:P18074 |
RNActi | P18074, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000104884, Expressed in stromal cell of endometrium and 146 other tissues |
ExpressionAtlasi | P18074, baseline and differential |
Genevisiblei | P18074, HS |
Family and domain databases
Gene3Di | 3.40.50.300, 2 hits |
InterProi | View protein in InterPro IPR006555, ATP-dep_Helicase_C IPR010614, DEAD_2 IPR045028, DinG/Rad3-like IPR002464, DNA/RNA_helicase_DEAH_CS IPR010643, HBB IPR014013, Helic_SF1/SF2_ATP-bd_DinG/Rad3 IPR006554, Helicase-like_DEXD_c2 IPR027417, P-loop_NTPase IPR013020, Rad3/Chl1-like IPR001945, RAD3/XPD |
PANTHERi | PTHR11472, PTHR11472, 1 hit PTHR11472:SF1, PTHR11472:SF1, 1 hit |
Pfami | View protein in Pfam PF06733, DEAD_2, 1 hit PF06777, HBB, 1 hit PF13307, Helicase_C_2, 1 hit |
PRINTSi | PR00852, XRODRMPGMNTD |
SMARTi | View protein in SMART SM00488, DEXDc2, 1 hit SM00491, HELICc2, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR00604, rad3, 1 hit |
PROSITEi | View protein in PROSITE PS00690, DEAH_ATP_HELICASE, 1 hit PS51193, HELICASE_ATP_BIND_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ERCC2_HUMAN | |
Accessioni | P18074Primary (citable) accession number: P18074 Secondary accession number(s): Q2TB78 Q8N721 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1990 |
Last sequence update: | November 1, 1990 | |
Last modified: | February 23, 2022 | |
This is version 242 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families