Overview
| Uniprot ID | P18074 |
|---|
| Protein Name | General transcription and DNA repair factor IIH helicase subunit XPD |
|---|
| Gene Name | ERCC2 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 583 |
ETSVALEKYQEACEN |
Function
ATP-dependent 5'-3' DNA helicase (PubMed:31253769, PubMed:8413672, PubMed:9771713). Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, not absolutely essential for minimal transcription in vitro (PubMed:10024882, PubMed:17466626, PubMed:9771713). Required for transcription-coupled nucleotide excision repair (NER) of damaged DNA; recognizes damaged bases (PubMed:17466626, PubMed:23352696, PubMed:9771713). Sequestered in chromatin on UV-damaged DNA (PubMed:23352696). When complexed to CDK-activating kinase (CAK), involved in 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. Involved in DNA lesion verification (PubMed:31253769). 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. The structure of the TFIIH transcription complex differs from the NER-TFIIH complex; large movements by XPD/ERCC2 and XPB/ERCC3 are stabilized by XPA which allow this subunit to contact ssDNA (PubMed:31253769, PubMed:33902107). 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
Protein Sequence
10
MKLNVDGLLV
20
YFPYDYIYPE
30
QFSYMRELKR
40
TLDAKGHGVL
50
EMPSGTGKTV
60
SLLALIMAYQ
70
RAYPLEVTKL
80
IYCSRTVPEI
90
EKVIEELRKL
100
LNFYEKQEGE
110
KLPFLGLALS
120
SRKNLCIHPE
130
VTPLRFGKDV
140
DGKCHSLTAS
150
YVRAQYQHDT
160
SLPHCRFYEE
170
FDAHGREVPL
180
PAGIYNLDDL
190
KALGRRQGWC
200
PYFLARYSIL
210
HANVVVYSYH
220
YLLDPKIADL
230
VSKELARKAV
240
VVFDEAHNID
250
NVCIDSMSVN
260
LTRRTLDRCQ
270
GNLETLQKTV
280
LRIKETDEQR
290
LRDEYRRLVE
300
GLREASAARE
310
TDAHLANPVL
320
PDEVLQEAVP
330
GSIRTAEHFL
340
GFLRRLLEYV
350
KWRLRVQHVV
360
QESPPAFLSG
370
LAQRVCIQRK
380
PLRFCAERLR
390
SLLHTLEITD
400
LADFSPLTLL
410
ANFATLVSTY
420
AKGFTIIIEP
430
FDDRTPTIAN
440
PILHFSCMDA
450
SLAIKPVFER
460
FQSVIITSGT
470
LSPLDIYPKI
480
LDFHPVTMAT
490
FTMTLARVCL
500
CPMIIGRGND
510
QVAISSKFET
520
REDIAVIRNY
530
GNLLLEMSAV
540
VPDGIVAFFT
550
SYQYMESTVA
560
SWYEQGILEN
570
IQRNKLLFIE
580
TQDGAETSVA
590
LEKYQEACEN
600
GRGAILLSVA
610
RGKVSEGIDF
620
VHHYGRAVIM
630
FGVPYVYTQS
640
RILKARLEYL
650
RDQFQIREND
660
FLTFDAMRHA
670
AQCVGRAIRG
680
KTDYGLMVFA
690
DKRFARGDKR
700
GKLPRWIQEH
710
LTDANLNLTV
720
DEGVQVAKYF
730
LRQMAQPFHR
740
EDQLGLSLLS
750
LEQLESEETL
760
KRIEQIAQQL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0070516 |
CAK-ERCC2 complex |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0071817 |
MMXD complex |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0005819 |
spindle |
| Cellular Component |
GO:0005669 |
transcription factor TFIID complex |
| Cellular Component |
GO:0000439 |
transcription factor TFIIH core complex |
| Cellular Component |
GO:0005675 |
transcription factor TFIIH holo complex |
| Molecular Function |
GO:0051539 |
4 iron, 4 sulfur cluster binding |
| Molecular Function |
GO:0043139 |
5'-3' DNA helicase activity |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0016887 |
ATP hydrolysis activity |
| Molecular Function |
GO:0003684 |
damaged DNA binding |
| Molecular Function |
GO:0003678 |
DNA helicase activity |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0030674 |
protein-macromolecule adaptor activity |
| Biological Process |
GO:0006915 |
apoptotic process |
| Biological Process |
GO:0007059 |
chromosome segregation |
| Biological Process |
GO:0035315 |
hair cell differentiation |
| Biological Process |
GO:0006289 |
nucleotide-excision repair |
| Biological Process |
GO:0045951 |
positive regulation of mitotic recombination |
| Biological Process |
GO:1901990 |
regulation of mitotic cell cycle phase transition |
| Biological Process |
GO:0006357 |
regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0006979 |
response to oxidative stress |
| Biological Process |
GO:0006366 |
transcription by RNA polymerase II |
| Biological Process |
GO:0006367 |
transcription initiation at RNA polymerase II promoter |
| Biological Process |
GO:0006283 |
transcription-coupled nucleotide-excision repair |
Reference
[1] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.