DNA damage repair proteins: XPD

DNA damage repair protein page: XPD (Rad3)

The XPD protein is part of the nucleotide-excision repair mechanism. It is a 5' to 3' helicase, and also has a role as a subunit of the basal transtription factor BT2/TIFIIH (according to Swissprot). (Obviously, a more detailed paragraph is needed here, but I don't want to violate someone's copyright.)

(Last Update: 04/20/00 )

protein sequences (names from Swissprot or NCBI's non-redundant data base):

(need script to generate links---too much work by hand)
gi|119540|sp|P18074|XPD_HUMAN
gi|2495146|sp|O08811|XPD_MOUSE
gi|2495145|sp|Q60452|XPD_CRIGR
gi|296645|emb|CAA36463|
gi|2134009|pir||I51720
gi|1709995|sp|P26659|RA15_SCHPO
gi|5022|emb|CAA43022|
gi|101069|pir||S22660
gi|4928442|gb|AAD33587.1|AF132140_1
gi|6321019|ref|NP_011098.1|RAD3|

Question: how far down the list of possible homologs should I go? For example, is DING_ECOLI a probable homolog? It is named in Swissprot as "probable ATP-dependent helicase DING", and has as synonym "DNA-damage-inducible protein G". What about YOAA_ECOLI and YOAA_HAEIN? They are also ATP-dependent helicases in the DING subfamily.

structures in PDB:

None--see predictions below.

multiple alignment (using SAM-T99 method)

pretty-printed (human-readable)
gzipped A2M format (machine-readable)

predicted secondary structure

CASP format
FASTA format
RDB format

labeled domains from Swissprot

still to fill in.

Potential bacterial matches

(Note: need to make sequence links below hot.)

All the bacterial matches are fairly weak helicase matches. They are unlikely to serve the same function as XPD.

Organism Score file Most likely homolog E-value Alignment

Deinococcus radiodurans drad.dist gi|6459005|gb|AAF10831.1|AE001973_4 2.5e-06

Microplasma genitalium geni.dist MG073 :excinuclease ABC subunit B (uvrB) E.coli 3.6e-06

Organism	Score file	Most likely homolog	E-value	Alignment
Deinococcus radiodurans	drad.dist	gi\|6459005\|gb\|AAF10831.1\|AE001973_4	2.5e-06
Microplasma genitalium	geni.dist	MG073 :excinuclease ABC subunit B (uvrB) E.coli	3.6e-06

Potential Archea matches

(Note: need to make sequence links below hot.)

Organism Score file Most likely homolog Alignment

Aeropyrum pernix aero.dist
gi|5103961|dbj|BAA79277.1|

Archaeoglobus fulgidus aful.dist
gi|2650581 (N-terminus only)

Methanobacterium thermoautotrophicum thermo.dist
gi|2622454 (MTH1347)

Methanococcus jannaschii jann.dist gi|1591610|gb|AAB98945.1| (MJ0942)

Pyrococcus abyssi pabyssi.dist gi|5458763|emb|CAB50250.1|

Pyrococcus horikoshii pyrohori.dist gi|3257105|gnl|PID|d1030731

Organism	Score file	Most likely homolog
Aeropyrum pernix	aero.dist	gi\|5103961\|dbj\|BAA79277.1\|
Archaeoglobus fulgidus	aful.dist	gi\|2650581 (N-terminus only)
Methanobacterium thermoautotrophicum	thermo.dist	gi\|2622454 (MTH1347)
Methanococcus jannaschii	jann.dist	gi\|1591610\|gb\|AAB98945.1\| (MJ0942)
Pyrococcus abyssi	pabyssi.dist	gi\|5458763\|emb\|CAB50250.1\|
Pyrococcus horikoshii	pyrohori.dist	gi\|3257105\|gnl\|PID\|d1030731

Mutation table from Summary of Mutations in UV-Sensitive Disorders

**Mutations in human XPD gene repair**
(from Cleaver et al. 1999)
Note: need to fill in full table and resort by AA site, to cluster similar mutations.
nucleotide change	aa/splice allele1,allele2	comments	references
xeroderma pigmentosum
	L461V,del716-730 (null?)
	G47R
	R683W
	Y542C
	R616P (null?)
	R683W
	R616P (null?)
	R683W
	R616W (null?)
	R683Q
	Q726ter
	R601L
	D234N
	R683W
	del36->61 (null?)
	R683W
	R616P
	R683W
	L461V, del716->730(null?)
	197fs/ter (null)
	S541R
XP-CS combined
	G675R
	669fs->708ter
	G602D
trichothiodystropy
	R112H
	del488->493,del460->493 (null?)
	730fs->744ter
	del488->493,del460->493 (null?)
	R112H
	R112H
	del482 (null?)
	D673G
	R722W
	L461V, del716->730(null?)
	R112H
	del121->159 (exon6) (null?)
	C259Y
	R722W
	L461V, del716->730(null?)
	R722W
	L461V, del716->730(null?)
	R658H
	R658H
	R658C, K751Q
	G713R
	L461V, del716->730(null?)
	A725P

How should references be handled? MEDLINE pointers?

Predicted alignments to PDB files

The strongest prediction is for 8ohm, an RNA helicase genotype 1B hepatitis C virus. Next strongest is for 1pjr (PCRA), a DNA helicase. Both helicases have fairly similar structure (Dali score 10.3), but the predictions have not yet been checked for consistency. Detailed alignments should probably be made both from the t99 model and from the 1pjr fssp alignment, but have not been done yet.

Predicted tertiary structure.

None yet---should there be links to sites like Swiss-Prot, or should we just do our own modeling?

What other information should be included in this?

This is a draft page with information about DNA-repair proteins. There is a lot more work to be done on these pages.


(icon needed) UCSC Center for Biomolecular Engineering	UCSC Engineering	(icon needed) DNA repair main page

The Bioinformatics group at UCSC is supported in part by NSF grant BIR-9408579, NSF grant MIP-9488395, DOE grant DE-FG03-95ER62112, LACOR grant 4158U0015-3A-01, and by GANN and NSF graduate fellowships.

The DNA-repair pages are not currently funded, so development of them is very slow.

Questions about page content should be directed to

Kevin Karplus
Computer Engineering
University of California, Santa Cruz
Santa Cruz, CA 95064
USA
karplus@soe.ucsc.edu
(831) 459-4250