Q01831 (XPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA repair protein complementing XP-C cells

Alternative name(s):
Xeroderma pigmentosum group C-complementing protein
p125

Gene names

Name:	XPC
Synonyms:	XPCC

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	940 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity. Ref.12 Ref.13 Ref.14 Ref.16 Ref.18 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1. Ref.12 Ref.13 Ref.14 Ref.16 Ref.18 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40
Subunit structure	Component of the XPC complex composed of XPC, RAD23B and CETN2. Interacts with RAD23A; the interaction is suggesting the existence of a functional equivalent variant XPC complex. Interacts with TDG; the interaction is demonstrated using the XPC:RAD23B dimer. Interacts with SMUG1; the interaction is demonstrated using the XPC:RAD23B dimer. Interacts with DDB2. Interacts with CCNH, GTF2H1 and ERCC3. Ref.10 Ref.11 Ref.13 Ref.15 Ref.17 Ref.19 Ref.20 Ref.21 Ref.40
Subcellular location	Nucleus. Cytoplasm. Note: Omnipresent in the nucleus and consistently associates with and dissociates from DNA in the absence of DNA damage. Continuously shuttles between the cytoplasm and the nucleus, which is impeded by the presence of NER lesions. Ref.10 Ref.15 Ref.33
Post-translational modification	Ubiquitinated upon UV irradiation; the ubiquitination requires the UV-DDB complex, appears to be reversible and does not serve as a signal for degradation. Ref.20
Involvement in disease	Xeroderma pigmentosum complementation group C (XP-C) [MIM:278720]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.31 Ref.32 Ref.36 Ref.45 Ref.46
Sequence similarities	Belongs to the XPC family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Xeroderma pigmentosum
Ligand	DNA-binding
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle checkpoint Inferred from mutant phenotype PubMed 17088560. Source: UniProtKB intra-S DNA damage checkpoint Inferred from electronic annotation. Source: Compara nucleotide-excision repair, DNA damage recognition Inferred from direct assay Ref.14Ref.37. Source: UniProtKB nucleotide-excision repair, DNA damage removal Traceable author statement. Source: Reactome response to UV-B Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara
Cellular_component	XPC complex Inferred from direct assay Ref.15. Source: UniProtKB cytoplasm Inferred from direct assay Ref.33. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	bubble DNA binding Traceable author statement Ref.37. Source: UniProtKB damaged DNA binding Inferred from direct assay Ref.14Ref.16. Source: UniProtKB loop DNA binding Traceable author statement Ref.37. Source: UniProtKB single-stranded DNA binding Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BGLF4	P13288	9	EBI-372610,EBI-1630636	From a different organism.
CETN2	P41208	3	EBI-372610,EBI-1789926
ERCC3	P19447	2	EBI-372610,EBI-1183307
GTF2H1	P32780	2	EBI-372610,EBI-715539
RAD23B	P54727	5	EBI-372610,EBI-954531

Alternative products

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

Isoform 1 (identifier: Q01831-1)

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: Q01831-2)

The sequence of this isoform differs from the canonical sequence as follows:
     136-172: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1

Chain

2 – 940

939

DNA repair protein complementing XP-C cells

PRO_0000218293

Regions

Region

496 – 734

239

Interaction with RAD23B

Region

607 – 766

160

Minimal sensor domain involved in damage recognition

Region

607 – 741

135

DNA-binding; preference for heteroduplex DNA

Region

767 – 831

65

DNA-binding; preference for single stranded DNA; required for formation of stable nucleoprotein complex

Region

816 – 940

125

Interaction with ERCC2 and GTF2H1

Region

847 – 866

20

Interaction with CETN2

Motif

390 – 395

6

Nuclear localization signal Potential

Compositional bias

30 – 177

148

Glu-rich (acidic)

Compositional bias

30 – 34

5

Poly-Glu

Compositional bias

124 – 130

7

Poly-Glu

Compositional bias

359 – 395

37

Lys-rich (basic)

Compositional bias

408 – 431

24

Arg/Lys-rich (basic)

Compositional bias

432 – 461

30

Asp/Glu-rich (acidic)

Compositional bias

466 – 493

28

Arg/Lys-rich (basic)

Compositional bias

501 – 507

7

Poly-Ser

Amino acid modifications

Modified residue

94

1

Phosphoserine Ref.22 Ref.26 Ref.29 Ref.30

Modified residue

129

1

Phosphoserine Ref.22 Ref.29

Modified residue

169

1

Phosphothreonine Ref.26

Modified residue

397

1

Phosphoserine By similarity

Modified residue

399

1

Phosphoserine By similarity

Modified residue

876

1

Phosphothreonine Ref.30

Modified residue

883

1

Phosphoserine Ref.26 Ref.29 Ref.30

Modified residue

884

1

Phosphoserine Ref.26 Ref.29 Ref.30

Modified residue

891

1

Phosphoserine Ref.26

Natural variations

Alternative sequence

136 – 172

37

Missing in isoform 2.

VSP_046344

Natural variant

16

1

L → V. Ref.3
Corresponds to variant rs1870134 [ dbSNP | Ensembl ].

VAR_018894

Natural variant

48

1

L → F. Ref.3
Corresponds to variant rs3731062 [ dbSNP | Ensembl ].

VAR_018895

Natural variant

86

1

K → R. Ref.3
Corresponds to variant rs3731063 [ dbSNP | Ensembl ].

VAR_018896

Natural variant

287

1

F → C.
Corresponds to variant rs35629274 [ dbSNP | Ensembl ].

VAR_057475

Natural variant

314

1

R → Q. Ref.3
Corresponds to variant rs3731126 [ dbSNP | Ensembl ].

VAR_018897

Natural variant

334

1

P → H in XP-C; severe. Ref.45

VAR_005846

Natural variant

492

1

R → H. Ref.3
Corresponds to variant rs2227999 [ dbSNP | Ensembl ].

VAR_018898

Natural variant

499

1

A → V. Ref.1 Ref.2 Ref.3
Corresponds to variant rs2228000 [ dbSNP | Ensembl ].

VAR_018899

Natural variant

511

1

K → Q.
Corresponds to variant rs6413541 [ dbSNP | Ensembl ].

VAR_059963

Natural variant

513

1

M → I. Ref.3

VAR_018900

Natural variant

514

1

C → S.
Corresponds to variant rs3731130 [ dbSNP | Ensembl ].

VAR_057476

Natural variant

632

1

Q → E. Ref.3
Corresponds to variant rs3731139 [ dbSNP | Ensembl ].

VAR_018901

Natural variant

671

1

R → H. Ref.3
Corresponds to variant rs3731140 [ dbSNP | Ensembl ].

VAR_018902

Natural variant

689

1

T → M. Ref.3
Corresponds to variant rs3731152 [ dbSNP | Ensembl ].

VAR_018903

Natural variant

690

1

W → S in XP-C; diminishes repair activity and impairs DNA binding. Ref.31 Ref.32 Ref.36 Ref.46

VAR_064039

Natural variant

697

1

V → VV in XP-C; mild. Ref.45

VAR_005847

Natural variant

928

1

K → Q. Ref.3
Corresponds to variant rs3731177 [ dbSNP | Ensembl ].

VAR_018904

Natural variant

939

1

Q → K. Ref.1 Ref.2 Ref.3
Corresponds to variant rs2228001 [ dbSNP | Ensembl ].

VAR_005848

Experimental info

Mutagenesis

531

1

W → A: Slightly diminishes repair activity and sligtly impairs DNA binding. Ref.36

Mutagenesis

542

1

W → A: Slightly diminishes repair activity and sligtly impairs DNA binding. Ref.36

Mutagenesis

733

1

F → A: Diminishes repair activity and impairs DNA binding. Ref.32 Ref.36

Mutagenesis

754

1

N → A: Reduces DNA repair activity; abolishes single stranded DNA binding; reduces binding to homoduplex DNA; reduces localization at DNA damaged foci. Ref.38

Mutagenesis

755

1

E → K: Reduces nuclear mobility and impairs repair activity. Ref.36

Mutagenesis

756

1

F → A: Reduces DNA repair activity; abolishes single stranded DNA binding; reduces binding to homoduplex DNA; reduces localization at DNA damaged foci. Ref.38

Mutagenesis

797

1

F → A: Reduces DNA repair activity; abolishes single stranded DNA binding; reduces binding to homoduplex DNA; reduces localization at DNA damaged foci; decreases recruitment of TFIIH complex to lesion sites. Ref.38

Mutagenesis

799

1

F → A: Reduces DNA repair activity; abolishes single stranded DNA binding; reduces binding to homoduplex DNA; greatly reduces localization at DNA damaged foci; decreases recruitment of TFIIH complex to lesion sites. Ref.38

Mutagenesis

848

1

W → A: Reduces NER activity and abolishes interaction with CETN2; when associated with A-851 and A-855. Ref.21

Mutagenesis

851

1

L → A: Reduces NER activity and abolishes interaction with CETN2; when associated with A-848 and A-855. Ref.21

Mutagenesis

855

1

L → A: Reduces NER activity and abolishes interaction with CETN2; when associated with A-848 and A-851. Ref.21

Sequence conflict

135

1

E → Q in BAG58555. Ref.4

Sequence conflict

489

1

G → E in BAG58555. Ref.4

Secondary structure

1

.

.

.

940

Helix Strand Turn

Details...

Helix

848 – 861

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 4. Checksum: 2F8C80D43FAA1256	FASTA	940	105,953
	10 20 30 40 50 60 MARKRAAGGE PRGRELRSQK SKAKSKARRE EEEEDAFEDE KPPKKSLLSK VSQGKRKRGC 70 80 90 100 110 120 SHPGGSADGP AKKKVAKVTV KSENLKVIKD EALSDGDDLR DFPSDLKKAH HLKRGATMNE 130 140 150 160 170 180 DSNEEEEESE NDWEEVEELS EPVLGDVRES TAFSRSLLPV KPVEIEIETP EQAKTRERSE 190 200 210 220 230 240 KIKLEFETYL RRAMKRFNKG VHEDTHKVHL LCLLANGFYR NNICSQPDLH AIGLSIIPAR 250 260 270 280 290 300 FTRVLPRDVD TYYLSNLVKW FIGTFTVNAE LSASEQDNLQ TTLERRFAIY SARDDEELVH 310 320 330 340 350 360 IFLLILRALQ LLTRLVLSLQ PIPLKSATAK GKKPSKERLT ADPGGSSETS SQVLENHTKP 370 380 390 400 410 420 KTSKGTKQEE TFAKGTCRPS AKGKRNKGGR KKRSKPSSSE EDEGPGDKQE KATQRRPHGR 430 440 450 460 470 480 ERRVASRVSY KEESGSDEAG SGSDFELSSG EASDPSDEDS EPGPPKQRKA PAPQRTKAGS 490 500 510 520 530 540 KSASRTHRGS HRKDPSLPAA SSSSSSSKRG KKMCSDGEKA EKRSIAGIDQ WLEVFCEQEE 550 560 570 580 590 600 KWVCVDCVHG VVGQPLTCYK YATKPMTYVV GIDSDGWVRD VTQRYDPVWM TVTRKCRVDA 610 620 630 640 650 660 EWWAETLRPY QSPFMDREKK EDLEFQAKHM DQPLPTAIGL YKNHPLYALK RHLLKYEAIY 670 680 690 700 710 720 PETAAILGYC RGEAVYSRDC VHTLHSRDTW LKKARVVRLG EVPYKMVKGF SNRARKARLA 730 740 750 760 770 780 EPQLREENDL GLFGYWQTEE YQPPVAVDGK VPRNEFGNVY LFLPSMMPIG CVQLNLPNLH 790 800 810 820 830 840 RVARKLDIDC VQAITGFDFH GGYSHPVTDG YIVCEEFKDV LLTAWENEQA VIERKEKEKK 850 860 870 880 890 900 EKRALGNWKL LAKGLLIRER LKRRYGPKSE AAAPHTDAGG GLSSDEEEGT SSQAEAARIL 910 920 930 940 AASWPQNRED EEKQKLKGGP KKTKREKKAA ASHLFPFEQL
	Isoform 2 [UniParc]. Checksum: AF2F96DDCC4DB78E	FASTA	903	101,847
	10 20 30 40 50 60 MARKRAAGGE PRGRELRSQK SKAKSKARRE EEEEDAFEDE KPPKKSLLSK VSQGKRKRGC 70 80 90 100 110 120 SHPGGSADGP AKKKVAKVTV KSENLKVIKD EALSDGDDLR DFPSDLKKAH HLKRGATMNE 130 140 150 160 170 180 DSNEEEEESE NDWEEAKTRE RSEKIKLEFE TYLRRAMKRF NKGVHEDTHK VHLLCLLANG 190 200 210 220 230 240 FYRNNICSQP DLHAIGLSII PARFTRVLPR DVDTYYLSNL VKWFIGTFTV NAELSASEQD 250 260 270 280 290 300 NLQTTLERRF AIYSARDDEE LVHIFLLILR ALQLLTRLVL SLQPIPLKSA TAKGKKPSKE 310 320 330 340 350 360 RLTADPGGSS ETSSQVLENH TKPKTSKGTK QEETFAKGTC RPSAKGKRNK GGRKKRSKPS 370 380 390 400 410 420 SSEEDEGPGD KQEKATQRRP HGRERRVASR VSYKEESGSD EAGSGSDFEL SSGEASDPSD 430 440 450 460 470 480 EDSEPGPPKQ RKAPAPQRTK AGSKSASRTH RGSHRKDPSL PAASSSSSSS KRGKKMCSDG 490 500 510 520 530 540 EKAEKRSIAG IDQWLEVFCE QEEKWVCVDC VHGVVGQPLT CYKYATKPMT YVVGIDSDGW 550 560 570 580 590 600 VRDVTQRYDP VWMTVTRKCR VDAEWWAETL RPYQSPFMDR EKKEDLEFQA KHMDQPLPTA 610 620 630 640 650 660 IGLYKNHPLY ALKRHLLKYE AIYPETAAIL GYCRGEAVYS RDCVHTLHSR DTWLKKARVV 670 680 690 700 710 720 RLGEVPYKMV KGFSNRARKA RLAEPQLREE NDLGLFGYWQ TEEYQPPVAV DGKVPRNEFG 730 740 750 760 770 780 NVYLFLPSMM PIGCVQLNLP NLHRVARKLD IDCVQAITGF DFHGGYSHPV TDGYIVCEEF 790 800 810 820 830 840 KDVLLTAWEN EQAVIERKEK EKKEKRALGN WKLLAKGLLI RERLKRRYGP KSEAAAPHTD 850 860 870 880 890 900 AGGGLSSDEE EGTSSQAEAA RILAASWPQN REDEEKQKLK GGPKKTKREK KAAASHLFPF EQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification and cloning of a nucleotide excision repair complex involving the Xeroderma pigmentosum group C protein and a human homologue of yeast RAD23." Masutani C., Sugasawa K., Yanagisawa J., Sonoyama T., Ui M., Enomoto T., Takio K., Tanaka K., van der Spek P.J., Bootsma D., Hoeijmakers J.H.J., Hanaoka F. EMBO J. 13:1831-1843(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 2-55, VARIANTS VAL-499 AND LYS-939.
[2]	"Splicing abnormalities in the xeroderma pigmentosum group C (XPC) gene." Khan S.G., Schneider T.D., Kraemer K.H. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-499 AND LYS-939.
[3]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-16; PHE-48; ARG-86; GLN-314; HIS-492; VAL-499; ILE-513; GLU-632; HIS-671; MET-689; GLN-928 AND LYS-939.
[4]	"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 2). Tissue: Hippocampus.
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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 1). Tissue: Testis.
[7]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 69-940 (ISOFORM 1). Tissue: Liver.
[8]	"Expression cloning of a human DNA repair gene involved in Xeroderma pigmentosum group C." Legerski R.J., Peterson C.A. Nature 359:70-73(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 119-940 (ISOFORM 1).
[9]	Erratum Legerski R.J., Peterson C.A. Nature 360:610-610(1992) [PubMed] [Europe PMC] [Abstract]
[10]	"XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes." van der Spek P.J., Eker A., Rademakers S., Visser C., Sugasawa K., Masutani C., Hanaoka F., Bootsma D., Hoeijmakers J.H. Nucleic Acids Res. 24:2551-2559(1996) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, SUBCELLULAR LOCATION.
[11]	"Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity." Sugasawa K., Ng J.M., Masutani C., Maekawa T., Uchida A., van der Spek P.J., Eker A.P., Rademakers S., Visser C., Aboussekhra A., Wood R.D., Hanaoka F., Bootsma D., Hoeijmakers J.H. Mol. Cell. Biol. 17:6924-6931(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAD23A.
[12]	"Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair." Sugasawa K., Ng J.M., Masutani C., Iwai S., van der Spek P.J., Eker A.P., Hanaoka F., Bootsma D., Hoeijmakers J.H. Mol. Cell 2:223-232(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE XPC COMPLEX.
[13]	"The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA." Yokoi M., Masutani C., Maekawa T., Sugasawa K., Ohkuma Y., Hanaoka F. J. Biol. Chem. 275:9870-9875(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH CCNH; GTF2H1 AND ERCC3.
[14]	"Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites." Batty D., Rapic'-Otrin V., Levine A.S., Wood R.D. J. Mol. Biol. 300:275-290(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE XPC COMPLEX.
[15]	"Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair." Araki M., Masutani C., Takemura M., Uchida A., Sugasawa K., Kondoh J., Ohkuma Y., Hanaoka F. J. Biol. Chem. 276:18665-18672(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CETN2 AND RAD23B, SUBCELLULAR LOCATION, CHARACTERIZATION OF THE XPC COMPLEX.
[16]	"A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex." Sugasawa K., Shimizu Y., Iwai S., Hanaoka F. DNA Repair 1:95-107(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE XPC COMPLEX.
[17]	"The carboxy-terminal domain of the XPC protein plays a crucial role in nucleotide excision repair through interactions with transcription factor IIH." Uchida A., Sugasawa K., Masutani C., Dohmae N., Araki M., Yokoi M., Ohkuma Y., Hanaoka F. DNA Repair 1:449-461(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING, INTERACTION WITH RAD23B; ERCC2 AND GTF2H1.
[18]	"DNA bending by the human damage recognition complex XPC-HR23B." Janicijevic A., Sugasawa K., Shimizu Y., Hanaoka F., Wijgers N., Djurica M., Hoeijmakers J.H., Wyman C. DNA Repair 2:325-336(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE XPC COMPLEX.
[19]	"Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase." Shimizu Y., Iwai S., Hanaoka F., Sugasawa K. EMBO J. 22:164-173(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TDG.
[20]	"UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex." Sugasawa K., Okuda Y., Saijo M., Nishi R., Matsuda N., Chu G., Mori T., Iwai S., Tanaka K., Tanaka K., Hanaoka F. Cell 121:387-400(2005) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH DDB2.
[21]	"Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein." Nishi R., Okuda Y., Watanabe E., Mori T., Iwai S., Masutani C., Sugasawa K., Hanaoka F. Mol. Cell. Biol. 25:5664-5674(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CETN2 AND RAD23B, MUTAGENESIS OF TRP-848; LEU-851 AND LEU-855.
[22]	"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-94 AND SER-129, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[23]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Prostate cancer.
[24]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[25]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[26]	"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-94; THR-169; SER-883; SER-884 AND SER-891, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Liver.
[28]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[29]	"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-94; SER-129; SER-883 AND SER-884, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[30]	"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-94; THR-876; SER-883 AND SER-884, MASS SPECTROMETRY.
[31]	"In vivo destabilization and functional defects of the xeroderma pigmentosum C protein caused by a pathogenic missense mutation." Yasuda G., Nishi R., Watanabe E., Mori T., Iwai S., Orioli D., Stefanini M., Hanaoka F., Sugasawa K. Mol. Cell. Biol. 27:6606-6614(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT XP-C SER-690.
[32]	"An aromatic sensor with aversion to damaged strands confers versatility to DNA repair." Maillard O., Solyom S., Naegeli H. PLoS Biol. 5:E79-E79(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT XP-C SER-690, MUTAGENESIS OF PHE-733.
[33]	"Versatile DNA damage detection by the global genome nucleotide excision repair protein XPC." Hoogstraten D., Bergink S., Ng J.M., Verbiest V.H., Luijsterburg M.S., Geverts B., Raams A., Dinant C., Hoeijmakers J.H., Vermeulen W., Houtsmuller A.B. J. Cell Sci. 121:2850-2859(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[34]	Erratum Hoogstraten D., Bergink S., Ng J.M., Verbiest V.H., Luijsterburg M.S., Geverts B., Raams A., Dinant C., Hoeijmakers J.H., Vermeulen W., Houtsmuller A.B. J. Cell Sci. 121:2972-2972(2008)
[35]	Erratum Hoogstraten D., Bergink S., Ng J.M., Verbiest V.H., Luijsterburg M.S., Geverts B., Raams A., Dinant C., Hoeijmakers J.H., Vermeulen W., Houtsmuller A.B. J. Cell Sci. 121:3991-3991(2008)
[36]	"Two-stage dynamic DNA quality check by xeroderma pigmentosum group C protein." Camenisch U., Trautlein D., Clement F.C., Fei J., Leitenstorfer A., Ferrando-May E., Naegeli H. EMBO J. 28:2387-2399(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF VARIANT OF VARIANT XP-C SER-690, MUTAGENESIS OF TRP-531; TRP-542; PHE-733 AND GLU-755.
[37]	"Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning." Sugasawa K., Akagi J., Nishi R., Iwai S., Hanaoka F. Mol. Cell 36:642-653(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE XPC COMPLEX.
[38]	"Dissection of the xeroderma pigmentosum group C protein function by site-directed mutagenesis." Clement F.C., Kaczmarek N., Mathieu N., Tomas M., Leitenstorfer A., Ferrando-May E., Naegeli H. Antioxid. Redox Signal. 14:2479-2490(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASN-754; PHE-756; PHE-797 AND PHE-799.
[39]	"Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct." Neher T.M., Rechkunova N.I., Lavrik O.I., Turchi J.J. Biochemistry 49:669-678(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE XPC COMPLEX.
[40]	"Stimulation of DNA glycosylase activities by XPC Protein Complex: Roles of protein-protein interactions." Shimizu Y., Uchimura Y., Dohmae N., Saitoh H., Hanaoka F., Sugasawa K. J. Nucleic Acids 2010:0-0(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE XPC COMPLEX, INTERACTION WITH TDG AND SMUG1.
[41]	"Flexibility and plasticity of human centrin 2 binding to the xeroderma pigmentosum group C protein (XPC) from nuclear excision repair." Yang A., Miron S., Mouawad L., Duchambon P., Blouquit Y., Craescu C.T. Biochemistry 45:3653-3663(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 847-863 IN COMPLEX WITH CETN2.
[42]	"The structure of the human centrin 2-xeroderma pigmentosum group C protein complex." Thompson J.R., Ryan Z.C., Salisbury J.L., Kumar R. J. Biol. Chem. 281:18746-18752(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 847-863 IN COMPLEX WITH CETN2.
[43]	"Structural, thermodynamic, and cellular characterization of human centrin 2 interaction with xeroderma pigmentosum group C protein." Charbonnier J.B., Renaud E., Miron S., Le Du M.H., Blouquit Y., Duchambon P., Christova P., Shosheva A., Rose T., Angulo J.F., Craescu C.T. J. Mol. Biol. 373:1032-1046(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 847-863 IN COMPLEX WITH CETN2.
[44]	"A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy." Cleaver J.E., Thompson L.H., Richardson A.S., States J.C. Hum. Mutat. 14:9-22(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS XP-C.
[45]	"Characterization of molecular defects in Xeroderma pigmentosum group C." Li L., Bales E.S., Peterson C.A., Legerski R.J. Nat. Genet. 5:413-417(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XP-C HIS-334 AND VAL-697 INS.
[46]	"Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels." Chavanne F., Broughton B.C., Pietra D., Nardo T., Browitt A., Lehmann A.R., Stefanini M. Cancer Res. 60:1974-1982(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XP-C SER-690.
+	Additional computationally mapped references.

Web resources

Allelic variations of the XP genes

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D21089 mRNA. Translation: BAA04651.1.
AF261901 , AF261892, AF261893, AF261894, AF261895, AF261896, AF261897, AF261898, AF261899, AF261900 Genomic DNA. Translation: AAF87574.1.
AY131066 Genomic DNA. Translation: AAM77801.1.
AK295711 mRNA. Translation: BAG58555.1.
AC093495 Genomic DNA. No translation available.
FJ695191 Genomic DNA. No translation available.
FJ695192 Genomic DNA. No translation available.
BC016620 mRNA. Translation: AAH16620.1.
AK222844 mRNA. Translation: BAD96564.1.
X65024 mRNA. Translation: CAA46158.1.

IPI

IPI00156793.
IPI00924991.

PIR

S44345.

RefSeq

NP_001139241.1. NM_001145769.1.
NP_004619.3. NM_004628.4.

UniGene

Hs.475538.
Hs.739296.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2A4J	NMR	-	B	847-863	[»]
2GGM	X-ray	2.35	C/D	847-863	[»]
2OBH	X-ray	1.80	C/D	847-863	[»]

ProteinModelPortal

Q01831.

SMR

Q01831. Positions 531-824.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31225N.

IntAct

Q01831. 12 interactions.

MINT

MINT-105410.

STRING

9606.ENSP00000285021.

PTM databases

PhosphoSite

Q01831.

Polymorphism databases

DMDM

296453081.

Proteomic databases

PaxDb

Q01831.

PeptideAtlas

Q01831.

PRIDE

Q01831.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000285021; ENSP00000285021; ENSG00000154767.
ENST00000449060; ENSP00000404002; ENSG00000154767.

GeneID

7508.

KEGG

hsa:7508.

UCSC

uc011ave.2. human.
uc011avg.2. human.

Organism-specific databases

CTD

7508.

GeneCards

GC03M014161.

HGNC

HGNC:12816. XPC.

HPA

CAB009932.

MIM

278720. phenotype.
613208. gene.

neXtProt

NX_Q01831.

Orphanet

276255. Xeroderma pigmentosum complementation group C.

PharmGKB

PA37413.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5535.

HOGENOM

HOG000124671.

HOVERGEN

HBG000407.

InParanoid

Q01831.

KO

K10838.

OMA

MKRFNKE.

OrthoDB

EOG40CHGQ.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

Q01831.

Bgee

Q01831.

CleanEx

HS_XPC.

Genevestigator

Q01831.

GermOnline

ENSG00000154767. Homo sapiens.

Family and domain databases

InterPro

IPR004583. DNA_repair_Rad4.
IPR018026. DNA_repair_Rad4_subgr.
IPR018325. Rad4/PNGase_transGLS-fold.
IPR018326. Rad4_beta-hairpin_dom1.
IPR018327. Rad4_beta-hairpin_dom2.
IPR018328. Rad4_beta-hairpin_dom3.
[Graphical view]

PANTHER

PTHR12135. PTHR12135. 1 hit.

Pfam

PF10403. BHD_1. 1 hit.
PF10404. BHD_2. 1 hit.
PF10405. BHD_3. 1 hit.
PF03835. Rad4. 1 hit.
[Graphical view]

SMART

SM01030. BHD_1. 1 hit.
SM01031. BHD_2. 1 hit.
SM01032. BHD_3. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00605. rad4. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

XPC. human.

EvolutionaryTrace

Q01831.

GenomeRNAi

7508.

NextBio

29391.

SOURCE

Search...

Entry information

Entry name

XPC_HUMAN

Accession

Primary (citable) accession number: Q01831
Secondary accession number(s): B4DIP3 , E9PH69, Q53GT7, Q96AX0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	May 18, 2010
Last modified:	May 29, 2013
This is version 140 of the entry and version 4 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.