Q13619 (CUL4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cullin-4A
Short name=CUL-4A

Gene names

Name:

CUL4A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	759 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. In association with RBX1, DDB1 and DDB2 is required for histone H3 and histone H4 ubiquitination in response to ultraviolet and may be important for subsequent DNA repair. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. Ref.2 Ref.11 Ref.13 Ref.14 Ref.18 Ref.20
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to consist of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the CSA complex (DCX(ERCC8) complex) containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Component of the DCX(DET1-COP1) complex with the substrate recognition component DET1 and COP1. Component of the DCX(DDB2) complex with the substrate recognition component DDB2. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Interacts with DDB1, RBX1, RNF7, CTD1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9. Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually exclusive. Interacts with VPRBP, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, RFWD2, PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5 and DCAF8. May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5. Can self-associate. Interacts with Epstein-Barr virus BPLF1. Ref.2 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.19 Ref.20 Ref.21 Ref.22 Ref.29
Post-translational modification	Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex By similarity. Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome.
Sequence similarities	Belongs to the cullin family.

Ontologies

Keywords
Biological process	DNA damage DNA repair Host-virus interaction Ubl conjugation pathway
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW G1/S transition of mitotic cell cycle Traceable author statement. Source: ProtInc cell cycle arrest Traceable author statement. Source: ProtInc induction of apoptosis by intracellular signals Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell proliferation Traceable author statement. Source: ProtInc ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	Cul4A-RING ubiquitin ligase complex Inferred from direct assay Ref.10. Source: UniProtKB
Molecular function	ubiquitin protein ligase binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAND1	Q86VP6	3	EBI-456106,EBI-456077
DDB2	Q92466	2	EBI-456106,EBI-1176171
RBBP5	Q15291	3	EBI-456106,EBI-592823

Alternative products

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

Isoform 1 (identifier: Q13619-1)

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: Q13619-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 759

759

Cullin-4A

PRO_0000119795

Amino acid modifications

Modified residue

10

1

Phosphoserine Ref.26 Ref.27

Modified residue

22

1

Phosphothreonine Ref.25

Modified residue

99

1

Phosphoserine Ref.28

Modified residue

227

1

Phosphotyrosine Ref.24

Cross-link

33

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.25

Cross-link

705

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) By similarity

Natural variations

Alternative sequence

1 – 100

100

Missing in isoform 2.

VSP_018577

Natural variant

644

1

K → R.
Corresponds to variant rs2302757 [ dbSNP | Ensembl ].

VAR_020341

Experimental info

Mutagenesis

86 – 90

5

LYQAV → AAAAA: Largely reduces interaction with DDB1; abolishes interaction with DDB2. Ref.16 Ref.17

Mutagenesis

139 – 142

4

WQDH → AADA: Largely reduces interaction with DDB1; abolishes interaction with DDB2. Ref.16 Ref.17

Sequence conflict

281

1

S → T in BAD93235. Ref.3

Sequence conflict

339 – 346

8

HWSEYIKT → NSARARAA in AAC50547. Ref.7

Sequence conflict

496

1

K → R in BAD93235. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

759

Helix Strand Turn

Details...

Turn

58 – 61

4

Helix

62 – 71

10

Helix

83 – 93

11

Turn

96 – 98

3

Helix

99 – 121

23

Helix

130 – 152

23

Helix

154 – 157

4

Turn

158 – 162

5

Beta strand

165 – 167

3

Turn

170 – 172

3

Helix

176 – 180

5

Turn

181 – 183

3

Beta strand

184 – 186

3

Helix

189 – 191

3

Helix

197 – 201

5

Helix

211 – 217

7

Turn

221 – 225

5

Turn

227 – 231

5

Helix

232 – 245

14

Helix

249 – 253

5

Helix

256 – 269

14

Turn

274 – 278

5

Turn

280 – 282

3

Helix

283 – 294

12

Helix

300 – 304

5

Helix

308 – 311

4

Turn

312 – 314

3

Helix

316 – 328

13

Helix

334 – 346

13

Turn

350 – 352

3

Helix

355 – 357

3

Turn

358 – 360

3

Helix

361 – 377

17

Turn

378 – 382

5

Helix

384 – 398

15

Helix

404 – 417

14

Helix

429 – 440

12

Helix

447 – 462

16

Helix

469 – 480

12

Turn

487 – 491

5

Helix

495 – 513

19

Beta strand

522 – 529

8

Helix

545 – 558

14

Beta strand

576 – 579

4

Beta strand

588 – 591

4

Helix

593 – 601

9

Helix

610 – 616

7

Helix

621 – 629

9

Beta strand

638 – 641

4

Beta strand

653 – 656

4

Beta strand

665 – 668

4

Helix

670 – 674

5

Helix

679 – 706

28

Beta strand

707 – 710

4

Helix

713 – 722

10

Beta strand

723 – 725

3

Helix

732 – 741

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2006. Version 3. Checksum: 3C4C6A1BBD94D51B	FASTA	759	87,680
	10 20 30 40 50 60 MADEAPRKGS FSALVGRTNG LTKPAALAAA PAKPGGAGGS KKLVIKNFRD RPRLPDNYTQ 70 80 90 100 110 120 DTWRKLHEAV RAVQSSTSIR YNLEELYQAV ENLCSHKVSP MLYKQLRQAC EDHVQAQILP 130 140 150 160 170 180 FREDSLDSVL FLKKINTCWQ DHCRQMIMIR SIFLFLDRTY VLQNSTLPSI WDMGLELFRT 190 200 210 220 230 240 HIISDKMVQS KTIDGILLLI ERERSGEAVD RSLLRSLLGM LSDLQVYKDS FELKFLEETN 250 260 270 280 290 300 CLYAAEGQRL MQEREVPEYL NHVSKRLEEE GDRVITYLDH STQKPLIACV EKQLLGEHLT 310 320 330 340 350 360 AILQKGLDHL LDENRVPDLA QMYQLFSRVR GGQQALLQHW SEYIKTFGTA IVINPEKDKD 370 380 390 400 410 420 MVQDLLDFKD KVDHVIEVCF QKNERFVNLM KESFETFINK RPNKPAELIA KHVDSKLRAG 430 440 450 460 470 480 NKEATDEELE RTLDKIMILF RFIHGKDVFE AFYKKDLAKR LLVGKSASVD AEKSMLSKLK 490 500 510 520 530 540 HECGAAFTSK LEGMFKDMEL SKDIMVHFKQ HMQNQSDSGP IDLTVNILTM GYWPTYTPME 550 560 570 580 590 600 VHLTPEMIKL QEVFKAFYLG KHSGRKLQWQ TTLGHAVLKA EFKEGKKEFQ VSLFQTLVLL 610 620 630 640 650 660 MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI KSPKGKEVED GDKFIFNGEF 670 680 690 700 710 720 KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI VRIMKMRKTL GHNLLVSELY 730 740 750 NQLKFPVKPG DLKKRIESLI DRDYMERDKD NPNQYHYVA
	Isoform 2 [UniParc]. Checksum: 56D4D196BB1074CB	FASTA	659	76,821
	10 20 30 40 50 60 MLYKQLRQAC EDHVQAQILP FREDSLDSVL FLKKINTCWQ DHCRQMIMIR SIFLFLDRTY 70 80 90 100 110 120 VLQNSTLPSI WDMGLELFRT HIISDKMVQS KTIDGILLLI ERERSGEAVD RSLLRSLLGM 130 140 150 160 170 180 LSDLQVYKDS FELKFLEETN CLYAAEGQRL MQEREVPEYL NHVSKRLEEE GDRVITYLDH 190 200 210 220 230 240 STQKPLIACV EKQLLGEHLT AILQKGLDHL LDENRVPDLA QMYQLFSRVR GGQQALLQHW 250 260 270 280 290 300 SEYIKTFGTA IVINPEKDKD MVQDLLDFKD KVDHVIEVCF QKNERFVNLM KESFETFINK 310 320 330 340 350 360 RPNKPAELIA KHVDSKLRAG NKEATDEELE RTLDKIMILF RFIHGKDVFE AFYKKDLAKR 370 380 390 400 410 420 LLVGKSASVD AEKSMLSKLK HECGAAFTSK LEGMFKDMEL SKDIMVHFKQ HMQNQSDSGP 430 440 450 460 470 480 IDLTVNILTM GYWPTYTPME VHLTPEMIKL QEVFKAFYLG KHSGRKLQWQ TTLGHAVLKA 490 500 510 520 530 540 EFKEGKKEFQ VSLFQTLVLL MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI 550 560 570 580 590 600 KSPKGKEVED GDKFIFNGEF KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI 610 620 630 640 650 VRIMKMRKTL GHNLLVSELY NQLKFPVKPG DLKKRIESLI DRDYMERDKD NPNQYHYVA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers." Chen L.-C., Manjeshwar S., Lu Y., Moore D., Ljung B.M., Kuo W.L., Dairkee S.H., Wernick M., Collins C., Smith H.S. Cancer Res. 58:3677-3683(1998) [PubMed: 9721878] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint." Higa L.A., Mihaylov I.S., Banks D.P., Zheng J., Zhang H. Nat. Cell Biol. 5:1008-1015(2003) [PubMed: 14578910] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDT1.
[3]	"DDB2, the xeroderma pigmentosum group E gene product, is directly ubiquitylated by Cullin 4A-based ubiquitin ligase complex." Matsuda N., Azuma K., Saijo M., Iemura S., Hioki Y., Natsume T., Chiba T., Tanaka K., Tanaka K. DNA Repair 4:537-545(2005) [PubMed: 15811626] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[6]	"A new NEDD8-ligating system for cullin-4A." Osaka F., Kawasaki H., Aida N., Saeki M., Chiba T., Kawashima S., Tanaka K., Kato S. Genes Dev. 12:2263-2268(1998) [PubMed: 9694792] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 236-759 (ISOFORMS 1/2), NEDDYLATION.
[7]	"cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family." Kipreos E.T., Lander L.E., Wing J.P., He W.W., Hedgecock E.M. Cell 85:829-839(1996) [PubMed: 8681378] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 339-759 (ISOFORMS 1/2).
[8]	"Covalent modification of all members of human cullin family proteins by NEDD8." Hori T., Osaka F., Chiba T., Miyamoto C., Okabayashi K., Shimbara N., Kato S., Tanaka K. Oncogene 18:6829-6834(1999) [PubMed: 10597293] [Abstract] Cited for: NEDDYLATION.
[9]	"ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity." Ohta T., Michel J.J., Schottelius A.J., Xiong Y. Mol. Cell 3:535-541(1999) [PubMed: 10230407] [Abstract] Cited for: INTERACTION WITH RBX1 AND RNF7.
[10]	"The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage." Groisman R., Polanowska J., Kuraoka I., Sawada J., Saijo M., Drapkin R., Kisselev A.F., Tanaka K., Nakatani Y. Cell 113:357-367(2003) [PubMed: 12732143] [Abstract] Cited for: IDENTIFICATION IN THE CSA COMPLEX WITH RBX1; DDB1 AND ERCC8, INTERACTION OF THE CSA COMPLEX WITH RNA POLYMERASE II AND THE COP9 SIGNALOSOME.
[11]	"CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein." Zhang Y., Morrone G., Zhang J., Chen X., Lu X., Ma L., Moore M., Zhou P. EMBO J. 22:6057-6067(2003) [PubMed: 14609952] [Abstract] Cited for: INTERACTION WITH HOXA9, FUNCTION IN UBIQUITINATION OF HOXA9.
[12]	"TIP120A associates with cullins and modulates ubiquitin ligase activity." Min K.-W., Hwang J.-W., Lee J.-S., Park Y., Tamura T.-A., Yoon J.-B. J. Biol. Chem. 278:15905-15910(2003) [PubMed: 12609982] [Abstract] Cited for: INTERACTION WITH TIP120A.
[13]	"Cul4A physically associates with MDM2 and participates in the proteolysis of p53." Nag A., Bagchi S., Raychaudhuri P. Cancer Res. 64:8152-8155(2004) [PubMed: 15548678] [Abstract] Cited for: INTERACTION WITH MDM2 AND TP53, FUNCTION IN UBIQUITINATION OF TP53.
[14]	"Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage." Hu J., McCall C.M., Ohta T., Xiong Y. Nat. Cell Biol. 6:1003-1009(2004) [PubMed: 15448697] [Abstract] Cited for: INTERACTION WITH DDB1, FUNCTION IN CTD1 UBIQUITINATION.
[15]	"Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase." Wertz I.E., O'Rourke K.M., Zhang Z., Dornan D., Arnott D., Deshaies R.J., Dixit V.M. Science 303:1371-1374(2004) [PubMed: 14739464] [Abstract] Cited for: IDENTIFICATION IN THE DCX(DET1-COP1) COMPLEX WITH DDB1; RBX1; COP1 AND DET1.
[16]	"Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis." Nishitani H., Sugimoto N., Roukos V., Nakanishi Y., Saijo M., Obuse C., Tsurimoto T., Nakayama K.I., Nakayama K., Fujita M., Lygerou Z., Nishimoto T. EMBO J. 25:1126-1136(2006) [PubMed: 16482215] [Abstract] Cited for: INTERACTION WITH DDB1; DDB2 AND CAND1, MUTAGENESIS OF 86-LEU--VAL-90 AND 139-TRP--HIS-142.
[17]	"DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases." He Y.J., McCall C.M., Hu J., Zeng Y., Xiong Y. Genes Dev. 20:2949-2954(2006) [PubMed: 17079684] [Abstract] Cited for: INTERACTION WITH VPRBP; DDB2; ERCC8; DCAF11; GRWD1; RFWD2; FBXW5; RBBP7; GNB2; WSB1; WSB2; NUP43; PWP1; FBXW8; ATG16L1; KATNB1 AND RBBP4, MUTAGENESIS OF 86-LEU--VAL-90 AND 139-TRP--HIS-142.
[18]	"Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage." Wang H., Zhai L., Xu J., Joo H.-Y., Jackson S., Erdjument-Bromage H., Tempst P., Xiong Y., Zhang Y. Mol. Cell 22:383-394(2006) [PubMed: 16678110] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH DDB1; DDB2 AND RBX1, MASS SPECTROMETRY, FUNCTION.
[19]	"A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1." Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C. Mol. Cell 23:709-721(2006) [PubMed: 16949367] [Abstract] Cited for: INTERACTION WITH VPRBP; DTL; DDA1; DCAF6; DCAF4; DCAF16; DCAF17; DDB2; DET1; WDTC1; DCAF5; DCAF11; WDR24A; RFWD2; PAFAH1B1 AND DCAF8.
[20]	"Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis involving the COP9 signalosome." Bondar T., Kalinina A., Khair L., Kopanja D., Nag A., Bagchi S., Raychaudhuri P. Mol. Cell. Biol. 26:2531-2539(2006) [PubMed: 16537899] [Abstract] Cited for: INTERACTION WITH SKP2 AND CDKN1B, FUNCTION IN UBIQUITINATION OF CDKN1B.
[21]	"CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation." Higa L.A., Wu M., Ye T., Kobayashi R., Sun H., Zhang H. Nat. Cell Biol. 8:1277-1283(2006) [PubMed: 17041588] [Abstract] Cited for: INTERACTION WITH DDB2; WDR26; RBBP5; RFWD2; WDR51B; SNRNP40; WDR61; WDR76 AND WDR5.
[22]	"Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery." Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N. Nature 443:590-593(2006) [PubMed: 16964240] [Abstract] Cited for: INTERACTION WITH DCAF16.
[23]	"Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells -- evidence for cullin dimerization." Chew E.H., Poobalasingam T., Hawkey C.J., Hagen T. Cell. Signal. 19:1071-1080(2007) [PubMed: 17254749] [Abstract] Cited for: SELF-ASSOCIATION.
[24]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-227, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed: 18781797] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-22, UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-33, MASS SPECTROMETRY.
[26]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[28]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[29]	"A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases." Gastaldello S., Hildebrand S., Faridani O., Callegari S., Palmkvist M., Di Guglielmo C., Masucci M.G. Nat. Cell Biol. 12:351-361(2010) [PubMed: 20190741] [Abstract] Cited for: INTERACTION WITH EPSTEIN-BARR VIRUS BPLF1, DENEDDYLATION BY EPSTEIN-BARR VIRUS BPLF1.
[30]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF077188 mRNA. Translation: AAD45191.1.
AY365124 mRNA. Translation: AAR13072.1.
AB178950 mRNA. Translation: BAD93235.1.
AL136221 Genomic DNA. Translation: CAM18410.1.
AL136221 Genomic DNA. Translation: CAI13795.1.
BC008308 mRNA. Translation: AAH08308.2.
AB012193 mRNA. Translation: BAA33146.1.
U58090 mRNA. Translation: AAC50547.1.

IPI

IPI00419273.
IPI00549919.

RefSeq

NP_001008895.1. NM_001008895.1.
NP_003580.1. NM_003589.2.

UniGene

Hs.339735.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HYE	X-ray	3.10	C	1-759	[»]

ProteinModelPortal

Q13619.

SMR

Q13619. Positions 41-759.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31610N.

IntAct

Q13619. 23 interactions.

MINT

MINT-4532640.

STRING

Q13619.

PTM databases

PhosphoSite

Q13619.

Polymorphism databases

DMDM

108936013.

Proteomic databases

PRIDE

Q13619.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375440; ENSP00000364589; ENSG00000139842.

GeneID

8451.

KEGG

hsa:8451.

UCSC

uc010ags.1. human.
uc010agt.1. human.

Organism-specific databases

CTD

8451.

GeneCards

GC13P113863.

HGNC

HGNC:2554. CUL4A.

MIM

603137. gene.

neXtProt

NX_Q13619.

PharmGKB

PA27050.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14304.

GeneTree

ENSGT00550000074299.

HOVERGEN

HBG003619.

InParanoid

Q13619.

PhylomeDB

Q13619.

Gene expression databases

ArrayExpress

Q13619.

Bgee

Q13619.

CleanEx

HS_CUL4A.

Genevestigator

Q13619.

GermOnline

ENSG00000139842. Homo sapiens.

Family and domain databases

InterPro

IPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_trsnscrt_rep_DNA-bd.
[Graphical view]

Gene3D

G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 2 hits.

KO

K10609.

Pfam

PF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]

SMART

SM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]

SUPFAM

SSF75632. Cullin_homology. 1 hit.
SSF74788. Cullin_repeat-like. 1 hit.

PROSITE

PS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

31624.

SOURCE

Search...

Entry information

Entry name

CUL4A_HUMAN

Accession

Primary (citable) accession number: Q13619
Secondary accession number(s): A2A2W2 , O75834, Q589T6, Q5TC62, Q6UP08, Q9UP17

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 30, 2006
Last modified:	January 25, 2012
This is version 108 of the entry and version 3 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.