Q13620 (CUL4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	CUL4B
Synonyms:	KIAA0695

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	913 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. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. Required for ubiquitination of cyclin E, and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8. Ref.1 Ref.14 Ref.15 Ref.19 Ref.20 Ref.22
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to be formed 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 DCX(DTL) complex with the putative substrate recognition component DTL. Component of the DCX(DDB2) complex with the putative substrate recognition component DDB2. Part of a complex with RBX1 and TIP120A/CAND1. Interacts with RBX1 GRWD1, MLST8, SMU1, TLE2, TLE3, VPRBP, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 and TMEM113. Interacts with cyclin E and with importins alpha-1 (KPNA2), alpha-3 (KPNA4), alpha-5 (KPNA1) and beta-1 (KPNB1). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5. Ref.1 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Ref.22
Subcellular location	Nucleus Ref.19 Ref.22.
Post-translational modification	Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.
Involvement in disease	Mental retardation, X-linked, syndromic, 15 (MRXS15) [MIM:300354]: A syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.24 Ref.29 Ref.30
Sequence similarities	Belongs to the cullin family.
Sequence caution	The sequence AAB67315.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAK16812.1 differs from that shown. Reason: Frameshift at position 115.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Mental retardation
PTM	Acetylation 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 cell cycle Non-traceable author statement Ref.10. Source: UniProtKB positive regulation of S phase of mitotic cell cycle Inferred from electronic annotation. Source: Compara positive regulation of protein catabolic process Inferred from electronic annotation. Source: Compara protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	Cul4B-RING ubiquitin ligase complex Inferred from direct assay PubMed 18794347. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAND1	Q86VP6	3	EBI-456067,EBI-456077
DDB1	Q16531	15	EBI-456067,EBI-350322
RBX1	P62877	4	EBI-456067,EBI-398523

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13620-2)

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: Q13620-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MMSQSSGSGDGNDDEATTSKDG → MFPT

Note: Contains a N-acetylmethionine at position 1. Contains a phosphoserine at position 8. Contains a phosphoserine at position 10.

Isoform 3 (identifier: Q13620-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-196: Missing.
     197-203: LVIKNFK → MIDPDFA

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 913

913

Cullin-4B

PRO_0000393946

Regions

Motif

55 – 58

4

Nuclear localization signal Ref.22

Compositional bias

3 – 193

191

Ser-rich

Amino acid modifications

Modified residue

49

1

Phosphothreonine Ref.21 Ref.23

Modified residue

53

1

Phosphoserine Ref.21

Modified residue

146

1

Phosphoserine Ref.21 Ref.23

Modified residue

193

1

Phosphoserine Ref.21

Cross-link

859

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

Natural variations

Alternative sequence

1 – 196

196

Missing in isoform 3.

VSP_039084

Alternative sequence

1 – 22

22

MMSQS…TSKDG → MFPT in isoform 2.

VSP_039085

Alternative sequence

197 – 203

7

LVIKNFK → MIDPDFA in isoform 3.

VSP_039086

Natural variant

103

1

L → P. Ref.29
Corresponds to variant rs61759504 [ dbSNP | Ensembl ].

VAR_032272

Natural variant

213

1

T → I in MRXS15; uncertain pathological significance. Ref.29 Ref.30

VAR_032273

Natural variant

572

1

R → C in MRXS15. Ref.29 Ref.30

VAR_032274

Natural variant

745

1

V → A in MRXS15. Ref.29 Ref.30

VAR_032275

Experimental info

Mutagenesis

55 – 58

4

Missing: Distributed in cytoplasm. Fails to promote cell proliferation. No binding to KPNA2, KPNA4 and KPNA1. Ref.22

Mutagenesis

55

1

K → A: No impairment in nuclear localization. Ref.22

Mutagenesis

56

1

K → A: Disrupts nuclear localization and does not bind KPNA2, KPNA4, KPNA1; when associated with A-57. Disrupts nuclear localization. Ref.22

Mutagenesis

57

1

R → A: Disrupts nuclear localization and does not bind KPNA2, KPNA4, KPNA1; when associated with A-56. Disrupts nuclear localization. Ref.22

Mutagenesis

58

1

K → A: No impairment in nuclear localization. Ref.22

Sequence conflict

69

1

S → R in BAG53936. Ref.3

Sequence conflict

126

1

E → G in CAD97843. Ref.4

Sequence conflict

142

1

S → P in BAG53936. Ref.3

Sequence conflict

196

1

K → N in AAK16812. Ref.2

Sequence conflict

265

1

E → G in BAG53936. Ref.3

Sequence conflict

268

1

I → M in AAK16812. Ref.2

Sequence conflict

485

1

G → D in CAD97843. Ref.4

Sequence conflict

664

1

Q → QVK in AAK16812. Ref.2

Sequence conflict

727

1

L → I in AAR13073. Ref.1

Sequence conflict

727

1

L → I in AAH36216. Ref.7

Secondary structure

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913

Helix Strand Turn

Details...

Beta strand

210 – 212

3

Helix

215 – 228

14

Helix

237 – 250

14

Helix

253 – 270

18

Helix

271 – 276

6

Helix

282 – 306

25

Helix

308 – 312

5

Turn

315 – 317

3

Helix

324 – 335

12

Turn

336 – 338

3

Helix

340 – 358

19

Helix

365 – 377

13

Helix

381 – 384

4

Helix

386 – 407

22

Helix

410 – 430

21

Helix

434 – 436

3

Helix

437 – 448

12

Helix

450 – 452

3

Helix

453 – 466

14

Helix

470 – 480

11

Helix

486 – 507

22

Beta strand

511 – 513

3

Helix

515 – 533

19

Helix

538 – 549

12

Helix

841 – 860

20

Beta strand

861 – 865

5

Helix

866 – 876

11

Helix

883 – 895

13

Beta strand

898 – 901

4

Beta strand

908 – 911

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 4. Checksum: 3E58C5868FDF0700	FASTA	913	103,982
	10 20 30 40 50 60 MMSQSSGSGD GNDDEATTSK DGGFSSPSPS AAAAAQEVRS ATDGNTSTTP PTSAKKRKLN 70 80 90 100 110 120 SSSSSSSNSS NEREDFDSTS SSSSTPPLQP RDSASPSTSS FCLGVSVAAS SHVPIQKKLR 130 140 150 160 170 180 FEDTLEFVGF DAKMAEESSS SSSSSSPTAA TSQQQQLKNK SILISSVASV HHANGLAKSS 190 200 210 220 230 240 TTVSSFANSK PGSAKKLVIK NFKDKPKLPE NYTDETWQKL KEAVEAIQNS TSIKYNLEEL 250 260 270 280 290 300 YQAVENLCSY KISANLYKQL RQICEDHIKA QIHQFREDSL DSVLFLKKID RCWQNHCRQM 310 320 330 340 350 360 IMIRSIFLFL DRTYVLQNSM LPSIWDMGLE LFRAHIISDQ KVQNKTIDGI LLLIERERNG 370 380 390 400 410 420 EAIDRSLLRS LLSMLSDLQI YQDSFEQRFL EETNRLYAAE GQKLMQEREV PEYLHHVNKR 430 440 450 460 470 480 LEEEADRLIT YLDQTTQKSL IATVEKQLLG EHLTAILQKG LNNLLDENRI QDLSLLYQLF 490 500 510 520 530 540 SRVRGGVQVL LQQWIEYIKA FGSTIVINPE KDKTMVQELL DFKDKVDHII DICFLKNEKF 550 560 570 580 590 600 INAMKEAFET FINKRPNKPA ELIAKYVDSK LRAGNKEATD EELEKMLDKI MIIFRFIYGK 610 620 630 640 650 660 DVFEAFYKKD LAKRLLVGKS ASVDAEKSML SKLKHECGAA FTSKLEGMFK DMELSKDIMI 670 680 690 700 710 720 QFKQYMQNQN VPGNIELTVN ILTMGYWPTY VPMEVHLPPE MVKLQEIFKT FYLGKHSGRK 730 740 750 760 770 780 LQWQSTLGHC VLKAEFKEGK KELQVSLFQT LVLLMFNEGE EFSLEEIKQA TGIEDGELRR 790 800 810 820 830 840 TLQSLACGKA RVLAKNPKGK DIEDGDKFIC NDDFKHKLFR IKINQIQMKE TVEEQASTTE 850 860 870 880 890 900 RVFQDRQYQI DAAIVRIMKM RKTLSHNLLV SEVYNQLKFP VKPADLKKRI ESLIDRDYME 910 RDKENPNQYN YIA
	Isoform 2 [UniParc]. Checksum: 25B25D253C1C2B71	FASTA	895	102,299
	10 20 30 40 50 60 MFPTGFSSPS PSAAAAAQEV RSATDGNTST TPPTSAKKRK LNSSSSSSSN SSNEREDFDS 70 80 90 100 110 120 TSSSSSTPPL QPRDSASPST SSFCLGVSVA ASSHVPIQKK LRFEDTLEFV GFDAKMAEES 130 140 150 160 170 180 SSSSSSSSPT AATSQQQQLK NKSILISSVA SVHHANGLAK SSTTVSSFAN SKPGSAKKLV 190 200 210 220 230 240 IKNFKDKPKL PENYTDETWQ KLKEAVEAIQ NSTSIKYNLE ELYQAVENLC SYKISANLYK 250 260 270 280 290 300 QLRQICEDHI KAQIHQFRED SLDSVLFLKK IDRCWQNHCR QMIMIRSIFL FLDRTYVLQN 310 320 330 340 350 360 SMLPSIWDMG LELFRAHIIS DQKVQNKTID GILLLIERER NGEAIDRSLL RSLLSMLSDL 370 380 390 400 410 420 QIYQDSFEQR FLEETNRLYA AEGQKLMQER EVPEYLHHVN KRLEEEADRL ITYLDQTTQK 430 440 450 460 470 480 SLIATVEKQL LGEHLTAILQ KGLNNLLDEN RIQDLSLLYQ LFSRVRGGVQ VLLQQWIEYI 490 500 510 520 530 540 KAFGSTIVIN PEKDKTMVQE LLDFKDKVDH IIDICFLKNE KFINAMKEAF ETFINKRPNK 550 560 570 580 590 600 PAELIAKYVD SKLRAGNKEA TDEELEKMLD KIMIIFRFIY GKDVFEAFYK KDLAKRLLVG 610 620 630 640 650 660 KSASVDAEKS MLSKLKHECG AAFTSKLEGM FKDMELSKDI MIQFKQYMQN QNVPGNIELT 670 680 690 700 710 720 VNILTMGYWP TYVPMEVHLP PEMVKLQEIF KTFYLGKHSG RKLQWQSTLG HCVLKAEFKE 730 740 750 760 770 780 GKKELQVSLF QTLVLLMFNE GEEFSLEEIK QATGIEDGEL RRTLQSLACG KARVLAKNPK 790 800 810 820 830 840 GKDIEDGDKF ICNDDFKHKL FRIKINQIQM KETVEEQAST TERVFQDRQY QIDAAIVRIM 850 860 870 880 890 KMRKTLSHNL LVSEVYNQLK FPVKPADLKK RIESLIDRDY MERDKENPNQ YNYIA
	Isoform 3 [UniParc]. Checksum: D50E2D33B73E6CB9	FASTA	717	84,017
	10 20 30 40 50 60 MIDPDFADKP KLPENYTDET WQKLKEAVEA IQNSTSIKYN LEELYQAVEN LCSYKISANL 70 80 90 100 110 120 YKQLRQICED HIKAQIHQFR EDSLDSVLFL KKIDRCWQNH CRQMIMIRSI FLFLDRTYVL 130 140 150 160 170 180 QNSMLPSIWD MGLELFRAHI ISDQKVQNKT IDGILLLIER ERNGEAIDRS LLRSLLSMLS 190 200 210 220 230 240 DLQIYQDSFE QRFLEETNRL YAAEGQKLMQ EREVPEYLHH VNKRLEEEAD RLITYLDQTT 250 260 270 280 290 300 QKSLIATVEK QLLGEHLTAI LQKGLNNLLD ENRIQDLSLL YQLFSRVRGG VQVLLQQWIE 310 320 330 340 350 360 YIKAFGSTIV INPEKDKTMV QELLDFKDKV DHIIDICFLK NEKFINAMKE AFETFINKRP 370 380 390 400 410 420 NKPAELIAKY VDSKLRAGNK EATDEELEKM LDKIMIIFRF IYGKDVFEAF YKKDLAKRLL 430 440 450 460 470 480 VGKSASVDAE KSMLSKLKHE CGAAFTSKLE GMFKDMELSK DIMIQFKQYM QNQNVPGNIE 490 500 510 520 530 540 LTVNILTMGY WPTYVPMEVH LPPEMVKLQE IFKTFYLGKH SGRKLQWQST LGHCVLKAEF 550 560 570 580 590 600 KEGKKELQVS LFQTLVLLMF NEGEEFSLEE IKQATGIEDG ELRRTLQSLA CGKARVLAKN 610 620 630 640 650 660 PKGKDIEDGD KFICNDDFKH KLFRIKINQI QMKETVEEQA STTERVFQDR QYQIDAAIVR 670 680 690 700 710 IMKMRKTLSH NLLVSEVYNQ LKFPVKPADL KKRIESLIDR DYMERDKENP NQYNYIA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH CDT1.
[2]	"Molecular cloning of a full-length cullin, CUL4B and identification of its interacting proteins." Du M., Zu Z., Sansores-Garcia L., Wu K.K. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"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] (ISOFORMS 1; 2 AND 3). Tissue: Chondrocyte, Teratocarcinoma and Testis.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Fetal liver.
[5]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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.
[8]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 133-913 (ISOFORMS 1/2). Tissue: Brain.
[9]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[10]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 626-913.
[11]	"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] [Europe PMC] [Abstract] Cited for: NEDDYLATION.
[12]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RBX1.
[13]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TIP120A, IDENTIFICATION IN A COMPLEX WITH RBX1 AND TIP120A.
[14]	"Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation." Higa L.A., Yang X., Zheng J., Banks D., Wu M., Ghosh P., Sun H., Zhang H. Cell Cycle 5:71-77(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CYCLIN E.
[15]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH DDB1; DDB2 AND RBX1, MASS SPECTROMETRY, FUNCTION.
[16]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VPRBP; DDA1; DCAF6; DCAF17; DDB2 AND DCAF8.
[17]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DTL; DDB2; TMEM113; WDR5B; WDR82; WDR26; GRWD1; WDR51B; SNRNP40; DCAF8; WDR61; WDR76; WDR5; SMU1; TLE2 AND TLE3.
[18]	"Mutation in CUL4B, which encodes a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation." Zou Y., Liu Q., Chen B., Zhang X., Guo C., Zhou H., Li J., Gao G., Guo Y., Yan C., Wei J., Shao C., Gong Y. Am. J. Hum. Genet. 80:561-566(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MRXS15.
[19]	"The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A." Guerrero-Santoro J., Kapetanaki M.G., Hsieh C.L., Gorbachinsky I., Levine A.S., Rapic-Otrin V. Cancer Res. 68:5014-5022(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.
[20]	"mTORC1 signaling requires proteasomal function and the involvement of CUL4-DDB1 ubiquitin E3 ligase." Ghosh P., Wu M., Zhang H., Sun H. Cell Cycle 7:373-381(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MLST8.
[21]	"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 THR-49; SER-53; SER-146 AND SER-193, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Characterization of nuclear localization signal in the N terminus of CUL4B and its essential role in cyclin E degradation and cell cycle progression." Zou Y., Mi J., Cui J., Lu D., Zhang X., Guo C., Gao G., Liu Q., Chen B., Shao C., Gong Y. J. Biol. Chem. 284:33320-33332(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH KPNA2; KPNA4; KPNA1 AND KPNB1, NUCLEAR LOCALIZATION SIGNAL, MUTAGENESIS OF LYS-55; LYS-56; ARG-57; LYS-58 AND 55-LYS--LYS-58.
[23]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49 AND SER-146, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[24]	"A novel nonsense mutation in CUL4B gene in three brothers with X-linked mental retardation syndrome." Badura-Stronka M., Jamsheer A., Materna-Kiryluk A., Sowinska A., Kiryluk K., Budny B., Latos-Bielenska A. Clin. Genet. 77:141-144(2010) [PubMed] [Europe PMC] [Abstract] Cited for: DISEASE, INVOLVEMENT IN MRXS15.
[25]	"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: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 2), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8 AND SER-10 (ISOFORM 2), MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[26]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]	"Solution structure of the winged helix-turn-helix motif of human cul-4b." RIKEN structural genomics initiative (RSGI) Submitted (APR-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 826-913.
[29]	"Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor." Tarpey P.S., Raymond F.L., O'Meara S., Edkins S., Teague J., Butler A., Dicks E., Stevens C., Tofts C., Avis T., Barthorpe S., Buck G., Cole J., Gray K., Halliday K., Harrison R., Hills K., Jenkinson A. , Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Varian J., West S., Widaa S., Mallya U., Moon J., Luo Y., Holder S., Smithson S.F., Hurst J.A., Clayton-Smith J., Kerr B., Boyle J., Shaw M., Vandeleur L., Rodriguez J., Slaugh R., Easton D.F., Wooster R., Bobrow M., Srivastava A.K., Stevenson R.E., Schwartz C.E., Turner G., Gecz J., Futreal P.A., Stratton M.R., Partington M. Am. J. Hum. Genet. 80:345-352(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MRXS15 ILE-213; CYS-572 AND ALA-745, VARIANT PRO-103.
[30]	"A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation." Tarpey P.S., Smith R., Pleasance E., Whibley A., Edkins S., Hardy C., O'Meara S., Latimer C., Dicks E., Menzies A., Stephens P., Blow M., Greenman C., Xue Y., Tyler-Smith C., Thompson D., Gray K., Andrews J. , Barthorpe S., Buck G., Cole J., Dunmore R., Jones D., Maddison M., Mironenko T., Turner R., Turrell K., Varian J., West S., Widaa S., Wray P., Teague J., Butler A., Jenkinson A., Jia M., Richardson D., Shepherd R., Wooster R., Tejada M.I., Martinez F., Carvill G., Goliath R., de Brouwer A.P., van Bokhoven H., Van Esch H., Chelly J., Raynaud M., Ropers H.H., Abidi F.E., Srivastava A.K., Cox J., Luo Y., Mallya U., Moon J., Parnau J., Mohammed S., Tolmie J.L., Shoubridge C., Corbett M., Gardner A., Haan E., Rujirabanjerd S., Shaw M., Vandeleur L., Fullston T., Easton D.F., Boyle J., Partington M., Hackett A., Field M., Skinner C., Stevenson R.E., Bobrow M., Turner G., Schwartz C.E., Gecz J., Raymond F.L., Futreal P.A., Stratton M.R. Nat. Genet. 41:535-543(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MRXS15 ILE-213; CYS-572 AND ALA-745.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY365125 mRNA. Translation: AAR13073.1.
AF212995 mRNA. Translation: AAK16812.1. Frameshift.
AK123688 mRNA. Translation: BAG53936.1.
AK299081 mRNA. Translation: BAH12944.1.
AK315037 mRNA. Translation: BAG37520.1.
BX537787 mRNA. Translation: CAD97843.1.
AC002476 Genomic DNA. Translation: AAB67315.1. Sequence problems.
AL451005, AC002476 Genomic DNA. Translation: CAI41370.1.
CH471107 Genomic DNA. Translation: EAX11877.1.
BC036216 mRNA. Translation: AAH36216.1.
AB014595 mRNA. Translation: BAA31670.2.
U58091 mRNA. Translation: AAC50548.1.

IPI

IPI00179057.
IPI00480142.
IPI00965290.

RefSeq

NP_001073341.1. NM_001079872.1.
NP_003579.3. NM_003588.3.

UniGene

Hs.102914.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DO7	NMR	-	A	826-913	[»]
4A0C	X-ray	3.80	C/E	192-913	[»]
4A0L	X-ray	7.40	E/H	192-913	[»]
4A64	X-ray	2.57	A/B/C/D	206-557	[»]

ProteinModelPortal

Q13620.

SMR

Q13620. Positions 206-913.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31609N.

IntAct

Q13620. 33 interactions.

STRING

9606.ENSP00000384109.

PTM databases

PhosphoSite

Q13620.

Polymorphism databases

DMDM

296439468.

Proteomic databases

PaxDb

Q13620.

PRIDE

Q13620.

Protocols and materials databases

DNASU

8450.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371322; ENSP00000360373; ENSG00000158290.
ENST00000404115; ENSP00000384109; ENSG00000158290.

GeneID

8450.

KEGG

hsa:8450.

UCSC

uc004esv.3. human.
uc004esw.3. human.

Organism-specific databases

CTD

8450.

GeneCards

GC0XM119658.

H-InvDB

HIX0017025.

HGNC

HGNC:2555. CUL4B.

HPA

CAB017786.
HPA011880.

MIM

300304. gene.
300354. phenotype.

neXtProt

NX_Q13620.

Orphanet

85293. Cabezas syndrome.

PharmGKB

PA27051.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5647.

HOVERGEN

HBG003619.

KO

K10609.

OMA

FEDSLDF.

OrthoDB

EOG42FSH0.

Enzyme and pathway databases

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q13620.

Bgee

Q13620.

CleanEx

HS_CUL4B.

Genevestigator

Q13620.

GermOnline

ENSG00000158290. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 2 hits.

InterPro

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

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

EvolutionaryTrace

Q13620.

GenomeRNAi

8450.

NextBio

31618.

PMAP-CutDB

Q13620.

SOURCE

Search...

Entry information

Entry name

CUL4B_HUMAN

Accession

Primary (citable) accession number: Q13620
Secondary accession number(s): B1APK5 , B3KVX4, B7Z5K8, Q6PIE4, Q6UP07, Q7Z673, Q9BY37, Q9UEB7, Q9UED7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 128 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.