Reviewed, UniProtKB/Swiss-Prot Q14999 (CUL7_HUMAN)

Names and origin

Protein names

Recommended name:
    Cullin-7
      Short name=CUL-7

Gene names

Name:	CUL7
Synonyms:	KIAA0076

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	1698 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of a probable SCF-like E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteosomal degradation of target proteins. Probably plays a role in the degradation of proteins involved in endothelial proliferation and/or differentiation By similarity. Seems not to promote polyubiquitination and proteosomal degradation of TP53. In vitro, complexes of CUL7 with either PARC or FBXW8 or TP53 contain E3 ubiquitin-protein ligase activity.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Part of a SCF-like complex consisting of CUL7, RBX1, SKP1, FBXW8 and GLMN isoform 1. Interacts with a complex of SKP1 and FBXW8, but not with SKP1 alone. Interacts with PARC. Interacts with FBXW8; interaction is mutually exclusive of binding to PARC or TP53. Interacts with TP53; the interaction preferentially involves tetrameric and dimeric TP53. The CUL7-PARC heterodimer seems to interact specifically with TP53. Interacts with CUL1; the interactions seems to be mediated by FBXW8 By similarity.
Subcellular location	Cytoplasm.
Tissue specificity	Highly expressed in fetal kidney and adult skeletal muscle. Also abundant in fetal brain, as well as in adult pancreas, kidney, placenta and heart. Detected in trophoblasts, lymphoblasts, osteoblasts, chondrocytes and skin fibroblasts.
Involvement in disease	Defects in CUL7 are the cause of 3M syndrome [MIM:273750]. 3M syndrome is an autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.
Sequence similarities	Belongs to the cullin family. Contains 1 DOC domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	regulation of mitotic metaphase/anaphase transition Inferred from electronic annotation. Source: InterPro ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro vasculogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	anaphase-promoting complex Ref.4 Non-traceable author statement. Source: UniProtKB cullin-RING ubiquitin ligase complex Inferred from electronic annotation. Source: InterPro cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ubiquitin protein ligase binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-308606,EBI-375543
TP53	P04637	1	EBI-308606,EBI-366083

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1698

1698

Cullin-7

PRO_0000119802

Regions

Domain

814 – 993

180

DOC

Region

360 – 460

101

Interaction with TP53

Amino acid modifications

Modified residue

329

1

Phosphoserine

Modified residue

339

1

Phosphoserine

Cross-link

1576

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

Natural variations

Natural variant

813

1

Q → R: dbSNP rs9381231.

VAR_026121

Natural variant

1014

1

L → R in 3M syndrome.

VAR_026122

Natural variant

1246

1

Q → G in 3M syndrome; requires 2 nucleotide substitutions.

VAR_026123

Natural variant

1464

1

H → P in 3M syndrome; impairs the ability to interact with RBX1, thus hampers the assembly of polyubiquitin chains.

VAR_026124

Secondary structure

1

.

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1698

Helix Strand Turn

Details...

Helix

360 – 362

3

Beta strand

363 – 366

4

Helix

367 – 376

10

Beta strand

382 – 385

4

Beta strand

397 – 403

7

Beta strand

407 – 414

8

Turn

415 – 418

4

Beta strand

419 – 424

6

Helix

425 – 427

3

Beta strand

428 – 430

3

Sequences

	Sequence		Length	Mass (Da)
	Q14999-1 [UniParc]. Last modified October 23, 2007. Version 2. Checksum: EC9EED17E98FC9A1	FASTA	1,698	191,161
	10 20 30 40 50 60 MVGELRYREF RVPLGPGLHA YPDELIRQRV GHDGHPEYQI RWLILRRGDE GDGGSGQVDC 70 80 90 100 110 120 KAEHILLWMS KDEIYANCHK MLGEDGQVIG PSQESAGEVG ALDKSVLEEM ETDVKSLIQR 130 140 150 160 170 180 ALRQLEECVG TIPPAPLLHT VHVLSAYASI EPLTGVFKDP RVLDLLMHML SSPDYQIRWS 190 200 210 220 230 240 AGRMIQALSS HDAGTRTQIL LSLSQQEAIE KHLDFDSRCA LLALFAQATL SEHPMSFEGI 250 260 270 280 290 300 QLPQVPGRVL FSLVKRYLHV TSLLDQLNDS AAEPGAQNTS APEELSGERG QLELEFSMAM 310 320 330 340 350 360 GTLISELVQA MRWDQASDRP RSSARSPGSI FQPQLADVSP GLPAAQAQPS FRRSRRFRPR 370 380 390 400 410 420 SEFASGNTYA LYVRDTLQPG MRVRMLDDYE EISAGDEGEF RQSNNGVPPV QVFWESTGRT 430 440 450 460 470 480 YWVHWHMLEI LGFEEDIEDM VEADEYQGAV ASRVLGRALP AWRWRPMTEL YAVPYVLPED 490 500 510 520 530 540 EDTEECEHLT LAEWWELLFF IKKLDGPDHQ EVLQILQENL DGEILDDEIL AELAVPIELA 550 560 570 580 590 600 QDLLLTLPQR LNDSALRDLI NCHVYKKYGP EALAGNQAYP SLLEAQEDVL LLDAQAQAKD 610 620 630 640 650 660 SEDAAKVEAK EPPSQSPNTP LQRLVEGYGP AGKILLDLEQ ALSSEGTQEN KVKPLLLQLQ 670 680 690 700 710 720 RQPQPFLALM QSLDTPETNR TLHLTVLRIL KQLVDFPEAL LLPWHEAVDA CMACLRSPNT 730 740 750 760 770 780 DREVLQELIF FLHRLTSVSR DYAVVLNQLG ARDAISKALE KHLGKLELAQ ELRDMVFKCE 790 800 810 820 830 840 KHAHLYRKLI TNILGGCIQM VLGQIEDHRR THQPINIPFF DVFLRYLCQG SSVEVKEDKC 850 860 870 880 890 900 WEKVEVSSNP HRASKLTDHN PKTYWESNGS AGSHYITLHM RRGILIRQLT LLVASEDSSY 910 920 930 940 950 960 MPARVVVCGG DSTSSLHTEL NSVNVMPSAS RVILLENLTR FWPIIQIRIK RCQQGGIDTR 970 980 990 1000 1010 1020 IRGLEILGPK PTFWPVFREQ LCRHTRLFYM VRAQAWSQDM AEDRRSLLHL SSRLNGALRQ 1030 1040 1050 1060 1070 1080 EQNFADRFLP DDEAAQALGK TCWEALVSPV VQNITSPDED GISPLGWLLD QYLECQEAVF 1090 1100 1110 1120 1130 1140 NPQSRGPAFF SRVRRLTHLL VHVEPCEAPP PVVATPRPKG RNRSHDWSSL ATRGLPSSIM 1150 1160 1170 1180 1190 1200 RNLTRCWRAV VEKQVNNFLT SSWRDDDFVP RYCEHFNILQ NSSSELFGPR AAFLLALQNG 1210 1220 1230 1240 1250 1260 CAGALLKLPF LKAAHVSEQF ARHIDQQIQG SRIGGAQEME RLAQLQQCLQ AVLIFSGLEI 1270 1280 1290 1300 1310 1320 ATTFEHYYQH YMADRLLGVV SSWLEGAVLE QIGPCFPNRL PQQMLQSLST SKELQRQFHV 1330 1340 1350 1360 1370 1380 YQLQQLDQEL LKLEDTEKKI QVGLGASGKE HKSEKEEEAG AAAVVDVAEG EEEEEENEDL 1390 1400 1410 1420 1430 1440 YYEGAMPEVS VLVLSRHSWP VASICHTLNP RTCLPSYLRG TLNRYSNFYN KSQSHPALER 1450 1460 1470 1480 1490 1500 GSQRRLQWTW LGWAELQFGN QTLHVSTVQM WLLLYLNDLK AVSVESLLAF SGLSADMLNQ 1510 1520 1530 1540 1550 1560 AIGPLTSSRG PLDLHEQKDI PGGVLKIRDG SKEPRSRWDI VRLIPPQTYL QAEGEDGQNL 1570 1580 1590 1600 1610 1620 EKRRNLLNCL IVRILKAHGD EGLHIDQLVC LVLEAWQKGP CPPRGLVSSL GKGSACSSTD 1630 1640 1650 1660 1670 1680 VLSCILHLLG KGTLRRHDDR PQVLSYAVPV TVMEPHTESL NPGSSGPNPP LTFHTLQIRS 1690 RGVPYASCTA TQSFSTFR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1." Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S. DNA Res. 1:223-229(1994) [PubMed: 7584044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-813. Tissue: Bone marrow.
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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], VARIANT ARG-813. Tissue: Eye.
[4]	"CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex." Dias D.C., Dolios G., Wang R., Pan Z.Q. Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002) [PubMed: 12481031] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH SKP1A; FBXW8 AND RBX1.
[5]	"Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis." Arai T., Kasper J.S., Skaar J.R., Ali S.H., Takahashi C., DeCaprio J.A. Proc. Natl. Acad. Sci. U.S.A. 100:9855-9860(2003) [PubMed: 12904573] [Abstract] Cited for: INTERACTION WITH RBX1, IDENTIFICATION IN A COMPLEX WITH SKP1; FBXW8; RBX1 AND GLMN.
[6]	"Cytoplasmic localized ubiquitin ligase cullin 7 binds to p53 and promotes cell growth by antagonizing p53 function." Andrews P., He Y.J., Xiong Y. Oncogene 25:4534-4548(2006) [PubMed: 16547496] [Abstract] Cited for: FUNCTION, INTERACTION WITH RBX1 AND TP53, SUBCELLULAR LOCATION.
[7]	"PARC and CUL7 form atypical cullin RING ligase complexes." Skaar J.R., Florens L., Tsutsumi T., Arai T., Tron A., Swanson S.K., Washburn M.P., DeCaprio J.A. Cancer Res. 67:2006-2014(2007) [PubMed: 17332328] [Abstract] Cited for: FUNCTION, INTERACTION WITH PARC; SKP1A; FBXW8; RBX1 AND TP53.
[8]	"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-329 AND SER-339, MASS SPECTROMETRY.
[9]	"The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of p53." Kaustov L., Lukin J., Lemak A., Duan S., Ho M., Doherty R., Penn L.Z., Arrowsmith C.H. J. Biol. Chem. 282:11300-11307(2007) [PubMed: 17298945] [Abstract] Cited for: STRUCTURE BY NMR OF 360-460, INTERACTION WITH TP53.
[10]	"Identification of mutations in CUL7 in 3-M syndrome." Huber C., Dias-Santagata D., Glaser A., O'Sullivan J., Brauner R., Wu K., Xu X., Pearce K., Wang R., Giovannucci Uzielli M.L., Dagoneau N., Chemaitilly W., Superti-Furga A., Dos Santos H., Megarbane A., Morin G., Gillessen-Kaesbach G., Hennekam R.C.M. , Van der Burgt I., Black G.C.M., Clayton P.E., Read A., Le Merrer M., Scambler P.J., Munnich A., Pan Z.-Q., Winter R., Cormier-Daire V. Nat. Genet. 37:1119-1124(2005) [PubMed: 16142236] [Abstract] Cited for: VARIANTS 3M SYNDROME ARG-1014; GLY-1246 AND PRO-1464, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

D38548 mRNA. Translation: BAA07551.2. Different initiation.
AL355385, AL136304 Genomic DNA. Translation: CAI13779.1.
AL136304, AL355385 Genomic DNA. Translation: CAI19793.1.
BC033647 mRNA. Translation: AAH33647.1.

RefSeq

NP_055595.2.

UniGene

Hs.520136

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JNG	NMR	-	A	360-460	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14999.

PTM databases

PhosphoSite

Q14999.

Genome annotation databases

Ensembl

ENSG00000044090. Homo sapiens. [Contig view]

GeneID

9820.

KEGG

hsa:9820.

Organism-specific databases

H-InvDB

HIX0005893.

HGNC

HGNC:21024. CUL7.

HPA

CAB015449.

MIM

273750. phenotype.
609577. gene.

Orphanet

2616. 3M syndrome.

PharmGKB

PA134897835.

HUGE

Search...

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q14999.

HOVERGEN

Q14999.

Gene expression databases

ArrayExpress

Q14999.

CleanEx

HS_CUL7.

GermOnline

ENSG00000044090. Homo sapiens.

Family and domain databases

InterPro

IPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
[Graphical view]

Pfam

PF00888. Cullin. 1 hit.
[Graphical view]

PROSITE

PS01256. CULLIN_1. False negative.
PS50069. CULLIN_2. 1 hit.
PS51284. DOC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

36986.

SOURCE

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Entry information

Entry name

CUL7_HUMAN

Accession

Primary (citable) accession number: Q14999
Secondary accession number(s): Q5T654

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 23, 2007
Last modified:	November 25, 2008
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)