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FLASH GENE

Symbol

CUL1

contributors: mct/pgu - updated : 20-02-2018

HGNC name	cullin 1
HGNC id	2551

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	102.27 kb     22 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003592 22 - 3226 NP_003583 - 776 - 2009 19679553

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Endocrine pancreas         Nervous brain           spinal cord         Reproductive male system prostate       Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac     Muscular striatum skeletal     Nervous central

cells

System Cell Pubmed Species Stage Rna symbol   digestive

cell lineage
cell lines	osteosarcoma, acute lymphoblastic leukemia, b-lymphoblastoid and cervical epitheloid carcinoma
fluid/secretion

at STAGE

cell cycle

cell cycle, checkpoint, G1S

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a globular segment binding RBX1
	a stalk bound to SKP1-F-box protein
	a conserved C terminal sequence required for nuclear accumulation

conjugated

Other

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	homolog to C.elegans CUL 1
	ortholog to murine Cul1
	ortholog to rattus Cul1_predicted

Homologene

FAMILY

cullin family

CATEGORY

chaperone/stress , regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	acting as a negative regulator of the cell cycle
	targeting protein for ubiquitin dependent proteolysis
	may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles
	matrix degrading enzyme known to be involved in the remodelling of extracellular matrix proteins
	play a key role in tumour progression and its presence is associated with poor clinical outcome for several different types of tumours
	scaffold protein in cullin-based ubiquitin ligases, playing an important role in early embryonic development
	promotes likely trophoblast cell invasion and dysregulation of CUL1 expression may be associated with preeclampsia
	is a scaffold protein of the ubiquitin E3 ligase SKP1/CUL1/RBX1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription
	is a scaffold protein of the ubiquitin E3 ligase SKP1/CUL1/RBX1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription
	unneddylated CUL1 is another central player involved in maintenance of the adaptor module pool through the formation of CUL1-SKP1-F-box complexes and promotion of rapid SCF (SKP1-CUL1-F-box protein) assembly

CELLULAR PROCESS	cell cycle, division
	cell cycle, checkpoint
	cell life, proliferation/growth
	cell life, cell death/apoptosis
	protein, ubiquitin dependent proteolysis
	cell migration & motility

PHYSIOLOGICAL PROCESS

text	G1/S transition

PATHWAY

metabolism

signaling

a component	constituent of a core ubiquitin-ligase SCF (SKP1, CUL1, SKP2), RRX1 with CIP1/WAF1, CDC34 and cyclin D(CCND)
	hyper-neddylated
	complex between GLMN, RBX1, and a fragment of CUL1

INTERACTION

DNA

RNA

small molecule

protein	targeting G1 cell cycle regulators (NAF1, CDC34, CCND) for ubiquitin-dependent proteolysis required with RBX1 for nuclear localization of NEDD8
	EIF3E and the COP9 signalosome play opposing roles in regulation of cullin neddylation
	binds to the components of the neddylation pathway (DCUN1D1, UBE2M, and CAND1)
	binding CAND1
	interacting with PLK4 (is critical for the degradation of active PLK4 following deregulation of cyclin E/cyclin-dependent kinase 2 activity, as is frequently observed in human cancer cells, as well as for baseline PLK4 protein stability)
	critical for the ubiquitin-dependent suppression of the KDM4A-dependent faster S phase progression
	DRG2 was a substrate of a SKP1-CUL1-F-box E3 ligase complex and inhibition the function of Cullin1 prevented the degradation of DRG2 during apoptosis
	SF3B3 overexpression reduces the binding of adaptor protein SKP1 and substrate receptor SKP2 to CUL1, whereas it has no effect on CAND1 binding to CUL1
	CUL1 promoted MTOR activity and cap-dependent translation by enhancing the ubiquitination and degradation of DEPTOR
	YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators (CUL4A, DDB1, CUL1, SKP2)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   significantly associated with high-grade tumours and poor prognosis tumoral     --over   in renal cell carcinoma (RCC) tumoral     --over   in melanoma, enhancing melanoma cell proliferation by promoting G1-S phase transition tumoral     --over   positively associated with lymph node metastasis and tumor diameter tumoral     --over   significantly increased in human glioma, and it may be involved in proliferation, migration and invasion of glioma cells

Susceptibility

may affect the susceptibility of rheumatoid arthritis (RA) via altering lymphocyte signal transduction

Variant & Polymorphism other	possible role of CUL1 variation(s) in RA and its response to methotrexate

Candidate gene
Marker	its expression may therefore be crucial for the prediction of disease outcome in breast cancer patients
	CUL1 may be an important prognosis marker for human hepatocellular carcinoma (HCC)
	may serve as promising prognostic markers in colorectal cancer (CRC) patients
Therapy target
	System Type Disorder Pubmed cancer urinary   CUL1 may constitute a potential therapeutic target in enal cell carcinoma (RCC)

ANIMAL & CELL MODELS

	dysregulation of cyclin E and early embryonic lethality in CUL1-/-
	cul1-/- sequestrate and inactivate Skp1 leading to genetic instability and neoplastic transformation