ELM Details - LIG

LIG_RB

Functional site class:	Rb ligand
Functional site description:	The LxCxE motif mediates protein-protein interaction with the retinoblastoma protein family members (pRb, p107 and p130 )
ELM(s):	LIG_RB
LIG_RB description:	Interacts with the Retinoblastoma protein
Pattern:	[LI].C.[DE]
Present in taxon(s):	Metazoa Viridiplantae
Not represented in taxon(s):

See instances for LIG_RB

Abstract

The LxCxE motif is a ligand to the conserved "pocket region" in the B-domain of the retinoblastoma proteins (Rb) (e.g. PMID:11226179, PMID:12502741, PMID:10958676). The Rb family includes Rb, p107 and p130, and are best known for their repression of E2F mediated transcription outside S-phase of the cell cycle. The Rb proteins are phosphoproteins that are regulated by cyclin/CDKs, and LxCxE binding is inactivated by the phosphorylation of Thr821 and Thr826 in Rb. Repression is mediated by recruitment of histone deacetylases and methytransferases via the LxCxE binding pocket. The E2F family consists of 6 members, E2F-1 -6, all of which, except E2F-6, interacts with the large Rb pocket defined by the Rb-A and Rb-B domains. The LxCxE motif was first identified in the adenovirus E1A and papilloma virus E7 proteins (PMID: 2198278). These viral proteins use their LxCxE motifs to compete with E2F for binding to Rb, thereby alleviating the Rb-mediated repression. Mutations in LxCxE motifs or the Rb pocket can result in abnormal cell proliferation and cancer.

Selected references

Dahiya A, Gavin MR, Luo RX, Dean DC

Role of the LXCXE binding site in Rb function.

Mol Cell Biol 2000 Sep;20(18) : 6799-805.

PMID: 10958676

Jones RE, Wegrzyn RJ, Patrick DR, Balishin NL, Vuocolo GA, Riemen MW, Defeo-Jones D, Garsky VM, Heimbrook DC, Oliff A

Identification of HPV-16 E7 peptides that are potent antagonists of E7 binding to the retinoblastoma suppressor protein.

J Biol Chem 1990 Aug 5;265(22) : 12782-5.

PMID: 2198278

Kim HY, Ahn BY, Cho Y

Structural basis for the inactivation of retinoblastoma tumor suppressor by SV40 large T antigen.

EMBO J 2001 Jan 15;20(1) : 295-304.

PMID: 11226179

Lee C, Chang JH, Lee HS, Cho Y

Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor.

Genes Dev 2002 Dec 15;16(24) : 3199-212.

PMID: 12502741

Puga A, Barnes SJ, Dalton TP, Chang C, Knudsen ES, Maier MA

Aromatic hydrocarbon receptor interaction with the retinoblastoma protein potentiates repression of E2F-dependent transcription and cell cycle arrest.

J Biol Chem 2000 Jan 28;275(4) : 2943-50.

PMID: 10644764

This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process

  viral life cycle

GO:0016032

  cell proliferation

GO:0008283

  regulation of cell growth

GO:0001558

Cellular Component

  nucleus

GO:0005634

Molecular Function

  transcription factor

GO:0003700

  transcription regulator

GO:0030528

Instances for LIG_RB

Sequence	Position	Subsequence (Click for evidence information)	PDB	Gene Name	Protein Description	Organism
IFI4_MOUSE	423-427	DRQPKLVCGEHSFIKI	-	Name=Ifi204;	Interferon-activable protein 204 (Ifi-204) (Interferon-inducible protein p204).	Mus musculus (Mouse).
UBP4_HUMAN	459-463	LFKSTLVCPECAKVSV	-	Name=USP4; Synonyms=UNP, UNPH;	Ubiquitin carboxyl-terminal hydrolase 4 (EC 3.1.2.15) (Ubiquitin thioesterase 4) (Ubiquitin-specific-processing protease 4) (Deubiquitinating enzyme 4) (Ubiquitous nuclear protein homolog).	Homo sapiens (Human).
ELF1_HUMAN	51-55	NSYAGLACVEEPNDMI	-	Name=ELF1;	ETS-related transcription factor Elf-1 (E74-like factor 1).	Homo sapiens (Human).
AHR_HUMAN	331-335	HAADMLYCAESHIRMI	-	Name=AHR;	Aryl hydrocarbon receptor precursor (Ah receptor) (AhR).	Homo sapiens (Human).
SMCA2_HUMAN	1290-1294	AEVERLTCEEEEEKIF	-	Name=SMARCA2; Synonyms=BRM, SNF2A, SNF2L2;	Probable global transcription activator SNF2L2 (EC 3.6.1.-) (ATP- dependent helicase SMARCA2) (SNF2-alpha) (SWI/SNF-related matrix- associated actin-dependent regulator of chromatin subfamily A member 2) (hBRM).	Homo sapiens (Human).
BRE1B_HUMAN	109-113	TVEALLRCHESQGELS	-	Name=RNF40; Synonyms=BRE1B, KIAA0661;	E3 ubiquitin-protein ligase BRE1B (EC 6.3.2.-) (BRE1-B) (RING finger protein 40) (95 kDa retinoblastoma-associated protein) (RBP95).	Homo sapiens (Human).
TRAP1_HUMAN	525-529	KDTEVLFCFEQFDELT	-	Name=TRAP1; Synonyms=HSP75;	Heat shock protein 75 kDa, mitochondrial precursor (HSP 75) (Tumor necrosis factor type 1 receptor-associated protein) (TRAP-1) (TNFR- associated protein 1).	Homo sapiens (Human).
RBBP9_HUMAN	63-67	FMETELHCDEKTIIIG	-	Name=RBBP9; Synonyms=BOG, RBBP10;	Retinoblastoma-binding protein 9 (RBBP-9) (Retinoblastoma-binding protein 10) (RBBP-10) (B5T overexpressed gene protein) (Bog protein).	Homo sapiens (Human).
EID1_HUMAN	178-182	RLTEELGCDEIIDRE	-	Name=EID1; Synonyms=C15orf3, CRI1, RBP21; ORFNames=PNAS-22, PTD014;	EP300-interacting inhibitor of differentiation 1 (EID-1) (E1A-like inhibitor of differentiation 1) (CREBBP/EP300 inhibitory protein 1) (21 kDa pRb-associated protein).	Homo sapiens (Human).
CCND1_HUMAN	5-9	MEHQLLCCEVETIRR	-	Name=CCND1; Synonyms=BCL1, PRAD1;	G1/S-specific cyclin-D1 (PRAD1 oncogene) (BCL-1 oncogene).	Homo sapiens (Human).
PRDM2_HUMAN	310-314	VKEPEIRCDEKPEDLL	-	Name=PRDM2; Synonyms=RIZ;	PR domain zinc finger protein 2 (PR domain-containing protein 2) (Retinoblastoma protein-interacting zinc finger protein) (Zinc finger protein RIZ) (MTE-binding protein) (MTB-ZF) (GATA-3-binding protein G3B).	Homo sapiens (Human).
Q9WKM8_9VIRU	111-115	SVYQDLYCDEVLSSSS	-	-	Putative uncharacterized protein (Fragment).	Banana bunchy top virus.
POLN_RUBVT	1901-1905	AALLGLPCAEDYRALR	-	-	Non-structural polyprotein p200 (p200) [Contains: Protease p150 (EC 3.4.22.-) (p150); RNA-directed RNA polymerase/triphosphatase/helicase p90 (EC 2.7.7.48) (EC 3.6.1.15) (EC 3.6.1.-) (p90)].	Rubella virus (strain Therien) (RUBV).
Q8UYK9_WDV	194-198	FPTESLICHETIESWK	-	Name=repA;	Replication-associated protein A.	Wheat dwarf virus - [Enkoping1].
Q9WIJ4_9VIRU	110-114	LDMDDLSCRELLPPEE	-	Name=C10-Eg;	Cell cycle link (CLINK) protein.	Faba bean necrotic yellows virus.
VE7_HPV16	22-26	PETTDLYCYEQLNDSS	1GUX	Name=E7;	Protein E7.	Human papillomavirus type 16.
LT_SV40	103-107	FNEENLFCSEEMPSSD	-	-	Large T antigen (LT) (LT-AG).	Simian virus 40 (SV40).
PP71_HCMVA	216-220	DALEQLACSDPNTYIH	-	Name=UL82;	71 kDa upper matrix phosphoprotein (PP71) (Tegument protein UL82).	Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5).
RBBP8_HUMAN	153-157	HQAAELECEEDVIPDS	-	Name=RBBP8; Synonyms=CTIP;	Retinoblastoma-binding protein 8 (RBBP-8) (CtBP-interacting protein) (CtIP) (Retinoblastoma-interacting protein and myosin-like) (RIM).	Homo sapiens (Human).
HP1_DROME	61-65	EPENNLDCQDLIQQYE	-	Name=Su(var)205; Synonyms=HP1; ORFNames=CG8409;	Heterochromatin protein 1 (HP1) (Non-histone chromosomal protein C1A9 antigen).	Drosophila melanogaster (Fruit fly).
M3K5_HUMAN	916-920	AKAFILKCFEPDPDKR	-	Name=MAP3K5; Synonyms=ASK1, MAPKKK5, MEKK5;	Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5) (Apoptosis signal- regulating kinase 1) (ASK-1).	Homo sapiens (Human).
ARI4A_HUMAN	957-961	IGPETLVCHEVDLDDL	-	Name=ARID4A; Synonyms=RBBP1, RBP1;	AT-rich interactive domain-containing protein 4A (ARID domain- containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1).	Homo sapiens (Human).
JAD1A_HUMAN	1373-1377	SLEPNLFCDEEIPIKS	-	Name=JARID1A; Synonyms=RBBP2, RBP2;	Histone demethylase JARID1A (EC 1.14.11.-) (Jumonji/ARID domain- containing protein 1A) (Retinoblastoma-binding protein 2) (RBBP-2).	Homo sapiens (Human).
RFC1_HUMAN	662-666	TTTASLVCQELGYSYV	-	Name=RFC1; Synonyms=RFC140;	Replication factor C subunit 1 (Replication factor C large subunit) (RF-C 140 kDa subunit) (Activator 1 140 kDa subunit) (Activator 1 large subunit) (A1 140 kDa subunit) (DNA-binding protein PO-GA).	Homo sapiens (Human).
II2A_MOUSE	416-420	GNTIRLVCFELTSNAD	-	Name=Ifi202a; Synonyms=Ifi202;	Interferon-activable protein 202a (Ifi-202a) (Interferon-inducible protein p202a).	Mus musculus (Mouse).