ELM Details - CLV

CLV_TASPASE1

Functional site class:	Taspase1 cleavage site
Functional site description:	Taspase1 is a threonine aspartase which was first identified as the trithorax (MLL) family processing enzyme.
ELM(s):	CLV_TASPASE1
CLV_TASPASE1 description:	MLL (alias HRX), a SET domain histone methyltransferase involved in epigenetic gene regulation, is cleaved at two sites (PMID:12482972; PMID: 12393701) by a threonine aspartase termed Taspase1 (PMID:14636557). Cleavage is between the conserved Asp-Gly in the motif. The resulting N- and C-terminal fragments (p320 and p180) associate to form a stable heterodimer which localises to the nucleus (PMID:12482972). In the absence of Taspase1 (by RNAi), MLL is not cleaved and HOX gene expression becomes deregulated (PMID:14636557). It was recently pointed out that the MLL cleavage sites are virtually identical to a conserved cleavage site in the general transcription factor TFIIA (the alfa/beta precursor) (PMID:15257296). Although it has not been shown that Taspase1 cleaves TFIIA, the regular expression for this motif takes this possibility into account. (e)
Pattern:	Q[MLVI]DG..[DE]
Present in taxon(s):	Eukaryota
Not represented in taxon(s):

See instances for CLV_TASPASE1

Abstract

MLL (alias HRX), a SET domain histone methyltransferase involved in epigenetic gene regulation, is cleaved at two sites (PMID:12482972; PMID: 12393701) by a threonine aspartase termed Taspase1 (PMID:14636557). Cleavage is between the conserved Asp-Gly in the motif. The resulting N- and C-terminal fragments (p320 and p180) associate to form a stable heterodimer which localises to the nucleus (PMID:12482972). In the absence of Taspase1 (by RNAi), MLL is not cleaved and HOX gene expression becomes deregulated (PMID:14636557). It was recently pointed out that the MLL cleavage sites are virtually identical to a conserved cleavage site in the general transcription factor TFIIA (the alfa/beta precursor) (PMID:15257296). Although it has not been shown that Taspase1 cleaves TFIIA, the regular expression for this motif takes this possibility into account.

Selected references

Hoiby T, Mitsiou DJ, Zhou H, Erdjument-Bromage H, Tempst P, Stunnenberg HG

Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA.

EMBO J 2004 Aug 4;23(15) : 3083-91.

PMID: 15257296

Hsieh JJ, Cheng EH, Korsmeyer SJ

Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression.

Cell 2003 Oct 31;115(3) : 293-303.

PMID: 14636557

Hsieh JJ, Ernst P, Erdjument-Bromage H, Tempst P, Korsmeyer SJ

Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization.

Mol Cell Biol 2003 Jan;23(1) : 186-94.

PMID: 12482972

Yokoyama A, Kitabayashi I, Ayton PM, Cleary ML, Ohki M

Leukemia proto-oncoprotein MLL is proteolytically processed into 2 fragments with opposite transcriptional properties.

Blood 2002 Nov 15;100(10) : 3710-8.

PMID: 12393701

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

Biological Process

transcription

GO:0006350

Cellular Component

nucleus

GO:0005634

Molecular Function

Instances for CLV_TASPASE1

Sequence	Position	Subsequence (Click for evidence information)	PDB	Gene Name	Protein Description	Organism
HRX_HUMAN	2664-2670	RSAEGQVDGADDLSTSDE	-	Name=MLL; Synonyms=ALL1, HRX, HTRX, TRX1;	Zinc finger protein HRX (ALL-1) (Trithorax-like protein).	Homo sapiens (Human).
HRX_HUMAN	2716-2722	LPKISQLDGVDDGTESDT	-	Name=MLL; Synonyms=ALL1, HRX, HTRX, TRX1;	Zinc finger protein HRX (ALL-1) (Trithorax-like protein).	Homo sapiens (Human).