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FLASH GENE

Symbol

PDLIM4

contributors: mct - updated : 19-03-2010

HGNC name	PDZ and LIM domain 4
HGNC id	16501

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	5q31.1      Physical location : 131.593.350 - 131.609.145
Synonym name	LIM domain protein
	LIM protein RIL
	reversion-induced LIM gene
	rat ril 1,homolog
	enigma homolog
Synonym symbol(s)	RILL, RIL1, RIL

DNA

TYPE	functioning gene
STRUCTURE	15.80 kb     7 Exon(s)

regulatory sequence	Promoter
text structure	two putative transcription start points (tsp)

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - IL4 - IL13 - RAD50 - IL5 - IRF1 - PDLIM4 - IL3 IL3 - qter

RNA

TRANSCRIPTS	type	messenger

text	with an alternative transcript missing exon six and the LIM domain (PMID: 9573374)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003687 7 splicing 2307 NP_003678 35.4 330 - 1998 9573374 NM_001131027 6 splicing 2189 NP_001124499 25.9 246 brain 1998 9573374 RILaltCterm 6 splicing - - 246 - 2011 21636573 shorter alternatively spliced isoform, intrinsically unstable due to an unstructured region at its C terminus, with a PEST motif that can destabilize heterologous target proteins lacks the sequence of exon 6 degraded by the core 20 S proteasome affects actin organization via interaction with full-length PDLIM4 functions as a dominant-negative modulator of PDLIM4-mediated actin reorganization accumulates particularly in response to oxidative stress

EXPRESSION

Type

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 mouth gingiva       Nervous brain         Reproductive male system prostate       Respiratory lung

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two N-terminal cysteine-rich LIM/double zinc finger motifs (LIM domains)
	a PDZ/DHR domain

HOMOLOGY

interspecies	homolog to rattus Ril 1
	ortholog to murine Ril-pending

Homologene

FAMILY

ALP/Enigma family of PDZ and LIM domain-containing adapter proteins

CATEGORY

transcription factor , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	may be involved in intracellular signaling cascade
	PDZ-LIM protein acting as a regulator of actin stress fiber turnover
	frequently lost in colon and other cancers as a result of epigenetic silencing, suppresses Src activation
	may function as a tumor suppressor, involved in the control of cell proliferation by associating with actin in prostate cancer cells
	implicated in regulation of actin stress fiber turnover

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

intracellular signaling cascade

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	associated with alpha-actinin via its PDZ domain
	interacting with PTPN13 and SRC (suppresses SRC activation through interacting with SRC and PTPN13, allowing PTPN13-dependent dephosphorylation of SRC at the activation loop)
	direct interaction of PDLIM4 with F-actin
	binds to alpha-actinin, enhances its ability to interact with actin filaments, and promotes formation of actin stress fibers

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   by hypermethylation in renal cell carcinoma tumoral     --low   by hypermethylation in acute myelogenous leukemia and colon cancer (60 p100 of cases)

Susceptibility

to osteoporosis

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     good candidate tumor suppressor gene silenced by hypermethylation in cancer

ANIMAL & CELL MODELS