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FLASH GENE

Symbol

SLC39A4

contributors: snh - updated : 23-02-2009

HGNC name	solute carrier family 39 (zinc transporter), member 4
HGNC id	17129

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AEZ acrodermatitis enteropathica
Location	8q24.3      Physical location : 145.637.798 - 145.642.273
Synonym name	zinc transporter ZIP4
	acrodermatitis enteropathica, zinc-deficiency type
	Zrt- and Irt-like protein 4
Synonym symbol(s)	ZIP4, AEZ, FLJ20327, MGC74741

DNA

TYPE	functioning gene
STRUCTURE	4.48 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D8S1836 - D8S373 - SLC39A4 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_017767 11 - 2342 NP_060237 73 622 intestin, pancreas (beta-cells) 2004 15358787 Westren blot abalysis from intestine and visceral yolk sac revealed a major 37 kDa band, which represents ZIP4 lacking the N-terminal extracellular domain or ectodomain (PMID: 18936158) NM_130849 12 - 2192 NP_570901 75 647 intestin, pancreas (beta-cells) 2004 15358787

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 intestine small intestine duodenum   highly   intestine small intestine ileum   highly   intestine small intestine     moderately   intestine small intestine jejunum   highly   intestine large intestine colon   highly   intestine large intestine caecum   highly   stomach       lowly Endocrine pancreas islet of Langerhans     predominantly Respiratory lung       lowly

cells

System Cell Pubmed Species Stage Rna symbol Digestive enterocyte

cell lineage
cell lines	ZIP4 mRNA expression is significantly higher in human pancreatic cancer cells than normal pancreatic ductal epithelial cells
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	eight transmembrane domains organized in two blocks of three and five segments separated by a variable intracytoplasmic metal binding site
	a cytoplasmic histidine-rich domain essential for ubiquitin-dependent degradation of ZIP4 and protection against zinc toxicity
	an ectodomain which is cleaved and internalized during periods of zinc deficiency

HOMOLOGY

interspecies	ortholog to Slc39a4, mus musculus
	ortholog to Slc39a4, Rattus norvegicus
	ortholog to SLC39A4, Pan troglodytes
	ortholog to slc39a4, Danio rerio

Homologene

FAMILY

zinc/iron-regulated transporter-like protein (ZIP) family

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome

basic FUNCTION	involved in intestinal absorption and homeostasis of zinc
	zinc importer required for zinc uptake in enterocytes and other cell types
	playing an important role in maintaining the cellular zinc level by uptaking dietary zinc into intestinal epithelial cells and releasing zinc from vesicular compartments
	in mice ZIP4 is essential for survival of the early embryo,and heterozygosity hypersensitizes mice to the effects of zinc deficiency

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

active transport

text	zinc specific transporter

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

AEZ

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   significantly higher in pancreatic cancer cells than pancreatic ductal epithelium

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive pancreas targeted to control pancreatic cancer growth

ANIMAL & CELL MODELS

bovine hereditary zinc deficiency has a clinical presentation similar to acrodermatitis enteropathica in humans