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FLASH GENE

Symbol

ALPL

contributors: mct - updated : 07-12-2016

HGNC name	alkaline phosphatase, liver/bone/kidney
HGNC id	438

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	69.43 kb     12 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	pter - ALPL ,HOPS1 - FUCA1 - RH - D1S57 - SLC2A1 SLC2A1 - MYCL1 - D1S15 - cen
Authors	CEPH (91)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000478 12 - 2613 NP_000469 - 524 - 2015 25775211 NM_001127501 11 - 2448 NP_001120973 - 469 - 2015 25775211 NM_001177520 10 - 2332 NP_001170991 - 447 - 2015 25775211

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       moderately Nervous brain       moderately Homo sapiens Reproductive male system prostate     moderately Respiratory lung       highly Urinary kidney         Visual eye retina       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	five potential N-glycosylation sites at N140, N230, N271, N303 and N430
	a complex of identical subunits, each subunit containing one active site
	two zinc Zn2+ molecules and magnesium Mg2+ as a cofactor

conjugated

GlycoP , MetalloP

mono polymer

homomer , dimer

HOMOLOGY

interspecies	homolog to murine Akp2
	homolog to Drosophila CG5656
	homolog to C.elegans C15B12.4

Homologene

FAMILY

alkaline phosphatase proteins family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
text	membrane bound glycosylated enzyme
	anchored to the external surface of the plasma membranes by means of a GPI (glycosylphosphatidylinositol) anchor

basic FUNCTION	involved in matrix mineralization
	regulating both ligand availability and protein expression of P2RX7, is essential for axonal development
	regulates inhibitory extracellular pyrophosphate through its pyrophosphatase activity to control mineral propagation in the matrix
	prominent non-redundant roles for both PHOSPHO1 and ALPL in dentin mineralization
	associated with earliest cementoblasts near forming acellular and cellular cementum
	during skeletal mineralization, the building Ca2+ gradient first activates ALPL, but gradually inactivates it at high Ca2+ concentrations, toward completion of mineralization
	is present on neuronal membranes and induces neuronal toxicity via MAPT dephosphorylation
	GPI-anchored ALPL can likely give rise to long reaching modifications that could influence membrane processes halfway through the bilayer

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	skeletal development

PATHWAY

metabolism

signaling

metabolism phosphocalcic

a component

INTERACTION

DNA

RNA

small molecule	metal binding, cofactor,
	zinc Zn2+
	magnesium Mg2+

protein	cooperative zinc handling of SLC30A4, metallothionein and SLC30A1 in the cytoplasm is required for full activation of ALPL in the early secretory pathway (ESP), and present clear evidence that the activation process of zinc enzymes is elaborately controlled
	FRP2 may promote cardiac fibrocalcification through coordinate activation of tolloid-like metalloproteinases and ALPL
	ACPT is expressed earlier than tissue-nonspecific alkaline phosphatase (ALPL) and partly overlaps with ALPL in differentiating odontoblasts

cell & other

REGULATION

Other

is activated not simply by passive zinc binding but by an elaborate two-step mechanism via protein stabilization followed by enzyme conversion from the apo- to the holo-form with zinc loaded by ZnT complexes in the early secretory pathway

ASSOCIATED DISORDERS

corresponding disease(s)

HOPS1

related resource

Tissue Nonspecific Alkaline Phosphatase Gene Mutation Database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   in cancer cells, seminoma constitutional       gain of function its activity is significantly increased in the brain in both the sporadic and familial forms of Alzheimer disease

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS