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FLASH GENE

Symbol

PTPRZ1

contributors: mct - updated : 05-11-2013

HGNC name	protein tyrosine phosphatase, receptor-type, Z polypeptide 1
HGNC id	9685

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	7q31.3      Physical location : 121.513.158 - 121.702.088
Synonym name	receptor-type tyrosine phosphatase beta/zeta
	soluble protein phosphacan
Synonym symbol(s)	PYPZ, PTP18, RPTPB, HPTPZ, HPTPzeta, PTPZ, RPTPbeta, PTPRZ
EC.number	3.1.3.48

DNA

TYPE	functioning gene
STRUCTURE	188.93 kb     30 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	binding of HIF and ELK1 to the PTPRZ1 promoter region

MAPPING

cloned

Y

linked

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001206838 30 splicing 5589 NP_001193767 - 1455 - 2008 18713734 NM_002851 30 splicing 8169 NP_002842 - 2315 - 2008 18713734 NM_001206839 29 splicing 5568 NP_001193768 - 1448 predominantly expressed in hypothalamic astrocytes 2007 17927663 short PTPRZ1 isoform that uses its carbonic anhydrase (CAH) extracellular subdomain to interact with neuronal contactin interacts with neuronal contactin to mediate glial-GNRH1 neurone adhesiveness

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 mouth       highly Nervous   hindbrain cerebellum     Homo sapiens   brain limbic system hippocampus dentate gyrus   Respiratory respiratory tract trachea     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte Homo sapiens Nervous oligodendrocyte Homo sapiens Nervous Purkinje cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal carbonic anhydrase-like (CA-like), interacting directly with the second and third immunoglobulin repeats of the members of the contactin (CNTN) family of neural recognition molecules
	a fibronectin type III (FNIII) repeat
	two protein-tyrosine phosphatase domains
	a spacer region, and a large insert with attachment sites for chondroitin sulfate proteoglycan
	cytoplasmic portion is composed of two tyrosine phosphatase domains
	extracellular region of PTPRZ controling the maturation of oligodendrocytes

HOMOLOGY

interspecies

homolog to murine Ptprz

Homologene

FAMILY

protein-tyrosine phosphatase family, receptor class 5 subfamily

CATEGORY

receptor membrane tyrosine

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	may be involved in the regulation of specific developmental processes in the CNS
	CSPG4 and PTPRZ1 were both present in the evolving astroglial scar and, therefore, might play an important role in the blockade of successful CNS regeneration
	mediate cell adhesion and signaling events during development
	PTPRG, PTPRZ1 and CNTNs are a group of receptors and ligands involved in the manifold recognition events that underlie the construction of neural networks
	soluble protein phosphacan regulating critical step of oligodendrogenesis and is a potential promyelinating factor to repair myelin lesions in the CNS

CELLULAR PROCESS	cell life, differentiation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

PTN/PTPRZ1 signaling pathway may be constitutively activated and potentially function to constitutively activate ALK in human breast cancer

a component

PTPRZ1/CNTN1 complex is a previously unknown modulator of oligodendrogenesis

INTERACTION

DNA

RNA

small molecule

protein	uses pleiotrophin as a ligand, and Pleiotrophin inactivates the phosphatase activity of PTPRZ1, resulting in the increase of tyrosine phosphorylation levels of its substrates
	pleiotrophin-PTPRZ1 signaling controls subcellular localization of DNER and thereby regulates neuritogenesis
	MGAT5B-mediated glycosylation of PTPRZ1 promotes galectin-1 binding and PTPRZ1 levels of retention on the cell surface
	binds only to CNTN1, not other CNTN
	multiple substrate proteins, including G protein-coupled receptor kinase-interactor 1 (GIT1), membrane-associated guanylate kinase, WW and PDZ domain-containing 1 (MAGI1), and GTPase-activating protein for Rho GTPase (ARHGAP35)
	binds specifically to CNTN1 expressed at the surface of oligodendrocyte precursor cells
	IGFBP2 stimulates osteoblast differentiation and this effect is mediated through its heparin-binding domain-1 interacting with PTPRZ1
	IGFBP2/IGF1 stimulated vimentin binding to PTPRZ1 and this was required for PTPRZ1 polymerization

cell & other

REGULATION

activated by	preferential activation of PTPRZ1 by EPAS1 results at least in part from cooperative binding of EPAS1 and ELK1 to nearby sites on the PTPRZ1 promoter region

Other	regulated by PTN, for enhancing the activity of different systems important in cytoskeletal stability and the strength of cell-cell adhesion in stimulating degradation of cytoskeletal proteins
	MGAT5B is a regulator of PTPRZ1 signaling that influences cell-cell and cell-matrix interactions in the developing nervous system

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in a number of tumors and has been implicated in glioblastoma pathogenesis

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Ptprz-deficient adult mice display impairments in spatial and contextual learning
	Ptprz-deficient mice show that the binding of Ptprz to Cntn1 expressed at the surface of oligodendrocyte precursor cells inhibits their proliferation and promotes their development into mature oligodendrocytes