PTPRN

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single catalytic domain, and thus represents a receptor-type PTP. This PTP was found to be an autoantigen that is reactive with insulin-dependent diabetes mellitus (IDDM) patient sera, and thus may be a potential target of autoimmunity in diabetes mellitus. [provided by RefSeq]

PTPRN

Plays a role in vesicle-mediated secretory processes (PubMed:24843546).
Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets (By similarity).
Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation (PubMed:24843546).
Plays a role in insulin secretion in response to glucose stimuli (PubMed:24843546).
Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain (By similarity).
In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (By similarity).
Required to maintain normal levels of renin expression and renin release (By similarity).
Seems to lack intrinsic enzyme activity (By similarity).
May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity).
ICA512-transmembrane fragment
ICA512-TMF regulates dynamics and exocytosis of insulin secretory granules (SGs); binding of ICA512-TMF to SNTB2/beta-2-syntrophin is proposed to restrain SGs mobility and exocytosis by tethering them to the actin cytoskeleton depending on UTRN; the function is inhibited by cytoplasmic ICA512-CFF dimerizing with ICA512-TMF and displacing SNTB2.
ICA512-cleaved cytosolic fragment
ICA512-CCF translocated to the nucleus promotes expression of insulin and other granule-related genes; the function implicates binding to and regulating activity of STAT5B probably by preventing its dephosphorylation and potentially by inducing its sumoylation by recruiting PIAS4 (PubMed:15596545, PubMed:16622421, PubMed:18178618).
Enhances pancreatic beta-cell proliferation by converging with signaling by STAT5B and STAT3 (PubMed:15596545, PubMed:16622421, PubMed:18178618).
ICA512-CCF located in the cytoplasm regulates dynamics and exocytosis of insulin secretory granules (SGs) by dimerizing with ICA512-TMF and displacing SNTB2 thus enhancing SGs mobility and exocytosis (PubMed:18824546, PubMed:20886068).

Dense core granule maturationManual Assertion Based On ExperimentIGI:GO_Central
Insulin secretionManual Assertion Based On ExperimentIGI:GO_Central
Insulin secretion involved in cellular response to glucose stimulusISS:UniProtKB
LuteinizationISS:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of type B pancreatic cell proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of secretionManual Assertion Based On ExperimentIBA:GO_Central
Response to reactive oxygen speciesManual Assertion Based On ExperimentIDA:UniProtKB

Membrane
Cytoplasmic vesicle, secretory vesicle membrane
Perikaryon
Cell projection, axon
Synapse
Cell membrane
Endosome
Detected on neuronal secretory vesicles, but not on synaptic vesicles. Colocalizes with insulin-containing secretory granules (PubMed:25561468).
Primarily detected on secretory vesicle membranes. Transiently found at the cell membrane, when secretory vesicles fuse with the cell membrane to release their cargo. Is then endocytosed and recycled to secretory vesicles via the Golgi apparatus membranes.
ICA512-transmembrane fragment
Cytoplasmic vesicle, secretory vesicle membrane
ICA512-cleaved cytosolic fragment
Nucleus

Autoantigen in insulin-dependent diabetes mellitus (IDDM).

Lumenal: 35-575
Helical: 576-600
Cytoplasmic: 601-979

N-glycosylated.
O-glycosylated with core 1 or possibly core 8 glycans.
Subject to proteolytic cleavage at multiple sites (PubMed:11483505).
Subject to cleavage on a pair of basic residues (By similarity).
On exocytosis of secretory granules in pancreatic beta-cells ICA512-TMF is transiently inserted in the plasma-membrane and cleaved by mu-type calpain CPN1 to yield ICA512-CCF (By similarity).
Sumoylated at two sites including Lys-754. Sumoylation decreases interaction with STAT5.