Q16849 · PTPRN_HUMAN
- ProteinReceptor-type tyrosine-protein phosphatase-like N
- GenePTPRN
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids979 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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-cleaved cytosolic fragment
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).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 448-449 | Cleavage | ||||
Sequence: KS |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | axon terminus | |
Cellular Component | endosome | |
Cellular Component | Golgi apparatus | |
Cellular Component | neuronal cell body | |
Cellular Component | nucleus | |
Cellular Component | perikaryon | |
Cellular Component | plasma membrane | |
Cellular Component | secretory granule | |
Cellular Component | synapse | |
Cellular Component | transport vesicle membrane | |
Molecular Function | spectrin binding | |
Molecular Function | transcription factor binding | |
Molecular Function | ubiquitin-like protein ligase binding | |
Biological Process | dense core granule maturation | |
Biological Process | insulin secretion | |
Biological Process | insulin secretion involved in cellular response to glucose stimulus | |
Biological Process | luteinization | |
Biological Process | positive regulation of transcription by RNA polymerase II | |
Biological Process | positive regulation of type B pancreatic cell proliferation | |
Biological Process | regulation of secretion | |
Biological Process | response to reactive oxygen species |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameReceptor-type tyrosine-protein phosphatase-like N
- Short namesR-PTP-N
- Alternative names
- Cleaved into 3 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ16849
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
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
ICA512-cleaved cytosolic fragment
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 35-575 | Lumenal | ||||
Sequence: VSAHGCLFDRRLCSHLEVCIQDGLFGQCQVGVGQARPLLQVTSPVLQRLQGVLRQLMSQGLSWHDDLTQYVISQEMERIPRLRPPEPRPRDRSGLAPKRPGPAGELLLQDIPTGSAPAAQHRLPQPPVGKGGAGASSSLSPLQAELLPPLLEHLLLPPQPPHPSLSYEPALLQPYLFHQFGSRDGSRVSEGSPGMVSVGPLPKAEAPALFSRTASKGIFGDHPGHSYGDLPGPSPAQLFQDSGLLYLAQELPAPSRARVPRLPEQGSSSRAEDSPEGYEKEGLGDRGEKPASPAVQPDAALQRLAAVLAGYGVELRQLTPEQLSTLLTLLQLLPKGAGRNPGGVVNVGADIKKTMEGPVEGRDTAELPARTSPMPGHPTASPTSSEVQQVPSPVSSEPPKAARPPVTPVLLEKKSPLGQSQPTVAGQPSARPAAEEYGYIVTDQKPLSLAAGVKLLEILAEHVHMSSGSFINISVVGPALTFRIRHNEQNLSLADVTQQAGLVKSELEAQTGLQILQTGVGQREEAAAVLPQTAHSTSPMR | ||||||
Transmembrane | 576-600 | Helical | ||||
Sequence: SVLLTLVALAGVAGLLVALAVALCV | ||||||
Topological domain | 601-979 | Cytoplasmic | ||||
Sequence: RQHARQQDKERLAALGPEGAHGDTTFEYQDLCRQHMATKSLFNRAEGPPEPSRVSSVSSQFSDAAQASPSSHSSTPSWCEEPAQANMDISTGHMILAYMEDHLRNRDRLAKEWQALCAYQAEPNTCATAQGEGNIKKNRHPDFLPYDHARIKLKVESSPSRSDYINASPIIEHDPRMPAYIATQGPLSHTIADFWQMVWESGCTVIVMLTPLVEDGVKQCDRYWPDEGASLYHVYEVNLVSEHIWCEDFLVRSFYLKNVQTQETRTLTQFHFLSWPAEGTPASTRPLLDFRRKVNKCYRGRSCPIIVHCSDGAGRTGTYILIDMVLNRMAKGVKEIDIAATLEHVRDQRPGLVRSKDQFEFALTAVAEEVNAILKALPQ |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_051762 | 419 | in dbSNP:rs35314717 | |||
Sequence: S → R | ||||||
Mutagenesis | 506 | Reduces N-glycosylation. | ||||
Sequence: N → A | ||||||
Mutagenesis | 524 | Reduces N-glycosylation. | ||||
Sequence: N → A | ||||||
Mutagenesis | 553 | Impairs normal processing and leads to retention in the endoplasmic reticulum and degradation. | ||||
Sequence: G → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,127 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, modified residue (large scale data), modified residue, glycosylation, cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-34 | UniProt | |||||
Sequence: MRRPRRPGGLGGSGGLRLLLCLLLLSSRPGGCSA | |||||||
Chain | PRO_0000438079 | 35-448 | UniProt | ICA512-N-terminal fragment | |||
Sequence: VSAHGCLFDRRLCSHLEVCIQDGLFGQCQVGVGQARPLLQVTSPVLQRLQGVLRQLMSQGLSWHDDLTQYVISQEMERIPRLRPPEPRPRDRSGLAPKRPGPAGELLLQDIPTGSAPAAQHRLPQPPVGKGGAGASSSLSPLQAELLPPLLEHLLLPPQPPHPSLSYEPALLQPYLFHQFGSRDGSRVSEGSPGMVSVGPLPKAEAPALFSRTASKGIFGDHPGHSYGDLPGPSPAQLFQDSGLLYLAQELPAPSRARVPRLPEQGSSSRAEDSPEGYEKEGLGDRGEKPASPAVQPDAALQRLAAVLAGYGVELRQLTPEQLSTLLTLLQLLPKGAGRNPGGVVNVGADIKKTMEGPVEGRDTAELPARTSPMPGHPTASPTSSEVQQVPSPVSSEPPKAARPPVTPVLLEKK | |||||||
Chain | PRO_0000025451 | 35-979 | UniProt | Receptor-type tyrosine-protein phosphatase-like N | |||
Sequence: VSAHGCLFDRRLCSHLEVCIQDGLFGQCQVGVGQARPLLQVTSPVLQRLQGVLRQLMSQGLSWHDDLTQYVISQEMERIPRLRPPEPRPRDRSGLAPKRPGPAGELLLQDIPTGSAPAAQHRLPQPPVGKGGAGASSSLSPLQAELLPPLLEHLLLPPQPPHPSLSYEPALLQPYLFHQFGSRDGSRVSEGSPGMVSVGPLPKAEAPALFSRTASKGIFGDHPGHSYGDLPGPSPAQLFQDSGLLYLAQELPAPSRARVPRLPEQGSSSRAEDSPEGYEKEGLGDRGEKPASPAVQPDAALQRLAAVLAGYGVELRQLTPEQLSTLLTLLQLLPKGAGRNPGGVVNVGADIKKTMEGPVEGRDTAELPARTSPMPGHPTASPTSSEVQQVPSPVSSEPPKAARPPVTPVLLEKKSPLGQSQPTVAGQPSARPAAEEYGYIVTDQKPLSLAAGVKLLEILAEHVHMSSGSFINISVVGPALTFRIRHNEQNLSLADVTQQAGLVKSELEAQTGLQILQTGVGQREEAAAVLPQTAHSTSPMRSVLLTLVALAGVAGLLVALAVALCVRQHARQQDKERLAALGPEGAHGDTTFEYQDLCRQHMATKSLFNRAEGPPEPSRVSSVSSQFSDAAQASPSSHSSTPSWCEEPAQANMDISTGHMILAYMEDHLRNRDRLAKEWQALCAYQAEPNTCATAQGEGNIKKNRHPDFLPYDHARIKLKVESSPSRSDYINASPIIEHDPRMPAYIATQGPLSHTIADFWQMVWESGCTVIVMLTPLVEDGVKQCDRYWPDEGASLYHVYEVNLVSEHIWCEDFLVRSFYLKNVQTQETRTLTQFHFLSWPAEGTPASTRPLLDFRRKVNKCYRGRSCPIIVHCSDGAGRTGTYILIDMVLNRMAKGVKEIDIAATLEHVRDQRPGLVRSKDQFEFALTAVAEEVNAILKALPQ | |||||||
Disulfide bond | 40 | UniProt | Interchain (with C-40 or C-47); in multimeric form | ||||
Sequence: C | |||||||
Disulfide bond | 47 | UniProt | Interchain (with C-40 or C-47); in multimeric form | ||||
Sequence: C | |||||||
Disulfide bond | 53↔62 | UniProt | |||||
Sequence: CIQDGLFGQC | |||||||
Modified residue (large scale data) | 226 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 301 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 308 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 345 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Glycosylation | 441 | UniProt | O-linked (GalNAc...) threonine | ||||
Sequence: T | |||||||
Chain | PRO_0000438080 | 449-979 | UniProt | ICA512-transmembrane fragment | |||
Sequence: SPLGQSQPTVAGQPSARPAAEEYGYIVTDQKPLSLAAGVKLLEILAEHVHMSSGSFINISVVGPALTFRIRHNEQNLSLADVTQQAGLVKSELEAQTGLQILQTGVGQREEAAAVLPQTAHSTSPMRSVLLTLVALAGVAGLLVALAVALCVRQHARQQDKERLAALGPEGAHGDTTFEYQDLCRQHMATKSLFNRAEGPPEPSRVSSVSSQFSDAAQASPSSHSSTPSWCEEPAQANMDISTGHMILAYMEDHLRNRDRLAKEWQALCAYQAEPNTCATAQGEGNIKKNRHPDFLPYDHARIKLKVESSPSRSDYINASPIIEHDPRMPAYIATQGPLSHTIADFWQMVWESGCTVIVMLTPLVEDGVKQCDRYWPDEGASLYHVYEVNLVSEHIWCEDFLVRSFYLKNVQTQETRTLTQFHFLSWPAEGTPASTRPLLDFRRKVNKCYRGRSCPIIVHCSDGAGRTGTYILIDMVLNRMAKGVKEIDIAATLEHVRDQRPGLVRSKDQFEFALTAVAEEVNAILKALPQ | |||||||
Glycosylation | 506 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 524 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue (large scale data) | 628 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Chain | PRO_0000438081 | 659-979 | UniProt | ICA512-cleaved cytosolic fragment | |||
Sequence: SQFSDAAQASPSSHSSTPSWCEEPAQANMDISTGHMILAYMEDHLRNRDRLAKEWQALCAYQAEPNTCATAQGEGNIKKNRHPDFLPYDHARIKLKVESSPSRSDYINASPIIEHDPRMPAYIATQGPLSHTIADFWQMVWESGCTVIVMLTPLVEDGVKQCDRYWPDEGASLYHVYEVNLVSEHIWCEDFLVRSFYLKNVQTQETRTLTQFHFLSWPAEGTPASTRPLLDFRRKVNKCYRGRSCPIIVHCSDGAGRTGTYILIDMVLNRMAKGVKEIDIAATLEHVRDQRPGLVRSKDQFEFALTAVAEEVNAILKALPQ | |||||||
Cross-link | 754 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K |
Post-translational modification
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts (via cytoplasmic domain) with phosphorylated SNTB2; this protects PTPRN against cleavage by CAPN1 to produce ICA512-CCF. Dephosphorylation of SNTB2 upon insulin stimulation disrupts the interaction and results in PTPRN cleavage (PubMed:11483505).
Interacts with SNX19 (PubMed:16273344).
ICA512-CCF interacts with PIAS4; in the nucleus (PubMed:15596545).
Interacts with STAT5B (phosphorylated); down-regulated by ICA512-CCF sumoylation; ICA512-CCF prevents STAT5B dephosphorylation; ICA512-CCF mediates interaction of STAT5B with PIAS4 (PubMed:15596545, PubMed:16622421).
Interacts (via RESP18 homology domain) with insulin and proinsulin (PubMed:26836020).
Interacts with PTPRN2, PTPRA and PTPRE (By similarity).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 35-131 | RESP18 homology domain | ||||
Sequence: VSAHGCLFDRRLCSHLEVCIQDGLFGQCQVGVGQARPLLQVTSPVLQRLQGVLRQLMSQGLSWHDDLTQYVISQEMERIPRLRPPEPRPRDRSGLAP | ||||||
Region | 112-173 | Disordered | ||||
Sequence: RIPRLRPPEPRPRDRSGLAPKRPGPAGELLLQDIPTGSAPAAQHRLPQPPVGKGGAGASSSL | ||||||
Compositional bias | 113-129 | Basic and acidic residues | ||||
Sequence: IPRLRPPEPRPRDRSGL | ||||||
Region | 289-329 | Disordered | ||||
Sequence: SRARVPRLPEQGSSSRAEDSPEGYEKEGLGDRGEKPASPAV | ||||||
Compositional bias | 307-321 | Basic and acidic residues | ||||
Sequence: DSPEGYEKEGLGDRG | ||||||
Region | 393-439 | Disordered | ||||
Sequence: VEGRDTAELPARTSPMPGHPTASPTSSEVQQVPSPVSSEPPKAARPP | ||||||
Compositional bias | 410-429 | Polar residues | ||||
Sequence: GHPTASPTSSEVQQVPSPVS | ||||||
Region | 449-575 | Sufficient for dimerization of proICA512 | ||||
Sequence: SPLGQSQPTVAGQPSARPAAEEYGYIVTDQKPLSLAAGVKLLEILAEHVHMSSGSFINISVVGPALTFRIRHNEQNLSLADVTQQAGLVKSELEAQTGLQILQTGVGQREEAAAVLPQTAHSTSPMR | ||||||
Region | 601-732 | Sufficient for dimerization of proICA512 | ||||
Sequence: RQHARQQDKERLAALGPEGAHGDTTFEYQDLCRQHMATKSLFNRAEGPPEPSRVSSVSSQFSDAAQASPSSHSSTPSWCEEPAQANMDISTGHMILAYMEDHLRNRDRLAKEWQALCAYQAEPNTCATAQGE | ||||||
Region | 643-680 | Disordered | ||||
Sequence: NRAEGPPEPSRVSSVSSQFSDAAQASPSSHSSTPSWCE | ||||||
Compositional bias | 652-680 | Polar residues | ||||
Sequence: SRVSSVSSQFSDAAQASPSSHSSTPSWCE | ||||||
Domain | 709-969 | Tyrosine-protein phosphatase | ||||
Sequence: LAKEWQALCAYQAEPNTCATAQGEGNIKKNRHPDFLPYDHARIKLKVESSPSRSDYINASPIIEHDPRMPAYIATQGPLSHTIADFWQMVWESGCTVIVMLTPLVEDGVKQCDRYWPDEGASLYHVYEVNLVSEHIWCEDFLVRSFYLKNVQTQETRTLTQFHFLSWPAEGTPASTRPLLDFRRKVNKCYRGRSCPIIVHCSDGAGRTGTYILIDMVLNRMAKGVKEIDIAATLEHVRDQRPGLVRSKDQFEFALTAVAEE |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
Q16849-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length979
- Mass (Da)105,848
- Last updated1997-11-01 v1
- ChecksumA852B9063D29399D
Q16849-2
- Name2
- Differences from canonical
- 479-508: KPLSLAAGVKLLEILAEHVHMSSGSFINIS → N
Q16849-3
- Name3
- Differences from canonical
- 1-90: Missing
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_045867 | 1-90 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 113-129 | Basic and acidic residues | ||||
Sequence: IPRLRPPEPRPRDRSGL | ||||||
Compositional bias | 307-321 | Basic and acidic residues | ||||
Sequence: DSPEGYEKEGLGDRG | ||||||
Compositional bias | 410-429 | Polar residues | ||||
Sequence: GHPTASPTSSEVQQVPSPVS | ||||||
Alternative sequence | VSP_043654 | 479-508 | in isoform 2 | |||
Sequence: KPLSLAAGVKLLEILAEHVHMSSGSFINIS → N | ||||||
Compositional bias | 652-680 | Polar residues | ||||
Sequence: SRVSSVSSQFSDAAQASPSSHSSTPSWCE | ||||||
Sequence conflict | 673 | in Ref. 2; BAG59024 | ||||
Sequence: S → G |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L18983 EMBL· GenBank· DDBJ | AAA90974.1 EMBL· GenBank· DDBJ | mRNA | ||
AK296335 EMBL· GenBank· DDBJ | BAG59024.1 EMBL· GenBank· DDBJ | mRNA | ||
AC114803 EMBL· GenBank· DDBJ | AAY24038.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471063 EMBL· GenBank· DDBJ | EAW70724.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471063 EMBL· GenBank· DDBJ | EAW70726.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC070053 EMBL· GenBank· DDBJ | AAH70053.1 EMBL· GenBank· DDBJ | mRNA | ||
X62899 EMBL· GenBank· DDBJ | CAA44688.2 EMBL· GenBank· DDBJ | mRNA |