Human PTPRA is located at Chromosome 20: 2844830-3019722 bp. Its Entrez gene ID is 5786 (NCBI) or 9664 (HGNC). PTPRA consists of 21 coding exons (protein isoform 1) or 20 coding exons (protein isoform 2). 82 organisms have orthologs with human gene PTPRA. The PTPRA gene is conserved across species including chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and C. elegans.

Three transcript variants encoding different isoforms have been found for PTPRA gene. Transcript variant 1 (NM_002836.3) represents the longest transcript and encodes the longer isoform1 including 802 aa residues. Transcript variant 2 (NM_080840.2) contains an alternate 5 UTR exon which is different from transcript variant 1, and lacks exons one to five and coding exon ten, when compared to variant 1. Transcript variant 3 (NM_080841.2) contains an additional exon within the 5 UTR, when compared to variant 2. Transcript variant 2 and transcript variant 3 encode the short isoform 2. Isoform 2 lacks a 9 aa internal segment, because exon ten missing, compared to Isoform 1. It is known that the expression of RPTPa mRNA is increased by 2 to 10-fold in 70% (10 of 14) of late-stage colon tumors compared to normal colonic mucosa (Tabiti et al., 1995). Another study demonstrated that RPTPa mRNA was increased in 29% (15 of 51) of primary breast carcinomas and correlated with its protein overexpression (Ardini et al., 2000). Recently, PTPRA mRNA splice mutants were described from Chinese colon, breast, and liver tumors (Huang et al., 2011).

One pseudogene (ID: PGOHUM00000236674) for PTPRA described on the website Pseudogenes.org.

The protein encoded by PTPRA gene is a member of the protein tyrosine phosphatase (PTP) family. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. Three alternatively spliced variants of this gene are well known to encode two distinct isoforms differing only in their extracellular region. The shorter form, expressed in most tissues, has 793 aa of which 123 are extracellular. The longer form, RPTPa802, has nine extra amino acids located just before the transmembrane region and is expressed only in a few tissues, especially in brain. It is noted that extensive N- and O-linked glycosylation of RPTPa gives rise to a mature 130 kD form of the protein (Daum et al., 1994).

PTPRA gene was originally isolated by PCR-based PTP identification and cloning from several groups (Sap et al., 1990; Kaplan et al., 1990; Matthews et al., 1990). The protein, RPTPa, is a widely distributed transmembrane molecule that is particularly highly expressed in the brain and kidney (Sap et al., 1990). RPTPa is highly expressed in the developing central and peripheral nervous system of mouse, especially in the dorsal root ganglia, cranial ganglia and adrenal gland (den Hertog et al., 1996). During chicken development, chicken RPTPa (ChPTPa) is expressed in pre-migratory and migrating granule cells, and in Bergmann glia and their radial processes as determined by in situ hybridization and immunostaining (Fang et al., 1996). Taken together, these studies demonstrate that RPTPa is highly expressed in the developing brain of various species (Shock et al., 1995; Yang and Friesel, 1998; den Hertog et al., 1999).

Membrane. A typical single-pass type I membrane protein.

Generally, RPTPa has been shown to dephosphorylate and activate Src family kinases (SFKs), and is implicated in the regulation of integrin signaling, cell adhesion and proliferation. Studies involving overexpression of RPTPa were the first to demonstrate that PTP can dephosphorylate tyrosine 527 of Src and activate c-Src in vivo and in vitro. This activation causes cellular transformation (Zheng et al., 1992). Dephosphorylation of tyrosine 527 of c-Src in RPTPa overexpressing P19 embryonal carcinoma cells activates c-Src and induces neuronal differentiation (den Hertog et al., 1993). This observation has been independent validated in studied involving RPTPa knockout mice that exhibit a dramatic decrease (50-70%) in c-Src activity in the brain (Ponniah et al., 1999; Su et al., 1999).
In addition to Src, RPTPa regulates other Src family kinases. As an example, Fyn dephosphorylation and activation is observed in cells co-expressing RPTPa and Fyn (Bhandari et al., 1998). Additionally, dephosphorylation of c-Src, Fyn and Yes, but not Lyn, was observed in A431 cells expressing RPTPa (Harder et al., 1998), indicating some degree of specificity of RPTPa. It is noteworthy that there is no evidence of gross physical abnormalities in the RPTPa-deficient mice, indicating that RPTPa is not essential for embryonic development. One explanation is that certain functions of RPTPa are compensated for by other PTPs in mice deficient in RPTPa (Pallen, 2003).
RPTPa is involved in promoting integrin signaling through activation of SFKs. An earlier study shows that c-Src activation by RPTPa can increase the association of c-Src with focal adhesion kinase (FAK), and enhance tyrosine phosphorylation of the Src/FAK substrate paxillin (Harder et al., 1998). Recently, Sun et al. described a novel molecular complex of RPTPa-BCAR3-Cas-Src that is important in integrin signaling (Sun et al., 2012). This complex forms in response to RPTPaTyr789 phosphorylation and mediates Cas localization to focal adhesions and Cas downstream signaling to promote cell migration (Sun et al., 2012). More recently, Cheng et al. identified two roles of Grb2 in integrin signaling: one as a regulator of paxillin stability and upstream promoter of FAKTyr397 phosphorylation that is required for Src-FAK complex activation and another as an essential coordinator of RPTPa and activation of the Src-FAK interaction thus enabling the phosphorylation of RPTPaTyr789 (Cheng et al., 2014).

Huang et al. sequence RPTPa cDNAs from five types of Chinese human tumors and paired normal samples. They observed three sequences encoding truncated proteins, designated RPTPa245, RPTPa445, or RPTPa652, lacking the D1 domain or both the D1 and D2 domains. One mutant, RPTPa245, widely expressed in colon, breast, and liver tumors from individuals of Chinese origin, can form an RPTPa-RPTPa245 heterodimer and activate c-Src. (Huang et al., 2011).