Biomarker: ASRGL1

Histology type: endometrioid endometrial carcinoma

Country: Finland

Region: Turku

Followed up time :

Subgroup 1 name : endometrial carcinoma cohort

Subgroup 1 number: 229

Subgroup 2 name: endometrial carcinoma cohort 2

Subgroup 2 number: 286

Conclusion: Loss of ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has a positive impact on survival. ASRGL1 immunohistochemistry has potential to become an additional tool for prognostication in cases where tailoring adjuvant treatment according to additional prognostic factors besides grade and stage is recommended.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : ≤75%

Expression elevation: The fraction of ASRGL1-immunoreactive tumor cells was scored semi-quantitatively in six classes (0–1%, 2–10%, 11–25%, 26–50%, 51–75% and N75%). Staining intensity was graded as negative, weak, moderate or strong. The cut-off value was determined in the discovery cohort using Kaplan–Meier analysis for frequency and intensity. Based on these analyses, the cutoff for “ASRGL1-high” was defined as ≥75% of tumor cells regardless of intensity.

Funtion Uniprot: Has both L-asparaginase and beta-aspartyl peptidase activity. May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester. Besides, has catalytic activity toward beta-aspartyl dipeptides and their methyl esters, including beta-L-Asp-L-Phe, beta-L-Asp-L-Phe methyl ester (aspartame), beta-L-Asp-L-Ala, beta-L-Asp-L-Leu and beta-L-Asp-L-Lys. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine.

UniProt ID: Q7L266

UniProt Link: https://www.uniprot.org/uniprotkb/Q7L266/entry

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in brain, kidney, testis and tissues of the gastrointestinal tract. Present in sperm (at protein level). Over-expressed in uterine, mammary, prostatic and ovarian carcinoma.

Subcellular UniProt: #Cytoplasm

Alternative name from UniProt:

Cleaved: Cleavage of a beta-linked Asp residue from the N-terminus of a polypeptide;Cleaved into 2 chains:Isoaspartyl peptidase/L-asparaginase alpha chain Isoaspartyl peptidase/L-asparaginase beta chain

Catalytic activity: H2O + L-asparagine = L-aspartate + NH4+

Activity regulation: Glycine accelerates autocleavage into an alpha and beta chain

Recommended name: Isoaspartyl peptidase/L-asparaginase

Gene name from HGNC: ASRGL1 (ALP, ALP1, FLJ22316)

HPA class: Enzymes Metabolic proteins

AlphaFold DB: Q7L266

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q7L266

Induction: By 5-alpha-di-hydrotestosterone and progesterone.

HPA link: https://www.proteinatlas.org/ENSG00000162174-ASRGL1

Tissue specificity RNA from HPA: Tissue enhanced (brain, cervix, testis)

Tissue expression from HPA: Cytoplasmic expression most abundant in seminiferous ducts and glandular cells of female genital tract.

Single cell type specificity Cell type enhanced (Late spermatids, Spermatocytes, Glandular and luminal cells, Endometrial ciliated cells, Early spermatids, Proximal tubular cells)

Immune cell specificity: Immune cell enhanced (basophil, eosinophil)

Subcellular summary HPA Located in Nucleoplasm, Microtubules, Cytokinetic bridge (Single cell variability

Cancer prognostic summary HPA Prognostic marker in renal cancer (favorable), endometrial cancer (favorable), colorectal cancer (favorable) and liver cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000162174-ASRGL1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000162174-ASRGL1/pathology/endometrial+cancer

OMIM: 609212

OMIM link2: https://www.omim.org/entry/609212

HGNC ID: HGNC:16448

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16448