HSA Human Sheddome Atlas

About the Human Sheddome Atlas

The Human Sheddome Atlas (HSA) catalogues predicted ectodomain shedding across the human membrane proteome, integrated with experimental cleavage evidence from multiple complementary sources.

What you'll find here

  • 5,211 human membrane proteins with predicted cleavage profiles
  • Per-residue cleavage probability curves at three stringency levels (stringent / moderate / permissive)
  • Topology (signal peptide, propeptide, transit peptide, extracellular, transmembrane, intracellular)
  • Domain annotations from UniProt, Pfam, SMART, CDD, Gene3D, and TED (CATH)
  • Experimental cleavage sites from 445 distinct proteases (MEROPS, UniProt, TopFIND, Schaeffer 2022, Weeks 2021)
  • AlphaFold-predicted 3D structures

How to read an entry

  • The topology backdrop shows the per-residue topology colour beneath the cleavage probability curve.
  • Predicted peak = a local maximum on the cleavage probability curve, after clustering centres closer than 5 aa.
  • IP0.9 window = 90 % inflection-point boundary of the peak — a tight functional interval around the predicted cut.
  • Cut-seq = P4–P4' octamer around the peak centre (P1-indexed).
  • Experimental diamonds = reported cleavage positions from the integrated databases.

Data & methods

Predictions are derived from a sequence-based probability model; peaks are called with scipy.signal.find_peaks at three prominence thresholds (0.01 / 0.03 / 0.05). IP0.9 boundaries come from the same peak-detection pipeline.

Experimental cleavage annotations are harmonised across sources:

  • UniProt — signal peptidase, propeptide processing, and curated protease notes
  • MEROPS — peptidase-substrate literature
  • TopFIND — cleavage annotations from proteomic studies
  • Schaeffer 2022 — cell-surface N-terminomics
  • Weeks 2021 — subtiligase TM N-terminomics

Team

Julie Laffy
Julie Laffy
Postdoctoral fellow
Broad Institute of MIT and Harvard — Hacohen, Chen & Uhler labs
 Fei Chen
Fei Chen
Core Institute Member
Broad Institute of MIT and Harvard — Harvard SCRB
 Nir Hacohen
Nir Hacohen
Institute Member, Director of the Cell Circuits Program
Broad Institute of MIT and Harvard — Harvard Medical School, MGH
 Caroline Uhler
Caroline Uhler
Core Member, Eric and Wendy Schmidt Center
Broad Institute — MIT EECS & IDSS

Affiliations

Broad Institute of MIT and Harvard Eric and Wendy Schmidt Center at the Broad Institute

Contact & citing

For questions, collaborations, or bulk-data access, email jlaffy@broadinstitute.org.

Manuscript in preparation. Please cite the website URL (sheddome.secretomeatlas.org) until a preprint is available.