Extracellular Matrix (ECM) Project

IN_PROGRESS BIOLOGY_DOMAINFLAGSHIP

Species: human

Genes: AGRN HSPG2 EPYC SPOCK1 SPOCK2 SPOCK3 NID1 FN1 DCN SPARC

Extracellular Matrix (ECM) Project

Bottom line: the extracellular matrix is the protein and proteoglycan
network that holds tissues together and signals to the cells within it. We
reviewed ten human ECM genes in three phases: the basement-membrane
proteoglycans AGRN and HSPG2 plus EPYC, the testican family SPOCK1-3, and a
diverse set (NID1, FN1, DCN, SPARC). All ten reviews are complete, although
the task list below still shows Phase 3 as open and AGRN/HSPG2 as in progress.
They assess 639 GOA rows: 284 ACCEPT, 193 KEEP_AS_NON_CORE, 73 REMOVE, 63
MODIFY, 17 NEW, 7 MARK_AS_OVER_ANNOTATED and 2 UNDECIDED. FN1 accounts for most
of the corrections: 52 generic protein binding rows removed and 38
extracellular region rows modified to extracellular matrix. The SPOCK2
metalloendopeptidase-inhibitor rows were modified to reflect its role as a
counter-inhibitor of SPOCK1/3, and EPYC gained NEW collagen-binding and matrix
terms. DCN still has no core_functions block, and no ECM module exists.

Overview

This project focuses on reviewing genes involved in the extracellular matrix (ECM), a complex network of proteins and polysaccharides that provides structural and biochemical support to surrounding cells.

Tasks

Phase 1: Core ECM Components

Phase 2: SPARC/Osteonectin Family (Testican/SPOCK proteins)

Phase 3: Diverse ECM Components

Status

Started: 2025-11-10
- Phase 1: AGRN and HSPG2 in progress, EPYC complete
- Phase 2 Added: 2025-11-11 - All three SPOCK genes reviewed and validated
- Phase 3 Added: 2025-11-11 - Expanding to diverse ECM protein classes

Notes

SPOCK proteins (Testican family):
- Proteoglycans belonging to the SPARC/osteonectin family
- Modular structure with follistatin-like and extracellular calcium-binding domains
- Chondroitin/heparan sulfate chains
- Key finding: SPOCK2 uniquely acts as counter-inhibitor, blocking SPOCK1/3 MMP inhibition
- Roles in ECM assembly, neurogenesis, angiogenesis, and cancer

Phase 3 rationale:
- NID1: Bridges laminin to collagen IV networks in basement membranes
- FN1: Cell adhesion, migration, wound healing
- DCN: Collagen fibrillogenesis, TGF-β regulation
- SPARC: Parent family member, Ca²⁺ binding, collagen binding, anti-adhesive

Slides