Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy chain family is downregulated in breast cancer.
-
ITIH5 contains the conserved VIT and von Willebrand factor A domains of the heavy-chain family.
"ITIH5 contains the two domains conserved in all known ITIHs, the vault protein inter-alpha-trypsin (VIT) domain and a von Willebrand type A (vWA) domain"
-
ITIH5 expression is strongly reduced in breast tumors.
"We found strong downregulation of ITIH5 expression in breast tumors"
The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation.
-
Forced full-length ITIH5 expression reduces proliferation of MDA-MB-231 breast-cancer cells.
"ITIH5-expressing clones showed a 40% reduced proliferation rate compared to mock-transfected cells."
-
ITIH5 promoter methylation is associated with expression loss in breast tumors.
"Methylation was significantly associated with mRNA loss"
Analysis of inter-alpha-trypsin inhibitor and a novel trypsin inhibitor, pre-alpha-trypsin inhibitor, from human plasma. Polypeptide chain stoichiometry and assembly by glycan.
-
Inter-alpha-inhibitor heavy chains are noninhibitory.
"Inter-alpha-trypsin inhibitor contains noninhibitory heavy chains of 65,000 and 70,000 Da"
-
A distinct 30-kDa light chain carries trypsin-inhibitory activity.
"each protein contained a single, identical, trypsin-inhibitory chain of 30,000 Da"
Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver.
Tumor Necrosis Factor-stimulated Gene 6 (TSG-6)-mediated Interactions with the Inter-α-inhibitor Heavy Chain 5 Facilitate Tumor Growth Factor β1 (TGFβ1)-dependent Fibroblast to Myofibroblast Differentiation.
-
HC5 is the principal ITIH heavy chain expressed by the studied human fibroblasts.
"The newly described HC5 was shown to be the principal HC expressed"
-
Hyaluronidase releases HC5 from the fibroblast surface, demonstrating association with cell-surface hyaluronan.
"HC5 was released by hyaluronidase treatment, confirming its association with cell surface HA."
-
HC5 knockdown supports a causal role in myofibroblast differentiation.
"HC5 knockdown by siRNA confirmed its role in myofibroblast differentiation."
Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics.
Genetic deletion of ITIH5 leads to increased development of adipose tissue in mice.
-
Mouse Itih5 deletion increases adipose-stem-cell proliferation and adipogenic differentiation.
"ITIH5-/- cells exhibited increased proliferation and adipogenic differentiation"
-
Recombinant ITIH5 reverses the knockout cellular phenotypes.
"the application of the rITIH5 protein reversed the observed knockout effects in ASCs."
Systems genetics reveals ITIH5 as a key mediator of adipocyte-Endothelial crosstalk.
-
Recombinant ITIH5 reduces leukocyte recruitment by human endothelial cells.
"ITIH5 treatment in human endothelial cells reduced leukocyte recruitment."
-
The functional monolayer assay found that ITIH5 alone blunts leukocyte adhesion.
"ITIH5 protein alone blunted this adhesion of leukocytes"
UniProtKB record for human ITIH5 (Q86UX2)
-
ITIH5 is a reviewed 942-amino-acid precursor.
"Reviewed; 942 AA."
-
Canonical ITIH5 has an N-terminal signal peptide.
"FT SIGNAL 1..16"
-
UniProt assigns a von Willebrand factor A domain.
"FT DOMAIN 295..478"
Manual literature and annotation review notes for human ITIH5
-
All five GOA annotation groups were manually adjudicated.
"## Existing annotation decisions"
-
The review distinguishes two supported extracellular roles.
"## HC5, bikunin, and the hyaluronan matrix"
Manual literature synthesis for human ITIH5 (Q86UX2)
-
ITIH5 is a secreted heavy-chain protein with matrix and adipose-endothelial roles, not a protease inhibitor.
"The best-supported core picture is of a secreted extracellular heavy-chain protein rather than a protease inhibitor."