Affinage

ITIH2

Inter-alpha-trypsin inhibitor heavy chain H2 · UniProt P19823

Round 2 corrected
Length
946 aa
Mass
106.5 kDa
Annotated
2026-04-28
117 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITIH2 encodes the H2 heavy chain of the inter-alpha-trypsin inhibitor (IαI) family, a liver-secreted plasma glycoprotein that is covalently linked to bikunin via an ester bond between its C-terminal Asp648 and an internal N-acetylgalactosamine of a chondroitin-4-sulfate chain (PMID:7682553, PMID:2476436). TSG-6 catalyzes transesterification of ITIH2 from this chondroitin sulfate linkage onto hyaluronan (HA) in a divalent cation-dependent reaction, forming SHAP·HA complexes that potentiate CD44-mediated leukocyte adhesion to HA substrates (PMID:15840581, PMID:16702221). In mesenchymal-like lung cancer cells, ITIH2 is transcriptionally upregulated by ZEB1 and cooperates with HAS2 and CD44 isoform switching to remodel the pericellular HA matrix and promote migration, invasion, and metastatic colonization (PMID:40178908). In hepatocellular carcinoma, tumor-derived ITIH2 drives angiogenesis by promoting ubiquitination-dependent degradation of the anti-angiogenic factor THBS1 in endothelial cells, thereby activating PI3K/AKT signaling (PMID:41616982).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1987 High

    Establishing that IαI is a multi-gene product resolved the longstanding question of how a single plasma inhibitor achieves its multi-chain architecture: cDNA cloning demonstrated that heavy and light chains are encoded by separate mRNAs, with heavy-chain transcripts restricted to liver.

    Evidence cDNA cloning, RNA blot analysis, and cell-free translation of hybrid-selected poly(A)+ RNA from human liver

    PMID:2446322

    Open questions at the time
    • Individual heavy chain functional distinctions (H1 vs H2) not resolved
    • Post-translational assembly mechanism unknown
  2. 1989 High

    Defining the subunit composition and inter-chain linkage of IαI established that ITIH2 (~70 kDa HC2) is held to bikunin not by disulfide bonds but by a chondroitin sulfate glycan cross-link, and that the ITIH2 gene maps to chromosome 10p15 separately from the other heavy chains.

    Evidence SDS-PAGE with trifluoromethanesulfonic acid deglycosylation and hyaluronidase treatment; in situ hybridization chromosomal mapping

    PMID:2465147 PMID:2476436

    Open questions at the time
    • Exact cross-link chemistry not yet determined at residue level
    • Functional consequence of chondroitin sulfate linkage unknown
  3. 1993 High

    Mass spectrometric identification of the ester bond between Asp648 of ITIH2 and C-6 of an N-acetylgalactosamine within chondroitin-4-sulfate defined the unique protein–glycosaminoglycan–protein cross-link at atomic resolution, while simultaneously, peptide sequencing proved that ITIH2 is identical to SHAP, covalently transferred onto hyaluronan in the extracellular matrix.

    Evidence Chondroitin sulfate ABC lyase and NaOH cleavage with mass spectrometry of cross-link peptides; affinity purification of SHAP·HA with N-terminal sequencing

    PMID:7504674 PMID:7682553

    Open questions at the time
    • Enzyme catalyzing heavy chain transfer to HA not yet identified
    • Physiological role of SHAP·HA complexes unknown
  4. 1994 High

    Discovery that TSG-6 forms a stable, chondroitin sulfate-mediated covalent complex with IαI (involving ITIH2) identified the catalyst candidate for heavy chain transfer and linked this pathway to inflammation.

    Evidence Affinity purification from human serum, N-terminal microsequencing of ITIH2 in complex, chondroitin sulfate ABC lyase sensitivity, temperature-dependence assays

    PMID:7516184

    Open questions at the time
    • Whether TSG-6 acts catalytically or stoichiometrically was unresolved
    • HA as the ultimate acceptor not yet formally demonstrated in vitro
  5. 2005 High

    Full in vitro reconstitution showed that TSG-6 is a true catalyst: it forms covalent TSG-6·HC2 intermediates via transesterification from chondroitin sulfate, then transfers HCs onto HA in a second transesterification requiring Mg²⁺/Mn²⁺, with TSG-6 recycled for further rounds.

    Evidence In vitro reconstitution with purified human IαI and recombinant TSG-6, SDS-PAGE intermediate characterization, metal ion dependence assays

    PMID:15840581

    Open questions at the time
    • Structural basis of TSG-6 catalysis unknown
    • Relative kinetics of HC1 vs HC2 transfer not quantified
    • In vivo validation of catalytic recycling lacking
  6. 2006 High

    Demonstrating that SHAP·HA (containing ITIH2) potentiates CD44-mediated leukocyte adhesion under physiological flow conditions established the downstream biological function of heavy chain transfer: enhancement of immune cell recruitment via ECM remodeling, with relevance to rheumatoid arthritis.

    Evidence Static and flow cell adhesion assays with anti-CD44 blocking and HA competition; immunohistochemistry of rheumatoid arthritis synovium showing SHAP·HA/CD44 colocalization

    PMID:16702221

    Open questions at the time
    • Contribution of HC2 vs HC1 individually to adhesion potentiation not distinguished
    • Signaling consequences of SHAP·HA/CD44 interaction not explored
  7. 2008 Medium

    Frequent loss of ITIH2 expression in breast cancer and other solid tumors, correlating with ER status, raised the possibility that ITIH2-dependent ECM stabilization acts as a tumor-suppressive mechanism.

    Evidence cDNA dot blot, RT-PCR, real-time PCR, and immunohistochemistry on breast cancer tissue microarray (n=185)

    PMID:18226209

    Open questions at the time
    • No functional experiments (knockdown, overexpression) performed
    • Causality between ITIH2 loss and tumor progression not tested
    • Mechanism of ER-associated regulation not defined
  8. 2025 High

    In a reversal of the tumor-suppressor model, ZEB1-driven ITIH2 expression in mesenchymal lung cancer cells was shown to promote HA matrix remodeling, migration, invasion, and metastasis, establishing ITIH2 as a context-dependent pro-tumorigenic factor.

    Evidence ITIH2/HAS2 siRNA knockdown, co-culture with cancer-associated fibroblasts, Transwell assays, in vivo mouse metastasis model with sincalide pharmacological inhibition

    PMID:40178908

    Open questions at the time
    • Precise mechanism by which ITIH2 integrates with CD44 isoform switching not defined
    • Sincalide target specificity not fully validated beyond computational prediction
    • Whether ZEB1 directly binds the ITIH2 promoter not shown
  9. 2026 Medium

    In hepatocellular carcinoma, tumor-secreted ITIH2 was found to promote angiogenesis not through HA remodeling but by inducing ubiquitination-dependent degradation of the anti-angiogenic factor THBS1 in endothelial cells, activating PI3K/AKT signaling — revealing a non-canonical, ECM-independent oncogenic mechanism.

    Evidence THBS1 overexpression rescue, PI3K/AKT pathway analysis, in vivo xenograft, CD31/CD34 immunohistochemistry

    PMID:41616982

    Open questions at the time
    • E3 ligase mediating THBS1 ubiquitination not identified
    • Whether ITIH2 directly binds THBS1 or an intermediate receptor is unknown
    • Single-lab finding not yet independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of TSG-6-catalyzed transesterification, the relative contributions of HC1 versus HC2 to distinct biological outcomes, how ITIH2 switches between tumor-suppressive (ECM stabilization) and pro-tumorigenic (HA remodeling, angiogenesis) roles across tissue contexts, and the identity of the E3 ubiquitin ligase that mediates ITIH2-dependent THBS1 degradation.
  • No crystal structure of ITIH2 or TSG-6·HC2 intermediate available
  • Context-dependent oncogenic versus protective roles not mechanistically reconciled
  • THBS1 ubiquitination pathway components unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 3
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 1 R-HSA-168256 Immune System 1
Partners
AMBPCD44HAS2ITIH1THBS1TNFAIP6ZEB1
Complex memberships
SHAP·HA complexinter-alpha-trypsin inhibitor (IαI)pre-alpha-inhibitor (PαI)

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 Isolation and characterization of cDNAs encoding two distinct heavy chain sequences of human inter-alpha-trypsin inhibitor (IαTI), demonstrating that IαTI is a multipolypeptide protein composed of separate heavy (H) chain (~95 kDa) and light (L) chain (~40 kDa) synthesized from distinct mRNAs (~3.3 kb and ~1.3 kb, respectively), with H-chain mRNA expressed exclusively in liver. The H chain contains potential calcium-binding sites and regions homologous to thiol-proteinase inhibitor reactive sites. cDNA cloning, RNA blot analysis, cell-free translation of hybrid-selected poly(A)+ RNA, partial amino acid sequencing of purified serum IαTI Proceedings of the National Academy of Sciences of the United States of America High 2446322
1989 Human inter-alpha-trypsin inhibitor plasma proteins exist as two distinct species (225 kDa inter-alpha-TI and 125 kDa pre-alpha-TI), each assembled from multiple polypeptide chains held together not by disulfide bonds but by a glycan (chondroitin sulfate) cross-link susceptible to trifluoromethanesulfonic acid or hyaluronidase. Both proteins share a single trypsin-inhibitory light chain (~30 kDa); inter-alpha-TI contains two noninhibitory heavy chains of ~65 kDa (HC1) and ~70 kDa (HC2, corresponding to ITIH2), whereas pre-alpha-TI contains a single ~90 kDa heavy chain. SDS-PAGE under reducing and denaturing conditions, trifluoromethanesulfonic acid deglycosylation, hyaluronidase treatment, polypeptide chain composition analysis, proteolytic derivative analysis The Journal of biological chemistry High 2476436
1989 The ITIH2 gene (encoding the H2 heavy chain, ~98 kDa) is located on human chromosome 10p15, distinct from ITIH1 and ITIH3 (chromosome 3p21) and the light-chain (bikunin/AMBP) gene (chromosome 9q32-33). Three heavy chains H1, H2, H3 are translated from distinct 3.3-kb mRNAs present only in liver. cDNA cloning of three heavy-chain sequences, in situ hybridization chromosomal localization, Northern blot analysis of liver poly(A)+ RNA, cell-free translation European journal of biochemistry High 2465147
1993 The cross-link between ITIH2 (HC2) and bikunin in the pre-alpha-inhibitor complex is a protein-glycosaminoglycan-protein (PGP) cross-link mediated by chondroitin-4-sulfate: the chondroitin sulfate chain originates from an O-glycosidic linkage to Ser10 of bikunin, and the COOH-terminal Asp648 of HC2 is esterified via its alpha-carbon to C-6 of an internal N-acetylgalactosamine residue of the chondroitin sulfate chain. This cross-link is sensitive to chondroitin sulfate-degrading enzymes and 50 mM NaOH but not to reducing conditions. Chondroitin sulfate ABC lyase treatment, NaOH cleavage, mass spectrometry of cross-link peptides, biochemical analysis of purified HC2/bikunin The Journal of biological chemistry High 7682553
1993 The heavy chains of inter-alpha-trypsin inhibitor (including HC2/ITIH2) correspond to SHAP (serum-derived hyaluronan-associated protein): SHAP is covalently linked to hyaluronan (HA) synthesized by cultured fibroblasts when serum is present. Peptide sequence analysis of SHAP components X and Y showed >80% (bovine) and essentially 100% (human) identity to HC2 and HC1 of IαTI, respectively. The HA-binding domain was localized to the COOH-terminal half of the ITI heavy chains, which contains an amphipathic alpha-helix structure. Affinity purification of SHAP·HA complex from serum, SDS-PAGE, V8 protease peptide mapping, NH2-terminal amino acid sequencing, anti-ITI antibody cross-reactivity, HA-lyase digestion The Journal of biological chemistry High 7504674
1994 TSG-6 (an inflammation-associated hyaluronan-binding protein) forms a stable, covalent complex with inter-alpha-inhibitor (IαI), specifically involving HC2 (ITIH2) and bikunin subunits. This TSG-6/IαI complex is stable under reducing SDS-PAGE and 8 M urea conditions, and is cleaved by chondroitin sulfate ABC lyase, indicating chondroitin sulfate mediates the cross-link. Complex formation requires 37°C but not 4°C, indicating a temperature-dependent process. Affinity purification of TSG-6/IαI complex from human serum, SDS-PAGE under reducing/denaturing conditions, N-terminal microsequencing, chondroitin sulfate ABC lyase treatment, temperature-dependence assay Biochemistry High 7516184
2005 TSG-6 acts as a catalyst and cofactor in the transfer of heavy chains (HC1 and HC2/ITIH2) from IαI onto hyaluronan (HA). TSG-6 forms covalent intermediates (TSG-6·HC1 and TSG-6·HC2) via transesterification from the chondroitin sulfate of IαI; these intermediates then transfer HCs onto HA in a second transesterification, releasing TSG-6 for recycling. HC transfer requires divalent metal ions (Mg2+ or Mn2+) and is inhibited by Co2+. The ester bond linking ITIH2 to chondroitin sulfate in IαI is the substrate for this reaction. In vitro reconstitution with purified human IαI and recombinant TSG-6, SDS-PAGE characterization of intermediates, chondroitin sulfate lyase treatment, metal ion requirement assays (Mg2+, Mn2+, Co2+), recycling assay The Journal of biological chemistry High 15840581
2006 SHAP (the heavy chains of IαI, including ITIH2) covalently modifies HA and potentiates CD44-mediated leukocyte adhesion to HA substrates. Under both static and flow conditions, CD44-positive cells (Hut78, CD44-transfected Jurkat) adhered preferentially to SHAP·HA over unmodified HA. The enhanced adhesion was specifically inhibited by free HA and anti-CD44 antibodies but not by IαI, demonstrating it is CD44-HA dependent. SHAP increases the avidity of HA for CD44 and alters CD44/HA distribution on cell surfaces. SHAP·HA complexes accumulate in rheumatoid arthritis synovium and colocalize with CD44 on infiltrating leukocytes. Cell adhesion assays under static and flow conditions, anti-CD44 antibody blocking, HA competitive inhibition, FACS analysis of surface distribution, immunohistochemistry of rheumatoid arthritis synovium The Journal of biological chemistry High 16702221
2008 ITIH2 expression is frequently lost (in ~70% of cases) in human breast cancer, with a strong positive correlation between ITIH2 protein expression and estrogen receptor (ER) expression (p<0.001), indicating that ER may regulate this ECM molecule. ITIH family genes are broadly downregulated across multiple solid tumor types (breast, colon, lung, and others), suggesting a putative tumor suppressor role for the ITI family in maintaining ECM stability. cDNA dot blot (Cancer Profiling Array), semiquantitative RT-PCR, real-time PCR (n=36 breast cancers), immunohistochemistry on tissue microarray (n=185 invasive breast cancers) BMC cancer Medium 18226209
2012 ITIH1 and ITIH2 are normally produced within pancreatic islets, with expression predominantly localized to β cells (insulin-producing cells) as shown by immunohistochemistry. Hyaluronan synthase isoforms 1 and 3, versican, TSG-6, and bikunin are also expressed in islets by distinct endocrine cell types, indicating that IαI components are assembled within the islet microenvironment and contribute to islet ECM composition. Immunohistochemistry (paraformaldehyde and Carnoy's fixation), mRNA expression analysis of isolated mouse pancreatic islets The journal of histochemistry and cytochemistry Medium 22821669
2003 ITIH heavy chain gene expression (ITIH1, ITIH2, ITIH3, ITIH4) is detected in pig endometrium throughout the oestrous cycle and early pregnancy, with no significant change in mRNA levels during these periods. However, Western blot analysis identified linkage forms of ITIH chains with bikunin, and pregnancy altered the release of inter-alpha-inhibitor forms from the endometrium during trophoblast attachment, implicating the ITI family in maintenance of the uterine surface glycocalyx during placentation. RT-PCR gene expression analysis, Western blot with ITIH antiserum identifying bikunin-linked forms, analysis across reproductive stages Reproduction (Cambridge, England) Medium 14611635
2025 ITIH2 expression is transcriptionally upregulated by the EMT-inducing transcription factor ZEB1 in mesenchymal-like lung cancer cells, and ITIH2 is secreted when these cells are co-cultured with cancer-associated fibroblasts. ZEB1 co-regulates hyaluronan synthase 2 (HAS2) and CD44 isoform switching (via alternative splicing). Depletion of ITIH2 or HAS2 reduced HA matrix formation and decreased migration and invasion of lung cancer cells. An ITIH2 inhibitor (sincalide, identified by a deep learning drug-target algorithm) inhibited HA matrix formation and lung cancer cell migration, and prevented metastatic colonization in mouse models. Co-culture of lung cancer cells with cancer-associated fibroblasts, ITIH2 siRNA knockdown, HAS2 siRNA knockdown, CD44 siRNA knockdown, HA matrix formation assay, Transwell migration and invasion assays, deep learning drug-target interaction prediction, in vivo mouse metastasis model with sincalide treatment The Journal of clinical investigation High 40178908
2026 Tumor-derived ITIH2 promotes hepatocellular carcinoma progression by enhancing angiogenesis in endothelial cells (ECs) via activation of the PI3K/AKT signaling pathway. ITIH2 overexpression did not alter tumor cell proliferation or apoptosis but enhanced EC angiogenic capacity in vitro and promoted tumor growth in vivo. Mechanistically, ITIH2 promotes ubiquitination-dependent degradation of THBS1 (thrombospondin-1, an angiogenesis inhibitor) in ECs, thereby activating PI3K/AKT signaling; overexpression of THBS1 reversed the pro-angiogenic effects of ITIH2. Colony formation assay, CCK-8 proliferation assay, flow cytometry (apoptosis), in vitro angiogenesis assays, in vivo tumor xenograft experiments, THBS1 overexpression rescue experiment, PI3K/AKT pathway analysis, immunohistochemistry for CD31/CD34 angiogenesis markers in clinical samples Biochimica et biophysica acta. Molecular basis of disease Medium 41616982

Source papers

Stage 0 corpus · 117 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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2003 Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature biotechnology 1176 12754519
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
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2020 Phosphorylated tau interactome in the human Alzheimer's disease brain. Brain : a journal of neurology 290 32812023
2000 Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha. Nature 285 10917520
2010 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunology and cell biology 221 20458337
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2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2014 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. BMC cancer 203 25037231
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2004 Association of Vimentin overexpression and hepatocellular carcinoma metastasis. Oncogene 198 14647434
2017 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics. Journal of proteome research 185 28675934
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1989 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. The Journal of biological chemistry 183 2476436
1977 A requirement for antigen-specific helper T cells in the generation of cytotoxic T cells from thymocyte precursors. The Journal of experimental medicine 183 233910
2008 Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: a systematic expression analysis. BMC cancer 182 18226209
2019 Plasma extracellular vesicle long RNA profiling identifies a diagnostic signature for the detection of pancreatic ductal adenocarcinoma. Gut 161 31562239
1993 A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the inter alpha-trypsin inhibitor. The Journal of biological chemistry 157 7504674
1986 High frequency and nonrandom distribution of alloreactivity in T cell clones selected for recognition of foreign antigen in association with self class II molecules. Journal of immunology (Baltimore, Md. : 1950) 153 2416806
2005 Characterization of complexes formed between TSG-6 and inter-alpha-inhibitor that act as intermediates in the covalent transfer of heavy chains onto hyaluronan. The Journal of biological chemistry 151 15840581
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2002 The crystal structure of IgE Fc reveals an asymmetrically bent conformation. Nature immunology 138 12068291
2005 A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. American journal of human genetics 137 16385451
2006 SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. The Journal of biological chemistry 133 16702221
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1994 Expression of a transgenic class II Ab gene confers susceptibility to collagen-induced arthritis. European journal of immunology 127 8026530
2017 Comprehensive proteomic characterization of stem cell-derived extracellular matrices. Biomaterials 125 28327460
1994 TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor. Biochemistry 102 7516184
1993 Presence of the protein-glycosaminoglycan-protein covalent cross-link in the inter-alpha-inhibitor-related proteinase inhibitor heavy chain 2/bikunin. The Journal of biological chemistry 102 7682553
2000 Phosphinic acid compounds in biochemistry, biology and medicine. Current medicinal chemistry 95 10702630
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1987 Isolation and characterization of cDNAs encoding the heavy chain of human inter-alpha-trypsin inhibitor (I alpha TI): unambiguous evidence for multipolypeptide chain structure of I alpha TI. Proceedings of the National Academy of Sciences of the United States of America 93 2446322
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2012 Hyaluronan and hyaluronan binding proteins are normal components of mouse pancreatic islets and are differentially expressed by islet endocrine cell types. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 34 22821669
2021 Molecular alterations in basal cell carcinoma subtypes. Scientific reports 33 34168209
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2016 Obese dogs with and without obesity-related metabolic dysfunction - a proteomic approach. BMC veterinary research 26 27646300
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2022 Maternal plasma proteome profiling of biomarkers and pathogenic mechanisms of early-onset and late-onset preeclampsia. Scientific reports 23 36351970
2004 Establishment of cell lines from a primary hepatocellular carcinoma and its metastatis. Cancer genetics and cytogenetics 23 14697646
2003 Comparative mapping of a region on chromosome 10 containing QTL for reproduction in swine. Animal genetics 21 12580785
2023 Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response. Clinical proteomics 20 37735622
2022 Multi-omics analysis of the cervical epithelial integrity of women using depot medroxyprogesterone acetate. PLoS pathogens 20 35533147
2003 Expression of inter-alpha-trypsin inhibitor heavy chains in endometrium of cyclic and pregnant gilts. Reproduction (Cambridge, England) 20 14611635
1998 Inhibition of an in vitro CD4+ T cell alloresponse using altered peptide ligands. Journal of immunology (Baltimore, Md. : 1950) 20 9531280
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2004 Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation. British journal of cancer 18 15138476
2023 LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1. Biomolecules 17 36979356
2017 The Association of Mammographic Density and Molecular Breast Cancer Subtype. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 17 28698184
2022 Profiling biotoxicities of hexafluoropropylene oxide trimer acid with human embryonic stem cell-based assays. Journal of environmental sciences (China) 14 35219423
2022 Quantitative proteomic analysis of GnRH agonist treated GBM cell line LN229 revealed regulatory proteins inhibiting cancer cell proliferation. BMC cancer 13 35109816
2021 Clinicopathological and molecular characterizations of pulmonary NUT midline carcinoma. Cancer medicine 13 34409758
2022 Plasma proteomics identify potential severity biomarkers from COVID-19 associated network. Proteomics. Clinical applications 12 36217943
2021 Profiling plasma-extracellular vesicle proteins and microRNAs in diabetes onset in middle-aged male participants in the ELSA-Brasil study. Physiological reports 12 33587339
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2020 Analysis of plasma protein biomarkers in childhood onset multiple sclerosis. Journal of neuroimmunology 11 32841722
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2023 Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis. Cancer research and treatment 10 37591783
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2024 Longitudinal Fluctuations in Protein Concentrations and Higher-Order Structures in the Plasma Proteome of Kidney Failure Patients Subjected to a Kidney Transplant. Journal of proteome research 8 38701233
2022 Label-free quantitative proteomic analysis of serum exosomes from patients of renal anemia: The Good and the Bad of Roxadustat. Clinical proteomics 8 35690731
2017 H2-P, a honokiol derivative, exerts anti-angiogenesis effects via c-MYC signaling pathway in glioblastoma. Journal of cellular biochemistry 8 29080353
2004 Critical role of the major histocompatibility complex and IL-10 in matrilin-1-induced relapsing polychondritis in mice. Arthritis research & therapy 8 15380048
2001 The H2-Ab gene influences the severity of experimental allergic encephalomyelitis induced by proteolipoprotein peptide 103-116. Journal of neuroimmunology 8 11694316
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2022 Establishment and verification of potential biomarkers for cholangiocarcinoma. Experimental and therapeutic medicine 7 35978916
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2025 Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells. The Journal of clinical investigation 6 40178908
2001 I-Aq and I-Ap bind and present similar antigenic peptides despite differing in their ability to mediate susceptibility to autoimmune arthritis. Autoimmunity 6 11905843
2024 Pyridine appended pyrimidine bis hydrazone: Zn2+/ATP detection, bioimaging and functional properties of its dinuclear Zn(II) complex. Talanta 5 38490021
2023 Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 36794668
1990 Effect of H-2 genes on expression of HLA-B27 and Yersinia-induced arthritis. Scandinavian journal of rheumatology. Supplement 5 2259892
1989 Two RFLPs in human inter-alpha-trypsin inhibitor heavy chain gene ITIH2 on chromosome 10. Nucleic acids research 5 2474798
2024 Discovery of candidate biomarkers from plasma-derived extracellular vesicles of patients with cirrhosis and hepatocellular carcinoma: an exploratory proteomic study. Molecular omics 4 39011654
2022 Transmembrane serine protease 2 cleaves nidogen 1 and inhibits extrahepatic liver cancer cell migration and invasion. Experimental biology and medicine (Maywood, N.J.) 4 36408877
2015 Distinguishing of tumor cell-targeting peptide ligands through a color-encoding microarray. Lab on a chip 4 26530232
1995 Polymorphism in the beta chain of IAq versus IAp influences presentation of protein but not peptide antigens. Cellular immunology 4 7553884
1992 Expression of HLA-B27 in transgenic mice is controlled by gene(s) mapping between H-2D and H-2L loci. Immunogenetics 4 1537610
1990 An hypervariable polymorphism detected in the human inter-alpha-trypsin inhibitor heavy chain gene ITIH2. Nucleic acids research 4 1690878
2024 Identification of Differentially Expressed mRNAs and lncRNAs Contributes to Elucidation of Underlying Pathogenesis and Therapeutic Strategy of Recurrent Implantation Failure. Reproductive sciences (Thousand Oaks, Calif.) 3 38955937
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2025 Ethnic-Specific and UV-Independent Mutational Signatures of Basal Cell Carcinoma in Koreans. International journal of molecular sciences 1 40725190
2025 Effects of the space environment and re-adaptation to Earth's gravity on astronauts' plasma proteome. Life sciences in space research 1 41565413
2022 Urine inter-alpha-trypsin inhibitor family-related proteins may serve as biomarkers for disease activity of lupus. Journal of clinical laboratory analysis 1 35870194
2015 Interrogating protonated/deuterated fibronectin fragment layers adsorbed to titania by neutron reflectivity and their concomitant control over cell adhesion. Journal of the Royal Society, Interface 1 25926699
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2025 Identification of Potential Salivary Biomarkers and Enriched Protein Domain/Motif Families for Early Detection and Lymph Node Invasion in OSCC Patients of the Indian Population. Journal of proteome research 0 40964852
2024 Elucidating the molecular markers and biological pathways associated with extrahepatic cholangiocarcinoma: a transcriptome sequencing study. Frontiers in oncology 0 39355132
2023 Changes in DNA Methylation and mRNA Expression in Lung Tissue after Long-Term Supplementation with an Increased Dose of Cholecalciferol. International journal of molecular sciences 0 38203636
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