rheumatoid arthritis

Serpin H1 is a serine proteinase inhibitors Which belongs to the serpin family. Serpin H1 is induced by heat shock. Serpin H1 localizes to the endoplasmic reticulum lumen and binds specifically to collagen. Thus it is thought to be a molecular chaperone involved in the maturation of collagen molecules. Autoantibodies to this protein have been found in patients with rheumatoid arthritis. Serpin H1 may be a marker for cancer and nucleotide polymorphisms in this gene may be associated with preterm birth caused by preterm premature rupture of membranes.

The cluster of differentiation (CD) system is a glycosyl phosphatidylinositol anchored membrane protein that belongs to the CD38 family.It is generally used in immunophynotyping. CD157 was discovered in a bone marrow stromal cell line where it facilitates pre-B-cell growth. CD157 is a bifunctional ectoenzyme that exhibits both ADP-ribosyl cyclase and cyclic ADP ribose hydrolase activities followed with CD38. It plays a role in rheumatoid arthritis (RA) due to its enhanced expression in RA-derived bone marrow stromal cell lines. Studies have shown that this protein have a role in predicted to function as a cell surface receptor and an immunoregulatory molecule.

ILDR2 is a member of the B7-like family of proteins that regulate T cell activity, is also a known endoplasmic reticulum molecule that regulates lipid homeostasis. The human ILDR2 lumenal domain shares a 99% and 98% homology with the mouse and rat respectively. The human gene encoding ILDR2 is located in a region on Chr1q23–25 that has been associated with type 2 diabetes. ILDR2 plays critical roles in hepatic clearance of lipoproteins and in lipid homeostasis. ILDR2 regulates human dendritic cells (DC2 cells, a subpopulation of polarized DCs that promotes Th2 differentiation). Recent publications reported that ILDR2 displayed negative regulatory functions on human and mouse T cells in various experimental systems. Fusion protein of ILDR2 lumenal domain with an Fc fragment, displays therapeutic effects in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). ILDR2 represents a novel B7-like ligand that exerts negative immune modulation via interaction with a putative counterpart receptor expressed on activated T cells.

C-C Motif Chemokine 3 (MIP-1 alpha,CCL3 ) is a member of the beta or CC subfamily of chemokines and is closely related to CCL4 MIP-1 beta. CCL3 expression can be induced in a variety of hematopoietic cells, fibroblasts, smooth muscle cells, and epithelial cells. Mature mouse CCL3 shares 73%, 91%, and 82% amino acid sequence identity with human, rat, and cotton rat CCL3, respectively. CCL3 exerts its biological functions through interactions with CCR1, CCR3, and CCR5. It is cleared from the extracellular space by internalization via the decoy chemokine receptor D6. CCL3 promotes the chemoattraction, adhesion to activated vascular endothelium, and cellular activation of many hematopoietic cell types including activated T cells, NK cells, neutrophils, monocytes, immature dendritic cells, and eosinophils. CCL3 is also known as stem cell inhibitor (SCI) and can inhibit the proliferation of hematopoietic progenitor cells. CCL3 bioactivity contributes to tumor metastasis and the inflammatory components of viral infection, rheumatoid arthritis, and hepatitis, although it also can suppress the replication of HIV.

Melanoma Inhibitory Activity Protein (MIA) is an autocrine growth regulatory protein secreted from chondrocytes and malignant melanoma cells, which was the first discovered member of a family of secreted cytokines termed the MIA OTOR family. The four known members of this family: MIA, MIA2, OTOR and TANGO each contain a Src homology-3 (SH3)-like domain. MIA acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas, in an autocrine fashion and promotes melanoma metastasis by binding competitively to fibronectin and laminin in a manner that results in melanoma cell detachment from the extracellular matrix in vivo. The protein MIA has been shown to represent a very sensitive and specific serum marker for systemic malignant melanoma that might be useful for staging of primary melanomas, detection of progression from localized to metastatic disease during follow-up, and monitoring therapy of advanced melanomas. Elevated levels of MIA may represent a clinically useful marker for diagnosis of melanoma metastasis as well as a potential marker for rheumatoid arthritis.

Interferon Regulatory Factor 5 (IRF5) is a member of the IRF family. It contains one IRF tryptophan pentad repeat DNA-binding domain. IRF5 shuttles between the nucleus and the cytoplasm. IRF5 can form homodimer when it is phosphorylated. IRF5 functions as a transcription factor involved in the induction of interferons IFNA and INFB and inflammatory cytokines upon virus infection. Genetic variations in IRF5 are associated with susceptibility to systemic lupus erythematosus type 10. In addition, the genetic variations wil result in susceptibility to rheumatoid arthritis.

Osteoclast-associated receptor (OSCAR) is a co-stimulatory receptor in osteoclastogenesis. Synovial tissues from active rheumatoid arthritis (RA) patients express higher levels of OSCAR compared with osteoarthritic and normal patients. OSCAR and tartrate-resistant acid phosphatase (TRAP) expression levels did not differ between the cartilage pannus junction (CPJ) and non-CPJ regions in active RA. OSCAR Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 49.8 kDa and the accession number is Q8IYS5-1.

Interleukin-17 is a potent pro-inflammatory cytokine produced by activated memory T cells. There are at least six members of the IL-17 family in humans and in mice. As IL-17 shares properties with IL-1 and TNF-alpha, it may induce joint inflammation and bone and cartilage destruction. This cytokine is found in synovial fluids of patients with rheumatoid arthritis, and produced by rheumatoid arthritis synovium. It increases IL-6 production, induces collagen degradation and decreases collagen synthesis by synovium and cartilage and proteoglycan synthesis in cartilage. IL-17 is also able to increase bone destruction and reduce its formation. Blocking of interleukin-17 with specific inhibitors provides a protective inhibition of cartilage and bone degradation.

Protein-arginine deiminase type-4, also known as HL-6 PAD, Peptidylarginine deiminase IV, Protein-arginine deiminase type I V and PADI4, is a cytoplasm and nucleus protein that belongs to the protein arginine deiminase family. PADI4 is expressed in CD34+stem cells in normal tissues, and many more CD34+ cells expressing PADI4 are present in tumour tissues. PADI4 post-translationally converts peptidylarginine to citrulline, a process called citrullination. Studies have demonstrated the high expression of PADI4 in various malignant tumor tissues. PADI4 is also expressed at high levels in the blood of patients with some malignant tumors. Citrullination of histone, cytokeratin, antithrombin and fibronectin have been confirmed to be involved in abnormal apoptosis, high coagulation, and disordered cell proliferation and differentiation, all of which are main features of malignant tumors. PADI4 may play an important role in tumorigenesis. Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA). It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.

G-protein coupled receptor kinase 2 (GRK2), also referred as Adrenergic, beta, receptor kinase 1 (ADRBK1), is a ubiquitous member of the G protein-coupled receptor kinase (GRK) family that appears to play a central, integrative role in signal transduction cascades. GRK2 can phosphorylate a growing number of non-GPCR substrates and associate with a variety of proteins related to signal transduction, thus suggesting that this kinase could also have diverse 'effector' functions. GRK2 has been reported to interact with a variety of signal transduction proteins related to cell migration such as MEK, Akt, PI3Kgamma or GIT. Interestingly, the levels of expression and activity of this kinase are altered in a number of inflammatory disorders (as rheumatoid arthritis or multiple sclerosis), thus suggesting that GRK2 may play an important role in the onset or development of these pathologies. The important physiological function of GRK2 as a modulator of the efficacy of GPCR signal transduction systems is exemplified by its relevance in cardiovascular physiopathology as well as by its emerging role in the regulation of chemokine receptors. Besides its canonical role in the modulation of the signalling mediated by many G protein-coupled receptors (GPCR), this protein can display a very complex network of functional interactions with a variety of signal transduction partners, in a stimulus, cell type, or context-specific way.

IL-32 is a recently discovered cytokine that induces various proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6) and chemokines in both human and mouse cells through the NF-kappaB and p38 MAPK inflammatory signal pathways. It is regulated robustly by other major proinflammatory cytokines and is crucial to inflammation and immune responses. Four of the IL-32 isoforms (alpha, beta, gamma, and delta) are the most representative IL-32 transcripts, and the gamma isoform of IL-32 is the most active, although all isoforms are biologically active. IL-32, a cytokine produced mainly by T, natural killer, and epithelial cells induces significant amounts of TNFalpha and MIP-2 and increases the production of both cytokines in a dose-dependent manner. IL-32 has been implicated in inflammatory disorders, Mycobacterium tuberculosis infections, inflammatory bowel disease, and influenza A virus infection, as well as in some autoimmune diseases, such as rheumatoid arthritis, ulcerative colitis, and in the human stomach cancer, human lung cancer, and breast cancer tissues. Thus, IL-32 expression might be valuable as a biomarker for cancer.

Tumor necrosis factor receptor superfamily member 12A(Tnfrsf12a) is a single-pass type I membrane protein and contains 1 TNFR-Cys repeat. It is weak inducer of apoptosis in some cell types.It promotes angiogenesis and it is the proliferation of endothelial cells. It may modulate cellular adhesion to matrix proteins.TNFR binds specifically to tumor necrosis factor (TNF) and blocks its interaction with cell surface TNF receptors. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It plays an important role in the inflammatory processes of rheumatoid arthritis (RA), polyarticular-course juvenile rheumatoid arthritis (JRA), and ankylosing spondylitis and the resulting joint pathology. In addition, TNF plays a role in the inflammatory process of plaque psoriasis. Elevated levels of TNF are found in involved tissues and fluids of patients with RA, psoriatic arthritis, ankylosing spondylitis (AS), and plaque psoriasis. Two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75), exist naturally as monomeric molecules on cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface TNFR.

Pentraxin-related protein PTX3, also known as Tumor necrosis factor-inducible gene 14 protein (TSG-14), belongs to the pentraxin family. PTX3 plays a role in the regulation of innate resistance to pathogens, inflammatory reactions, possibly clearance of self-components and female fertility. It’s subunit is a disulfide-linked homooctamer that binds to C1q. PTX3 concentration is elevated in the joint fluid of patients with rheumatoid arthritis (RA), indicating that PTX3 may be a potential mediator of immune response. PTX3 may also function in the regulation of the uptake and clearance of apoptotic cells by dendritic cells. An in vivo study showed that PTX3 transgenic mice are more resistant to sepsis and endotoxemia compared to wild-type during inflammatory injury.

B7-H4, also known as B7x and B7S1, is a 50-80 kDa glycosylated member of the B7 family of immunomodulatory proteins.B7-H4 is up-regulated in several carcinomas in correlation with tumor progression and metastasis. A soluble form of B7-H4 is elevated in the serum of ovarian cancer, renal cell carcinoma, and rheumatoid arthritis patients, also in correlation with advanced disease status .

Osteoclast-associated receptor (OSCAR) is a co-stimulatory receptor in osteoclastogenesis. Synovial tissues from active rheumatoid arthritis (RA) patients express higher levels of OSCAR compared with osteoarthritic and normal patients. OSCAR and tartrate-resistant acid phosphatase (TRAP) expression levels did not differ between the cartilage pannus junction (CPJ) and non-CPJ regions in active RA. OSCAR Protein, Mouse, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 49.7 kDa and the accession number is Q8VBT3-1.

Cartilage Oligomeric Matrix Protein (COMP), also referred to as Thrombospondin-5, is a non-collagenous extracellular matrix (ECM) protein and belongs to the subgroup B of the thrombospondin protein family. This protein is expressed primarily in cartilage, ligament, and tendon, and binds to other ECM proteins such as collagen I, II and IX with high affinities depending on the divalent cations Zn2+ or Ni2+. COMP is a secreted glycoprotein that is important for growth plate organization and function. It is suggested to play a role in cell growth and development, and recent studies have revealed the possible mechanism that it protects cells against death by elevating members of the IAP (inhibitor of apoptosis protein) family of survival proteins. Mutations in COMP cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1), and up-regulated expression of COMP are observed in rheumatoid arthritis and certain carcinomas.

Chondrocyte protein 39 (YKL-39), also known as Chitinase 3-like 2 (CHI3L2), is a secretory protein of articular chondrocytes belonging to the glycosyl hydrolase 18 family. Its highest expression is in chondrocytes, followed by synoviocytes, lung and heart. YKL-39 CHI3L2 is not detected in spleen, pancreas, and liver. YKL-39 CHI3L2 may also be expressed in developing brain and placenta. YKL-39 CHI3L2, a cartilage-related protein, is found to induce arthritis accompanied by pathologic changes in bone and cartilage. A better understanding of the immune response against cartilage-related components including YKL-39 may help to elucidate the pathological processes of arthritic disorders. Upregulation of YKL-39 CHI3L2 in osteoarthritic cartilage suggests that YKL-39 CHI3L2 may be a more accurate marker of chondrocyte activation than YKL-40, although it has yet to be established as a suitable marker in synovial fluid and serum. The decreased expression of YKL-40 by osteoarthritic chondrocytes is surprising as increased levels have been reported in rheumatoid and osteoarthritic synovial fluid, where it may derive from activated synovial cells or osteophytic tissue or by increased matrix destruction in the osteoarthritic joint. YKL-39 and YKL-40 are potentially interesting marker molecules for arthritic joint disease because they are abundantly expressed by both normal and osteoarthritic chondrocytes.

LGALS3 (Galectin 3) is a Protein Coding gene. This gene encodes a member of the galectin family of carbohydrate-binding proteins. The encoded protein is characterized by an N-terminal proline-rich tandem repeat domain and a single C-terminal carbohydrate recognition domain. LGALS3 is a beta-galactoside-binding lectin and plays a role in numerous cellular functions including apoptosis, innate immunity, cell adhesion, and T-cell regulation. LGALS3 has an important role in tumor progression through inhibition of apoptosis. LGALS3 expression is associated with neoplastic transformation and with differentiation of monocytes to macrophages. Elevated expression of LGALS3 has been demonstrated in the synovium of rheumatoid arthritis (RA). Diseases associated with LGALS3 include Follicular Adenoma and Papillary Carcinoma.

Sialate O-acetylesterase belongs to the family of hydrolases, specifically those acting on carboxylic ester bonds. It is widely expressed with high expression in the testis, prostate, and colon. The systematic name of this enzyme class is N-acyl-O-acetylneuraminate O-acetylhydrolase. Other names in common use include N-acetylneuraminate acetyltransferase, sialate 9(4)-O-acetylesterase, and sialidase. Sialate O-acetylesterase catalyzes the removal of O-acetyl ester groups from position 9 of the parent sialic acid, N-acetylneuraminic acid. Defects in Sialate O-acetylesterase are a cause of autoimmune disease type 6 (AIS6). Individuals manifesting susceptibility to autoimmune disease type 6 can suffer from juvenile idiopathic arthritis, rheumatoid arthritis, multiple sclerosis, Sjogren syndrome, systemic lupus erythematosus, type 1 diabetes, ulcerative colitis, and Crohn disease.

Thymic stromal lymphopoietin (TSLP) is a novel member of the hemopoietic cytokine family that promotes the development of B cells and shares overlapping activity with IL-7. The human TSLP protein comprises a 28 amino acids (aa) signal sequence and 131 aa mature region. Human TSLP has two isoforms lfTSLP and sfTSLP produced by alternative splicing . lfTSLP is expressed in a number of tissues including heart, liver and prostate, and sfTSLP (63aa) is predominantly expressed in keratinocytes of oral mucosa, skin and in salivary glands. In aa sequence level, Human TSLP displays about 43% identity with mouse TSLP.TSLP is a cytokine that functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines from monocytes and enhances the maturation of CD11c(+) dendritic cells.TSLP has proliferative effects on the myeloid cell line and may initiate asthma or atopic dermatitis responses by directly activating mast cells . TSLP signals cells via the interleukin-7 receptor-α chain (IL-7Rα),shared with IL-7, together with the TSLP receptor (TSLPR) subunit. Recent studies indicate that TSLP and its receptor are novel therapeutic targets for rheumatoid arthritis,for increased intraarticular TSLP concentrations in patients has caused chemotaxis and activation of arthritogenic T cells.

Protein CYR61, also known as CCN family member 1, Cysteine-rich angiogenic inducer 61,Insulin-like growth factor-binding protein 10 , GIG1, CYR61, CCN1 and IGFBP10, belongs to the CCN family, CYR61 is a secreted protein and contains one CTCK (C-terminal cystine knot-like) domain,one IGFBP N-terminal domain,one TSP type-1 domain and one VWFC domain. CYR61 promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. CYR61 plays important roles in inflammation and tissue repair. CYR61 is associated with diseases related to chronic inflammation, including rheumatoid arthritis, atherosclerosis, diabetes-related nephropathy and retinopathy, and many different forms of cancers.

Butyrophilin-like 2 (BTNL2) is a member of the BTN MOG Ig-superfamily and functions as a negative regulator of immune cell activation. Mouse BTNL2 is type I transmembrane glycoprotein that contains an extracellular domain (ECD), a transmembrane region and a short cytoplasmic domain. The ECD features two V-type Ig-like domains, two C-type Ig-like domains, and four glycosylation sites. BTNL2 is expressed in epithelial cells of the small intestine, colonic dendritic cells, and in cells of the lymph node. BTNL2 expression is upregulated in T cells following activation, a characteristic BTNL2 shares with the homologous B7 family of costimulatory molecules. BTNL2 negatively regulates T cells by inhibiting proliferation and inflammatory cytokine secretion. It also increases the expression of FoxP3 in T cells to promote regulatory T cell development. Single nucleotide polymorphisms in BTNL2 are associated with a risk for sporadic prostate cancer, rheumatoid arthritis, sarcoidosis, ulcerative colitis, and other inflammatory diseases.

Interleukin-17 is a potent pro-inflammatory cytokine produced by activated memory T cells. There are at least six members of the IL-17 family in humans and in mice. Mature mouse IL-17A shares 61% and 89% amino acid sequence identity with human and rat IL-17A, respectively. As IL-17 shares properties with IL-1 and TNF-alpha, it may induce joint inflammation and bone and cartilage destruction. This cytokine is found in synovial fluids of patients with rheumatoid arthritis, and produced by rheumatoid arthritis synovium. It increases IL-6 production, induces collagen degradation and decreases collagen synthesis by synovium and cartilage and proteoglycan synthesis in cartilage. IL-17 is also able to increase bone destruction and reduce its formation. Blocking of interleukin-17 with specific inhibitors provides a protective inhibition of cartilage and bone degradation.

Macrophage colony-stimulating factor 1 receptor (CSF1R) is a member of the type III subfamily of receptor tyrosine kinases that also includes receptors for SCF and PDGF. These receptors each contain five immunoglobulin-like domains in their extracellular domain (ECD) and a split kinase domain in their intracellular region. CSF1R is expressed primarily on cells of the monocyte macrophage lineage, dendritic cells, stem cells and in the developing placenta. CSF1 and its receptor (CSF1R, product of c-fms proto-oncogene) were initially implicated as essential for normal monocyte development as well as for trophoblastic implantation. It plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. It is required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.

Protein-Arginine Deiminase Type-4 (PADI4) belongs to the Protein Arginine Deiminase family. PADI4 is expressed in eosinophils and neutrophils, but it is not expressed in peripheral monocytes or lymphocytes. PADI4 catalyzes the citrullination deimination of arginine residues of proteins. In addition, PADI4 may play an important role in tumourigenesis. Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA), which is a systemic inflammatory disease with autoimmune features and a complex genetic component.

Follistatin-Related Protein 1 (FSTL1) is a secreted protein that contains two EF-hand domains, one follistatin-like domain, one Kazal-like domain, and one VWFC domain. Its functional significance in physiological and pathological processes is not completely understood. However, FSTL1 is thought to modulate the action of some growth factors on cell proliferation and differentiation. FSTL1 maybe an autoantigen associated with rheumatoid arthritis.

LILRB1, also known as CD85j and ILT2, is a transmembrane glycoprotein in the LILR immunoregulatory protein family. LILRB1 is expressed on NK cells that have expanded in response to acute HCMV infection. LILRB1 exhibits considerable diversity in the population, and polymorphisms in the LILRB1 gene have been associated with susceptibility to rheumatoid arthritis and weakly associated with HCMV disease in a subset of patients with HIV. The regulation of phagocytosis by macrophages is an additional key role of LILRB1 signaling. LILRB1 recognizes a wide variety of HLA haplotypes due to its interaction with the invariant β2M subunit of MHC class I, which suggests that this signaling axis is relevant across diverse patient populations.

Interleukin-1 receptor antagonist protein (Il1rn), also known as IL-1ra, IRAP or IL1 inhibitor, is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1 alpha (IL1A) and interleukin 1 beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. The mouse Il1rn gene encodes a 178 amino acids (aa) protein with a 26 aa signal peptide. Mouse Il1rn protein shares 26% and 19% identity with its homologues IL-1 beta and IL-1 alpha, respectively. Il1rn can Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling, but has no interleukin-1 like activity. Recently, an recombinant human Il1rn protein is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role.

Interleukin (IL)‑12B, which encodes the p40 subunit common to IL‑12 and IL‑23, as one of the genes for which expression in fibroblast‑like synoviocytes from patients with rheumatoid arthritis (RA‑FLS) is induced by DcR3.Decoy receptor 3 (DcR3) competitively binds to three ligands, Fas ligand, lymphotoxin‑related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells and tumor necrosis factor‑like ligand 1A (TL1A), to prevent their effects. Recent studies have suggested that DcR3 directly affects cells as a ligand.

Suppressor of cytokine signaling 3, also known as SOCS-3, Cytokine-inducible SH2 protein 3, CIS-3, STAT-induced STAT inhibitor 3, SOCS3 and CIS3, is a protein which is widely expressed with high expression in heart, placenta, skeletal muscle, peripheral blood leukocytes, fetal and adult lung, and fetal liver and kidney. SOCS3 CIS3 contains one SH2 domain and one SOCS box domain. SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 CIS3 is involved in negative regulation of cytokines that signal through the JAK STAT pathway. SOCS3 CIS3 inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp13, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. SOCS3 CIS3 suppresses fetal liver erythropoiesis. It regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. SOCS3 CIS3 regulates IL-6 signaling. SOCS3 CIS3 interacts with multiple activated proteins of the tyrosine kinase signaling pathway including IGF1 receptor, insulin receptor and JAK2. SOCS3 CIS3 could be used as a possible therapeutic agent for treating rheumatoid arthritis.

MMP19, also known as RASI-1, is a member of the peptidase M1A family. It contains 4 hemopexin-like domains and is expressed in the mammary gland, placenta, lung, pancreas, ovary, small intestine, spleen, thymus, prostate, testis colon, heart, and blood vessel walls. It is a matrix metalloproteinase (MMP). Proteins of the MMP family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. MMP19 may play a role in pathological processes participating in rheumatoid arthritis (RA)-associated joint tissue destruction. Autoantigen anti-MMP19 is frequent in RA patients.