TRPV4 Antibody – Rabbit Polyclonal

Function: Non-selective calcium permeant cation channel probably involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by low pH, citrate and phorbol esters. Increase of intracellular Ca2+ potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. Acts as a regulator of intracellular Ca2+ in synoviocytes. Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8. Ref.2 Ref.11 Ref.12

Subunit structure: Homotetramer

Probable. Self-associates in a isoform-specific manner. Isoforms 1/A and 5/D but not isoform 2/B, 4/C and 6/E can oligomerize. Interacts with calmodulin. Interacts with Map7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES. Interacts with CTNNB1. The TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain)

By similarity. Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1. Ref.11 Ref.15

Subcellular location: Cell membrane; Multi-pass membrane protein

By similarity. Cell junction › adherens junction

By similarity. Note: Assembly of the putative homotetramer occurs primarily in the endoplasmic reticulum. Ref.7 Ref.22 Ref.23Isoform 1: Cell membrane Ref.7 Ref.22 Ref.23. Isoform 5: Cell membrane Ref.7 Ref.22 Ref.23.

Tissue specificity: Found in the synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis (at protein level). Ref.12

Post-translational modification: Phosphorylation results in enhancement of its channel function.

Polymorphism: Genetic variations in TRPV4 determine the sodium serum level quantitative trait locus 1 (SSQTL1) [

MIM:613508]. In some populations, variant Pro19Ser has been shown to be significantly associated with hyponatremia defined as serum sodium concentration below or equal to 135 mEq/L.

Involvement in disease: Brachyolmia 3 (BRAC3) [MIM:113500]: The brachyolmias constitute a clinically and genetically heterogeneous group of skeletal dysplasias characterized by a short trunk, scoliosis and mild short stature. BRAC3 is an autosomal dominant form with severe kyphoscoliosis and flattened, irregular cervical vertebrae.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17Spondylometaphyseal dysplasia Kozlowski type (SMDK) [MIM:184252]: A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. It is characterized by postnatal dwarfism, significant scoliosis and mild metaphyseal abnormalities in the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.21Metatropic dysplasia (MTD) [MIM:156530]: A severe spondyloepimetaphyseal dysplasia characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis. Radiologic features include severe platyspondyly, severe metaphyseal enlargement and shortening of long bones.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.18 Ref.19 Ref.21Distal spinal muscular atrophy, congenital non-progressive (DSMAC) [MIM:600175]: A clinically variable, neuromuscular disorder characterized by congenital lower motor neuron disorder restricted to the lower part of the body. Clinical manifestations include non-progressive muscular atrophy, thigh muscle atrophy, weak thigh adductors, weak knee and foot extensors, minimal jaw muscle and neck flexor weakness, flexion contractures of knees and pes equinovarus. Tendon reflexes are normal.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.28Charcot-Marie-Tooth disease 2C (CMT2C) [MIM:606071]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.23 Ref.24 Ref.25 Ref.27Scapuloperoneal spinal muscular atrophy (SPSMA) [MIM:181405]: A clinically variable neuromuscular disorder characterized by neurogenic scapuloperoneal amyotrophy, laryngeal palsy, congenital absence of muscles, progressive scapuloperoneal atrophy and progressive distal weakness and amyotrophy.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23Spondyloepiphyseal dysplasia Maroteaux type (SEDM) [MIM:184095]: A clinically variable spondyloepiphyseal dysplasia with manifestations limited to the musculoskeletal system. Clinical features include short stature, brachydactyly, platyspondyly, short and stubby hands and feet, epiphyseal hypoplasia of the large joints, and iliac hypoplasia. Intelligence is normal.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20Parastremmatic dwarfism (PSTD) [MIM:168400]: A bone dysplasia characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. Radiographically, the disease is characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses and apophyses.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20Digital arthropathy-brachydactyly, familial (FDAB) [MIM:606835]: A disorder characterized by irregularities in the proximal articular surfaces of the distal interphalangeal joints of the hand. Individuals appear normal at birth, with no clinical or radiographic evidence of a developmental skeletal dysplasia. The earliest changes appear during the first decade of life. By adulthood, all interphalangeal, metacarpophalangeal, and metatarsophalangeal joints are affected by a deforming, painful osteoarthritis. The remainder of the skeleton is clinically and radiographically unaffected.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26

Sequence similarities: Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV4 sub-subfamily. [View classification]Contains 3 ANK repeats.