InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TRPV4

Summary

InnateDB Protein

IDBP-586606.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TRPV4

Protein Name

transient receptor potential cation channel, subfamily V, member 4

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000442167

InnateDB Gene

IDBG-56364 (TRPV4)

Protein Structure

UniProt Annotation

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 Ca(2+) 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 Ca(2+) 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. {ECO:0000269PubMed:11025659, ECO:0000269PubMed:12724311, ECO:0000269PubMed:19759329}.

Subcellular Localization

Cell membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Cell junction, adherens junction {ECO:0000250}. Note=Assembly of the putative homotetramer occurs primarily in the endoplasmic reticulum. {ECO:0000269PubMed:16293632, ECO:0000269PubMed:20037587, ECO:0000269PubMed:20037588}.Isoform 1: Cell membrane.Isoform 5: Cell membrane.

Disease Associations

Brachyolmia 3 (BRAC3) [MIM:113500]: A form of brachyolmia, a clinically and genetically heterogeneous skeletal dysplasia primarily affecting the spine and characterized by a short trunk, short stature, and platyspondyly without significant epiphyseal or metaphyseal changes in the long bones. BRAC3 is an autosomal dominant form with severe scoliosis with or without kyphosis, and flattened irregular cervical vertebrae. {ECO:0000269PubMed:18587396}. Note=The disease is caused by mutations affecting the gene represented in this entry.Spondylometaphyseal 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. {ECO:0000269PubMed:19232556, ECO:0000269PubMed:20577006}. Note=The disease is caused by mutations affecting the gene represented in this entry.Metatropic 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. {ECO:0000269PubMed:19232556, ECO:0000269PubMed:20425821, ECO:0000269PubMed:20577006, ECO:0000269Ref.6}. Note=The disease is caused by mutations affecting the gene represented in this entry.Distal 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. {ECO:0000269PubMed:20037588, ECO:0000269PubMed:22526352}. Note=The disease is caused by mutations affecting the gene represented in this entry.Charcot-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 degeneration 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. {ECO:0000269PubMed:20037586, ECO:0000269PubMed:20037587, ECO:0000269PubMed:20037588, ECO:0000269PubMed:21115951, ECO:0000269PubMed:21288981}. Note=The disease is caused by mutations affecting the gene represented in this entry.Scapuloperoneal 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. {ECO:0000269PubMed:20037587}. Note=The disease is caused by mutations affecting the gene represented in this entry.Spondyloepiphyseal 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. {ECO:0000269PubMed:20503319}. Note=The disease is caused by mutations affecting the gene represented in this entry.Parastremmatic 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. {ECO:0000269PubMed:20503319}. Note=The disease is caused by mutations affecting the gene represented in this entry.Digital 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. {ECO:0000269PubMed:21964574}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Found in the synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis (at protein level). {ECO:0000269PubMed:19759329}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.

Experimentally validated
Total	19 [view]
Protein-Protein	17 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0005080	protein kinase C binding
GO:0005216	ion channel activity
GO:0005261	cation channel activity
GO:0005262	calcium channel activity
GO:0005515	protein binding
GO:0005516	calmodulin binding
GO:0005524	ATP binding
GO:0008017	microtubule binding
GO:0019901	protein kinase binding
GO:0042169	SH2 domain binding
GO:0043014	alpha-tubulin binding
GO:0048487	beta-tubulin binding
GO:0051015	actin filament binding

Biological Process

GO:0006811	ion transport
GO:0006816	calcium ion transport
GO:0006874	cellular calcium ion homeostasis
GO:0006884	cell volume homeostasis
GO:0007015	actin filament organization
GO:0007043	cell-cell junction assembly
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0007231	osmosensory signaling pathway
GO:0008219	cell death
GO:0009612	response to mechanical stimulus
GO:0010977	negative regulation of neuron projection development
GO:0031117	positive regulation of microtubule depolymerization
GO:0031532	actin cytoskeleton reorganization
GO:0034220	ion transmembrane transport
GO:0034605	cellular response to heat
GO:0043622	cortical microtubule organization
GO:0046785	microtubule polymerization
GO:0055085	transmembrane transport
GO:0070509	calcium ion import
GO:0070588	calcium ion transmembrane transport
GO:0071470	cellular response to osmotic stress
GO:0071476	cellular hypotonic response

Cellular Component

GO:0005881	cytoplasmic microtubule
GO:0005886	plasma membrane
GO:0005912	adherens junction
GO:0005925	focal adhesion
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0030027	lamellipodium
GO:0030175	filopodium
GO:0030426	growth cone
GO:0030864	cortical actin cytoskeleton
GO:0032587	ruffle membrane

Protein Structure and Domains

PDB ID

InterPro

IPR002110 Ankyrin repeat
IPR005821 Ion transport domain
IPR008347 Transient receptor potential channel, vanilloid 1-4
IPR008348 Transient receptor potential channel, vanilloid 4
IPR020683 Ankyrin repeat-containing domain

PFAM

PF00023
PF13606
PF00520
PF11929
PF12796

PRINTS

PR01415
PR01768
PR01769

PIRSF

SMART

SM00248

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt