(data stored in ACNUC9435 zone)

HOGENOM: HS12_PE2162

ID   HS12_PE2162                          STANDARD;      PRT;   871 AA.
AC   HS12_PE2162;
DT   00-JAN-0000 (Rel. 1, Created)
DT   00-JAN-0000 (Rel. 2, Last sequence update)
DT   00-JAN-0000 (Rel. 3, Last annotation update)
DE   RecName: Full=Transient receptor potential cation channel subfamily V
DE   member 4; Short=TrpV4;AltName: Full=Osm-9-like TRP channel 4;
DE   Short=OTRPC4;AltName: Full=Transient receptor potential protein 12;
DE   Short=TRP12;AltName: Full=Vanilloid receptor-like channel 2;AltName:
DE   Full=Vanilloid receptor-like protein 2; Short=VRL-2;AltName:
DE   Full=Vanilloid receptor-related osmotically-activated channel;
DE   Short=VR-OAC; (HS12.PE2162).
GN   Name=TRPV4; Synonyms=VRL2, VROAC;
OS   HOMO SAPIENS.
OC   Eukaryota; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia;
OC   Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi;
OC   Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria;
OC   Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini;
OC   Hominoidea; Hominidae; Homininae; Homo.
OX   NCBI_TaxID=9606;
RN   [0]
RP   -.;
RG   -.;
RL   -.;
CC   -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS HS12.PE2162.
CC       Homo sapiens chromosome 12 GRCh37  sequence 1..133841895 annotated by
CC       Ensembl
CC   -!- ANNOTATIONS ORIGIN:TRPV4_HUMAN
CC   -!- FUNCTION: Non-selective calcium permeant cation channel probably
CC       involved in osmotic sensitivity and mechanosensitivity. Activation
CC       by exposure to hypotonicity within the physiological range
CC       exhibits an outward rectification. Also activated by low pH,
CC       citrate and phorbol esters. Increase of intracellular Ca(2+)
CC       potentiates currents. Channel activity seems to be regulated by a
CC       calmodulin-dependent mechanism with a negative feedback mechanism.
CC       Promotes cell-cell junction formation in skin keratinocytes and
CC       plays an important role in the formation and/or maintenance of
CC       functional intercellular barriers. Acts as a regulator of
CC       intracellular Ca(2+) in synoviocytes. Plays an obligatory role as
CC       a molecular component in the nonselective cation channel
CC       activation induced by 4-alpha-phorbol 12,13-didecanoate and
CC       hypotonic stimulation in synoviocytes and also regulates
CC       production of IL-8.
CC   -!- SUBUNIT: Homotetramer (Probable). Self-associates in a isoform-
CC       specific manner. Isoforms 1/A and 5/D but not isoform 2/B, 4/C and
CC       6/E can oligomerize. Interacts with calmodulin. Interacts with
CC       Map7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK
CC       and YES. Interacts with CTNNB1. The TRPV4 and CTNNB1 complex can
CC       interact with CDH1 (By similarity).
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein
CC       (By similarity). Cell junction, adherens junction (By similarity).
CC       Note=Assembly of the putative homotetramer occurs primarily in the
CC       endoplasmic reticulum.
CC   -!- SUBCELLULAR LOCATION: Isoform 1: Cell membrane.
CC   -!- SUBCELLULAR LOCATION: Isoform 5: Cell membrane.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC       Name=1; Synonyms=A;
CC         IsoId=Q9HBA0-1; Sequence=Displayed;
CC       Name=2; Synonyms=B, OTRPC4beta;
CC         IsoId=Q9HBA0-2; Sequence=VSP_013436;
CC       Name=3; Synonyms=TRPV-SV;
CC         IsoId=Q9HBA0-3; Sequence=VSP_013437;
CC       Name=4; Synonyms=C;
CC         IsoId=Q9HBA0-4; Sequence=VSP_026615;
CC       Name=5; Synonyms=D;
CC         IsoId=Q9HBA0-5; Sequence=VSP_026614;
CC       Name=6; Synonyms=E;
CC         IsoId=Q9HBA0-6; Sequence=VSP_026615, VSP_013436;
CC   -!- TISSUE SPECIFICITY: Found in the synoviocytes from patients with
CC       (RA) and without (CTR) rheumatoid arthritis (at protein level).
CC   -!- PTM: Phosphorylation results in enhancement of its channel
CC       function.
CC   -!- POLYMORPHISM: Genetic variations in TRPV4 determine the sodium
CC       serum level quantitative trait locus 1 (SSQTL1) [MIM:613508]. In
CC       some populations, variant Pro19Ser has been shown to be
CC       significantly associated with hyponatremia defined as serum sodium
CC       concentration below or equal to 135 mEq/L.
CC   -!- DISEASE: Defects in TRPV4 are the cause of brachyolmia type 3
CC       (BRAC3) [MIM:113500]; also known as brachyrachia. The brachyolmias
CC       constitute a clinically and genetically heterogeneous group of
CC       skeletal dysplasias characterized by a short trunk, scoliosis and
CC       mild short stature. BRAC3 is an autosomal dominant form with
CC       severe kyphoscoliosis and flattened, irregular cervical vertebrae.
CC   -!- DISEASE: Defects in TRPV4 are the cause of spondylometaphyseal
CC       dysplasia Kozlowski type (SMDK) [MIM:184252]. The
CC       spondylometaphyseal dysplasias (SMDs) are a group of short-stature
CC       disorders distinguished by abnormalities in the vertebrae and the
CC       metaphyses of the tubular bones. SMDK is an autosomal dominant
CC       disorder characterized by significant scoliosis and mild
CC       metaphyseal abnormalities in the pelvis. The vertebrae exhibit
CC       platyspondyly and overfaced pedicles.
CC   -!- DISEASE: Defects in TRPV4 are the cause of metatropic dysplasia
CC       (MTD) [MIM:156530]; also called metatropic dwarfism. Metatropic
CC       dysplasia is a severe spondyloepimetaphyseal dysplasia
CC       characterized by short limbs with limitation and enlargement of
CC       joints and usually severe kyphoscoliosis. Radiologic features
CC       include severe platyspondyly, severe metaphyseal enlargement and
CC       shortening of long bones.
CC   -!- DISEASE: Defects in TRPV4 are the cause of distal spinal muscular
CC       atrophy congenital non-progressive (DSMAC) [MIM:600175]; a
CC       clinically variable, neuromuscular disorder characterized by
CC       congenital lower motor neuron disorder restricted to the lower
CC       part of the body. Clinical manifestations include non-progressive
CC       muscular atrophy, thigh muscle atrophy, weak thigh adductors, weak
CC       knee and foot extensors, minimal jaw muscle and neck flexor
CC       weakness, flexion contractures of knees and pes equinovarus.
CC       Tendon reflexes are normal.
CC   -!- DISEASE: Defects in TRPV4 are the cause of Charcot-Marie-Tooth
CC       disease type 2C (CMT2C) [MIM:606071]; an axonal form of Charcot-
CC       Marie-Tooth disease, a disorder of the peripheral nervous system,
CC       characterized by progressive weakness and atrophy, initially of
CC       the peroneal muscles and later of the distal muscles of the arms.
CC       Charcot-Marie-Tooth disease is classified in two main groups on
CC       the basis of electrophysiologic properties and histopathology:
CC       primary peripheral demyelinating neuropathies (designated CMT1
CC       when they are dominantly inherited) and primary peripheral axonal
CC       neuropathies (CMT2). Neuropathies of the CMT2 group are
CC       characterized by signs of axonal regeneration in the absence of
CC       obvious myelin alterations, normal or slightly reduced nerve
CC       conduction velocities, and progressive distal muscle weakness and
CC       atrophy. Nerve conduction velocities are normal or slightly
CC       reduced.
CC   -!- DISEASE: Defects in TRPV4 are the cause of Scapuloperoneal spinal
CC       muscular atrophy (SPSMA) [MIM:181405]. It is a clinically variable
CC       neuromuscular disorder characterized by neurogenic scapuloperoneal
CC       amyotrophy, laryngeal palsy, congenital absence of muscles,
CC       progressive scapuloperoneal atrophy and progressive distal
CC       weakness and amyotrophy.
CC   -!- DISEASE: Defects in TRPV4 are the cause of spondyloepiphyseal
CC       dysplasia Maroteaux type (SEDM) [MIM:184095]. It is a clinically
CC       variable spondyloepiphyseal dysplasia with manifestations limited
CC       to the musculoskeletal system. Clinical features include short
CC       stature, brachydactyly, platyspondyly, short and stubby hands and
CC       feet, epiphyseal hypoplasia of the large joints, and iliac
CC       hypoplasia. Intelligence is normal.
CC   -!- DISEASE: Defects in TRPV4 are the cause of parastremmatic dwarfism
CC       (PSTD) [MIM:168400]. It is a bone dysplasia characterized by
CC       severe dwarfism, kyphoscoliosis, distortion and bowing of the
CC       extremities, and contractures of the large joints.
CC       Radiographically, the disease is characterized by a combination of
CC       decreased bone density, bowing of the long bones, platyspondyly
CC       and striking irregularities of endochondral ossification with
CC       areas of calcific stippling and streaking in radiolucent
CC       epiphyses, metaphyses and apophyses.
CC   -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family.
CC       TrpV subfamily. TRPV4 sub-subfamily.
CC   -!- SIMILARITY: Contains 3 ANK repeats.
CC   -!- GENE_FAMILY: HOG000234630 [ FAMILY / ALN / TREE ]
DR   HOGENOM:Homo_sapiens;ENSG00000111199;ENST00000261740;ENSP00000261740.
DR   EMBL; AB032427; - ;
DR   EMBL; AB073669; - ;
DR   EMBL; AB100308; - ;
DR   EMBL; AF258465; - ;
DR   EMBL; AF263523; - ;
DR   EMBL; AF279673; - ;
DR   EMBL; AJ296305; - ;
DR   EMBL; BC117426; - ;
DR   EMBL; BC143315; - ;
DR   EMBL; CH471054; - ;
DR   EMBL; DQ059644; - ;
DR   EMBL; DQ059645; - ;
DR   EMBL; DQ059646; - ;
DR   UniProtKB/Swiss-Prot; Q9HBA0; B7ZKQ6; Q17R79; Q2Y122; Q2Y123; Q2Y124; Q86YZ6; Q8NDY7; -.
DR   UniProtKB/Swiss-Prot; Q8NG64; Q96Q92; Q96RS7; Q9HBC0; -.
DR   EMBL; AF263523; AAG28029.1; -; mRNA.
DR   EMBL; AF258465; AAG16127.1; -; mRNA.
DR   EMBL; AB100308; BAC55864.1; -; mRNA.
DR   EMBL; AB032427; BAB69040.1; -; mRNA.
DR   EMBL; AB073669; BAC06573.1; -; mRNA.
DR   EMBL; AJ296305; CAC82937.1; -; mRNA.
DR   EMBL; DQ059644; AAZ04918.1; -; mRNA.
DR   EMBL; DQ059645; AAZ04919.1; -; mRNA.
DR   EMBL; DQ059646; AAZ04920.1; -; mRNA.
DR   EMBL; CH471054; EAW97879.1; -; Genomic_DNA.
DR   EMBL; BC117426; AAI17427.1; -; mRNA.
DR   EMBL; BC143315; AAI43316.1; -; mRNA.
DR   EMBL; AF279673; AAK69487.1; -; mRNA.
DR   IPI; IPI00168624; -.
DR   IPI; IPI00168926; -.
DR   IPI; IPI00555678; -.
DR   IPI; IPI00657947; -.
DR   IPI; IPI00658012; -.
DR   IPI; IPI00853621; -.
DR   RefSeq; NP_001170899.1; NM_001177428.1.
DR   RefSeq; NP_001170902.1; NM_001177431.1.
DR   RefSeq; NP_001170904.1; NM_001177433.1.
DR   RefSeq; NP_067638.3; NM_021625.4.
DR   RefSeq; NP_671737.1; NM_147204.2.
DR   UniGene; Hs.506713; -.
DR   ProteinModelPortal; Q9HBA0; -.
DR   SMR; Q9HBA0; 146-396.
DR   IntAct; Q9HBA0; 10.
DR   STRING; Q9HBA0; -.
DR   PhosphoSite; Q9HBA0; -.
DR   PRIDE; Q9HBA0; -.
DR   Ensembl; ENST00000261740; ENSP00000261740; ENSG00000111199.
DR   GeneID; 59341; -.
DR   KEGG; hsa:59341; -.
DR   UCSC; uc001tpg.1; human.
DR   UCSC; uc001tph.1; human.
DR   UCSC; uc001tpi.1; human.
DR   UCSC; uc001tpj.1; human.
DR   UCSC; uc001tpl.1; human.
DR   CTD; 59341; -.
DR   GeneCards; GC12M107238; -.
DR   H-InvDB; HIX0010981; -.
DR   HGNC; HGNC:18083; TRPV4.
DR   HPA; HPA007150; -.
DR   MIM; 113500; phenotype.
DR   MIM; 156530; phenotype.
DR   MIM; 168400; phenotype.
DR   MIM; 181405; phenotype.
DR   MIM; 184095; phenotype.
DR   MIM; 184252; phenotype.
DR   MIM; 600175; phenotype.
DR   MIM; 605427; gene.
DR   MIM; 606071; phenotype.
DR   MIM; 613508; phenotype.
DR   neXtProt; NX_Q9HBA0; -.
DR   PharmGKB; PA38293; -.
DR   eggNOG; prNOG07571; -.
DR   GeneTree; ENSGT00550000074425; -.
DR   InParanoid; Q9HBA0; -.
DR   OMA; QPQSPKA; -.
DR   OrthoDB; EOG4JQ3WW; -.
DR   PhylomeDB; Q9HBA0; -.
DR   NextBio; 65228; -.
DR   ArrayExpress; Q9HBA0; -.
DR   Bgee; Q9HBA0; -.
DR   Genevestigator; Q9HBA0; -.
DR   GermOnline; ENSG00000111199; Homo sapiens.
DR   GO; GO:0030864; C:cortical actin cytoskeleton; ISS:BHF-UCL.
DR   GO; GO:0030175; C:filopodium; ISS:BHF-UCL.
DR   GO; GO:0005925; C:focal adhesion; ISS:BHF-UCL.
DR   GO; GO:0030426; C:growth cone; ISS:BHF-UCL.
DR   GO; GO:0016021; C:integral to membrane; NAS:UniProtKB.
DR   GO; GO:0030027; C:lamellipodium; ISS:BHF-UCL.
DR   GO; GO:0032587; C:ruffle membrane; ISS:BHF-UCL.
DR   GO; GO:0051015; F:actin filament binding; ISS:BHF-UCL.
DR   GO; GO:0043014; F:alpha-tubulin binding; ISS:BHF-UCL.
DR   GO; GO:0048487; F:beta-tubulin binding; ISS:BHF-UCL.
DR   GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR   GO; GO:0005516; F:calmodulin binding; IMP:UniProtKB.
DR   GO; GO:0008017; F:microtubule binding; ISS:BHF-UCL.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0005080; F:protein kinase C binding; ISS:BHF-UCL.
DR   GO; GO:0042169; F:SH2 domain binding; ISS:BHF-UCL.
DR   GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:BHF-UCL.
DR   GO; GO:0007015; P:actin filament organization; ISS:BHF-UCL.
DR   GO; GO:0070509; P:calcium ion import; ISS:BHF-UCL.
DR   GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR   GO; GO:0006884; P:cell volume homeostasis; TAS:UniProtKB.
DR   GO; GO:0007043; P:cell-cell junction assembly; ISS:UniProtKB.
DR   GO; GO:0071476; P:cellular hypotonic response; ISS:BHF-UCL.
DR   GO; GO:0043622; P:cortical microtubule organization; ISS:BHF-UCL.
DR   GO; GO:0007204; P:elevation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR   GO; GO:0046785; P:microtubule polymerization; ISS:BHF-UCL.
DR   GO; GO:0010977; P:negative regulation of neuron projection development; ISS:BHF-UCL.
DR   GO; GO:0007231; P:osmosensory signaling pathway; TAS:UniProtKB.
DR   GO; GO:0031117; P:positive regulation of microtubule depolymerization; ISS:BHF-UCL.
DR   GO; GO:0009612; P:response to mechanical stimulus; TAS:UniProtKB.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR   InterPro; IPR005821; Ion_trans.
DR   InterPro; IPR004729; TRP_channel.
DR   InterPro; IPR008348; TRPV4_channel.
DR   InterPro; IPR008347; TRPV_channel.
DR   Gene3D; G3DSA:1.25.40.20; ANK; 1.
DR   Pfam; PF00023; Ank; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   PRINTS; PR01768; TRPVRECEPTOR.
DR   PRINTS; PR01769; VRL2RECEPTOR.
DR   SMART; SM00248; ANK; 3.
DR   SUPFAM; SSF48403; ANK; 1.
DR   TIGRFAMs; TIGR00870; Trp; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 1.
DR   HOGENOMDNA; HS12.PE2162; -.
KW   ENSG000001111991755old_1320000031; ENSP000002617407901old_1320000031;
KW   AB032427; AB073669; AB100308; AF258465; AF263523; AF279673; AJ296305;
KW   BC143315; CH471054; DQ059644; DQ059645; DQ059646;
KW   Alternative splicing; ANK repeat; Calcium; Calcium channel;
KW   Calcium transport; Calmodulin-binding; Cell junction; Cell membrane;
KW   Charcot-Marie-Tooth disease; Complete proteome; Disease mutation;
KW   Dwarfism; Ion transport; Ionic channel; Membrane; Neurodegeneration;
KW   Neuropathy; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW   Transmembrane; Transmembrane helix; Transport.
SQ   SEQUENCE   871 AA;  UNKNOWN MW;  UNKNOWN CRC64;
     MADSSEGPRA GPGEVAELPG DESGTPGGEA FPLSSLANLF EGEDGSLSPS PADASRPAGP
     GDGRPNLRMK FQGAFRKGVP NPIDLLESTL YESSVVPGPK KAPMDSLFDY GTYRHHSSDN
     KRWRKKIIEK QPQSPKAPAP QPPPILKVFN RPILFDIVSR GSTADLDGLL PFLLTHKKRL
     TDEEFREPST GKTCLPKALL NLSNGRNDTI PVLLDIAERT GNMREFINSP FRDIYYRGQT
     ALHIAIERRC KHYVELLVAQ GADVHAQARG RFFQPKDEGG YFYFGELPLS LAACTNQPHI
     VNYLTENPHK KADMRRQDSR GNTVLHALVA IADNTRENTK FVTKMYDLLL LKCARLFPDS
     NLEAVLNNDG LSPLMMAAKT GKIGIFQHII RREVTDEDTR HLSRKFKDWA YGPVYSSLYD
     LSSLDTCGEE ASVLEILVYN SKIENRHEML AVEPINELLR DKWRKFGAVS FYINVVSYLC
     AMVIFTLTAY YQPLEGTPPY PYRTTVDYLR LAGEVITLFT GVLFFFTNIK DLFMKKCPGV
     NSLFIDGSFQ LLYFIYSVLV IVSAALYLAG IEAYLAVMVF ALVLGWMNAL YFTRGLKLTG
     TYSIMIQKIL FKDLFRFLLV YLLFMIGYAS ALVSLLNPCA NMKVCNEDQT NCTVPTYPSC
     RDSETFSTFL LDLFKLTIGM GDLEMLSSTK YPVVFIILLV TYIILTFVLL LNMLIALMGE
     TVGQVSKESK HIWKLQWATT ILDIERSFPV FLRKAFRSGE MVTVGKSSDG TPDRRWCFRV
     DEVNWSHWNQ NLGIINEDPG KNETYQYYGF SHTVGRLRRD RWSSVVPRVV ELNKNSNPDE
     VVVPLDSMGN PRCDGHQQGY PRKWRTDDAP L
//

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