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UniProtKB/Swiss-Prot Q9HBA0 (TRPV4_HUMAN)
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March 2, 2010.
Version 79.
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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents
Names and origin
| Protein names | Recommended name: Transient receptor potential cation channel subfamily V member 4 Short name=TrpV4 Alternative name(s): Osm-9-like TRP channel 4 Short name=OTRPC4 Vanilloid receptor-like channel 2 Vanilloid receptor-like protein 2 Short name=VRL-2 Vanilloid receptor-related osmotically-activated channel Short name=VR-OAC Transient receptor potential protein 12 Short name=TRP12 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 871 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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. Ref.2 Ref.11 |
| 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 By similarity. Ref.11 |
| Subcellular location | Membrane; Multi-pass membrane protein Probable. Note: Assembly of the putative homotetramer occurs primarily in the endoplasmic reticulum. Ref.7 Isoform 1: Cell membrane Ref.7. Isoform 5: Cell membrane Ref.7. |
| Involvement in disease | Defects in TRPV4 are the cause of brachyolmia type 3 (BRAC3) [MIM:113500]; also known as brachyrachia. 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. Ref.12 Defects in TRPV4 are the cause of spondylometaphyseal dysplasia Kozlowski type (SMDK) [MIM:184252]. The spondylometaphyseal dysplasias (SMDs) are a group of short-stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDK is an autosomal dominant disorder characterized by significant scoliosis and mild metaphyseal abnormalities in the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles. Defects in TRPV4 are the cause of metatropic dysplasia (MTD) [MIM:156530]; also called metatropic dwarfism. Metatropic dysplasia is 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. |
| Sequence similarities | Belongs to the transient receptor family. TrpV subfamily. Contains 3 ANK repeats. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 1 | EBI-962786,EBI-962786 | ||
| Q9HBA0-1 | 1 | EBI-1514303,EBI-961969 |
Alternative products
| This entry describes 6 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9HBA0-1) Also known as: A; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q9HBA0-2) Also known as: B; OTRPC4beta; The sequence of this isoform differs from the canonical sequence as follows: 385-444: Missing. | ||||||
| Isoform 3 (identifier: Q9HBA0-3) Also known as: TRPV-SV; The sequence of this isoform differs from the canonical sequence as follows: 844-871: PLDSMGNPRCDGHQQGYPRKWRTDDAPL → RHLCRVRRKR | ||||||
| Isoform 4 (identifier: Q9HBA0-4) Also known as: C; The sequence of this isoform differs from the canonical sequence as follows: 239-285: Missing. | ||||||
| Isoform 5 (identifier: Q9HBA0-5) Also known as: D; The sequence of this isoform differs from the canonical sequence as follows: 28-61: Missing. | ||||||
| Isoform 6 (identifier: Q9HBA0-6) Also known as: E; The sequence of this isoform differs from the canonical sequence as follows: 239-285: Missing. 385-444: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 871 | 871 | Transient receptor potential cation channel subfamily V member 4 | PRO_0000215347 | |||||
Regions | |||||||||
| Topological domain | 1 – 465 | 465 | Cytoplasmic Potential | ||||||
| Transmembrane | 466 – 486 | 21 | Potential | ||||||
| Topological domain | 487 – 508 | 22 | Extracellular Potential | ||||||
| Transmembrane | 509 – 529 | 21 | Potential | ||||||
| Topological domain | 530 – 550 | 21 | Cytoplasmic Potential | ||||||
| Transmembrane | 551 – 571 | 21 | Potential | ||||||
| Topological domain | 572 | 1 | Extracellular Potential | ||||||
| Transmembrane | 573 – 593 | 21 | Potential | ||||||
| Topological domain | 594 – 616 | 23 | Cytoplasmic Potential | ||||||
| Transmembrane | 617 – 637 | 21 | Potential | ||||||
| Topological domain | 638 – 690 | 53 | Pore forming Probable | ||||||
| Transmembrane | 691 – 711 | 21 | Potential | ||||||
| Topological domain | 712 – 871 | 160 | Cytoplasmic Potential | ||||||
| Repeat | 237 – 266 | 30 | ANK 1 | ||||||
| Repeat | 284 – 313 | 30 | ANK 2 | ||||||
| Repeat | 369 – 398 | 30 | ANK 3 | ||||||
| Region | 812 – 831 | 20 | Interaction with calmodulin | ||||||
Amino acid modifications | |||||||||
| Modified residue | 253 | 1 | Phosphotyrosine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 28 – 61 | 34 | Missing in isoform 5. | VSP_026614 | |||||
| Alternative sequence | 239 – 285 | 47 | Missing in isoform 4 and isoform 6. | VSP_026615 | |||||
| Alternative sequence | 385 – 444 | 60 | Missing in isoform 2 and isoform 6. | VSP_013436 | |||||
| Alternative sequence | 844 – 871 | 28 | PLDSM…DDAPL → RHLCRVRRKR in isoform 3. | VSP_013437 | |||||
| Natural variant | 19 | 1 | P → S: dbSNP rs3742030. | VAR_052391 | |||||
| Natural variant | 331 | 1 | I → F in MTD. | VAR_062331 | |||||
| Natural variant | 333 | 1 | D → G in SMDK. | VAR_062332 | |||||
| Natural variant | 594 | 1 | R → H in SMDK. | VAR_062333 | |||||
| Natural variant | 616 | 1 | R → Q in BRAC3; this mutation results in a gain of function and a constitutive activation of the channel. Ref.12 | VAR_054805 | |||||
| Natural variant | 620 | 1 | V → I in BRAC3; this mutation results in a gain of function and a constitutive activation of the channel. Ref.12 | VAR_054806 | |||||
| Natural variant | 716 | 1 | A → S in SMDK. | VAR_062334 | |||||
| Natural variant | 799 | 1 | P → L in MTD. | VAR_062335 | |||||
Experimental info | |||||||||
| Mutagenesis | 816 – 821 | 6 | RLRRDR → ELEEDE: Loss of calmodulin binding; when associated with A-828. | ||||||
| Mutagenesis | 821 – 824 | 4 | RWSS → AASA: Loss of calmodulin binding. | ||||||
| Mutagenesis | 822 | 1 | W → A: Loss of Ca(2+) dependent current potentiation. | ||||||
| Mutagenesis | 828 | 1 | R → A: Loss of calmodulin binding; when associated with 816-ELEEDE-821. Ref.11 | ||||||
| Sequence conflict | 385 | 1 | I → V in AAG28029. Ref.1 | ||||||
| Sequence conflict | 452 | 1 | V → A in BAC06573. Ref.6 | ||||||
| Sequence conflict | 618 | 1 | L → P in BAC06573. Ref.6 | ||||||
| Sequence conflict | 781 | 1 | D → N in AAG28029. Ref.1 | ||||||
| Sequence conflict | 820 | 1 | D → T in BAB69040. Ref.4 | ||||||
| Sequence conflict | 861 | 1 | P → T in BAC06573. Ref.6 | ||||||
| Sequence conflict | 867 | 1 | D → E in AAG16127. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor." Liedtke W.B., Choe Y., Marti-Renom M.A., Bell A.M., Denis C.S., Sali A., Hudspeth A.J., Friedman J.M., Heller S. Cell 103:525-535(2000) [PubMed: 11081638] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity." Strotmann R., Harteneck C., Nunnenmacher K., Schultz G., Plant T.D. Nat. Cell Biol. 2:695-702(2000) [PubMed: 11025659] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION. Tissue: Kidney cortex. |
| [3] | "Impaired pressure sensation in mice lacking TRPV4." Suzuki M., Mizuno A., Kodaira K., Imai M. J. Biol. Chem. 278:22664-22668(2003) [PubMed: 12692122] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). |
| [4] | "Molecular cloning of a new member of vanilloid receptor channel-like proteins." Ishibashi K. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [5] | Kelsell R.E. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [6] | Xu F., Satoh E., Iijima T. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Aortic endothelium. |
| [7] | "Human TRPV4 channel splice variants revealed a key role of ankyrin domains in multimerization and trafficking." Arniges M., Fernandez-Fernandez J.M., Albrecht N., Schaefer M., Valverde M.A. J. Biol. Chem. 281:1580-1586(2006) [PubMed: 16293632] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5 AND 6), SUBCELLULAR LOCATION, SELF-ASSOCIATION. |
| [8] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R.  Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [9] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon. |
| [10] | "Cloning of mouse and human vanilloid receptor-like protein 2 (VRL-2)." Derst C., Schafer M.K. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 69-871. |
| [11] | "Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site." Strotmann R., Schultz G., Plant T.D. J. Biol. Chem. 278:26541-26549(2003) [PubMed: 12724311] [Abstract] Cited for: FUNCTION, INTERACTION WITH CALMODULIN, MUTAGENESIS OF 186-ARG--SER-824 AND ARG-828. |
| [12] | "Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia." Rock M.J., Prenen J., Funari V.A., Funari T.L., Merriman B., Nelson S.F., Lachman R.S., Wilcox W.R., Reyno S., Quadrelli R., Vaglio A., Owsianik G., Janssens A., Voets T., Ikegawa S., Nagai T., Rimoin D.L., Nilius B., Cohn D.H. Nat. Genet. 40:999-1003(2008) [PubMed: 18587396] [Abstract] Cited for: VARIANTS BRAC3 GLN-616 AND ILE-620, CHARACTERIZATION OF VARIANTS BRAC3 GLN-616 AND ILE-620. |
| [13] | "Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia." Krakow D., Vriens J., Camacho N., Luong P., Deixler H., Funari T.L., Bacino C.A., Irons M.B., Holm I.A., Sadler L., Okenfuss E.B., Janssens A., Voets T., Rimoin D.L., Lachman R.S., Nilius B., Cohn D.H. Am. J. Hum. Genet. 84:307-315(2009) [PubMed: 19232556] [Abstract] Cited for: VARIANTS SMDK GLY-333; HIS-594 AND SER-716, VARIANTS MTD PHE-331 AND LEU-799. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF263523 mRNA. Translation: AAG28029.1. AF258465 mRNA. Translation: AAG16127.1. AB100308 mRNA. Translation: BAC55864.1. AB032427 mRNA. Translation: BAB69040.1. AB073669 mRNA. Translation: BAC06573.1. AJ296305 mRNA. Translation: CAC82937.1. DQ059644 mRNA. Translation: AAZ04918.1. DQ059645 mRNA. Translation: AAZ04919.1. DQ059646 mRNA. Translation: AAZ04920.1. CH471054 Genomic DNA. Translation: EAW97879.1. BC117426 mRNA. Translation: AAI17427.1. BC143315 mRNA. Translation: AAI43316.1. AF279673 mRNA. Translation: AAK69487.1. |
| IPI | IPI00168624. IPI00168926. IPI00555678. IPI00657947. IPI00658012. IPI00853621. |
| RefSeq | NP_067638.3. NP_671737.1. |
| UniGene | Hs.506713 |
3D structure databases | |
| SMR | Q9HBA0. Positions 149-393. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9HBA0. 9 interactions. |
| STRING | Q9HBA0. |
PTM databases | |
| PhosphoSite | Q9HBA0. |
Proteomic databases | |
| PRIDE | Q9HBA0. |
Genome annotation databases | |
| Ensembl | ENST00000261740; ENSP00000261740; ENSG00000111199; Homo sapiens. [Genome view] |
| GeneID | 59341. |
| KEGG | hsa:59341. |
| UCSC | uc001tpg.1. human. uc001tph.1. human. uc001tpi.1. human. uc001tpj.1. human. uc001tpl.1. human. |
Organism-specific databases | |
| CTD | 59341. |
| GeneCards | GC12M108683. |
| H-InvDB | HIX0010981. |
| HGNC | HGNC:18083. TRPV4. |
| HPA | HPA007150. |
| MIM | 113500. phenotype. 156530. phenotype. 184252. phenotype. 605427. gene. |
| PharmGKB | PA38293. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG07571. |
| HOVERGEN | HBG054085. |
| InParanoid | Q9HBA0. |
| OMA | ESTLYES. |
| OrthoDB | EOG9SR0FX. |
| PhylomeDB | Q9HBA0. |
Gene expression databases | |
| ArrayExpress | Q9HBA0. |
| Bgee | Q9HBA0. |
| Genevestigator | Q9HBA0. |
| GermOnline | ENSG00000111199. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR005821. Ion_trans. IPR004729. TRP_channel. IPR008347. Vanilpoid_rcpt. IPR008348. Vanilpoid_rcpt_2. [Graphical view] |
| Gene3D | G3DSA:1.25.40.20. ANK. 1 hit. |
| Pfam | PF00023. Ank. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view] |
| PRINTS | PR01768. TRPVRECEPTOR. PR01769. VRL2RECEPTOR. |
| SMART | SM00248. ANK. 3 hits. [Graphical view] |
| SUPFAM | SSF48403. ANK. 1 hit. |
| TIGRFAMs | TIGR00870. trp. 1 hit. |
| PROSITE | PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 65228. |
| SOURCE | Search... |
Entry information
| Entry name | TRPV4_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9HBA0 Secondary accession number(s): B7ZKQ6 Q9HBC0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 12 Human chromosome 12: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |
