Reviewed,
UniProtKB/Swiss-Prot Q9BX84 (TRPM6_HUMAN)
Last modified
June 16, 2009.
Version 62.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Transient receptor potential cation channel subfamily M member 6 EC=2.7.11.1 Alternative name(s): Channel kinase 2 Melastatin-related TRP cation channel 6 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 2022 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Essential ion channel and serine/threonine-protein kinase. Crucial for magnesium homeostasis. Has an important role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Isoforms of the type M6-kinase lack the ion channel region. |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Subunit structure | Forms heterodimers with TRPM7. TRPM6 requires the presence of TRPM7 to be targeted to the cell membrane (in HEK 293 cells). |
| Subcellular location | |
| Tissue specificity | Highly expressed in kidney and colon. Isoform TRPM6a and isoform TRPM6b, are coexpressed with TRPM7 in kidney, and testis, and are also found in several cell lines of lung origin. Isoform TRPM6c is detected only in testis and in H510 small cell lung carcinoma cells. |
| Involvement in disease | Defects in TRPM6 are the cause of hypomagnesemia type 1 (HOMG1) [MIM:602014]; also known as hypomagnesemia with secondary hypocalcemia (HSH). HOMG1 is a disorder due to a primary defect in intestinal magnesium absorption. It is characterized by low levels of serum magnesium alongside with a normal renal magnesium secretion, secondary hypocalcemia and calcinocis. Affected individuals show neurologic symptoms of hypomagnesemic hypocalcemia, including seizures and muscle spasms, during infancy. Hypocalcemia is secondary to parathyroid failure resulting from magnesium deficiency. Untreated, the disorder may be fatal or may result in neurological damage. Ref.2 Ref.3 |
| Sequence similarities | In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily. In the N-terminal section; belongs to the transient receptor family. LTrpC subfamily. Contains 1 alpha-type protein kinase domain. |
Ontologies
Alternative products
| This entry describes 7 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform TRPM6a (identifier: Q9BX84-1) 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 TRPM6b (identifier: Q9BX84-2) The sequence of this isoform differs from the canonical sequence as follows: 1-11: MKEQPVLERLQ → MIILSK | ||||||
| Isoform TRPM6c (identifier: Q9BX84-3) The sequence of this isoform differs from the canonical sequence as follows: 1-11: MKEQPVLERLQ → MTAPVT | ||||||
| Isoform TRPM6t (identifier: Q9BX84-4) The sequence of this isoform differs from the canonical sequence as follows: 1926-1943: GVGENLTDPSVIKPEVKQ → ALWFWDSMLKARLGGWRM 1944-2022: Missing. | ||||||
| Isoform M6-kinase 1 (identifier: Q9BX84-5) The sequence of this isoform differs from the canonical sequence as follows: 547-1595: Missing. | ||||||
| Note: Lacks the ion channel region. | ||||||
| Isoform M6-kinase 2 (identifier: Q9BX84-6) The sequence of this isoform differs from the canonical sequence as follows: 500-1666: Missing. | ||||||
| Note: Lacks the ion channel region. | ||||||
| Isoform M6-kinase 3 (identifier: Q9BX84-7) The sequence of this isoform differs from the canonical sequence as follows: 281-281: R → P 282-1734: Missing. | ||||||
| Note: Lacks the ion channel region. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2022 | 2022 | Transient receptor potential cation channel subfamily M member 6 | PRO_0000215329 | |||||
Regions | |||||||||
| Topological domain | 1 – 741 | 741 | Cytoplasmic Potential | ||||||
| Transmembrane | 742 – 762 | 21 | Potential | ||||||
| Topological domain | 763 – 841 | 79 | Extracellular Potential | ||||||
| Transmembrane | 842 – 862 | 21 | Potential | ||||||
| Topological domain | 863 – 905 | 43 | Cytoplasmic Potential | ||||||
| Transmembrane | 906 – 926 | 21 | Potential | ||||||
| Topological domain | 927 – 939 | 13 | Extracellular Potential | ||||||
| Transmembrane | 940 – 960 | 21 | Potential | ||||||
| Topological domain | 961 – 972 | 12 | Cytoplasmic Potential | ||||||
| Transmembrane | 973 – 993 | 21 | Potential | ||||||
| Topological domain | 994 – 1012 | 19 | Extracellular Potential | ||||||
| Topological domain | 1013 – 1033 | 21 | Pore forming Potential | ||||||
| Topological domain | 1034 – 1047 | 14 | Extracellular Potential | ||||||
| Transmembrane | 1048 – 1068 | 21 | Potential | ||||||
| Topological domain | 1069 – 2022 | 954 | Cytoplasmic Potential | ||||||
| Domain | 1750 – 1980 | 231 | Alpha-type protein kinase | ||||||
| Nucleotide binding | 1950 – 1956 | 7 | ATP By similarity | ||||||
Sites | |||||||||
| Active site | 1923 | 1 | Proton acceptor By similarity | ||||||
| Metal binding | 1909 | 1 | Zinc By similarity | ||||||
| Metal binding | 1966 | 1 | Zinc By similarity | ||||||
| Metal binding | 1968 | 1 | Zinc By similarity | ||||||
| Metal binding | 1972 | 1 | Zinc By similarity | ||||||
| Binding site | 1780 | 1 | ATP By similarity | ||||||
| Binding site | 1804 | 1 | ATP By similarity | ||||||
| Binding site | 1876 | 1 | ATP By similarity | ||||||
| Binding site | 1925 | 1 | ATP By similarity | ||||||
| Binding site | 1933 | 1 | ATP By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 11 | 11 | MKEQPVLERLQ → MIILSK in isoform TRPM6b. | VSP_012069 | |||||
| Alternative sequence | 1 – 11 | 11 | MKEQPVLERLQ → MTAPVT in isoform TRPM6c. | VSP_012070 | |||||
| Alternative sequence | 281 | 1 | R → P in isoform M6-kinase 3. | VSP_012071 | |||||
| Alternative sequence | 282 – 1734 | 1453 | Missing in isoform M6-kinase 3. | VSP_012072 | |||||
| Alternative sequence | 500 – 1666 | 1167 | Missing in isoform M6-kinase 2. | VSP_012073 | |||||
| Alternative sequence | 547 – 1595 | 1049 | Missing in isoform M6-kinase 1. | VSP_012074 | |||||
| Alternative sequence | 1926 – 1943 | 18 | GVGEN…PEVKQ → ALWFWDSMLKARLGGWRM in isoform TRPM6t. | VSP_012075 | |||||
| Alternative sequence | 1944 – 2022 | 79 | Missing in isoform TRPM6t. | VSP_012076 | |||||
| Natural variant | 75 | 1 | G → V in a lung adenocarcinoma sample; somatic mutation. Ref.5 | VAR_042387 | |||||
| Natural variant | 141 | 1 | S → L in HOMG1; impairs heterodimer formation resulting in intracellular retention. Ref.2 Ref.3 | VAR_019963 | |||||
| Natural variant | 338 | 1 | M → I Ref.5 | VAR_042388 | |||||
| Natural variant | 948 | 1 | F → L: dbSNP rs13290391. | VAR_052380 | |||||
| Natural variant | 1007 | 1 | W → C in a lung large cell carcinoma sample; somatic mutation. Ref.5 | VAR_042389 | |||||
| Natural variant | 1071 | 1 | N → D: dbSNP rs2274922. | VAR_019964 | |||||
| Natural variant | 1243 | 1 | H → R Ref.5 | VAR_042390 | |||||
| Natural variant | 1274 | 1 | Q → R: dbSNP rs34608911. Ref.5 | VAR_042391 | |||||
| Natural variant | 1393 | 1 | V → I: dbSNP rs3750425. Ref.5 | VAR_019965 | |||||
| Natural variant | 1584 | 1 | K → E: dbSNP rs2274924. Ref.5 | VAR_019966 | |||||
| Natural variant | 1663 | 1 | Q → R Ref.5 | VAR_042392 | |||||
| Natural variant | 1673 | 1 | L → S Ref.5 | VAR_042393 | |||||
| Natural variant | 1724 | 1 | T → I Ref.5 | VAR_042394 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Novel type of signaling molecules: protein kinases covalently linked to ion channels." Riazanova L.V., Pavur K.S., Petrov A.N., Dorovkov M.V., Riazanov A.G. Mol. Biol. (Mosk.) 35:321-332(2001) [PubMed: 11357414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRPM6A), CHARACTERIZATION. Tissue: Kidney. |
| [2] | "Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family." Schlingmann K.P., Weber S., Peters M., Niemann Nejsum L.N., Vitzthum H., Klingel K., Kratz M., Haddad E., Ristoff E., Dinour D., Syrrou M., Nielsen S., Sassen M.C., Waldegger S., Seyberth H.W., Konrad M. Nat. Genet. 31:166-170(2002) [PubMed: 12032568] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRPM6A), VARIANT HOMG1 LEU-141. Tissue: Kidney and Small intestine. |
| [3] | "Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia." Chubanov V., Waldegger S., Mederos y Schnitzler M., Vitzthum H., Sassen M.C., Seyberth H.W., Konrad M., Gudermann T. Proc. Natl. Acad. Sci. U.S.A. 101:2894-2899(2004) [PubMed: 14976260] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TRPM6A; TRPM6B; TRPM6C; TRPM6T; M6-KINASE 1; M6-KINASE 2 AND M6-KINASE 3), CHARACTERIZATION OF VARIANT HOMG1 LEU-141, INTERACTION WITH TRPM7. Tissue: Lung cancer. |
| [4] | "DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. Dunham I.Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-75; ILE-338; CYS-1007; ARG-1243; ARG-1274; ILE-1393; GLU-1584; ARG-1663; SER-1673 AND ILE-1724. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AF350881 mRNA. Translation: AAK31202.2. AF448232 mRNA. Translation: AAM21562.1. AY333282 mRNA. Translation: AAR03487.1. AY333283 mRNA. Translation: AAR03488.1. AY333284 mRNA. Translation: AAR03489.1. AY333285 mRNA. Translation: AAR03490.1. AY333286 mRNA. Translation: AAR03491.1. AY333287 mRNA. Translation: AAR03492.1. AY333288 mRNA. Translation: AAR03493.1. AL354795 Genomic DNA. Translation: CAH70894.1. | |
| IPI | IPI00151366. IPI00438874. IPI00438875. IPI00438890. IPI00472524. IPI00478589. IPI00479402. |
| RefSeq | NP_060132.3. |
| UniGene | Hs.272225 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1IAJ based on UniProtKB Q9JLQ1. |
| SMR | Q9BX84. Positions 1707-1986. |
| ModBase | Search... |
Protein family/group databases | |
| TCDB | 1.A.4.5.8. transient receptor potential Ca2+ channel (TRP-CC) family. |
PTM databases | |
| PhosphoSite | Q9BX84. |
Proteomic databases | |
| PRIDE | Q9BX84. |
Genome annotation databases | |
| Ensembl | ENSG00000119121. Homo sapiens. [Contig view] |
| GeneID | 140803. |
| KEGG | hsa:140803. |
Organism-specific databases | |
| GeneCards | GC09M076527. |
| H-InvDB | HIX0008102. |
| HGNC | HGNC:17995. TRPM6. |
| HPA | HPA007037. |
| MIM | 602014. phenotype. 607009. gene. |
| Orphanet | 30924. Hypomagnesemia caused by selective magnesium malabsorption. |
| PharmGKB | PA38479. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | Q9BX84. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 247. |
Gene expression databases | |
| ArrayExpress | Q9BX84. |
| Bgee | Q9BX84. |
| CleanEx | HS_TRPM6. |
| GermOnline | ENSG00000119121. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR005821. Ion_trans. IPR004166. MHCK_EF2_kinase. [Graphical view] |
| Pfam | PF02816. Alpha_kinase. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view] |
| SMART | SM00811. Alpha_kinase. 1 hit. [Graphical view] |
| PROSITE | PS51158. ALPHA_KINASE. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 84406. |
| SOURCE | Search... |
Entry information
| Entry name | TRPM6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9BX84 Secondary accession number(s): Q6VPR8 Q6VPS2 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 9 Human chromosome 9: 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 |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


