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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2''' is a [[protein]] that in humans is encoded by the ''HCN2'' [[gene]].<ref name="pmid9405696">{{cite journal | vauthors = Santoro B, Grant SG, Bartsch D, Kandel ER | title = Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 26 | pages = 14815–20 | date = Dec 1997 | pmid = 9405696 | pmc = 25120 | doi = 10.1073/pnas.94.26.14815 }}</ref><ref name="pmid9630217">{{cite journal | vauthors = Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR | title = Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain | journal = Cell | volume = 93 | issue = 5 | pages = 717–29 | date = May 1998 | pmid = 9630217 | pmc =  | doi = 10.1016/S0092-8674(00)81434-8 }}</ref><ref name="pmid16382102">{{cite journal | vauthors = Hofmann F, Biel M, Kaupp UB | title = International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 455–62 | date = Dec 2005 | pmid = 16382102 | pmc = | doi = 10.1124/pr.57.4.8 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HCN2 hyperpolarization activated cyclic nucleotide-gated potassium channel 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=610| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Interactions ==
{{GNF_Protein_box
| image = PBB_Protein_HCN2_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1q3e.
| PDB = {{PDB2|1q3e}}, {{PDB2|1q43}}, {{PDB2|1q5o}}
| Name = Hyperpolarization activated cyclic nucleotide-gated potassium channel 2
| HGNCid = 4846
| Symbol = HCN2
| AltSymbols =; BCNG-2; BCNG2; HAC-1
| OMIM = 602781
| ECnumber = 
| Homologene = 31022
| MGIid = 1298210
| GeneAtlas_image1 = PBB_GE_HCN2_207592_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_HCN2_214893_x_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0005249 |text = voltage-gated potassium channel activity}} {{GNF_GO|id=GO:0005272 |text = sodium channel activity}} {{GNF_GO|id=GO:0030552 |text = cAMP binding}} {{GNF_GO|id=GO:0030955 |text = potassium ion binding}} {{GNF_GO|id=GO:0031402 |text = sodium ion binding}}
| Component = {{GNF_GO|id=GO:0005624 |text = membrane fraction}} {{GNF_GO|id=GO:0008076 |text = voltage-gated potassium channel complex}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006812 |text = cation transport}} {{GNF_GO|id=GO:0006813 |text = potassium ion transport}} {{GNF_GO|id=GO:0006814 |text = sodium ion transport}} {{GNF_GO|id=GO:0006936 |text = muscle contraction}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 610
    | Hs_Ensembl = ENSG00000099822
    | Hs_RefseqProtein = NP_001185
    | Hs_RefseqmRNA = NM_001194
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 540893
    | Hs_GenLoc_end = 568157
    | Hs_Uniprot = Q9UL51
    | Mm_EntrezGene = 15166
    | Mm_Ensembl = ENSMUSG00000020331
    | Mm_RefseqmRNA = XM_985431
    | Mm_RefseqProtein = XP_990525
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 10
    | Mm_GenLoc_start = 79119763
    | Mm_GenLoc_end = 79139237
    | Mm_Uniprot = O88703
  }}
}}
'''Hyperpolarization activated cyclic nucleotide-gated potassium channel 2''', also known as '''HCN2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HCN2 hyperpolarization activated cyclic nucleotide-gated potassium channel 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=610| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
HCN2 has been shown to [[Protein-protein interaction|interact]] with [[HCN1]]<ref name=pmid12928435>{{cite journal | vauthors = Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M | title = Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels | journal = The Journal of Biological Chemistry | volume = 278 | issue = 44 | pages = 43781–6 | date = Oct 2003 | pmid = 12928435 | doi = 10.1074/jbc.M306958200 }}</ref><ref name=pmid12034718>{{cite journal | vauthors = Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA | title = Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels | journal = The Journal of Biological Chemistry | volume = 277 | issue = 33 | pages = 29634–42 | date = Aug 2002 | pmid = 12034718 | doi = 10.1074/jbc.M200504200 }}</ref> and [[HCN4]].<ref name=pmid12928435/>
{{PBB_Summary
| section_title =  
| summary_text =  
}}


==See also==
== Function ==
 
The function of the channel is not known although its activation by hyperpolarization alludes to the [[funny channel]]s in the [[sinoatrial node]] of the heart (which form the basis of spontaneous generation of electrical rhythm). These channels have recently been associated with chronic pain and blocking the gene is associated with resolution of neuropathic episodes of [[pain]].<ref>{{cite news| url=http://articles.timesofindia.indiatimes.com/2011-09-10/science/30138741_1_chronic-pain-neuropathic-pain-gene | work=The Times Of India | title=Gene find may lead to pills that kill chronic pain | date=10 September 2011}}</ref>
 
== See also ==
* [[Cyclic nucleotide-gated ion channel]]
* [[Cyclic nucleotide-gated ion channel]]


==References==
== References ==
{{reflist|2}}
{{reflist}}
{{Clear}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Kleiderlein JJ, Nisson PE, Jessee J, Li WB, Becker KG, Derby ML, Ross CA, Margolis RL | title = CCG repeats in cDNAs from human brain | journal = Human Genetics | volume = 103 | issue = 6 | pages = 666–73 | date = Dec 1998 | pmid = 9921901 | doi = 10.1007/s004390050889 }}
| citations =
* {{cite journal | vauthors = Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M | title = Two pacemaker channels from human heart with profoundly different activation kinetics | journal = The EMBO Journal | volume = 18 | issue = 9 | pages = 2323–9 | date = May 1999 | pmid = 10228147 | pmc = 1171315 | doi = 10.1093/emboj/18.9.2323 }}
*{{cite journal | author=Hofmann F, Biel M, Kaupp UB |title=International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. |journal=Pharmacol. Rev. |volume=57 |issue= 4 |pages= 455-62 |year= 2006 |pmid= 16382102 |doi= 10.1124/pr.57.4.8 }}
* {{cite journal | vauthors = Vaccari T, Moroni A, Rocchi M, Gorza L, Bianchi ME, Beltrame M, DiFrancesco D | title = The human gene coding for HCN2, a pacemaker channel of the heart | journal = Biochimica et Biophysica Acta | volume = 1446 | issue = 3 | pages = 419–25 | date = Sep 1999 | pmid = 10524219 | doi = 10.1016/s0167-4781(99)00092-5 }}
*{{cite journal  | author=Santoro B, Grant SG, Bartsch D, Kandel ER |title=Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 26 |pages= 14815-20 |year= 1998 |pmid= 9405696 |doi=  }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
*{{cite journal  | author=Santoro B, Liu DT, Yao H, ''et al.'' |title=Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. |journal=Cell |volume=93 |issue= 5 |pages= 717-29 |year= 1998 |pmid= 9630217 |doi=  }}
* {{cite journal | vauthors = Ulens C, Tytgat J | title = Functional heteromerization of HCN1 and HCN2 pacemaker channels | journal = The Journal of Biological Chemistry | volume = 276 | issue = 9 | pages = 6069–72 | date = Mar 2001 | pmid = 11133998 | doi = 10.1074/jbc.C000738200 }}
*{{cite journal  | author=Kleiderlein JJ, Nisson PE, Jessee J, ''et al.'' |title=CCG repeats in cDNAs from human brain. |journal=Hum. Genet. |volume=103 |issue= 6 |pages= 666-73 |year= 1999 |pmid= 9921901 |doi= }}
* {{cite journal | vauthors = Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA | title = Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels | journal = The Journal of Biological Chemistry | volume = 277 | issue = 33 | pages = 29634–42 | date = Aug 2002 | pmid = 12034718 | doi = 10.1074/jbc.M200504200 }}
*{{cite journal | author=Ludwig A, Zong X, Stieber J, ''et al.'' |title=Two pacemaker channels from human heart with profoundly different activation kinetics. |journal=EMBO J. |volume=18 |issue= 9 |pages= 2323-9 |year= 1999 |pmid= 10228147 |doi= 10.1093/emboj/18.9.2323 }}
* {{cite journal | vauthors = Qu J, Altomare C, Bucchi A, DiFrancesco D, Robinson RB | title = Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells | journal = Pflügers Archiv | volume = 444 | issue = 5 | pages = 597–601 | date = Aug 2002 | pmid = 12194012 | doi = 10.1007/s00424-002-0860-7 }}
*{{cite journal | author=Vaccari T, Moroni A, Rocchi M, ''et al.'' |title=The human gene coding for HCN2, a pacemaker channel of the heart. |journal=Biochim. Biophys. Acta |volume=1446 |issue= 3 |pages= 419-25 |year= 1999 |pmid= 10524219 |doi= }}
* {{cite journal | vauthors = Sesti F, Rajan S, Gonzalez-Colaso R, Nikolaeva N, Goldstein SA | title = Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel | journal = Nature Neuroscience | volume = 6 | issue = 4 | pages = 353–61 | date = Apr 2003 | pmid = 12640457 | doi = 10.1038/nn1028 }}
*{{cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi= }}
* {{cite journal | vauthors = Stieber J, Thomer A, Much B, Schneider A, Biel M, Hofmann F | title = Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 36 | pages = 33672–80 | date = Sep 2003 | pmid = 12813043 | doi = 10.1074/jbc.M305318200 }}
*{{cite journal | author=Ulens C, Tytgat J |title=Functional heteromerization of HCN1 and HCN2 pacemaker channels. |journal=J. Biol. Chem. |volume=276 |issue= 9 |pages= 6069-72 |year= 2001 |pmid= 11133998 |doi= 10.1074/jbc.C000738200 }}
* {{cite journal | vauthors = Bender RA, Soleymani SV, Brewster AL, Nguyen ST, Beck H, Mathern GW, Baram TZ | title = Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus | journal = The Journal of Neuroscience | volume = 23 | issue = 17 | pages = 6826–36 | date = Jul 2003 | pmid = 12890777 | doi =  }}
*{{cite journal | author=Proenza C, Tran N, Angoli D, ''et al.'' |title=Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels. |journal=J. Biol. Chem. |volume=277 |issue= 33 |pages= 29634-42 |year= 2002 |pmid= 12034718 |doi= 10.1074/jbc.M200504200 }}
* {{cite journal | vauthors = Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M | title = Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels | journal = The Journal of Biological Chemistry | volume = 278 | issue = 44 | pages = 43781–6 | date = Oct 2003 | pmid = 12928435 | doi = 10.1074/jbc.M306958200 }}
*{{cite journal | author=Qu J, Altomare C, Bucchi A, ''et al.'' |title=Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells. |journal=Pflugers Arch. |volume=444 |issue= 5 |pages= 597-601 |year= 2003 |pmid= 12194012 |doi= 10.1007/s00424-002-0860-7 }}
* {{cite journal | vauthors = Michels G, Er F, Khan I, Südkamp M, Herzig S, Hoppe UC | title = Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias | journal = Circulation | volume = 111 | issue = 4 | pages = 399–404 | date = Feb 2005 | pmid = 15687126 | doi = 10.1161/01.CIR.0000153799.65783.3A }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Akhavan A, Atanasiu R, Noguchi T, Han W, Holder N, Shrier A | title = Identification of the cyclic-nucleotide-binding domain as a conserved determinant of ion-channel cell-surface localization | journal = Journal of Cell Science | volume = 118 | issue = Pt 13 | pages = 2803–12 | date = Jul 2005 | pmid = 15961404 | doi = 10.1242/jcs.02423 }}
*{{cite journal  | author=Sesti F, Rajan S, Gonzalez-Colaso R, ''et al.'' |title=Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel. |journal=Nat. Neurosci. |volume=6 |issue= 4 |pages= 353-61 |year= 2003 |pmid= 12640457 |doi= 10.1038/nn1028 }}
* {{cite journal | vauthors = Calloe K, Elmedyb P, Olesen SP, Jorgensen NK, Grunnet M | title = Hypoosmotic cell swelling as a novel mechanism for modulation of cloned HCN2 channels | journal = Biophysical Journal | volume = 89 | issue = 3 | pages = 2159–69 | date = Sep 2005 | pmid = 15980171 | pmc = 1366717 | doi = 10.1529/biophysj.105.063792 }}
*{{cite journal | author=Stieber J, Thomer A, Much B, ''et al.'' |title=Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4. |journal=J. Biol. Chem. |volume=278 |issue= 36 |pages= 33672-80 |year= 2003 |pmid= 12813043 |doi= 10.1074/jbc.M305318200 }}
*{{cite journal | author=Bender RA, Soleymani SV, Brewster AL, ''et al.'' |title=Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus. |journal=J. Neurosci. |volume=23 |issue= 17 |pages= 6826-36 |year= 2003 |pmid= 12890777 |doi=  }}
*{{cite journal | author=Much B, Wahl-Schott C, Zong X, ''et al.'' |title=Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels. |journal=J. Biol. Chem. |volume=278 |issue= 44 |pages= 43781-6 |year= 2003 |pmid= 12928435 |doi= 10.1074/jbc.M306958200 }}
*{{cite journal | author=Grimwood J, Gordon LA, Olsen A, ''et al.'' |title=The DNA sequence and biology of human chromosome 19. |journal=Nature |volume=428 |issue= 6982 |pages= 529-35 |year= 2004 |pmid= 15057824 |doi= 10.1038/nature02399 }}
*{{cite journal  | author=Michels G, Er F, Khan I, ''et al.'' |title=Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias. |journal=Circulation |volume=111 |issue= 4 |pages= 399-404 |year= 2005 |pmid= 15687126 |doi= 10.1161/01.CIR.0000153799.65783.3A }}
*{{cite journal | author=Akhavan A, Atanasiu R, Noguchi T, ''et al.'' |title=Identification of the cyclic-nucleotide-binding domain as a conserved determinant of ion-channel cell-surface localization. |journal=J. Cell. Sci. |volume=118 |issue= Pt 13 |pages= 2803-12 |year= 2005 |pmid= 15961404 |doi= 10.1242/jcs.02423 }}
*{{cite journal | author=Calloe K, Elmedyb P, Olesen SP, ''et al.'' |title=Hypoosmotic cell swelling as a novel mechanism for modulation of cloned HCN2 channels. |journal=Biophys. J. |volume=89 |issue= 3 |pages= 2159-69 |year= 2006 |pmid= 15980171 |doi= 10.1529/biophysj.105.063792 }}
}}
{{refend}}
{{refend}}


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* {{MeshName|HCN2+protein,+human}}
* {{MeshName|HCN2+protein,+human}}


{{membrane-protein-stub}}
{{NLM content}}
{{NLM content}}
{{Ion channels}}
{{PDB Gallery|geneid=610}}
{{Ion channels|g4}}
 
[[Category:Ion channels]]
[[Category:Ion channels]]
{{WikiDoc Sources}}
 
 
{{membrane-protein-stub}}

Latest revision as of 13:29, 31 August 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 is a protein that in humans is encoded by the HCN2 gene.[1][2][3][4]

Interactions

HCN2 has been shown to interact with HCN1[5][6] and HCN4.[5]

Function

The function of the channel is not known although its activation by hyperpolarization alludes to the funny channels in the sinoatrial node of the heart (which form the basis of spontaneous generation of electrical rhythm). These channels have recently been associated with chronic pain and blocking the gene is associated with resolution of neuropathic episodes of pain.[7]

See also

References

  1. ↑ Santoro B, Grant SG, Bartsch D, Kandel ER (Dec 1997). "Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels". Proceedings of the National Academy of Sciences of the United States of America. 94 (26): 14815–20. doi:10.1073/pnas.94.26.14815. PMC 25120. PMID 9405696.
  2. ↑ Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR (May 1998). "Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain". Cell. 93 (5): 717–29. doi:10.1016/S0092-8674(00)81434-8. PMID 9630217.
  3. ↑ Hofmann F, Biel M, Kaupp UB (Dec 2005). "International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels". Pharmacological Reviews. 57 (4): 455–62. doi:10.1124/pr.57.4.8. PMID 16382102.
  4. ↑ "Entrez Gene: HCN2 hyperpolarization activated cyclic nucleotide-gated potassium channel 2".
  5. ↑ 5.0 5.1 Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M (Oct 2003). "Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels". The Journal of Biological Chemistry. 278 (44): 43781–6. doi:10.1074/jbc.M306958200. PMID 12928435.
  6. ↑ Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA (Aug 2002). "Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels". The Journal of Biological Chemistry. 277 (33): 29634–42. doi:10.1074/jbc.M200504200. PMID 12034718.
  7. ↑ "Gene find may lead to pills that kill chronic pain". The Times Of India. 10 September 2011.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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