KCNH1

KCNH1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	5J7E
Identifikatori
Aliasi	KCNH1
Vanjski ID-jevi	OMIM: 603305 MGI: 1341721 HomoloGene: 68242 GeneCards: KCNH1
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	211,134,165 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	192,192,467 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• phosphorelay sensor kinase activity; • voltage-gated potassium channel activity; • calmodulin binding; • cyclic nucleotide binding; • ion channel activity; • potassium channel activity; • voltage-gated ion channel activity; • GO:0001948, GO:0016582 vezivanje za proteine; • lipid binding; • phosphatidylinositol bisphosphate binding; • delayed rectifier potassium channel activity; • vezivanje identičnih proteina; • protein kinase binding; • transmembrane transporter binding; • protein heterodimerization activity; • 14-3-3 protein binding;
Ćelijska komponenta	• sinapsa; • integral component of membrane; • jedro; • Akson; • nuclear inner membrane; • presynaptic membrane; • membrana; • early endosome membrane; • dendrit; • ćelijska membrana; • endozom; • voltage-gated potassium channel complex; • GO:0097483, GO:0097481 postsynaptic density; • međućelijske veze; • projekcija ćelije; • perikaryon; • intracellular membrane-bounded organelle; • postsynaptic membrane; • integral component of plasma membrane; • cell surface; • axolemma; • potassium channel complex; • neuronal cell body; • perinuklearno područje citoplazme; • integral component of presynaptic membrane;
Biološki proces	• transmembrane transport; • regulation of cell population proliferation; • potassium ion transport; • GO:0072468 Transdukcija signala; • phosphorelay signal transduction system; • regulation of ion transmembrane transport; • ion transport; • potassium ion transmembrane transport; • myoblast fusion; • regulation of membrane potential; • phosphatidylinositol-mediated signaling; • startle response; • ion transmembrane transport; • cellular response to calcium ion;
	Izvori:Amigo / QuickGO
Ortolozi
	3756
	16510
	ENSG00000143473
	ENSMUSG00000058248
	O95259
	Q60603
	NM_002238; NM_172362
	NM_001038607; NM_010600
	NP_002229; NP_758872
	NP_001033696; NP_034730
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Član 1 potporodice H kanala sa kalijskim naponom jest protein koji je kod ljudi kodiran genom KCNH1 sa hromosoma 1.^[5]^[6]^[7]

Aminokiselinska sekvenca uredi

Dužina polipeptidnog lanca je 989 aminokiselina, a molekulska težina 111.423 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MTMAGGRRGL	VAPQNTFLEN	IVRRSNDTNF	VLGNAQIVDW	PIVYSNDGFC
KLSGYHRAEV	MQKSSTCSFM	YGELTDKDTI	EKVRQTFENY	EMNSFEILMY
KKNRTPVWFF	VKIAPIRNEQ	DKVVLFLCTF	SDITAFKQPI	EDDSCKGWGK
FARLTRALTS	SRGVLQQLAP	SVQKGENVHK	HSRLAEVLQL	GSDILPQYKQ
EAPKTPPHII	LHYCVFKTTW	DWIILILTFY	TAILVPYNVS	FKTRQNNVAW
LVVDSIVDVI	FLVDIVLNFH	TTFVGPAGEV	ISDPKLIRMN	YLKTWFVIDL
LSCLPYDVIN	AFENVDEVSA	FMGDPGKIGF	ADQIPPPLEG	RESQGISSLF
SSLKVVRLLR	LGRVARKLDH	YIEYGAAVLV	LLVCVFGLAA	HWMACIWYSI
GDYEIFDEDT	KTIRNNSWLY	QLAMDIGTPY	QFNGSGSGKW	EGGPSKNSVY
ISSLYFTMTS	LTSVGFGNIA	PSTDIEKIFA	VAIMMIGSLL	YATIFGNVTT
IFQQMYANTN	RYHEMLNSVR	DFLKLYQVPK	GLSERVMDYI	VSTWSMSRGI
DTEKVLQICP	KDMRADICVH	LNRKVFKEHP	AFRLASDGCL	RALAMEFQTV
HCAPGDLIYH	AGESVDSLCF	VVSGSLEVIQ	DDEVVAILGK	GDVFGDVFWK
EATLAQSCAN	VRALTYCDLH	VIKRDALQKV	LEFYTAFSHS	FSRNLILTYN
LRKRIVFRKI	SDVKREEEER	MKRKNEAPLI	LPPDHPVRRL	FQRFRQQKEA
RLAAERGGRD	LDDLDVEKGN	VLTEHASANH	SLVKASVVTV	RESPATPVSF
QAASTSGVPD	HAKLQAPGSE	CLGPKGGGGD	CAKRKSWARF	KDACGKSEDW
NKVSKAESME	TLPERTKASG	EATLKKTDSC	DSGITKSDLR	LDNVGEARSP
QDRSPILAEV	KHSFYPIPEQ	TLQATVLEVR	HELKEDIKAL	NAKMTNIEKQ
LSEILRILTS	RRSSQSPQEL	FEISRPQSPE	SERDIFGAS

Funkcija uredi

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms.^[7]

Interakcije uredi

Pokazalo se da KCNH1 ima interakcije sa KCNB1.^[9]

Klinički značaj uredi

Nedavna studija je pokazala da misens mutacije de novo u genu KCNH1 rezultiraju štetnim povećanjem funkcije, što rezultira multisistemskim razvojnim poremećajem poznatim kao Temple-Baraitserov sindrom ( TBS). TBS je kategoriziran prema intelektualnim teškoćama, epilepsiji i aplaziji noktiju. Simons et al. sugerirali su da je mutacijski mozaicizam prisutan kod majki nekih probanada odgovoran za fenotip TBS njihove djece. Ovo je još jedan dokaz uloge koju genetički mozaicizam ima u etiologiji neuroloških poremećaja.^[10]

Također pogledajte uredi

Kalijev kanal

Reference uredi

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000143473 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000058248 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Occhiodoro T, Bernheim L, Liu JH, Bijlenga P, Sinnreich M, Bader CR, Fischer-Lougheed J (Sep 1998). "Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion". FEBS Lett. 434 (1–2): 177–82. doi:10.1016/S0014-5793(98)00973-9. PMID 9738473.
^ Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.
^ ^a ^b "Entrez Gene: KCNH1 potassium voltage-gated channel, subfamily H (eag-related), member 1".
^ "UniProt, O95259" (jezik: engleski). Pristupljeno 13. 12. 2021.
^ Ottschytsch, N; Raes A; Van Hoorick D; Snyders D J (Jun 2002). "Obligatory heterotetramerization of three previously uncharacterized Kv channel α-subunits identified in the human genome". Proc. Natl. Acad. Sci. U.S.A. 99 (12): 7986–91. Bibcode:2002PNAS...99.7986O. doi:10.1073/pnas.122617999. ISSN 0027-8424. PMC 123007. PMID 12060745.
^ Simons, Cas; Rash, Lachlan D.; Crawford, Joanna; Ma, Linlin; Cristofori-Armstrong, Ben; Miller, David; Ru, Kelin; Baillie, Gregory J.; Alanay, Yasemin (januar 2015). "Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy". Nature Genetics (jezik: engleski). 47 (1): 73–77. doi:10.1038/ng.3153. ISSN 1061-4036. PMID 25420144. S2CID 52799681.

Dopunska literatura uredi

Warmke JW, Ganetzky B (1994). "A family of potassium channel genes related to eag in Drosophila and mammals". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 3438–42. Bibcode:1994PNAS...91.3438W. doi:10.1073/pnas.91.8.3438. PMC 43592. PMID 8159766.
Hoshi N, Takahashi H, Shahidullah M, et al. (1998). "KCR1, a membrane protein that facilitates functional expression of non-inactivating K+ currents associates with rat EAG voltage-dependent K+ channels". J. Biol. Chem. 273 (36): 23080–5. doi:10.1074/jbc.273.36.23080. PMID 9722534.
Pardo LA, del Camino D, Sánchez A, et al. (1999). "Oncogenic potential of EAG K(+) channels". EMBO J. 18 (20): 5540–7. doi:10.1093/emboj/18.20.5540. PMC 1171622. PMID 10523298.
Schönherr R, Löber K, Heinemann SH (2000). "Inhibition of human ether à go-go potassium channels by Ca2+/calmodulin". EMBO J. 19 (13): 3263–71. doi:10.1093/emboj/19.13.3263. PMC 313935. PMID 10880439.
Cayabyab FS, Schlichter LC (2002). "Regulation of an ERG K+ current by Src tyrosine kinase". J. Biol. Chem. 277 (16): 13673–81. doi:10.1074/jbc.M108211200. PMID 11834728.
Schönherr R, Gessner G, Löber K, Heinemann SH (2002). "Functional distinction of human EAG1 and EAG2 potassium channels". FEBS Lett. 514 (2–3): 204–8. doi:10.1016/S0014-5793(02)02365-7. PMID 11943152.
Ottschytsch N, Raes A, Van Hoorick D, Snyders DJ (2002). "Obligatory heterotetramerization of three previously uncharacterized Kv channel α-subunits identified in the human genome". Proc. Natl. Acad. Sci. U.S.A. 99 (12): 7986–91. Bibcode:2002PNAS...99.7986O. doi:10.1073/pnas.122617999. PMC 123007. PMID 12060745.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Farias LM, Ocaña DB, Díaz L, et al. (2004). "Ether a go-go potassium channels as human cervical cancer markers". Cancer Res. 64 (19): 6996–7001. doi:10.1158/0008-5472.CAN-04-1204. PMID 15466192.
Kang J, Chen XL, Wang H, et al. (2005). "Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel". Mol. Pharmacol. 67 (3): 827–36. doi:10.1124/mol.104.006577. PMID 15548764. S2CID 35049797.
Ziechner U, Schönherr R, Born AK, et al. (2006). "Inhibition of human ether à go-go potassium channels by Ca2+/calmodulin binding to the cytosolic N- and C-termini". FEBS J. 273 (5): 1074–86. doi:10.1111/j.1742-4658.2006.05134.x. PMID 16478480.
Weber C, Mello de Queiroz F, Downie BR, et al. (2006). "Silencing the activity and proliferative properties of the human EagI Potassium Channel by RNA Interference". J. Biol. Chem. 281 (19): 13030–7. doi:10.1074/jbc.M600883200. PMID 16537547.
Mello de Queiroz F, Suarez-Kurtz G, Stühmer W, Pardo LA (2006). "Ether à go-go potassium channel expression in soft tissue sarcoma patients". Mol. Cancer. 5: 42. doi:10.1186/1476-4598-5-42. PMC 1618397. PMID 17022811.
Ocorr K, Reeves NL, Wessells RJ, et al. (2007). "KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging". Proc. Natl. Acad. Sci. U.S.A. 104 (10): 3943–8. Bibcode:2007PNAS..104.3943O. doi:10.1073/pnas.0609278104. PMC 1820688. PMID 17360457.
Ding XW, Yan JJ, An P, et al. (2007). "Aberrant expression of ether à go-go potassium channel in colorectal cancer patients and cell lines". World J. Gastroenterol. 13 (8): 1257–61. doi:10.3748/wjg.v13.i8.1257. PMC 4147004. PMID 17451210.
Borowiec AS, Hague F, Harir N, et al. (2007). "IGF-1 activates hEAG K(+) channels through an Akt-dependent signaling pathway in breast cancer cells: role in cell proliferation". J. Cell. Physiol. 212 (3): 690–701. doi:10.1002/jcp.21065. PMID 17520698. S2CID 39833770.

Vanjski linkovi uredi

KCNH1 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000143473 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000058248 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9738473-5] Occhiodoro T, Bernheim L, Liu JH, Bijlenga P, Sinnreich M, Bader CR, Fischer-Lougheed J (Sep 1998). "Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion". FEBS Lett. 434 (1–2): 177–82. doi:10.1016/S0014-5793(98)00973-9. PMID 9738473.

[pmid16382104-6] Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.

[entrez-7] "Entrez Gene: KCNH1 potassium voltage-gated channel, subfamily H (eag-related), member 1".

[UniProt-8] "UniProt, O95259" (jezik: engleski). Pristupljeno 13. 12. 2021.

[pmid12060745-9] Ottschytsch, N; Raes A; Van Hoorick D; Snyders D J (Jun 2002). "Obligatory heterotetramerization of three previously uncharacterized Kv channel α-subunits identified in the human genome". Proc. Natl. Acad. Sci. U.S.A. 99 (12): 7986–91. Bibcode:2002PNAS...99.7986O. doi:10.1073/pnas.122617999. ISSN 0027-8424. PMC 123007. PMID 12060745.

[10] Simons, Cas; Rash, Lachlan D.; Crawford, Joanna; Ma, Linlin; Cristofori-Armstrong, Ben; Miller, David; Ru, Kelin; Baillie, Gregory J.; Alanay, Yasemin (januar 2015). "Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy". Nature Genetics (jezik: engleski). 47 (1): 73–77. doi:10.1038/ng.3153. ISSN 1061-4036. PMID 25420144. S2CID 52799681.

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