HCN3_HUMAN
ID HCN3_HUMAN Reviewed; 774 AA.
AC Q9P1Z3; D3DV90; Q4VX12; Q8N6W6; Q9BWQ2;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3;
GN Name=HCN3; Synonyms=KIAA1535;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-774.
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 204-774.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ACTIVITY
RP REGULATION.
RX PubMed=16043489; DOI=10.1074/jbc.m502508200;
RA Stieber J., Stockl G., Herrmann S., Hassfurth B., Hofmann F.;
RT "Functional expression of the human HCN3 channel.";
RL J. Biol. Chem. 280:34635-34643(2005).
CC -!- FUNCTION: Hyperpolarization-activated potassium channel. May also
CC facilitate the permeation of sodium ions.
CC {ECO:0000269|PubMed:16043489}.
CC -!- ACTIVITY REGULATION: Inhibited by Cs(1+) and ZD7288. Is apparently not
CC activated by cAMP. {ECO:0000269|PubMed:16043489}.
CC -!- SUBUNIT: Homotetramer. The potassium channel is probably composed of a
CC homo- or heterotetrameric complex of pore-forming subunits. Interacts
CC with KCTD3 and PEX5L. {ECO:0000250|UniProtKB:O88705,
CC ECO:0000250|UniProtKB:Q9UL51}.
CC -!- INTERACTION:
CC Q9P1Z3; Q4ACU6-1: Shank3; Xeno; NbExp=3; IntAct=EBI-11178054, EBI-16201983;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16043489};
CC Multi-pass membrane protein {ECO:0000269|PubMed:16043489}.
CC -!- TISSUE SPECIFICITY: Detected in brain. {ECO:0000269|PubMed:16043489}.
CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position.
CC -!- SIMILARITY: Belongs to the potassium channel HCN family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH28024.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AL713999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB040968; BAA96059.2; -; mRNA.
DR EMBL; CH471121; EAW53084.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53086.1; -; Genomic_DNA.
DR EMBL; BC000066; AAH00066.1; -; mRNA.
DR EMBL; BC028024; AAH28024.2; ALT_INIT; mRNA.
DR CCDS; CCDS1108.1; -.
DR RefSeq; NP_065948.1; NM_020897.2.
DR AlphaFoldDB; Q9P1Z3; -.
DR SMR; Q9P1Z3; -.
DR BioGRID; 121691; 6.
DR ComplexPortal; CPX-267; HCN3 channel complex.
DR DIP; DIP-62039N; -.
DR IntAct; Q9P1Z3; 2.
DR STRING; 9606.ENSP00000357342; -.
DR BindingDB; Q9P1Z3; -.
DR ChEMBL; CHEMBL1795173; -.
DR DrugCentral; Q9P1Z3; -.
DR GuidetoPHARMACOLOGY; 402; -.
DR GlyGen; Q9P1Z3; 1 site.
DR iPTMnet; Q9P1Z3; -.
DR PhosphoSitePlus; Q9P1Z3; -.
DR BioMuta; HCN3; -.
DR DMDM; 29840780; -.
DR MassIVE; Q9P1Z3; -.
DR PaxDb; Q9P1Z3; -.
DR PeptideAtlas; Q9P1Z3; -.
DR PRIDE; Q9P1Z3; -.
DR ProteomicsDB; 83687; -.
DR ABCD; Q9P1Z3; 1 sequenced antibody.
DR Antibodypedia; 20417; 307 antibodies from 37 providers.
DR DNASU; 57657; -.
DR Ensembl; ENST00000368358.4; ENSP00000357342.3; ENSG00000143630.10.
DR Ensembl; ENST00000575670.1; ENSP00000458364.1; ENSG00000263324.5.
DR GeneID; 57657; -.
DR KEGG; hsa:57657; -.
DR MANE-Select; ENST00000368358.4; ENSP00000357342.3; NM_020897.3; NP_065948.1.
DR UCSC; uc001fjz.3; human.
DR CTD; 57657; -.
DR DisGeNET; 57657; -.
DR GeneCards; HCN3; -.
DR HGNC; HGNC:19183; HCN3.
DR HPA; ENSG00000143630; Tissue enhanced (liver).
DR MIM; 609973; gene.
DR neXtProt; NX_Q9P1Z3; -.
DR OpenTargets; ENSG00000143630; -.
DR PharmGKB; PA38821; -.
DR VEuPathDB; HostDB:ENSG00000143630; -.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000162023; -.
DR HOGENOM; CLU_005746_15_1_1; -.
DR InParanoid; Q9P1Z3; -.
DR OMA; SSIPMDC; -.
DR OrthoDB; 281394at2759; -.
DR PhylomeDB; Q9P1Z3; -.
DR TreeFam; TF318250; -.
DR PathwayCommons; Q9P1Z3; -.
DR Reactome; R-HSA-1296061; HCN channels.
DR SignaLink; Q9P1Z3; -.
DR BioGRID-ORCS; 57657; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; HCN3; human.
DR GeneWiki; HCN3; -.
DR GenomeRNAi; 57657; -.
DR Pharos; Q9P1Z3; Tclin.
DR PRO; PR:Q9P1Z3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9P1Z3; protein.
DR Bgee; ENSG00000143630; Expressed in cortical plate and 95 other tissues.
DR Genevisible; Q9P1Z3; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0044316; C:cone cell pedicle; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0098855; C:HCN channel complex; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IMP:UniProtKB.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IMP:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:ComplexPortal.
DR GO; GO:1903351; P:cellular response to dopamine; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:2001257; P:regulation of cation channel activity; IC:ComplexPortal.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IC:ComplexPortal.
DR GO; GO:0003254; P:regulation of membrane depolarization; IDA:ComplexPortal.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:UniProtKB.
DR GO; GO:0098907; P:regulation of SA node cell action potential; IC:ComplexPortal.
DR GO; GO:0072718; P:response to cisplatin; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IMP:UniProtKB.
DR CDD; cd00038; CAP_ED; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR013621; Ion_trans_N.
DR InterPro; IPR003938; K_chnl_volt-dep_EAG/ELK/ERG.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF08412; Ion_trans_N; 1.
DR PRINTS; PR01463; EAGCHANLFMLY.
DR SMART; SM00100; cNMP; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
PE 1: Evidence at protein level;
KW cAMP; cAMP-binding; Cell membrane; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Nucleotide-binding;
KW Phosphoprotein; Potassium; Potassium channel; Potassium transport;
KW Reference proteome; Sodium; Sodium channel; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..774
FT /note="Potassium/sodium hyperpolarization-activated cyclic
FT nucleotide-gated channel 3"
FT /id="PRO_0000054114"
FT TOPO_DOM 1..97
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..118
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..124
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 146..171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..201
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..253
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..274
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 275..297
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 298..319
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..329
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 330..350
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 351..774
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 46..91
FT /note="Involved in subunit assembly"
FT /evidence="ECO:0000250"
FT REGION 354..774
FT /note="Interaction with KCTD3"
FT /evidence="ECO:0000250|UniProtKB:O88705"
FT REGION 682..774
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..35
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 747..764
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 492..495
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 502..503
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 543..546
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT MOD_RES 634
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88705"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 630
FT /note="P -> L (in dbSNP:rs35001694)"
FT /id="VAR_048746"
FT CONFLICT 206
FT /note="A -> G (in Ref. 4; AAH00066)"
FT /evidence="ECO:0000305"
FT CONFLICT 734
FT /note="S -> T (in Ref. 3; BAA96059)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 774 AA; 86032 MW; 37B9BC13E5E2C097 CRC64;
MEAEQRPAAG ASEGATPGLE AVPPVAPPPA TAASGPIPKS GPEPKRRHLG TLLQPTVNKF
SLRVFGSHKA VEIEQERVKS AGAWIIHPYS DFRFYWDLIM LLLMVGNLIV LPVGITFFKE
ENSPPWIVFN VLSDTFFLLD LVLNFRTGIV VEEGAEILLA PRAIRTRYLR TWFLVDLISS
IPVDYIFLVV ELEPRLDAEV YKTARALRIV RFTKILSLLR LLRLSRLIRY IHQWEEIFHM
TYDLASAVVR IFNLIGMMLL LCHWDGCLQF LVPMLQDFPP DCWVSINHMV NHSWGRQYSH
ALFKAMSHML CIGYGQQAPV GMPDVWLTML SMIVGATCYA MFIGHATALI QSLDSSRRQY
QEKYKQVEQY MSFHKLPADT RQRIHEYYEH RYQGKMFDEE SILGELSEPL REEIINFTCR
GLVAHMPLFA HADPSFVTAV LTKLRFEVFQ PGDLVVREGS VGRKMYFIQH GLLSVLARGA
RDTRLTDGSY FGEICLLTRG RRTASVRADT YCRLYSLSVD HFNAVLEEFP MMRRAFETVA
MDRLLRIGKK NSILQRKRSE PSPGSSGGIM EQHLVQHDRD MARGVRGRAP STGAQLSGKP
VLWEPLVHAP LQAAAVTSNV AIALTHQRGP LPLSPDSPAT LLARSAWRSA GSPASPLVPV
RAGPWASTSR LPAPPARTLH ASLSRAGRSQ VSLLGPPPGG GGRRLGPRGR PLSASQPSLP
QRATGDGSPG RKGSGSERLP PSGLLAKPPR TAQPPRPPVP EPATPRGLQL SANM
