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Protein

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

Gene

HCN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli.5 Publications

Miscellaneous

Inhibited by extracellular cesium ions.

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by cAMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi659 – 662cAMP2 Publications4
Nucleotide bindingi669 – 670cAMP2 Publications2
Nucleotide bindingi710 – 713cAMP2 Publications4

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Potassium channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Sodium transport, Transport
LigandcAMP, cAMP-binding, Nucleotide-binding, Potassium, Sodium

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-1296061 HCN channels

SIGNOR Signaling Network Open Resource

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SIGNORi
Q9Y3Q4

Protein family/group databases

Transport Classification Database

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TCDBi
1.A.1.5.10 the voltage-gated ion channel (vic) superfamily
1.A.1.5.11 the voltage-gated ion channel (vic) superfamily

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:HCN4
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 15

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000138622.3

Human Gene Nomenclature Database

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HGNCi
HGNC:16882 HCN4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
605206 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q9Y3Q4

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 266CytoplasmicSequence analysisAdd BLAST266
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei267 – 287Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini288 – 293ExtracellularSequence analysis6
Transmembranei294 – 314Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini315 – 340CytoplasmicSequence analysisAdd BLAST26
Transmembranei341 – 361Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini362 – 368ExtracellularSequence analysis7
Transmembranei369 – 389Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST21
Topological domaini390 – 420CytoplasmicSequence analysisAdd BLAST31
Transmembranei421 – 441Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini442 – 464ExtracellularSequence analysisAdd BLAST23
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a region that is buried within a membrane, but does not cross it.<p><a href='/help/intramem' target='_top'>More...</a></p>Intramembranei465 – 486Pore-forming; Name=Segment H5Sequence analysisAdd BLAST22
Topological domaini487 – 496ExtracellularSequence analysis10
Transmembranei497 – 517Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini518 – 1203CytoplasmicSequence analysisAdd BLAST686

Keywords - Cellular componenti

Cell membrane, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Sick sinus syndrome 2 (SSS2)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThe term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS2 onset is in utero or at birth.
See also OMIM:163800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_066614485A → V in SSS2; results in a significant reduction of current density compared to wild-type. 1 Publication1
Natural variantiVAR_026534553D → N in SSS2. 1 PublicationCorresponds to variant dbSNP:rs104894485EnsemblClinVar.1
Natural variantiVAR_026535672S → R in SSS2; results in decreased affinity for cAMP but does not abolish channel activation; shifts the current activation range to hyperpolarized voltages; slows channel opening and speeds up channel closure. 2 PublicationsCorresponds to variant dbSNP:rs104894488EnsemblClinVar.1
Brugada syndrome 8 (BRGDA8)1 Publication
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.
See also OMIM:613123

Keywords - Diseasei

Brugada syndrome, Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
10021

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
HCN4

MalaCards human disease database

More...
MalaCardsi
HCN4
MIMi163800 phenotype
613123 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000138622

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
130 Brugada syndrome
166282 Familial sick sinus syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA394

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL1250417

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
403

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
HCN4

Domain mapping of disease mutations (DMDM)

More...
DMDMi
38605641

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000541171 – 1203Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Add BLAST1203

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei138PhosphoserineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi458N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1105PhosphoserineBy similarity1
Modified residuei1108PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
Q9Y3Q4

MaxQB - The MaxQuant DataBase

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MaxQBi
Q9Y3Q4

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q9Y3Q4

PeptideAtlas

More...
PeptideAtlasi
Q9Y3Q4

PRoteomics IDEntifications database

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PRIDEi
Q9Y3Q4

ProteomicsDB human proteome resource

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ProteomicsDBi
86060

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q9Y3Q4

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q9Y3Q4

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Highly expressed in thalamus, testis and in heart, both in ventricle and atrium. Detected at much lower levels in amygdala, substantia nigra, cerebellum and hippocampus.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000138622 Expressed in 64 organ(s), highest expression level in heart left ventricle

CleanEx database of gene expression profiles

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CleanExi
HS_HCN4

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q9Y3Q4 HS

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homotetramer. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits.2 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-1753521,EBI-1753521

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
115338, 3 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-131 HCN4 channel complex

Database of interacting proteins

More...
DIPi
DIP-52325N

Protein interaction database and analysis system

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IntActi
Q9Y3Q4, 3 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000261917

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q9Y3Q4

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11203
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q9Y3Q4

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q9Y3Q4

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
Q9Y3Q4

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni209 – 260Involved in subunit assemblyBy similarityAdd BLAST52

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi924 – 1076Pro-richAdd BLAST153

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the potassium channel HCN family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG0498 Eukaryota
ENOG410XPSE LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000154743

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000230717

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG039490

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9Y3Q4

KEGG Orthology (KO)

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KOi
K04957

Identification of Orthologs from Complete Genome Data

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OMAi
AIPGQHV

Database of Orthologous Groups

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OrthoDBi
EOG091G0JQU

Database for complete collections of gene phylogenies

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PhylomeDBi
Q9Y3Q4

TreeFam database of animal gene trees

More...
TreeFami
TF318250

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00038 CAP_ED, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.20.120.350, 1 hit
2.60.120.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR018490 cNMP-bd-like
IPR018488 cNMP-bd_CS
IPR000595 cNMP-bd_dom
IPR030173 HCN4
IPR005821 Ion_trans_dom
IPR013621 Ion_trans_N
IPR003938 K_chnl_volt-dep_EAG/ELK/ERG
IPR014710 RmlC-like_jellyroll
IPR027359 Volt_channel_dom_sf

The PANTHER Classification System

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PANTHERi
PTHR10217:SF375 PTHR10217:SF375, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF08412 Ion_trans_N, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR01463 EAGCHANLFMLY

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00100 cNMP, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF51206 SSF51206, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00888 CNMP_BINDING_1, 1 hit
PS50042 CNMP_BINDING_3, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

Q9Y3Q4-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDKLPPSMRK RLYSLPQQVG AKAWIMDEEE DAEEEGAGGR QDPSRRSIRL
60 70 80 90 100
RPLPSPSPSA AAGGTESRSS ALGAADSEGP ARGAGKSSTN GDCRRFRGSL
110 120 130 140 150
ASLGSRGGGS GGTGSGSSHG HLHDSAEERR LIAEGDASPG EDRTPPGLAA
160 170 180 190 200
EPERPGASAQ PAASPPPPQQ PPQPASASCE QPSVDTAIKV EGGAAAGDQI
210 220 230 240 250
LPEAEVRLGQ AGFMQRQFGA MLQPGVNKFS LRMFGSQKAV EREQERVKSA
260 270 280 290 300
GFWIIHPYSD FRFYWDLTML LLMVGNLIII PVGITFFKDE NTTPWIVFNV
310 320 330 340 350
VSDTFFLIDL VLNFRTGIVV EDNTEIILDP QRIKMKYLKS WFMVDFISSI
360 370 380 390 400
PVDYIFLIVE TRIDSEVYKT ARALRIVRFT KILSLLRLLR LSRLIRYIHQ
410 420 430 440 450
WEEIFHMTYD LASAVVRIVN LIGMMLLLCH WDGCLQFLVP MLQDFPDDCW
460 470 480 490 500
VSINNMVNNS WGKQYSYALF KAMSHMLCIG YGRQAPVGMS DVWLTMLSMI
510 520 530 540 550
VGATCYAMFI GHATALIQSL DSSRRQYQEK YKQVEQYMSF HKLPPDTRQR
560 570 580 590 600
IHDYYEHRYQ GKMFDEESIL GELSEPLREE IINFNCRKLV ASMPLFANAD
610 620 630 640 650
PNFVTSMLTK LRFEVFQPGD YIIREGTIGK KMYFIQHGVV SVLTKGNKET
660 670 680 690 700
KLADGSYFGE ICLLTRGRRT ASVRADTYCR LYSLSVDNFN EVLEEYPMMR
710 720 730 740 750
RAFETVALDR LDRIGKKNSI LLHKVQHDLN SGVFNYQENE IIQQIVQHDR
760 770 780 790 800
EMAHCAHRVQ AAASATPTPT PVIWTPLIQA PLQAAAATTS VAIALTHHPR
810 820 830 840 850
LPAAIFRPPP GSGLGNLGAG QTPRHLKRLQ SLIPSALGSA SPASSPSQVD
860 870 880 890 900
TPSSSSFHIQ QLAGFSAPAG LSPLLPSSSS SPPPGACGSP SAPTPSAGVA
910 920 930 940 950
ATTIAGFGHF HKALGGSLSS SDSPLLTPLQ PGARSPQAAQ PSPAPPGARG
960 970 980 990 1000
GLGLPEHFLP PPPSSRSPSS SPGQLGQPPG ELSLGLATGP LSTPETPPRQ
1010 1020 1030 1040 1050
PEPPSLVAGA SGGASPVGFT PRGGLSPPGH SPGPPRTFPS APPRASGSHG
1060 1070 1080 1090 1100
SLLLPPASSP PPPQVPQRRG TPPLTPGRLT QDLKLISASQ PALPQDGAQT
1110 1120 1130 1140 1150
LRRASPHSSG ESMAAFPLFP RAGGGSGGSG SSGGLGPPGR PYGAIPGQHV
1160 1170 1180 1190 1200
TLPRKTSSGS LPPPLSLFGA RATSSGGPPL TAGPQREPGA RPEPVRSKLP

SNL
Length:1,203
Mass (Da):129,042
Last modified:November 1, 1999 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i7EFDD2D69CF1F9D9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti110S → T in CAB52754 (PubMed:10430953).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066614485A → V in SSS2; results in a significant reduction of current density compared to wild-type. 1 Publication1
Natural variantiVAR_026534553D → N in SSS2. 1 PublicationCorresponds to variant dbSNP:rs104894485EnsemblClinVar.1
Natural variantiVAR_026535672S → R in SSS2; results in decreased affinity for cAMP but does not abolish channel activation; shifts the current activation range to hyperpolarized voltages; slows channel opening and speeds up channel closure. 2 PublicationsCorresponds to variant dbSNP:rs104894488EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
AJ132429 mRNA Translation: CAB42604.1
AJ238850 mRNA Translation: CAB52754.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS10248.1

NCBI Reference Sequences

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RefSeqi
NP_005468.1, NM_005477.2

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Hs.86941

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000261917; ENSP00000261917; ENSG00000138622

Database of genes from NCBI RefSeq genomes

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GeneIDi
10021

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:10021

UCSC genome browser

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UCSCi
uc002avp.3 human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ132429 mRNA Translation: CAB42604.1
AJ238850 mRNA Translation: CAB52754.1
CCDSiCCDS10248.1
RefSeqiNP_005468.1, NM_005477.2
UniGeneiHs.86941

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MNGNMR-A579-707[»]
3OTFX-ray2.40A521-739[»]
3U11X-ray2.50A/B521-723[»]
4HBNX-ray2.60A521-724[»]
4KL1X-ray2.70A/B/C/D521-713[»]
4NVPX-ray2.50A521-723[»]
ProteinModelPortaliQ9Y3Q4
SMRiQ9Y3Q4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115338, 3 interactors
ComplexPortaliCPX-131 HCN4 channel complex
DIPiDIP-52325N
IntActiQ9Y3Q4, 3 interactors
STRINGi9606.ENSP00000261917

Chemistry databases

BindingDBiQ9Y3Q4
ChEMBLiCHEMBL1250417
GuidetoPHARMACOLOGYi403

Protein family/group databases

TCDBi1.A.1.5.10 the voltage-gated ion channel (vic) superfamily
1.A.1.5.11 the voltage-gated ion channel (vic) superfamily

PTM databases

iPTMnetiQ9Y3Q4
PhosphoSitePlusiQ9Y3Q4

Polymorphism and mutation databases

BioMutaiHCN4
DMDMi38605641

Proteomic databases

EPDiQ9Y3Q4
MaxQBiQ9Y3Q4
PaxDbiQ9Y3Q4
PeptideAtlasiQ9Y3Q4
PRIDEiQ9Y3Q4
ProteomicsDBi86060

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
10021
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261917; ENSP00000261917; ENSG00000138622
GeneIDi10021
KEGGihsa:10021
UCSCiuc002avp.3 human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
10021
DisGeNETi10021
EuPathDBiHostDB:ENSG00000138622.3

GeneCards: human genes, protein and diseases

More...
GeneCardsi
HCN4
GeneReviewsiHCN4
HGNCiHGNC:16882 HCN4
MalaCardsiHCN4
MIMi163800 phenotype
605206 gene
613123 phenotype
neXtProtiNX_Q9Y3Q4
OpenTargetsiENSG00000138622
Orphaneti130 Brugada syndrome
166282 Familial sick sinus syndrome
PharmGKBiPA394

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
GeneTreeiENSGT00940000154743
HOGENOMiHOG000230717
HOVERGENiHBG039490
InParanoidiQ9Y3Q4
KOiK04957
OMAiAIPGQHV
OrthoDBiEOG091G0JQU
PhylomeDBiQ9Y3Q4
TreeFamiTF318250

Enzyme and pathway databases

ReactomeiR-HSA-1296061 HCN channels
SIGNORiQ9Y3Q4

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
HCN4 human
EvolutionaryTraceiQ9Y3Q4

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
HCN4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
10021

Protein Ontology

More...
PROi
PR:Q9Y3Q4

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000138622 Expressed in 64 organ(s), highest expression level in heart left ventricle
CleanExiHS_HCN4
GenevisibleiQ9Y3Q4 HS

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
Gene3Di1.20.120.350, 1 hit
2.60.120.10, 1 hit
InterProiView protein in InterPro
IPR018490 cNMP-bd-like
IPR018488 cNMP-bd_CS
IPR000595 cNMP-bd_dom
IPR030173 HCN4
IPR005821 Ion_trans_dom
IPR013621 Ion_trans_N
IPR003938 K_chnl_volt-dep_EAG/ELK/ERG
IPR014710 RmlC-like_jellyroll
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR10217:SF375 PTHR10217:SF375, 1 hit
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF08412 Ion_trans_N, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
PROSITEiView protein in PROSITE
PS00888 CNMP_BINDING_1, 1 hit
PS50042 CNMP_BINDING_3, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiHCN4_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9Y3Q4
Secondary accession number(s): Q9UMQ7
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1999
Last modified: December 5, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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