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Protein Page:
HCN4 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
HCN4 Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. May contribute to the native pacemaker currents in heart (If) and in neurons (Ih). Activated by cAMP. May mediate responses to sour stimuli. Defects in HCN4 are a cause of sick sinus syndrome type 2 (SSS2); also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. The 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, in which case it is considered to be a congenital disorder. Defects in HCN4 are the cause of Brugada syndrome type 8 (BRGDA8). A 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 (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset. Belongs to the potassium channel HCN family. Note: This description may include information from UniProtKB.
Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass
Cellular Component: integral to plasma membrane; plasma membrane; terminal button; intrinsic to plasma membrane
Molecular Function: identical protein binding; voltage-gated potassium channel activity; intracellular cAMP activated cation channel activity; voltage-gated sodium channel activity; cation channel activity; cAMP binding
Biological Process: synaptic transmission; regulation of membrane potential; muscle contraction; in utero embryonic development; blood circulation; regulation of heart rate; cation transport
Reference #:  Q9Y3Q4 (UniProtKB)
Alt. Names/Synonyms: HCN4; hyperpolarization activated cyclic nucleotide-gated cation channel 4; hyperpolarization activated cyclic nucleotide-gated potassium channel 4; Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4; SSS2
Gene Symbols: HCN4
Molecular weight: 129,042 Da
Basal Isoelectric point: 9.07  Predict pI for various phosphorylation states
Select Structure to View Below

HCN4

Protein Structure Not Found.


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Sites Implicated In
activity, induced: Y531‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
1 1 S14-p SMRKRLYsLPQQVGA
0 1 S67-p AAAGGTEsRsSALGA
0 1 S69-p AGGTEsRsSALGAAD
1 0 S99 DCRRFRGSLASLGSR
0 1 S102 RFRGSLASLGSRGGG
0 1 S105 GSLASLGSRGGGSGG
1 0 S110 LGSRGGGSGGTGSGS
1 0 S117 SGGTGSGSSHGHLHD
0 1 S125 SHGHLHDSAEERRLI
0 1 S138 LIAEGDASPGEDRTP
0 2 K238 LRMFGSQKAVEREQE
0 1 S349 FMVDFISSIPVDYIF
0 1 T361 YIFLIVETRIDSEVY
1 0 Y531-p RRQYQEKyKQVEQYM
2 0 Y554-p TRQRIHDyYEHRYQG
0 1 K588 IINFNCRKLVASMPL
0 1 T650-p LTKGNKEtKLADGSY
1 0 S719-p DRIGKKNsILLHKVQ
1 0 S831 RHLKRLQSLIPSALG
1 0 S917 FHKALGGSLSSsDSP
0 1 S921-p LGGSLSSsDSPLLTP
0 3 S935 PLQPGARSPQAAQPS
1 0 S1005 PRQPEPPSLVAGASG
1 0 S1011 PSLVAGASGGAsPVG
0 1 S1015-p AGASGGAsPVGFtPR
0 1 T1020-p GAsPVGFtPRGGLsP
0 1 S1026-p FtPRGGLsPPGHSPG
1 0 S1051 RASGSHGSLLLPPAS
1 5 T1071-p QVPQRRGtPPLtPGR
0 3 T1075-p RRGtPPLtPGRLTQD
0 1 S1105 AQTLRRASPHSSGES
0 1 S1108 LRRASPHSSGESMAA
0 1 S1109 RRASPHSSGESMAAF
1 0 S1112 SPHSSGESMAAFPLF
1 0 S1131 GGSGGSGSSGGLGPP
1 0 T1156 HVTLPRKTSSGSLPP
1 0 S1157 VTLPRKTSSGSLPPP
1 0 S1158 TLPRKTSSGSLPPPL
1 0 S1160 PRKTSSGSLPPPLSL
  mouse

 
S14-p SMRKRLYsLPQQVGA
S67 VAAGCSESRGAALGA
G69 AGCSESRGAALGATE
S99-p DCRRFRGsLAsLGsR
S102-p RFRGsLAsLGsRGGG
S105-p GsLAsLGsRGGGsGG
S110-p LGsRGGGsGGAGGGs
S117-p sGGAGGGsSLGHLHD
S125-p SLGHLHDsAEERRLI
S139-p IAAEGDAsPGEDRTP
K238-ub LRMFGSQkAVEREQE
S349-p FVVDFISsIPVEYIF
T361-p YIFLIVEtRIDSEVY
Y531 RRQYQEKYKQVEQYM
Y554-p TRQRIHDyYEHRYQG
K588-ub IINFNCRkLVASMPL
T650 LTKGNKETRLADGSY
S704-p PMMRKKNsILLHKVQ
S816-p RHPRRLQsLIPSALG
S903-p FHKALGGsLSSSDSP
S907 LGGsLSSSDSPLLTP
S921-p PLQPGARsPQAAQPP
S990-p PPRPERPsFMAGAsG
S996-p PsFMAGAsGGASPVA
S1000 AGAsGGASPVAFTPR
T1005 GASPVAFTPRGGLsP
S1011-p FTPRGGLsPPGHSPG
S1036-p RASGSHGsLLLPPAS
T1056-p QVPQRRGtPPLtPGR
T1060-p RRGtPPLtPGRLTQD
S1090-p AQTLRRAsPHssGEs
S1093-p LRRAsPHssGEsVAA
S1094-p RRAsPHssGEsVAAF
S1097-p sPHssGEsVAAFSLY
S1113-p RAGGGSGsSGGLGPP
T1138-p HVTLPRKtssGsLPP
S1139-p VTLPRKtssGsLPPP
S1140-p TLPRKtssGsLPPPL
S1142-p PRKtssGsLPPPLSL
  rat

 
S14 SMRKRLYSLPQQVGA
S67 VAAGCSESRGAALGA
G69 AGCSESRGAALGAAD
S99 DCRRFRGSLASLGSR
S102 RFRGSLASLGSRGGG
S105 GSLASLGSRGGGSGG
S110 LGSRGGGSGGAGGGS
S117 SGGAGGGSSLGHLHD
S125 SLGHLHDSAEERRLI
S139 IAAEGDASPGEDRTP
K238 LRMFGSQKAVEREQE
S349 FVVDFISSIPVDYIF
T361 YIFLIVETRIDSEVY
Y531 RRQYQEKYKQVEQYM
Y554 TRQRIHDYYEHRYQG
K588 IINFNCRKLVASMPL
T650 LTKGNKETKLADGSY
S719 DRIGKKNSILLHKVQ
S831 RHPRRLQSLIPSALG
S916 FHKALGGSLSSSDSP
S920 LGGSLSSSDSPLLTP
S934 PLQPGARSPQAAQPP
S1003 PPRPERPSFMAGASG
S1009 PSFMAGASGGASPVA
S1013 AGASGGASPVAFTPR
T1018 GASPVAFTPRGGLsP
S1024-p FTPRGGLsPPGHSPG
S1049 RASGSHGSLLLPPAS
T1069 QVPQRRGTPPLTPGR
T1073 RRGTPPLTPGRLTQD
S1103 AQTLRRASPHSSGES
S1106 LRRASPHSSGESMAA
S1107 RRASPHSSGESMAAF
S1110 SPHSSGESMAAFSLY
S1126 RAGGGSGSSGGLGPP
T1151 HVTLPRKTSSGSLPP
S1152 VTLPRKTSSGSLPPP
S1153 TLPRKTSSGSLPPPL
S1155 PRKTSSGSLPPPLSL
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