KCND2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KCND2_HUMAN
• UniProt AC: Q9NZV8
• Protein Name: Potassium voltage-gated channel subfamily D member 2
• Gene Name: KCND2
• Organism: Homo sapiens (Human).
• Sequence Length: 630
• Subcellular Localization: Cell membrane ; Multi-pass membrane protein . Cell projection, dendrite . Cell junction, synapse . Perikaryon . Cell junction, synapse, postsynaptic cell membrane . Cell projection, dendritic spine . Cell junction . In neurons, primarily detected on
• Protein Description: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. [PubMed: 10551270]
• Protein Sequence: MAAGVAAWLPFARAAAIGWMPVASGPMPAPPRQERKRTQDALIVLNVSGTRFQTWQDTLERYPDTLLGSSERDFFYHPETQQYFFDRDPDIFRHILNFYRTGKLHYPRHECISAYDEELAFFGLIPEIIGDCCYEEYKDRRRENAERLQDDADTDTAGESALPTMTARQRVWRAFENPHTSTMALVFYYVTGFFIAVSVIANVVETVPCGSSPGHIKELPCGERYAVAFFCLDTACVMIFTVEYLLRLAAAPSRYRFVRSVMSIIDVVAILPYYIGLVMTDNEDVSGAFVTLRVFRVFRIFKFSRHSQGLRILGYTLKSCASELGFLLFSLTMAIIIFATVMFYAEKGSSASKFTSIPAAFWYTIVTMTTLGYGDMVPKTIAGKIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRAQKKARLARIRAAKSGSANAYMQSKRNGLLSNQLQSSEDEQAFVSKSGSSFETQHHHLLHCLEKTTNHEFVDEQVFEESCMEVATVNRPSSHSPSLSSQQGVTSTCCSRRHKKTFRIPNANVSGSHQGSIQELSTIQIRCVERTPLSNSRSSLNAKMEECVKLNCEQPYVTTAIISIPTPPVTTPEGDDRPESPEYSGGNIVRVSAL

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
38	Phosphorylation	PRQERKRTQDALIVL CHHHCCCCCCEEEEE	33.56	-
62	Phosphorylation	WQDTLERYPDTLLGS HHHHHHHCCCCCCCC	8.97	23403867
65	Phosphorylation	TLERYPDTLLGSSER HHHHCCCCCCCCCCC	21.27	23403867
69	Phosphorylation	YPDTLLGSSERDFFY CCCCCCCCCCCCCCC	29.06	23403867
134	Phosphorylation	EIIGDCCYEEYKDRR HHHCHHCHHHHHHHH	20.37	22817900
154	Phosphorylation	RLQDDADTDTAGESA HHHHCCCCCCCCHHC	36.65	22210691
156	Phosphorylation	QDDADTDTAGESALP HHCCCCCCCCHHCCC	38.36	22210691
160	Phosphorylation	DTDTAGESALPTMTA CCCCCCHHCCCHHHH	33.90	-
166	Phosphorylation	ESALPTMTARQRVWR HHCCCHHHHHHHHHH	22.59	22210691
260	Phosphorylation	SRYRFVRSVMSIIDV HHHHHHHHHHHHHHH	19.50	-
291	Phosphorylation	DVSGAFVTLRVFRVF CCCCCCHHHHHHHHH	11.46	-
438	Phosphorylation	ARIRAAKSGSANAYM HHHHHHHCCCHHHHH	33.00	15071113
440	Phosphorylation	IRAAKSGSANAYMQS HHHHHCCCHHHHHHH	25.99	-
444	Phosphorylation	KSGSANAYMQSKRNG HCCCHHHHHHHHHCC	8.76	-
447	Phosphorylation	SANAYMQSKRNGLLS CHHHHHHHHHCCCCH	19.63	-
459	Phosphorylation	LLSNQLQSSEDEQAF CCHHCCCCCHHHHHH	44.26	15071113
537	Phosphorylation	CSRRHKKTFRIPNAN CCCCCCCEEECCCCC	23.97	-
548	Phosphorylation	PNANVSGSHQGSIQE CCCCCCCCCCCCCEE	12.72	25307156
552	Phosphorylation	VSGSHQGSIQELSTI CCCCCCCCCEEEEEE	17.96	22817900
572	Phosphorylation	ERTPLSNSRSSLNAK ECCCCCCCCHHHHHC	30.11	-
575	Phosphorylation	PLSNSRSSLNAKMEE CCCCCCHHHHHCHHH	25.24	30576142
602	Phosphorylation	TAIISIPTPPVTTPE EEEEEECCCCCCCCC	38.26	-
607	Phosphorylation	IPTPPVTTPEGDDRP ECCCCCCCCCCCCCC	21.41	-
616	Phosphorylation	EGDDRPESPEYSGGN CCCCCCCCCCCCCCC	26.22	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
38	T	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
438	S	Phosphorylation	Kinase	CAMK2-FAMILY	-	GPS
438	S	Phosphorylation	Kinase	CAM-KII_GROUP	-	PhosphoELM
447	S	Phosphorylation	Kinase	PKC-FAMILY	-	GPS
459	S	Phosphorylation	Kinase	CAMK2-FAMILY	-	GPS
459	S	Phosphorylation	Kinase	CAM-KII_GROUP	-	PhosphoELM
537	T	Phosphorylation	Kinase	PKC-FAMILY	-	GPS
552	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
552	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
602	T	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
607	T	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
616	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
438	S	Phosphorylation	Phosphorylation at Ser-438 in response to MAPK activation is increased in stimulated dendrites.	-
552	S	Phosphorylation	Interaction with KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552.	-
552	S	Phosphorylation	Phosphorylation at Ser-552 has no effect on interaction with KCNIP3, but is required for the regulation of channel activity by KCNIP3.	-
552	S	Phosphorylation	Phosphorylation at Ser-552 leads to KCND2 internalization (By similarity).	-
616	S	Phosphorylation	Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5 (By similarity).	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of KCND2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NCS1_HUMAN	NCS1	physical	11606724
FLNC_HUMAN	FLNC	physical	11102480
KCIP2_HUMAN	KCNIP2	physical	20709747
KCIP1_HUMAN	KCNIP1	physical	14980207
KCIP2_HUMAN	KCNIP2	physical	11287421
KCIP2_HUMAN	KCNIP2	physical	19361449
KCNE4_HUMAN	KCNE4	physical	20498229
KCIP1_HUMAN	KCNIP1	physical	10676964
KCIP2_HUMAN	KCNIP2	physical	15358149
KCIP1_HUMAN	KCNIP1	physical	15358149
DPP10_HUMAN	DPP10	physical	15454437
DPP6_HUMAN	DPP6	physical	15454437
KCIP2_HUMAN	KCNIP2	physical	14623880
DPP6_HUMAN	DPP6	physical	23692269
CSEN_HUMAN	KCNIP3	physical	23692269
KCD17_HUMAN	KCTD17	physical	28514442
HSP7C_HUMAN	HSPA8	physical	28514442
BAG1_HUMAN	BAG1	physical	28514442
KCTD2_HUMAN	KCTD2	physical	28514442
BAG3_HUMAN	BAG3	physical	28514442
GBB4_HUMAN	GNB4	physical	28514442
KCTD5_HUMAN	KCTD5	physical	28514442
CHIP_HUMAN	STUB1	physical	28514442

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• DB00321: Amitriptyline
• DB06637: Dalfampridine
• DB00280: Disopyramide
• DB00458: Imipramine