dbPTM

KCNB1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KCNB1_HUMAN
UniProt AC	Q14721
Protein Name	Potassium voltage-gated channel subfamily B member 1 {ECO:0000312\|HGNC:HGNC:6231}
Gene Name	KCNB1 {ECO:0000312\|HGNC:HGNC:6231}
Organism	Homo sapiens (Human).
Sequence Length	858
Subcellular Localization	Cell membrane . Perikaryon . Cell projection, axon . Cell projection, dendrite . Membrane Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane . Cell junction, synapse . Cell junction, synapse, synaptosome . Lateral cell membra
Protein Description	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain. [PubMed: 23161216 Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization]
Protein Sequence	MPAGMTKHGSRSTSSLPPEPMEIVRSKACSRRVRLNVGGLAHEVLWRTLDRLPRTRLGKLRDCNTHDSLLEVCDDYSLDDNEYFFDRHPGAFTSILNFYRTGRLHMMEEMCALSFSQELDYWGIDEIYLESCCQARYHQKKEQMNEELKREAETLREREGEEFDNTCCAEKRKKLWDLLEKPNSSVAAKILAIISIMFIVLSTIALSLNTLPELQSLDEFGQSTDNPQLAHVEAVCIAWFTMEYLLRFLSSPKKWKFFKGPLNAIDLLAILPYYVTIFLTESNKSVLQFQNVRRVVQIFRIMRILRILKLARHSTGLQSLGFTLRRSYNELGLLILFLAMGIMIFSSLVFFAEKDEDDTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCCIAGVLVIALPIPIIVNNFSEFYKEQKRQEKAIKRREALERAKRNGSIVSMNMKDAFARSIEMMDIVVEKNGENMGKKDKVQDNHLSPNKWKWTKRTLSETSSSKSFETKEQGSPEKARSSSSPQHLNVQQLEDMYNKMAKTQSQPILNTKESAAQSKPKEELEMESIPSPVAPLPTRTEGVIDMRSMSSIDSFISCATDFPEATRFSHSPLTSLPSKTGGSTAPEVGWRGALGASGGRFVEANPSPDASQHSSFFIESPKSSMKTNNPLKLRALKVNFMEGDPSPLLPVLGMYHDPLRNRGSAAAAVAGLECATLLDKAVLSPESSIYTTASAKTPPRSPEKHTAIAFNFEAGVHQYIDADTDDEGQLLYSVDSSPPKSLPGSTSPKFSTGTRSEKNHFESSPLPTSPKFLRQNCIYSTEALTGKGPSGQEKCKLENHISPDVRVLPGGGAHGSTRDQSI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
6	Phosphorylation	--MPAGMTKHGSRST --CCCCCCCCCCCCC	20.97	29083192
10	Phosphorylation	AGMTKHGSRSTSSLP CCCCCCCCCCCCCCC	23.83	29083192
13	Phosphorylation	TKHGSRSTSSLPPEP CCCCCCCCCCCCCCC	22.64	22210691
15	Phosphorylation	HGSRSTSSLPPEPME CCCCCCCCCCCCCHH	45.01	-
26	Phosphorylation	EPMEIVRSKACSRRV CCHHHHHCHHCCCCE	17.45	-
93	Phosphorylation	DRHPGAFTSILNFYR CCCCCHHHHHHHHHH	17.83	22817900
99	Phosphorylation	FTSILNFYRTGRLHM HHHHHHHHHHCCHHH	13.24	22817900
128	Dephosphorylation	YWGIDEIYLESCCQA CCCCCHHHHHHHHHH	11.45	12615930
128	Phosphorylation	YWGIDEIYLESCCQA CCCCCHHHHHHHHHH	11.45	22745487
323	Phosphorylation	GLQSLGFTLRRSYNE CHHHHCHHHHCCHHH	19.98	24719451
359	Phosphorylation	AEKDEDDTKFKSIPA HCCCCCCCCCCCCCH	51.18	-
374	Phosphorylation	SFWWATITMTTVGYG HHHEEEEEEEECCCC	12.24	-
380	Phosphorylation	ITMTTVGYGDIYPKT EEEEECCCCCCCCHH	13.80	22817900
384	Phosphorylation	TVGYGDIYPKTLLGK ECCCCCCCCHHHHHH	11.92	-
444	Phosphorylation	ERAKRNGSIVSMNMK HHHHHHCCEEECCHH	24.30	32142685
457	Phosphorylation	MKDAFARSIEMMDIV HHHHHHHHHHHHEEE	21.33	22617229
484	Phosphorylation	KVQDNHLSPNKWKWT CCCCCCCCCCCCCCC	20.90	25307156
494	Phosphorylation	KWKWTKRTLSETSSS CCCCCCCHHHCCCCC	35.87	27732954
496	Phosphorylation	KWTKRTLSETSSSKS CCCCCHHHCCCCCCC	37.91	27732954
498	Phosphorylation	TKRTLSETSSSKSFE CCCHHHCCCCCCCCC	30.45	27732954
499	Phosphorylation	KRTLSETSSSKSFET CCHHHCCCCCCCCCC	28.67	27732954
500	Phosphorylation	RTLSETSSSKSFETK CHHHCCCCCCCCCCC	49.56	27732954
501	Phosphorylation	TLSETSSSKSFETKE HHHCCCCCCCCCCCC	31.89	27732954
503	Phosphorylation	SETSSSKSFETKEQG HCCCCCCCCCCCCCC	30.20	27732954
517	Phosphorylation	GSPEKARSSSSPQHL CCHHHHHCCCCCCCC	39.16	25307156
519	Phosphorylation	PEKARSSSSPQHLNV HHHHHCCCCCCCCCH	47.48	25332170
520	Phosphorylation	EKARSSSSPQHLNVQ HHHHCCCCCCCCCHH	30.44	24076635
539	Phosphorylation	MYNKMAKTQSQPILN HHHHHHHHCCCCCCC	24.74	27732954
541	Phosphorylation	NKMAKTQSQPILNTK HHHHHHCCCCCCCHH	43.06	27732954
567	Phosphorylation	LEMESIPSPVAPLPT HCCCCCCCCCCCCCC	30.27	-
590	Phosphorylation	RSMSSIDSFISCATD HHHHHHHHHHHHCCC	23.86	-
605	Phosphorylation	FPEATRFSHSPLTSL CCCCCCCCCCCCCCC	21.55	29396449
607	Phosphorylation	EATRFSHSPLTSLPS CCCCCCCCCCCCCCC	22.02	29396449
610	Phosphorylation	RFSHSPLTSLPSKTG CCCCCCCCCCCCCCC	31.44	29396449
611	Phosphorylation	FSHSPLTSLPSKTGG CCCCCCCCCCCCCCC	46.06	29396449
614	Phosphorylation	SPLTSLPSKTGGSTA CCCCCCCCCCCCCCC	48.41	24719451
651	Phosphorylation	PDASQHSSFFIESPK CCHHHCCCCEECCCC	23.27	30266825
656	Phosphorylation	HSSFFIESPKSSMKT CCCCEECCCCHHCCC	32.58	30266825
691	Phosphorylation	LLPVLGMYHDPLRNR CHHHHCCCCCCCCCC	10.98	25884760
720	Phosphorylation	LLDKAVLSPESSIYT HHHHHHCCCCCCCCC	21.74	24117733
723	Phosphorylation	KAVLSPESSIYTTAS HHHCCCCCCCCCCCC	25.97	25954137
724	Phosphorylation	AVLSPESSIYTTASA HHCCCCCCCCCCCCC	20.25	24117733
726	Phosphorylation	LSPESSIYTTASAKT CCCCCCCCCCCCCCC	10.45	25954137
727	Phosphorylation	SPESSIYTTASAKTP CCCCCCCCCCCCCCC	17.76	24117733
728	Phosphorylation	PESSIYTTASAKTPP CCCCCCCCCCCCCCC	11.14	24117733
730	Phosphorylation	SSIYTTASAKTPPRS CCCCCCCCCCCCCCC	28.36	24117733
733	Phosphorylation	YTTASAKTPPRSPEK CCCCCCCCCCCCCCC	37.94	24117733
737	Phosphorylation	SAKTPPRSPEKHTAI CCCCCCCCCCCCEEE	43.09	24117733
769	Phosphorylation	DEGQLLYSVDSSPPK CCCCEEEEECCCCCC	21.29	28787133
772	Phosphorylation	QLLYSVDSSPPKSLP CEEEEECCCCCCCCC	42.46	-
777	Phosphorylation	VDSSPPKSLPGSTSP ECCCCCCCCCCCCCC	45.64	26437602
781	Phosphorylation	PPKSLPGSTSPKFST CCCCCCCCCCCCCCC	24.62	28787133
782	Phosphorylation	PKSLPGSTSPKFSTG CCCCCCCCCCCCCCC	55.77	26437602
783	Phosphorylation	KSLPGSTSPKFSTGT CCCCCCCCCCCCCCC	27.99	30266825
788	Phosphorylation	STSPKFSTGTRSEKN CCCCCCCCCCCCCCC	45.78	24275569
799	Phosphorylation	SEKNHFESSPLPTSP CCCCCCCCCCCCCCH	35.99	30266825
800	Phosphorylation	EKNHFESSPLPTSPK CCCCCCCCCCCCCHH	24.21	30266825
804	Phosphorylation	FESSPLPTSPKFLRQ CCCCCCCCCHHHHHH	66.40	30266825
805	Phosphorylation	ESSPLPTSPKFLRQN CCCCCCCCHHHHHHC	24.93	30266825
816	Phosphorylation	LRQNCIYSTEALTGK HHHCCEEECHHHCCC	10.40	25884760

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
128	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
520	S	Phosphorylation	Kinase	CDK5	Q00535	Uniprot
607	S	Phosphorylation	Kinase	CDK5	Q00535	Uniprot
656	S	Phosphorylation	Kinase	CDK5	Q00535	Uniprot
800	S	Phosphorylation	Kinase	P38A	Q16539	PSP
800	S	Phosphorylation	Kinase	P38-SUBFAMILY	-	GPS
805	S	Phosphorylation	Kinase	CDK5	Q00535	Uniprot
805	S	Phosphorylation	Kinase	P38A	Q16539	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
15	S	Phosphorylation	-
Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties.
457	S	Phosphorylation	-
In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-720 are less dephosphorylated.
457	S	Phosphorylation	-
Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties.
474	K	Sumoylation	19223394
Sumoylated on Lys-474, preferentially with SUMO1; sumoylation induces a positive shift in the voltage-dependence of activation and inhibits channel activity.
520	S	Phosphorylation	-
Phosphorylated on Ser-520, Ser-607, Ser-656 and Ser-805 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation.
541	S	Phosphorylation	-
Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties.
567	S	Phosphorylation	-
In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-720 are less dephosphorylated.
567	S	Phosphorylation	-
In response to brain seizures, phosphorylation levels on Ser-567 and Ser-607 are greatly reduced.
567	S	Phosphorylation	-
Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties.
567	S	Phosphorylation	-
Phosphorylation on Ser-567 is reduced during postnatal development with low levels at P2 and P5; levels then increase to reach adult levels by P14.
607	S	Phosphorylation	-
In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-720 are less dephosphorylated.
607	S	Phosphorylation	-
The Ser-607 phosphorylation state differs between KCNB1-containing clusters on the proximal and distal portions of the axon initial segment (AIS).
607	S	Phosphorylation	-
Ser-607 and Tyr-128 are significant sites of voltage-gated regulation through phosphorylation/dephosphorylation activities.
607	S	Phosphorylation	-
Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties.
607	S	Phosphorylation	-
Phosphorylated on Ser-520, Ser-607, Ser-656 and Ser-805 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation.
607	S	Phosphorylation	-
In response to brain seizures, phosphorylation levels on Ser-567 and Ser-607 are greatly reduced.
607	S	Phosphorylation	-
Dephosphorylated at Ser-607 by protein phosphatase PPP1CA.
607	S	Phosphorylation	-
CDK5-induced Ser-607 phosphorylation increases in response to acute blockade of neuronal activity.
656	S	Phosphorylation	-
Phosphorylated on Ser-520, Ser-607, Ser-656 and Ser-805 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation.
656	S	Phosphorylation	-
Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties.
720	S	Phosphorylation	-
In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-720 are less dephosphorylated.
720	S	Phosphorylation	-
Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties.
805	S	Phosphorylation	-
Phosphorylated on Ser-520, Ser-607, Ser-656 and Ser-805 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation.
805	S	Phosphorylation	-
Phosphorylated on Tyr-128 by Src and on Ser-805 by MAPK14/P38MAPK; phosphorylations are necessary and sufficient for an increase in plasma membrane insertion, apoptotic potassium current surge and completion of the neuronal cell death program.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of KCNB1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KCNB1_HUMAN	KCNB1	physical	12060745
KCNG3_HUMAN	KCNG3	physical	12060745
KCNH1_HUMAN	KCNH1	physical	12060745
KCNV2_HUMAN	KCNV2	physical	12060745
SNP25_HUMAN	SNAP25	physical	12403834
KCNB1_HUMAN	KCNB1	physical	8980147
KCNG1_HUMAN	KCNG1	physical	8980147
KCNB1_HUMAN	KCNB1	physical	19074135
KCNB2_HUMAN	KCNB2	physical	19074135
KCNG3_HUMAN	KCNG3	physical	19074135
KCNG4_HUMAN	KCNG4	physical	19074135
STX1A_HUMAN	STX1A	physical	22411134
STX1A_HUMAN	STX1A	physical	15518587

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
616056	Epileptic encephalopathy, early infantile, 26 (EIEE26)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB06637	Dalfampridine

Regulatory Network of KCNB1_HUMAN

Related Literatures of Post-Translational Modification

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