AiPD: Autoinhibited Protein Database

Q9NS61

Gene name	KCNIP2 (KCHIP2)
Protein name	Kv channel-interacting protein 2
Names	KChIP2, A-type potassium channel modulatory protein 2, Cardiac voltage-gated potassium channel modulatory subunit, Potassium channel-interacting protein 2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:30819
EC number
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

1-61 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

1-61 (Predicted disordered autoinhibitory region)

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

No accessory elements

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell Systems, 2, 89-100

Autoinhibited structure

Activated structure

3 structures for Q9NS61

Entry ID	Method	Resolution	Chain	Position	Source
7UKH	EM	233 A	I/J/K/L	1-270	PDB
7W6S	EM	280 A	A/C/E/G	1-270	PDB
AF-Q9NS61-F1	Predicted				AlphaFoldDB

164 variants for Q9NS61

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA378147980 rs1412099896	2	R>Q		No	ClinGen TOPMed
CA5658946 rs751549899	2	R>W		No	ClinGen ExAC TOPMed gnomAD
rs763751174 CA5658945	3	G>R		No	ClinGen ExAC gnomAD
rs1314142531 CA378147955	4	Q>E		No	ClinGen gnomAD
rs576902320 CA5658944	6	R>C		No	ClinGen 1000Genomes ExAC gnomAD
rs775190231 CA5658943	6	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA5658942 rs764939924	8	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1328090417 CA378147799	10	L>S		No	ClinGen TOPMed
rs776223860 CA5658940	12	D>N		No	ClinGen ExAC TOPMed gnomAD
rs748625236 CA5658938	16	L>R		No	ClinGen ExAC gnomAD
rs1275650170 CA378147667	16	L>V		No	ClinGen TOPMed gnomAD
CA212192141 rs12572354	17	D>V		No	ClinGen Ensembl
CA378147603 rs1216235984	19	S>F		No	ClinGen TOPMed
CA5658937 rs774944132	20	Y>H		No	ClinGen ExAC gnomAD
rs1196476904 CA378147535	23	L>V		No	ClinGen gnomAD
rs142584989 CA5658935	24	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs1589864215 CA378146180	26	H>P		No	ClinGen Ensembl
CA5658868 rs72552059	26	H>Y		No	ClinGen ExAC TOPMed gnomAD
CA378146169 rs1352547605	27	P>L		No	ClinGen gnomAD
rs1564665564 CA378146160	28	P>L		No	ClinGen Ensembl
rs575471302 CA212183095	28	P>S		No	ClinGen gnomAD
rs745729177 CA5658867	29	G>R		No	ClinGen ExAC gnomAD
rs757004027 CA5658865	30	P>T		No	ClinGen ExAC TOPMed gnomAD
CA5658864 rs751058723	31	T>A		No	ClinGen ExAC TOPMed gnomAD
rs1169743441 CA378146139	31	T>S		No	ClinGen TOPMed
CA378146100 rs1157769010	34	A>G		No	ClinGen TOPMed gnomAD
rs1157769010 CA378146099	34	A>V		No	ClinGen TOPMed gnomAD
rs1345972709 CA378146073	37	Q>*		No	ClinGen TOPMed
rs1589864079 CA378146069	37	Q>H		No	ClinGen Ensembl
rs755413672 CA5658862	38	R>Q		No	ClinGen ExAC gnomAD
rs754374069 CA5658861	41	K>Q		No	ClinGen ExAC
CA378146010 rs1298789134	46	C>R		No	ClinGen TOPMed
CA5658855 rs762181863	51	L>R		No	ClinGen ExAC gnomAD
CA378145973 rs1268879184	52	P>T		No	ClinGen gnomAD
TCGA novel	57	T>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs769608348 CA5658831	59	A>T		No	ClinGen ExAC gnomAD
CA378145273 rs1286011013	60	A>T		No	ClinGen gnomAD
CA212181680 rs867618475	61	P>L		No	ClinGen Ensembl
CA5658829 rs776223482	62	A>D		No	ClinGen ExAC gnomAD
rs759534660 CA5658830	62	A>P		No	ClinGen ExAC
rs1292753085 CA378145242	64	L>F		No	ClinGen gnomAD
rs1351588072 CA378145223	65	R>H		No	ClinGen gnomAD
CA5658828 rs770746068	66	P>L		No	ClinGen ExAC gnomAD
CA212181646 rs888138861	67	H>N		No	ClinGen Ensembl
CA378145208 rs1184563346	67	H>R		No	ClinGen gnomAD
rs1589859961 CA378145193	68	R>S		No	ClinGen Ensembl
CA212181633 rs1048035903	70	R>C		No	ClinGen TOPMed gnomAD
rs929916944 CA212181624	70	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
CA378145161 rs1589859908	72	L>P		No	ClinGen Ensembl
CA378145006 rs374306816	78	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA5658811 rs776653520	79	D>G		No	ClinGen ExAC gnomAD
CA212181136 rs778040255	79	D>Y		No	ClinGen Ensembl
CA5658809 rs760430839	84	S>F		No	ClinGen ExAC gnomAD
CA5658810 rs770905334	84	S>P		No	ClinGen ExAC
rs1042449640 CA212181112	86	V>L		No	ClinGen Ensembl
CA378144778 rs1401607923	91	E>G		No	ClinGen gnomAD
CA212181099 rs945367630	91	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
rs747848743 CA5658806	92	G>A		No	ClinGen ExAC gnomAD
CA378144765 rs747848743	92	G>D		No	ClinGen ExAC gnomAD
CA5658807 rs771698676	92	G>R		No	ClinGen ExAC gnomAD
CA5658805 rs200389374	93	L>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA5658804 COSM3790418 COSM3790419 rs768239994	94	E>Q	Variant assessed as Somatic; 0.0 impact. urinary_tract [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs1189788352 CA378144651	98	E>K		No	ClinGen TOPMed gnomAD
CA5658803 rs746309023	99	Q>*		No	ClinGen ExAC gnomAD
TCGA novel	102	F>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	102	F>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
COSM1345408 COSM1345407 rs72546683 CA5658801	104	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA378144512 rs1296662909	104	R>P		No	ClinGen TOPMed
CA378144517 rs72546683	104	R>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA378144421 rs1339953903	108	Q>H		No	ClinGen gnomAD
CA378144410 rs1589857341	109	V>G		No	ClinGen Ensembl
CA378144337 rs1228074712	112	R>Q		No	ClinGen TOPMed gnomAD
CA5658797 rs374578874	115	K>M		No	ClinGen ESP ExAC gnomAD
rs752421414 CA5658748	117	E>Q		No	ClinGen ExAC gnomAD
CA5658747 rs765031048	120	S>I		No	ClinGen ExAC TOPMed gnomAD
rs776347690 CA212180683	121	G>*		No	ClinGen ExAC gnomAD
CA5658745 rs776347690	121	G>R		No	ClinGen ExAC gnomAD
CA212180675 rs985025793	122	I>T		No	ClinGen gnomAD
rs772616913 CA5658744	123	V>L		No	ClinGen ExAC gnomAD
rs952215963 CA212180672	126	E>D		No	ClinGen Ensembl
CA378143366 rs1440960502	126	E>K		No	ClinGen gnomAD
rs919400815 CA212180669	129	K>E		No	ClinGen TOPMed gnomAD
CA5658743 rs762238622	135	F>L		No	ClinGen ExAC gnomAD
rs774709500 CA5658742	137	P>R		No	ClinGen ExAC gnomAD
CA378143259 rs1564661369	138	Q>P		No	ClinGen Ensembl
rs202200570 CA5658741	139	G>*		No	ClinGen ExAC TOPMed gnomAD
rs763269682 CA5658721	152	F>L		No	ClinGen ExAC TOPMed gnomAD
CA378142988 rs1365674686	159	S>L		No	ClinGen TOPMed
rs1175436543 CA378142838	166	V>A		No	ClinGen TOPMed
rs1564660814 CA378142816	167	A>V		No	ClinGen Ensembl
rs747056785 CA5658697	168	G>S		No	ClinGen ExAC gnomAD
CA5658694 rs748098631	169	L>F		No	ClinGen ExAC gnomAD
CA5658692 rs779537282	170	S>C		No	ClinGen ExAC
CA5658690 rs779537282	170	S>F		No	ClinGen ExAC
CA5658693 rs778809471	170	S>T		No	ClinGen ExAC
CA5658691 rs779537282	170	S>Y		No	ClinGen ExAC
rs758865366 CA5658686	171	V>G		No	ClinGen ExAC
CA5658687 COSM1702944 rs767022101 COSM1702943	171	V>L	skin [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA5658688 rs767022101	171	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1317251072 CA5658683	172	I>F		No	ClinGen gnomAD
rs753228547 CA5658682	172	I>S		No	ClinGen ExAC
CA5658684 rs1317251072	172	I>V		No	ClinGen gnomAD
rs1168238363 CA378142725	173	L>R		No	ClinGen TOPMed
COSM200202 CA378142715 rs1389251072	174	R>Q	large_intestine Variant assessed as Somatic; impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated NCI-TCGA TOPMed
CA378142719 rs1398216871	174	R>W	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
rs759788279 COSM1730274 COSM1730275 CA5658680	175	G>V	liver [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs151131105 CA212180196	177	V>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA5658678 rs151131105	177	V>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1434391072 CA378142632	178	D>A		No	ClinGen gnomAD
rs1326646168 CA378142634	178	D>H		No	ClinGen gnomAD
TCGA novel	179	D>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1290808881 CA378142598	180	R>K		No	ClinGen gnomAD
CA378142578 rs1170304011	181	L>I		No	ClinGen TOPMed gnomAD
CA5658675 rs772308939	184	A>G		No	ClinGen ExAC gnomAD
rs748048987 CA5658674	186	N>H		No	ClinGen ExAC gnomAD
rs1396275107 CA378142412	188	Y>C		No	ClinGen gnomAD
rs369988905 CA378142323	193	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA212180128 rs930867098	193	D>Y		No	ClinGen Ensembl
CA5658672 rs768750070 COSM1211512 COSM1211511	194	G>S	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA378142292 rs1486019728	196	I>V		No	ClinGen gnomAD
CA212180115 rs919453232	197	T>S		No	ClinGen TOPMed
CA5658668 rs201641890	199	E>D		No	ClinGen ExAC gnomAD
CA378142067 rs1399328063	211	M>I		No	ClinGen gnomAD
rs745716009 CA5658648	212	M>I		No	ClinGen ExAC gnomAD
rs769656412 CA5658649	212	M>T		No	ClinGen ExAC gnomAD
rs1367411008 CA378142048	214	K>T		No	ClinGen gnomAD
CA378142042 rs1185283889	215	Y>N		No	ClinGen gnomAD
rs780795809 COSM282089 CA5658647	216	T>M	large_intestine Variant assessed as Somatic; impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated ExAC NCI-TCGA gnomAD
CA378142005 rs201481729	221	R>G		No	ClinGen ExAC gnomAD
rs149050202 CA5658644	221	R>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD
rs149050202 CA5658643	221	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA5658645 rs201481729	221	R>W		No	ClinGen ExAC gnomAD
rs1271376821 CA378141997	222	E>D		No	ClinGen gnomAD
CA5658641 rs144960412	223	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
TCGA novel	224	A>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA212179876 rs776074231	224	A>V		No	ClinGen Ensembl
rs1564660032 CA378141978	225	P>L		No	ClinGen Ensembl
CA212179869 rs770579729	226	R>T		No	ClinGen TOPMed
CA5658639 rs115921182	229	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA378141949 rs1382030903	230	E>K		No	ClinGen TOPMed
CA212179856 rs746575299	231	S>N		No	ClinGen Ensembl
CA5658638 rs767843104	231	S>R		No	ClinGen ExAC gnomAD
rs751628876 CA5658636	233	F>L		No	ClinGen ExAC TOPMed gnomAD
CA5658635 rs764236283	234	Q>K		No	ClinGen ExAC gnomAD
CA212179679 rs951526453	235	K>N		No	ClinGen TOPMed
rs1195427122 CA378141888	236	M>I		No	ClinGen gnomAD
rs1312469485 CA378141875	238	R>K		No	ClinGen TOPMed
CA378141872 rs1564659710	238	R>S		No	ClinGen Ensembl
CA378141864 rs758477233 CA5658615	239	N>K		No	ClinGen ExAC gnomAD
CA378141844 rs1247512621	242	G>D		No	ClinGen gnomAD
CA378141841 rs1448996748	243	V>M		No	ClinGen gnomAD
CA5658614 rs752790110	245	T>A		No	ClinGen ExAC gnomAD
rs374874936 CA5658613	246	I>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs759484365 CA5658612	249	F>L		No	ClinGen ExAC gnomAD
rs776347807 CA378141792	250	I>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs776347807 CA5658611	250	I>T		No	ClinGen ExAC TOPMed gnomAD
CA5658610 rs766195922	254	Q>E		No	ClinGen ExAC gnomAD
CA378141634 rs1589852516	257	E>*		No	ClinGen Ensembl
COSM3699838 COSM3699837 CA212179214 rs747817704	260	M>K	liver [Cosmic]	No	ClinGen cosmic curated Ensembl
TCGA novel	262	S>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs771634355 CA5658583	264	Q>K		No	ClinGen ExAC gnomAD
CA378141566 rs1260017510	266	F>S		No	ClinGen gnomAD
rs1189180837 CA378141561	267	D>N		No	ClinGen gnomAD
COSM172773 CA378141542 rs1216006695	269	V>A	large_intestine Variant assessed as Somatic; impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated NCI-TCGA TOPMed

No associated diseases with Q9NS61

4 regional properties for Q9NS61

Type	Name	Position	InterPro Accession
domain	EF-hand domain	120 - 259	IPR002048
binding_site	EF-Hand 1, calcium-binding site	153 - 165	IPR018247-1
binding_site	EF-Hand 1, calcium-binding site	189 - 201	IPR018247-2
binding_site	EF-Hand 1, calcium-binding site	237 - 249	IPR018247-3

Functions

		Description
EC Number
Subcellular Localization	[Isoform 1]: Cell membrane ; Lipid-anchor	Detected on lipid rafts (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

6 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
dendrite	A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
potassium channel complex	An ion channel complex through which potassium ions pass.
synapse	The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.
voltage-gated potassium channel complex	A protein complex that forms a transmembrane channel through which potassium ions may cross a cell membrane in response to changes in membrane potential.

9 GO annotations of molecular function

Name	Definition
calcium ion binding	Binding to a calcium ion (Ca2+).
ER retention sequence binding	Binding to an endoplasmic reticulum (ER) retention sequence, a specific peptide sequence that ensures a protein is retained within the ER.
identical protein binding	Binding to an identical protein or proteins.
potassium channel activity	Enables the facilitated diffusion of a potassium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
potassium channel regulator activity	Binds to and modulates the activity of a potassium channel.
protein N-terminus binding	Binding to a protein N-terminus, the end of any peptide chain at which the 2-amino (or 2-imino) function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
protein-containing complex binding	Binding to a macromolecular complex.
transmembrane transporter binding	Binding to a transmembrane transporter, a protein or protein complex that enables the transfer of a substance, usually a specific substance or a group of related substances, from one side of a membrane to the other.
voltage-gated ion channel activity	Enables the transmembrane transfer of an ion by a voltage-gated channel. An ion is an atom or group of atoms carrying an electric charge by virtue of having gained or lost one or more electrons. A voltage-gated channel is a channel whose open state is dependent on the voltage across the membrane in which it is embedded.

13 GO annotations of biological process

Name	Definition
chemical synaptic transmission	The vesicular release of classical neurotransmitter molecules from a presynapse, across a chemical synapse, the subsequent activation of neurotransmitter receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.
clustering of voltage-gated potassium channels	The process in which voltage-gated potassium channels become localized together in high densities. In animals, voltage-gated potassium (Kv) channels are clustered beneath the myelin sheath in regions immediately adjacent to paranodes, called juxtaparanodes, and along the inner mesaxon within the internode.
detection of calcium ion	The series of events in which a calcium ion stimulus is received by a cell and converted into a molecular signal.
membrane repolarization	The process in which ions are transported across a membrane such that the membrane potential changes in the repolarizing direction, toward the steady state potential. For example, the repolarization during an action potential is from a positive membrane potential towards a negative resting potential.
membrane repolarization during cardiac muscle cell action potential	The process in which ions are transported across a membrane such that the cardiac muscle cell plasma membrane potential changes in the direction from the positive membrane potential at the peak of the action potential towards the negative resting potential.
muscle contraction	A process in which force is generated within muscle tissue, resulting in a change in muscle geometry. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis.
positive regulation of potassium ion export across plasma membrane	Any process that activates or increases the frequency, rate or extent of potassium ion export across the plasma membrane.
positive regulation of voltage-gated potassium channel activity	Any process that activates or increases the frequency, rate or extent of voltage-gated potassium channel activity.
potassium ion export across plasma membrane	The directed movement of potassium ions from inside of a cell, across the plasma membrane and into the extracellular region.
potassium ion transport	The directed movement of potassium ions (K+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
regulation of heart contraction	Any process that modulates the frequency, rate or extent of heart contraction. Heart contraction is the process in which the heart decreases in volume in a characteristic way to propel blood through the body.
regulation of potassium ion transmembrane transport	Any process that modulates the frequency, rate or extent of potassium ion transmembrane transport.
signal transduction	The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.

4 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q9QXT8	Kcnip3	Calsenilin	Mus musculus (Mouse)	PR
Q9JJ69	Kcnip2	Kv channel-interacting protein 2	Mus musculus (Mouse)	PR
Q75KU4	CBL4	Calcineurin B-like protein 4	Oryza sativa subsp japonica (Rice)	PR
Q7XC27	CBL1	Calcineurin B-like protein 1	Oryza sativa subsp japonica (Rice)	PR

10	20	30	40	50	60
MRGQGRKESL	SDSRDLDGSY	DQLTGHPPGP	TKKALKQRFL	KLLPCCGPQA	LPSVSETLAA
70	80	90	100	110	120
PASLRPHRPR	LLDPDSVDDE	FELSTVCHRP	EGLEQLQEQT	KFTRKELQVL	YRGFKNECPS
130	140	150	160	170	180
GIVNEENFKQ	IYSQFFPQGD	SSTYATFLFN	AFDTNHDGSV	SFEDFVAGLS	VILRGTVDDR
190	200	210	220	230	240
LNWAFNLYDL	NKDGCITKEE	MLDIMKSIYD	MMGKYTYPAL	REEAPREHVE	SFFQKMDRNK
250	260
DGVVTIEEFI	ESCQKDENIM	RSMQLFDNVI