KCNIP2 potassium voltage-gated channel interacting protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNIP2provided by HGNC
Official Full Name: potassium voltage-gated channel interacting protein 2provided by HGNC
Primary source: HGNC:HGNC:15522
See related: Ensembl:ENSG00000120049 MIM:604661; AllianceGenome:HGNC:15522
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KCHIP2
Summary: This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belongs to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified from this gene. [provided by RefSeq, Jul 2008]
Expression: Biased expression in fat (RPKM 117.8), heart (RPKM 37.5) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 10q24.32

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (101825974..101843800, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (102709458..102727289, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (103585731..103603557, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The palmitoylation status of KChIP2 determines its subcellular distribution in cardiac myocytes. Stress promotes nuclear entry of KChIP2, diverting it from ion channel modulation at the plasma membrane to other functions in the nuclear compartment.
Title: Dynamic palmitoylation regulates trafficking of K channel interacting protein 2 (KChIP2) across multiple subcellular compartments in cardiac myocytes.
polybasic motif in alternatively spliced KChIP2 isoforms prevents Ca(2+) regulation of Kv4 channels
Title: A polybasic motif in alternatively spliced KChIP2 isoforms prevents Ca(2+) regulation of Kv4 channels.
Binding of Ca(2+) to KChIP2 EF-hands can acutely modulate Kv4.3/KChIP2 channel inactivation gating.
Title: Modulation of human Kv4.3/KChIP2 channel inactivation kinetics by cytoplasmic Ca(2).
although there is a baseline presence of KChIP2 in the nucleus both in vivo and in vitro, KChIP2 does not directly regulate transcriptional activity. Moreover, the nuclear transport of KChIP2 is not dependent on Ca(2+). Thus, KChIP2 does not function as a conventional transcription factor in the heart.
Title: Potassium Channel Interacting Protein 2 (KChIP2) is not a transcriptional regulator of cardiac electrical remodeling.
Our results do not support the notion that accessory KChIP2 binding is a prerequisite for dendritic trafficking and functional surface expression of Kv4.2 channels, however, accessory KChIP2 binding may play a potential role in Kv4.2 modulation during intrinsic plasticity processes.
Title: Somatodendritic surface expression of epitope-tagged and KChIP binding-deficient Kv4.2 channels in hippocampal neurons.
Results identify the KChIP2/miR-34 axis as a central regulator in developing cardiac electrical dysfunction.
Title: KChIP2 is a core transcriptional regulator of cardiac excitability.
A novel KCNQ1-G229D mutation identified in a juvenile-onset AF patient altered the IKs activity and kinetics, thereby increasing the arrhythmogenicity to AF.
Title: A novel KCNQ1 missense mutation identified in a patient with juvenile-onset atrial fibrillation causes constitutively open IKs channels.
mutations cause a gainoffunction of KV4.3/KChIP2encoded channels by increasing membrane protein expression and slowing channel inactivation.
Title: Two novel Brugada syndrome-associated mutations increase KV4.3 membrane expression and function.
The "structurally minimal" isoform KChIP2d modulates recovery of K(v)4.3 N-terminal deletion mutant Delta2-39.
Title: The "structurally minimal" isoform KChIP2d modulates recovery of K(v)4.3 N-terminal deletion mutant Δ2-39.
KChIP2 differentially regulates total and cell surface Kv4.2 protein expression and Kv4 current densities.
Title: Co-assembly of Kv4 {alpha} subunits with K+ channel-interacting protein 2 stabilizes protein expression and promotes surface retention of channel complexes.

Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH93099 (e-PCR)
- UniSTS:88591

MARC_12017-12018:1003953684:1 (e-PCR)
- UniSTS:267309

D10S2382 (e-PCR)
- UniSTS:77636

G20725 (e-PCR)
- UniSTS:68189

A006D27 (e-PCR)
- UniSTS:68190

Kcnip2 (e-PCR), detects polymorphism
- UniSTS:547251

Kcnip2 (e-PCR), detects polymorphism
- UniSTS:478917

RH92563 (e-PCR)
- UniSTS:87252

Bda26a02 (e-PCR)
- UniSTS:53975

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to A-type (transient outward) potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to A-type (transient outward) potassium channel activity	TAS Traceable Author Statement more info	PubMed
enables ER retention sequence binding	NAS Non-traceable Author Statement more info	PubMed
enables calcium ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	TAS Traceable Author Statement more info	PubMed
enables potassium channel regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables potassium channel regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables transmembrane transporter binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in action potential	IDA Inferred from Direct Assay more info	PubMed
involved_in chemical synaptic transmission	NAS Non-traceable Author Statement more info	PubMed
involved_in clustering of voltage-gated potassium channels	IDA Inferred from Direct Assay more info	PubMed
involved_in detection of calcium ion	TAS Traceable Author Statement more info	PubMed
involved_in membrane repolarization	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane repolarization during cardiac muscle cell action potential	TAS Traceable Author Statement more info	PubMed
involved_in muscle contraction	IDA Inferred from Direct Assay more info	PubMed
involved_in muscle contraction	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of potassium ion export across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of voltage-gated potassium channel activity	TAS Traceable Author Statement more info	PubMed
involved_in potassium ion export across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion transport	TAS Traceable Author Statement more info	PubMed
involved_in regulation of heart contraction	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of heart contraction	TAS Traceable Author Statement more info	PubMed
involved_in regulation of potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of potassium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of Kv4.2-KChIP2 channel complex	IPI Inferred from Physical Interaction more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of potassium channel complex	TAS Traceable Author Statement more info	PubMed
located_in synapse	IEA Inferred from Electronic Annotation more info
part_of voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated potassium channel complex	IDA Inferred from Direct Assay more info	PubMed
part_of voltage-gated potassium channel complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: Kv channel-interacting protein 2

Names: A-type potassium channel modulatory protein 2; Kv channel interacting protein 2; cardiac voltage-gated potassium channel modulatory subunit; potassium channel-interacting protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029836.1 RefSeqGene

Range

5121..22947

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_014591.5 → NP_055406.2 Kv channel-interacting protein 2 isoform 1

See identical proteins and their annotated locations for NP_055406.2

Status: REVIEWED

Description

Transcript Variant: This variant (1), also known as KChIP4.2, encodes the longest isoform (1).

Source sequence(s)

AF367018, AJ276317, AK094668, AL136722, BC034685

Consensus CDS

CCDS7521.1

UniProtKB/TrEMBL

B3KNV3

Related

ENSP00000420040.1, ENST00000461105.5

Conserved Domains (1) summary

COG5126
Location:108 → 274

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]
NM_173191.3 → NP_775283.1 Kv channel-interacting protein 2 isoform 2

See identical proteins and their annotated locations for NP_775283.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as KChIP2.4 or KChIP2L, lacks an in-frame segment in the coding region, as compared to variant 1. Isoform 2 is thus shorter than isoform 1.

Source sequence(s)

AF367021, AJ276317, AK094668, AL136722, BC034685

Consensus CDS

CCDS7522.1

UniProtKB/Swiss-Prot

A6NJE5, A8MQ75, Q3YAC6, Q3YAC8, Q3YAC9, Q7Z6F1, Q96K86, Q96T41, Q96T42, Q96T43, Q96T44, Q9H0N4, Q9HD10, Q9HD11, Q9NS60, Q9NS61, Q9NY10, Q9NZI1

UniProtKB/TrEMBL

B3KNV3

Related

ENSP00000349055.2, ENST00000356640.7

Conserved Domains (1) summary

COG5126
Location:93 → 259

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]
NM_173192.3 → NP_775284.1 Kv channel-interacting protein 2 isoform 3

See identical proteins and their annotated locations for NP_775284.1

Status: REVIEWED

Description

Transcript Variant: This variant (3), also known as KChIP2.1, lacks an in-frame segment in the coding region, as compared to variant 1. Isoform 3 is thus shorter than isoform 1.

Source sequence(s)

AJ276317, AK094668, AL136722, BC034685

Consensus CDS

CCDS41562.1

UniProtKB/TrEMBL

B3KNV3

Related

ENSP00000350733.3, ENST00000358038.7

Conserved Domains (1) summary

COG5126
Location:75 → 241

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]
NM_173193.3 → NP_775285.1 Kv channel-interacting protein 2 isoform 4

See identical proteins and their annotated locations for NP_775285.1

Status: REVIEWED

Description

Transcript Variant: This variant (4), also known as KChIP2S, lacks two consecutive in-frame segment and has an additional in-frame segment in the coding region, as compared to variant 1. Isoform 4 is shorter, but has the same N- and C-termini, as compared to isoform 1.

Source sequence(s)

AF295530, AJ276317, AK094668, AL136722, BC034685

Consensus CDS

CCDS7523.1

UniProtKB/TrEMBL

Q09MK0

Related

ENSP00000341624.3, ENST00000353068.7

Conserved Domains (1) summary

COG5126
Location:43 → 216

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]
NM_173194.3 → NP_775286.1 Kv channel-interacting protein 2 isoform 5

See identical proteins and their annotated locations for NP_775286.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) has a shorter and alternate 5' sequence including the 5' UTR and the 5' coding region, as compared to variant 1. Isoform 5 is shorter and has a distinct N-terminus, as compared to isoform 1.

Source sequence(s)

AC010789, AJ276317, AL136722, BC034685

Consensus CDS

CCDS7525.1

UniProtKB/TrEMBL

B4DW99

Related

ENSP00000239118.6, ENST00000348850.9

Conserved Domains (1) summary

COG5126
Location:48 → 214

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]
NM_173195.3 → NP_775287.1 Kv channel-interacting protein 2 isoform 6

See identical proteins and their annotated locations for NP_775287.1

Status: REVIEWED

Description

Transcript Variant: This variant (6), also known as KChIP2.2, KChIP2T or KChIP2S, lacks two consecutive in-frame segments in the coding region, as compared to variant 1. It encodes a shorter isoform (6), that is missing an internal segment compared to isoform 1.

Source sequence(s)

AJ276317, AK094668, AL136722, BC034685

Consensus CDS

CCDS7524.1

UniProtKB/TrEMBL

Q09MK0

Related

ENSP00000344169.4, ENST00000343195.8

Conserved Domains (1) summary

COG5126
Location:43 → 209

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]
NM_173197.3 → NP_775289.1 Kv channel-interacting protein 2 isoform 7

See identical proteins and their annotated locations for NP_775289.1

Status: REVIEWED

Description

Transcript Variant: This variant (7), also known as KChIP2.5, lacks four coding segments: two consecutive in the 5' region, one in the middle, and one at the 3' end, but has an alternate segment at the 3' end, as compared to variant 1. The alternate segment contains the stop codon. Therefore, isoform 7 has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AF367019, AK094668, BC034685

Consensus CDS

CCDS7526.1

UniProtKB/TrEMBL

A6NFF4

Related

ENSP00000239117.3, ENST00000239117.3

Conserved Domains (1) summary

cd00051
Location:94 → 165

EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

101825974..101843800 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005269730.3 → XP_005269787.1 Kv channel-interacting protein 2 isoform X4

UniProtKB/TrEMBL

Q09MK0

Conserved Domains (2) summary

COG5126
Location:43 → 201

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

cd00051
Location:130 → 201

EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
XM_005269729.3 → XP_005269786.1 Kv channel-interacting protein 2 isoform X3

UniProtKB/TrEMBL

B3KNV3

Conserved Domains (2) summary

COG5126
Location:75 → 233

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

cd00051
Location:162 → 233

EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
XM_006717812.3 → XP_006717875.1 Kv channel-interacting protein 2 isoform X2

UniProtKB/TrEMBL

B3KNV3

Conserved Domains (2) summary

COG5126
Location:93 → 251

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

cd00051
Location:180 → 251

EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
XM_011539731.3 → XP_011538033.1 Kv channel-interacting protein 2 isoform X1

UniProtKB/TrEMBL

B4DW99

Conserved Domains (2) summary

COG5126
Location:48 → 206

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

cd00051
Location:135 → 206

EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
XM_017016161.2 → XP_016871650.1 Kv channel-interacting protein 2 isoform X5

UniProtKB/TrEMBL

A0A2R8Y6D7, Q09MK0

Related

ENSP00000495474.1, ENST00000642874.1

Conserved Domains (1) summary

COG5126
Location:53 → 219

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

Alternate T2T-CHM13v2.0

Genomic

NC_060934.1 Alternate T2T-CHM13v2.0

Range

102709458..102727289 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054365684.1 → XP_054221659.1 Kv channel-interacting protein 2 isoform X4
XM_054365683.1 → XP_054221658.1 Kv channel-interacting protein 2 isoform X3
XM_054365682.1 → XP_054221657.1 Kv channel-interacting protein 2 isoform X2
XM_054365681.1 → XP_054221656.1 Kv channel-interacting protein 2 isoform X1
XM_054365685.1 → XP_054221660.1 Kv channel-interacting protein 2 isoform X5

UniProtKB/TrEMBL

A0A2R8Y6D7

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_173342.2: Suppressed sequence

Description

NM_173342.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.