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Protein

Kv channel-interacting protein 2

Gene

KCNIP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Modulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND2/Kv4.2 and KCND3/Kv4.3 currents. Involved in KCND2 and KCND3 trafficking to the cell surface. May be required for the expression of I(To) currents in the heart (By similarity).By similarity6 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi189 – 2001PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi237 – 2482PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

  • A-type (transient outward) potassium channel activity Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • ER retention sequence binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • ion channel binding Source: BHF-UCL
  • potassium channel regulator activity Source: BHF-UCL
  • protein N-terminus binding Source: UniProtKB

GO - Biological processi

  • cardiac conduction Source: Reactome
  • chemical synaptic transmission Source: ProtInc
  • clustering of voltage-gated potassium channels Source: UniProtKB
  • detection of calcium ion Source: ProtInc
  • membrane repolarization Source: BHF-UCL
  • membrane repolarization during cardiac muscle cell action potential Source: BHF-UCL
  • muscle contraction Source: UniProtKB
  • potassium ion export Source: BHF-UCL
  • potassium ion export across plasma membrane Source: BHF-UCL
  • potassium ion transmembrane transport Source: BHF-UCL
  • potassium ion transport Source: UniProtKB
  • regulation of cation channel activity Source: BHF-UCL
  • regulation of heart contraction Source: UniProtKB
  • regulation of potassium ion transmembrane transport Source: UniProtKB
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionIon channel, Potassium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Transport
LigandCalcium, Metal-binding, Potassium

Enzyme and pathway databases

ReactomeiR-HSA-5576894. Phase 1 - inactivation of fast Na+ channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Kv channel-interacting protein 2
Short name:
KChIP21 Publication
Alternative name(s):
A-type potassium channel modulatory protein 2
Cardiac voltage-gated potassium channel modulatory subunit
Potassium channel-interacting protein 2
Gene namesi
Name:KCNIP2
Synonyms:KCHIP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000120049.18.
HGNCiHGNC:15522. KCNIP2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi30819.
OpenTargetsiENSG00000120049.
PharmGKBiPA30042.

Polymorphism and mutation databases

BioMutaiKCNIP2.
DMDMi338817979.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000738211 – 270Kv channel-interacting protein 2Add BLAST270

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei9PhosphoserineBy similarity1
Lipidationi45S-palmitoyl cysteineBy similarity1
Lipidationi46S-palmitoyl cysteineBy similarity1

Post-translational modificationi

Palmitoylated. Palmitoylation enhances association with the plasma membrane.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PeptideAtlasiQ9NS61.
PRIDEiQ9NS61.

PTM databases

iPTMnetiQ9NS61.
PhosphoSitePlusiQ9NS61.

Expressioni

Tissue specificityi

Expressed in brain. Colocalizes with KCND2 in excitatory neurons including cortical and hippocampal CA1 pyramidal cells. Isoform 3 is expressed in heart and in umbilical vein endothelial cells. Not expressed in fetal heart.3 Publications

Gene expression databases

BgeeiENSG00000120049.
ExpressionAtlasiQ9NS61. baseline and differential.
GenevisibleiQ9NS61. HS.

Organism-specific databases

HPAiHPA066717.

Interactioni

Subunit structurei

Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). The KCND2-KCNIP2 channel complex contains four KCND2 and four KCNIP2 subunits (PubMed:14623880, PubMed:14980201). Interacts with KCND2 (PubMed:10676964, PubMed:14623880, PubMed:14980201). Isoform 1 and isoform 3 interact with KCND3 isoform 1. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. At least isoform 2 and isoform 3 can self-associate to form homodimers and homotetramers. Isoform 3 interacts with KCNIP1 in a calcium-dependent manner.By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • ion channel binding Source: BHF-UCL
  • protein N-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi119043. 11 interactors.
IntActiQ9NS61. 3 interactors.
MINTiMINT-4712078.

Structurei

3D structure databases

ProteinModelPortaliQ9NS61.
SMRiQ9NS61.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 137EF-hand 1; degeneratePROSITE-ProRule annotationAdd BLAST57
Domaini140 – 175EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini176 – 211EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini224 – 259EF-hand 4PROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni257 – 270Interaction with KCND2By similarityAdd BLAST14

Sequence similaritiesi

Belongs to the recoverin family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

GeneTreeiENSGT00760000118820.
HOVERGENiHBG108179.
InParanoidiQ9NS61.
OMAiMNRCPRR.
OrthoDBiEOG091G11T4.
TreeFamiTF318560.

Family and domain databases

CDDicd00051. EFh. 2 hits.
InterProiView protein in InterPro
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR029532. KCNIP2.
PANTHERiPTHR23055:SF133. PTHR23055:SF133. 1 hit.
PfamiView protein in Pfam
PF13499. EF-hand_7. 1 hit.
PF13833. EF-hand_8. 1 hit.
SMARTiView protein in SMART
SM00054. EFh. 3 hits.
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiView protein in PROSITE
PS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 3 hits.

Sequences (9)i

Sequence statusi: Complete.

This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NS61-1) [UniParc]FASTAAdd to basket
Also known as: KChIP2a, KChIP2b, KCHIP2.4, KCHIP2L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRGQGRKESL SDSRDLDGSY DQLTGHPPGP TKKALKQRFL KLLPCCGPQA
60 70 80 90 100
LPSVSETLAA PASLRPHRPR LLDPDSVDDE FELSTVCHRP EGLEQLQEQT
110 120 130 140 150
KFTRKELQVL YRGFKNECPS GIVNEENFKQ IYSQFFPQGD SSTYATFLFN
160 170 180 190 200
AFDTNHDGSV SFEDFVAGLS VILRGTVDDR LNWAFNLYDL NKDGCITKEE
210 220 230 240 250
MLDIMKSIYD MMGKYTYPAL REEAPREHVE SFFQKMDRNK DGVVTIEEFI
260 270
ESCQKDENIM RSMQLFDNVI
Length:270
Mass (Da):30,907
Last modified:June 28, 2011 - v3
Checksum:iB75AD02B9E273243
GO
Isoform 2 (identifier: Q9NS61-2) [UniParc]FASTAAdd to basket
Also known as: 3, KChIP2.1, KChIP2b

The sequence of this isoform differs from the canonical sequence as follows:
     57-75: TLAAPASLRPHRPRLLDPD → N

Show »
Length:252
Mass (Da):28,943
Checksum:i7502F0C69D2B35FE
GO
Isoform 3 (identifier: Q9NS61-3) [UniParc]FASTAAdd to basket
Also known as: 2, KChIP2.2, KChIP2c, KCHIP2S

The sequence of this isoform differs from the canonical sequence as follows:
     25-74: Missing.

Show »
Length:220
Mass (Da):25,562
Checksum:i52FD8C601356338F
GO
Isoform 4 (identifier: Q9NS61-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MRGQGRKESL...LRPHRPRLLD → MNRCPRRCRSPLGQAARSLYQLVTGSLS

Show »
Length:225
Mass (Da):26,066
Checksum:i7919AFDD3A5FACF1
GO
Isoform 5 (identifier: Q9NS61-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     25-74: Missing.
     160-163: Missing.

Show »
Length:216
Mass (Da):25,100
Checksum:iEDDF7A3B16108F08
GO
Isoform 6 (identifier: Q9NS61-6) [UniParc]FASTAAdd to basket
Also known as: KCHIP4.2

The sequence of this isoform differs from the canonical sequence as follows:
     57-57: T → IGRVFRFLGDSSLPSA

Show »
Length:285
Mass (Da):32,510
Checksum:i38A62414577BCF49
GO
Isoform 7 (identifier: Q9NS61-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     25-74: Missing.
     116-116: N → NPGALSFQ

Show »
Length:227
Mass (Da):26,263
Checksum:i7F1D2B8E7F85D8B9
GO
Isoform 8 (identifier: Q9NS61-8) [UniParc]FASTAAdd to basket
Also known as: KCHIP2.6

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: Missing.
     94-162: EQLQEQTKFT...DTNHDGSVSF → MWLSWTAWTM...SRFTPSSFLK

Show »
Length:177
Mass (Da):20,482
Checksum:i8CF26C549F293353
GO
Isoform 9 (identifier: Q9NS61-9) [UniParc]FASTAAdd to basket
Also known as: KCHIP2.5

The sequence of this isoform differs from the canonical sequence as follows:
     25-74: Missing.
     163-198: Missing.
     256-270: DENIMRSMQLFDNVI → VQLPALYITLTWTQA

Show »
Length:184
Mass (Da):21,401
Checksum:i4B810CA98F45A052
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti50A → V in BAA96740 (PubMed:11263977).Curated1
Sequence conflicti71L → P in BAA96740 (PubMed:11263977).Curated1
Sequence conflicti75D → V in BAA96741 (PubMed:11263977).Curated1
Sequence conflicti76S → R in BAB55052 (PubMed:14702039).Curated1
Sequence conflicti78D → E in BAA96740 (PubMed:11263977).Curated1
Sequence conflicti83L → S in CAB66656 (PubMed:11230166).Curated1
Sequence conflicti224A → P in BAA96740 (PubMed:11263977).Curated1
Sequence conflicti224A → P in BAA96741 (PubMed:11263977).Curated1
Sequence conflicti239N → S in AAP57633 (Ref. 9) Curated1
Sequence conflicti246I → N in CAB66656 (PubMed:11230166).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0150491 – 93Missing in isoform 8. 1 PublicationAdd BLAST93
Alternative sequenceiVSP_0150501 – 73MRGQG…PRLLD → MNRCPRRCRSPLGQAARSLY QLVTGSLS in isoform 4. 3 PublicationsAdd BLAST73
Alternative sequenceiVSP_01505125 – 74Missing in isoform 3, isoform 5, isoform 7 and isoform 9. 10 PublicationsAdd BLAST50
Alternative sequenceiVSP_01505257 – 75TLAAP…LLDPD → N in isoform 2. 8 PublicationsAdd BLAST19
Alternative sequenceiVSP_01505357T → IGRVFRFLGDSSLPSA in isoform 6. 1 Publication1
Alternative sequenceiVSP_01505494 – 162EQLQE…GSVSF → MWLSWTAWTMNLNCPPCVTG LRVWSSCRSKPNSRARSCRS CTGASRTNVPAELSMRRTSS RFTPSSFLK in isoform 8. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_015055116N → NPGALSFQ in isoform 7. 1 Publication1
Alternative sequenceiVSP_015056160 – 163Missing in isoform 5. 1 Publication4
Alternative sequenceiVSP_015057163 – 198Missing in isoform 9. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_015058256 – 270DENIM…FDNVI → VQLPALYITLTWTQA in isoform 9. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF199598 mRNA. Translation: AAF33683.1.
AB044584 mRNA. Translation: BAA96740.1.
AB044585 mRNA. Translation: BAA96741.1.
AY026328 mRNA. Translation: AAK07674.1.
AY026331, AY026329, AY026330 Genomic DNA. Translation: AAK21972.1.
AF347114 mRNA. Translation: AAK70356.1.
AF295076 mRNA. Translation: AAG02120.1.
AF295530 mRNA. Translation: AAG02121.1.
AF367018 mRNA. Translation: AAK53707.1.
AF367019 mRNA. Translation: AAK53708.1.
AF367020 mRNA. Translation: AAK53709.1.
AF367021 mRNA. Translation: AAK53710.1.
DQ148480 mRNA. Translation: AAZ77797.1.
DQ148481 mRNA. Translation: AAZ77798.1.
DQ148483 mRNA. Translation: AAZ77800.1.
AL136722 mRNA. Translation: CAB66656.1.
AY302141 mRNA. Translation: AAP57633.1.
AK027347 mRNA. Translation: BAB55052.1.
AK315042 mRNA. Translation: BAG37523.1.
AC010789 Genomic DNA. No translation available.
CH471066 Genomic DNA. Translation: EAW49733.1.
BC034685 mRNA. Translation: AAH34685.1.
AJ276317 mRNA. Translation: CAB77054.1.
CCDSiCCDS41562.1. [Q9NS61-2]
CCDS7521.1. [Q9NS61-6]
CCDS7522.1. [Q9NS61-1]
CCDS7523.1. [Q9NS61-7]
CCDS7524.1. [Q9NS61-3]
CCDS7525.1. [Q9NS61-4]
CCDS7526.1. [Q9NS61-9]
RefSeqiNP_055406.2. NM_014591.4. [Q9NS61-6]
NP_775283.1. NM_173191.2. [Q9NS61-1]
NP_775284.1. NM_173192.2. [Q9NS61-2]
NP_775285.1. NM_173193.2. [Q9NS61-7]
NP_775286.1. NM_173194.2. [Q9NS61-4]
NP_775287.1. NM_173195.2. [Q9NS61-3]
NP_775289.1. NM_173197.2. [Q9NS61-9]
UniGeneiHs.97044.

Genome annotation databases

EnsembliENST00000239117; ENSP00000239117; ENSG00000120049. [Q9NS61-9]
ENST00000343195; ENSP00000344169; ENSG00000120049. [Q9NS61-3]
ENST00000348850; ENSP00000239118; ENSG00000120049. [Q9NS61-4]
ENST00000353068; ENSP00000341624; ENSG00000120049. [Q9NS61-7]
ENST00000356640; ENSP00000349055; ENSG00000120049. [Q9NS61-1]
ENST00000358038; ENSP00000350733; ENSG00000120049. [Q9NS61-2]
ENST00000434163; ENSP00000411679; ENSG00000120049. [Q9NS61-8]
ENST00000461105; ENSP00000420040; ENSG00000120049. [Q9NS61-6]
GeneIDi30819.
KEGGihsa:30819.
UCSCiuc001ktz.4. human. [Q9NS61-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKCIP2_HUMAN
AccessioniPrimary (citable) accession number: Q9NS61
Secondary accession number(s): A6NJE5
, A8MQ75, Q3YAC6, Q3YAC8, Q3YAC9, Q7Z6F1, Q96K86, Q96T41, Q96T42, Q96T43, Q96T44, Q9H0N4, Q9HD10, Q9HD11, Q9NS60, Q9NY10, Q9NZI1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: June 28, 2011
Last modified: September 27, 2017
This is version 148 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families