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Protein

KN motif and ankyrin repeat domain-containing protein 2

Gene

KANK2

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

Functioni

Involved in transcription regulation by sequestering nuclear receptor coactivators, such as NCOA1, NCOA2 and NCOA3, in the cytoplasm; the function is deregulated by phosphorylation. Involved in the negative control of vitamin D receptor signaling pathway (PubMed:24671081). May be involved in the control of cytoskeleton formation by regulating actin polymerization. Involved in regulation of caspase-independent apoptosis; proposed to sequester AIFM1 in mitochondria and apoptotic stimuli lead to its proteasomal degradation allowing the release of AIFM1 to the nucleus (PubMed:22371500). May be involved in promotion of cell proliferation (By similarity).By similarity3 Publications

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
  • negative regulation of intracellular estrogen receptor signaling pathway Source: UniProtKB
  • negative regulation of programmed cell death Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of vitamin D receptor signaling pathway Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
KN motif and ankyrin repeat domain-containing protein 2
Alternative name(s):
Ankyrin repeat domain-containing protein 25
Matrix-remodeling-associated protein 3
SRC-1-interacting protein
Short name:
SIP
Short name:
SRC-interacting protein
Short name:
SRC1-interacting protein
Gene namesi
Name:KANK2
Synonyms:ANKRD25, KIAA1518, MXRA3, SIP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:29300. KANK2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Palmoplantar keratoderma and woolly hair (PPKWH)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe.
See also OMIM:616099
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072431670A → V in PPKWH. 1 PublicationCorresponds to variant rs606231303dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi510 – 512SSS → AAA: Impairs phosphorylation; when associated with A-515. 1 Publication3
Mutagenesisi515S → A: Impairs phosphorylation; when associated with 510-A--A-512. 1 Publication1

Keywords - Diseasei

Disease mutation, Palmoplantar keratoderma

Organism-specific databases

DisGeNETi25959.
MalaCardsiKANK2.
MIMi616099. phenotype.
OpenTargetsiENSG00000197256.
PharmGKBiPA162392581.

Polymorphism and mutation databases

BioMutaiKANK2.
DMDMi74757262.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002408401 – 851KN motif and ankyrin repeat domain-containing protein 2Add BLAST851

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19PhosphoserineCombined sources1
Modified residuei83PhosphoserineBy similarity1
Modified residuei86PhosphoserineBy similarity1
Modified residuei89PhosphoserineBy similarity1
Modified residuei92PhosphoserineCombined sources1
Modified residuei105Omega-N-methylarginineCombined sources1
Modified residuei168PhosphothreonineBy similarity1
Modified residuei323PhosphoserineCombined sources1
Modified residuei329PhosphothreonineCombined sources1
Modified residuei356PhosphoserineCombined sources1
Modified residuei375PhosphoserineCombined sources1
Modified residuei472PhosphothreonineCombined sources1
Modified residuei540PhosphoserineCombined sources1
Modified residuei552PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated by CaMK2 upon estrogen stimulation.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ63ZY3.
MaxQBiQ63ZY3.
PaxDbiQ63ZY3.
PeptideAtlasiQ63ZY3.
PRIDEiQ63ZY3.

PTM databases

iPTMnetiQ63ZY3.
PhosphoSitePlusiQ63ZY3.

Expressioni

Tissue specificityi

Strongly expressed in cervix, colon, heart, kidney and lung. Expressed in kidney glomerular podocytes and mesangial cells (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000197256.
CleanExiHS_KANK2.
ExpressionAtlasiQ63ZY3. baseline and differential.
GenevisibleiQ63ZY3. HS.

Organism-specific databases

HPAiHPA015643.

Interactioni

Subunit structurei

Interacts (phosphorylated) with NCOA1; NCOA2 AND NCOA3. Interacts with AIFM1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABI3Q9P2A45EBI-2556193,EBI-742038
AESQ081173EBI-2556193,EBI-717810
AIFM1O958314EBI-6244894,EBI-356440
CCDC36Q8IYA85EBI-2556193,EBI-8638439
CEP70Q8NHQ15EBI-2556193,EBI-739624
DYNLL1P631675EBI-2556193,EBI-349105
EIF4EP067305EBI-2556193,EBI-73440
FHL2Q141923EBI-2556193,EBI-701903
GOLGA2Q083794EBI-2556193,EBI-618309
GPSM1Q86YR5-33EBI-2556193,EBI-10261098
LMO1P258005EBI-2556193,EBI-8639312
LMO2P257913EBI-2556193,EBI-739696
LMO4P619685EBI-2556193,EBI-2798728
MAGEB4O154815EBI-2556193,EBI-751857
MOB1AQ9H8S95EBI-2556193,EBI-748229
NCOA1Q157884EBI-2556193,EBI-455189
RALBP1Q153114EBI-2556193,EBI-749285
STACQ8WUK83EBI-2556193,EBI-10276615
TXLNAP402225EBI-2556193,EBI-359793
VPS52Q8N1B43EBI-2556193,EBI-2799833

Protein-protein interaction databases

BioGridi117449. 54 interactors.
IntActiQ63ZY3. 164 interactors.
MINTiMINT-4540700.
STRINGi9606.ENSP00000395650.

Structurei

Secondary structure

1851
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi592 – 606Combined sources15
Helixi613 – 632Combined sources20
Helixi638 – 651Combined sources14
Helixi653 – 660Combined sources8
Helixi670 – 676Combined sources7
Helixi680 – 688Combined sources9
Helixi704 – 707Combined sources4
Helixi708 – 710Combined sources3
Helixi716 – 728Combined sources13
Turni736 – 738Combined sources3
Helixi742 – 748Combined sources7
Helixi752 – 760Combined sources9
Helixi775 – 782Combined sources8
Helixi785 – 792Combined sources8
Helixi809 – 816Combined sources8
Helixi819 – 828Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HBDX-ray1.72A578-832[»]
ProteinModelPortaliQ63ZY3.
SMRiQ63ZY3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati666 – 696ANK 1Add BLAST31
Repeati700 – 733ANK 2Add BLAST34
Repeati738 – 767ANK 3Add BLAST30
Repeati771 – 801ANK 4Add BLAST31
Repeati805 – 835ANK 5Add BLAST31

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 72Interaction with AIFM11 PublicationAdd BLAST72
Regioni669 – 835Interaction with NCOA11 PublicationAdd BLAST167

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili183 – 234Sequence analysisAdd BLAST52
Coiled coili282 – 312Sequence analysisAdd BLAST31

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi425 – 428Poly-Ser4

Sequence similaritiesi

Contains 5 ANK repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG0514. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00530000063448.
HOVERGENiHBG062256.
InParanoidiQ63ZY3.
OMAiLHVPAPF.
OrthoDBiEOG091G0D3F.
PhylomeDBiQ63ZY3.
TreeFamiTF324499.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR021939. KN_motif.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF12075. KN_motif. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q63ZY3-1) [UniParc]FASTAAdd to basket

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
MAQVLHVPAP FPGTPGPASP PAFPAKDPDP PYSVETPYGY RLDLDFLKYV
60 70 80 90 100
DDIEKGHTLR RVAVQRRPRL SSLPRGPGSW WTSTESLCSN ASGDSRHSAY
110 120 130 140 150
SYCGRGFYPQ YGALETRGGF NPRVERTLLD ARRRLEDQAA TPTGLGSLTP
160 170 180 190 200
SAAGSTASLV GVGLPPPTPR SSGLSTPVPP SAGHLAHVRE QMAGALRKLR
210 220 230 240 250
QLEEQVKLIP VLQVKLSVLQ EEKRQLTVQL KSQKFLGHPT AGRGRSELCL
260 270 280 290 300
DLPDPPEDPV ALETRSVGTW VRERDLGMPD GEAALAAKVA VLETQLKKAL
310 320 330 340 350
QELQAAQARQ ADPQPQAWPP PDSPVRVDTV RVVEGPREVE VVASTAAGAP
360 370 380 390 400
AQRAQSLEPY GTGLRALAMP GRPESPPVFR SQEVVETMCP VPAAATSNVH
410 420 430 440 450
MVKKISITER SCDGAAGLPE VPAESSSSPP GSEVASLTQP EKSTGRVPTQ
460 470 480 490 500
EPTHREPTRQ AASQESEEAG GTGGPPAGVR SIMKRKEEVA DPTAHRRSLQ
510 520 530 540 550
FVGVNGGYES SSEDSSTAEN ISDNDSTENE APEPRERVPS VAEAPQLRPA
560 570 580 590 600
GTAAAKTSRQ ECQLSRESQH IPTAEGASGS NTEEEIRMEL SPDLISACLA
610 620 630 640 650
LEKYLDNPNA LTERELKVAY TTVLQEWLRL ACRSDAHPEL VRRHLVTFRA
660 670 680 690 700
MSARLLDYVV NIADSNGNTA LHYSVSHANF PVVQQLLDSG VCKVDKQNRA
710 720 730 740 750
GYSPIMLTAL ATLKTQDDIE TVLQLFRLGN INAKASQAGQ TALMLAVSHG
760 770 780 790 800
RVDVVKALLA CEADVNVQDD DGSTALMCAC EHGHKEIAGL LLAVPSCDIS
810 820 830 840 850
LTDRDGSTAL MVALDAGQSE IASMLYSRMN IKCSFAPMSD DESPTSSSAE

E
Length:851
Mass (Da):91,174
Last modified:October 25, 2004 - v1
Checksum:iC14CD8B937A7B6E8
GO
Isoform 2 (identifier: Q63ZY3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     472-472: T → TAPPLSSPP

Note: No experimental confirmation available.
Show »
Length:859
Mass (Da):91,921
Checksum:i0629BE4E0E29FCEE
GO
Isoform 3 (identifier: Q63ZY3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     835-841: FAPMSDD → VSLNPAG
     842-851: Missing.

Note: No experimental confirmation available.
Show »
Length:841
Mass (Da):90,044
Checksum:iD82155CD26E514F1
GO

Sequence cautioni

The sequence BAA92081 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA96042 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB14531 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti525D → N in BAA96042 (PubMed:10819331).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048304118G → S.Corresponds to variant rs755237dbSNPEnsembl.1
Natural variantiVAR_048305401M → T.Corresponds to variant rs17616661dbSNPEnsembl.1
Natural variantiVAR_072431670A → V in PPKWH. 1 PublicationCorresponds to variant rs606231303dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_019427472T → TAPPLSSPP in isoform 2. 1 Publication1
Alternative sequenceiVSP_019428835 – 841FAPMSDD → VSLNPAG in isoform 3. 1 Publication7
Alternative sequenceiVSP_019429842 – 851Missing in isoform 3. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY639929 mRNA. Translation: AAT57879.1.
AB284125 mRNA. Translation: BAG06864.1.
AB040951 mRNA. Translation: BAA96042.2. Different initiation.
CH471106 Genomic DNA. Translation: EAW84177.1.
BC082762 mRNA. Translation: AAH82762.1.
BC098105 mRNA. Translation: AAH98105.1.
BC098286 mRNA. Translation: AAH98286.1.
BC098312 mRNA. Translation: AAH98312.1.
BC105989 mRNA. Translation: AAI05990.1.
AK002094 mRNA. Translation: BAA92081.1. Different initiation.
AK023332 mRNA. Translation: BAB14531.1. Different initiation.
CCDSiCCDS12255.1. [Q63ZY3-1]
CCDS54219.1. [Q63ZY3-2]
RefSeqiNP_001129663.1. NM_001136191.2. [Q63ZY3-1]
NP_001316380.1. NM_001329451.1. [Q63ZY3-1]
NP_056308.3. NM_015493.6. [Q63ZY3-2]
UniGeneiHs.284208.
Hs.723365.
Hs.744940.

Genome annotation databases

EnsembliENST00000586659; ENSP00000465650; ENSG00000197256. [Q63ZY3-1]
ENST00000589359; ENSP00000468002; ENSG00000197256. [Q63ZY3-2]
ENST00000589894; ENSP00000467029; ENSG00000197256. [Q63ZY3-3]
GeneIDi25959.
KEGGihsa:25959.
UCSCiuc002mqo.5. human. [Q63ZY3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY639929 mRNA. Translation: AAT57879.1.
AB284125 mRNA. Translation: BAG06864.1.
AB040951 mRNA. Translation: BAA96042.2. Different initiation.
CH471106 Genomic DNA. Translation: EAW84177.1.
BC082762 mRNA. Translation: AAH82762.1.
BC098105 mRNA. Translation: AAH98105.1.
BC098286 mRNA. Translation: AAH98286.1.
BC098312 mRNA. Translation: AAH98312.1.
BC105989 mRNA. Translation: AAI05990.1.
AK002094 mRNA. Translation: BAA92081.1. Different initiation.
AK023332 mRNA. Translation: BAB14531.1. Different initiation.
CCDSiCCDS12255.1. [Q63ZY3-1]
CCDS54219.1. [Q63ZY3-2]
RefSeqiNP_001129663.1. NM_001136191.2. [Q63ZY3-1]
NP_001316380.1. NM_001329451.1. [Q63ZY3-1]
NP_056308.3. NM_015493.6. [Q63ZY3-2]
UniGeneiHs.284208.
Hs.723365.
Hs.744940.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HBDX-ray1.72A578-832[»]
ProteinModelPortaliQ63ZY3.
SMRiQ63ZY3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117449. 54 interactors.
IntActiQ63ZY3. 164 interactors.
MINTiMINT-4540700.
STRINGi9606.ENSP00000395650.

PTM databases

iPTMnetiQ63ZY3.
PhosphoSitePlusiQ63ZY3.

Polymorphism and mutation databases

BioMutaiKANK2.
DMDMi74757262.

Proteomic databases

EPDiQ63ZY3.
MaxQBiQ63ZY3.
PaxDbiQ63ZY3.
PeptideAtlasiQ63ZY3.
PRIDEiQ63ZY3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000586659; ENSP00000465650; ENSG00000197256. [Q63ZY3-1]
ENST00000589359; ENSP00000468002; ENSG00000197256. [Q63ZY3-2]
ENST00000589894; ENSP00000467029; ENSG00000197256. [Q63ZY3-3]
GeneIDi25959.
KEGGihsa:25959.
UCSCiuc002mqo.5. human. [Q63ZY3-1]

Organism-specific databases

CTDi25959.
DisGeNETi25959.
GeneCardsiKANK2.
HGNCiHGNC:29300. KANK2.
HPAiHPA015643.
MalaCardsiKANK2.
MIMi614610. gene.
616099. phenotype.
neXtProtiNX_Q63ZY3.
OpenTargetsiENSG00000197256.
PharmGKBiPA162392581.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0514. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00530000063448.
HOVERGENiHBG062256.
InParanoidiQ63ZY3.
OMAiLHVPAPF.
OrthoDBiEOG091G0D3F.
PhylomeDBiQ63ZY3.
TreeFamiTF324499.

Miscellaneous databases

GeneWikiiANKRD25.
GenomeRNAii25959.
PROiQ63ZY3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197256.
CleanExiHS_KANK2.
ExpressionAtlasiQ63ZY3. baseline and differential.
GenevisibleiQ63ZY3. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR021939. KN_motif.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF12075. KN_motif. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKANK2_HUMAN
AccessioniPrimary (citable) accession number: Q63ZY3
Secondary accession number(s): B0I1P4
, Q3KQZ3, Q6GUF5, Q9H8S4, Q9NUP0, Q9P210
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: October 25, 2004
Last modified: November 30, 2016
This is version 123 of the entry and version 1 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.