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Protein

Kelch-like protein 2

Gene

KLHL2

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

Functioni

Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation (By similarity). Responsible for degradative ubiquitination of the WNK kinases WNK1, WNK3 and WNK4. Plays a role in the reorganization of the actin cytoskeleton. Promotes growth of cell projections in oligodendrocyte precursors.By similarity2 Publications

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • identical protein binding Source: IntAct

GO - Biological processi

Keywordsi

Molecular functionActin-binding
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like protein 2
Alternative name(s):
Actin-binding protein Mayven
Gene namesi
Name:KLHL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000109466.13
HGNCiHGNC:6353 KLHL2
MIMi605774 gene
neXtProtiNX_O95198

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 projection, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Organism-specific databases

DisGeNETi11275
OpenTargetsiENSG00000109466
PharmGKBiPA30143

Polymorphism and mutation databases

BioMutaiKLHL2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001191011 – 593Kelch-like protein 2Add BLAST593

Proteomic databases

EPDiO95198
PaxDbiO95198
PeptideAtlasiO95198
PRIDEiO95198
ProteomicsDBi50705
50706 [O95198-2]

PTM databases

iPTMnetiO95198
PhosphoSitePlusiO95198

Expressioni

Tissue specificityi

Ubiquitous. Detected throughout the brain.1 Publication

Gene expression databases

BgeeiENSG00000109466 Expressed in 223 organ(s), highest expression level in brain
CleanExiHS_KLHL2
ExpressionAtlasiO95198 baseline and differential
GenevisibleiO95198 HS

Organism-specific databases

HPAiHPA051637

Interactioni

Subunit structurei

Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Interacts with NPTXR and CUL3 (By similarity). Binds actin. Interacts with KLHL12. Interacts (via N-terminus) with FYN (via SH3 domain).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116431, 75 interactors
ELMiO95198
IntActiO95198, 29 interactors
MINTiO95198
STRINGi9606.ENSP00000424198

Structurei

Secondary structure

1593
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95198
SMRiO95198
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95198

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 123BTBPROSITE-ProRule annotationAdd BLAST68
Repeati308 – 353Kelch 1Add BLAST46
Repeati354 – 400Kelch 2Add BLAST47
Repeati402 – 447Kelch 3Add BLAST46
Repeati449 – 496Kelch 4Add BLAST48
Repeati497 – 543Kelch 5Add BLAST47
Repeati545 – 591Kelch 6Add BLAST47

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00760000118931
HOGENOMiHOG000230814
HOVERGENiHBG014286
InParanoidiO95198
KOiK10443
OMAiNMQDRRS
OrthoDBiEOG091G04QJ
PhylomeDBiO95198
TreeFamiTF329218

Family and domain databases

Gene3Di2.120.10.80, 1 hit
InterProiView protein in InterPro
IPR011705 BACK
IPR017096 BTB-kelch_protein
IPR000210 BTB/POZ_dom
IPR015915 Kelch-typ_b-propeller
IPR006652 Kelch_1
IPR011333 SKP1/BTB/POZ_sf
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits
PIRSFiPIRSF037037 Kelch-like_protein_gigaxonin, 1 hit
SMARTiView protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits
SUPFAMiSSF117281 SSF117281, 1 hit
SSF54695 SSF54695, 1 hit
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O95198-1) [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
METPPLPPAC TKQGHQKPLD SKDDNTEKHC PVTVNPWHMK KAFKVMNELR
60 70 80 90 100
SQNLLCDVTI VAEDMEISAH RVVLAACSPY FHAMFTGEMS ESRAKRVRIK
110 120 130 140 150
EVDGWTLRML IDYVYTAEIQ VTEENVQVLL PAAGLLQLQD VKKTCCEFLE
160 170 180 190 200
SQLHPVNCLG IRAFADMHAC TDLLNKANTY AEQHFADVVL SEEFLNLGIE
210 220 230 240 250
QVCSLISSDK LTISSEEKVF EAVIAWVNHD KDVRQEFMAR LMEHVRLPLL
260 270 280 290 300
PREYLVQRVE EEALVKNSSA CKDYLIEAMK YHLLPTEQRI LMKSVRTRLR
310 320 330 340 350
TPMNLPKLMV VVGGQAPKAI RSVECYDFKE ERWHQVAELP SRRCRAGMVY
360 370 380 390 400
MAGLVFAVGG FNGSLRVRTV DSYDPVKDQW TSVANMRDRR STLGAAVLNG
410 420 430 440 450
LLYAVGGFDG STGLSSVEAY NIKSNEWFHV APMNTRRSSV GVGVVGGLLY
460 470 480 490 500
AVGGYDGASR QCLSTVECYN ATTNEWTYIA EMSTRRSGAG VGVLNNLLYA
510 520 530 540 550
VGGHDGPLVR KSVEVYDPTT NAWRQVADMN MCRRNAGVCA VNGLLYVVGG
560 570 580 590
DDGSCNLASV EYYNPTTDKW TVVSSCMSTG RSYAGVTVID KPL
Length:593
Mass (Da):65,975
Last modified:September 27, 2004 - v2
Checksum:i397AE02E69E56A18
GO
Isoform 2 (identifier: O95198-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: METPPLPPA → MVWLEARPQILFV

Note: No experimental confirmation available.
Show »
Length:597
Mass (Da):66,624
Checksum:iAFF604F55F423755
GO
Isoform 3 (identifier: O95198-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-88: Missing.

Note: Gene prediction based on EST data.
Show »
Length:505
Mass (Da):56,086
Checksum:i9CB9E11BFCA6DCFD
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PEX9E9PEX9_HUMAN
Kelch-like protein 2
KLHL2
496Annotation score:
B4DFZ5B4DFZ5_HUMAN
cDNA FLJ60241, highly similar to Ke...
KLHL2
427Annotation score:
D6RGC3D6RGC3_HUMAN
Kelch-like protein 2
KLHL2
117Annotation score:
D6R9G5D6R9G5_HUMAN
Kelch-like protein 2
KLHL2
144Annotation score:
D6RAP5D6RAP5_HUMAN
Kelch-like protein 2
KLHL2
55Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti273D → N in AAC67502 (PubMed:10397770).Curated1
Sequence conflicti342R → G in AAH36468 (PubMed:15489334).Curated1
Sequence conflicti457G → V in AAH22503 (PubMed:15489334).Curated1
Sequence conflicti462C → Y in AAC67502 (PubMed:10397770).Curated1
Sequence conflicti592P → R in BAG37765 (PubMed:14702039).Curated1
Sequence conflicti592P → R in AAH22503 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0470041 – 88Missing in isoform 3. CuratedAdd BLAST88
Alternative sequenceiVSP_0428371 – 9METPPLPPA → MVWLEARPQILFV in isoform 2. 1 Publication9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF059569 mRNA Translation: AAC67502.1
AK294103 mRNA Translation: BAG57438.1
AK315372 mRNA Translation: BAG37765.1
AC012504 Genomic DNA No translation available.
AC055120 Genomic DNA No translation available.
AC107059 Genomic DNA No translation available.
BC022503 mRNA Translation: AAH22503.1
BC036468 mRNA Translation: AAH36468.1
CCDSiCCDS34094.1 [O95198-1]
CCDS54815.1 [O95198-2]
CCDS54816.1 [O95198-3]
RefSeqiNP_001154993.1, NM_001161521.1 [O95198-2]
NP_001154994.1, NM_001161522.1 [O95198-3]
NP_001317952.1, NM_001331023.1
NP_001317953.1, NM_001331024.1
NP_009177.3, NM_007246.3 [O95198-1]
XP_016863165.1, XM_017007676.1 [O95198-3]
UniGeneiHs.388668

Genome annotation databases

EnsembliENST00000226725; ENSP00000226725; ENSG00000109466 [O95198-1]
ENST00000514860; ENSP00000424198; ENSG00000109466 [O95198-2]
ENST00000538127; ENSP00000437526; ENSG00000109466 [O95198-3]
GeneIDi11275
KEGGihsa:11275
UCSCiuc003irb.4 human [O95198-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF059569 mRNA Translation: AAC67502.1
AK294103 mRNA Translation: BAG57438.1
AK315372 mRNA Translation: BAG37765.1
AC012504 Genomic DNA No translation available.
AC055120 Genomic DNA No translation available.
AC107059 Genomic DNA No translation available.
BC022503 mRNA Translation: AAH22503.1
BC036468 mRNA Translation: AAH36468.1
CCDSiCCDS34094.1 [O95198-1]
CCDS54815.1 [O95198-2]
CCDS54816.1 [O95198-3]
RefSeqiNP_001154993.1, NM_001161521.1 [O95198-2]
NP_001154994.1, NM_001161522.1 [O95198-3]
NP_001317952.1, NM_001331023.1
NP_001317953.1, NM_001331024.1
NP_009177.3, NM_007246.3 [O95198-1]
XP_016863165.1, XM_017007676.1 [O95198-3]
UniGeneiHs.388668

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XN4X-ray1.99A/B294-591[»]
4CHBX-ray1.56A/B294-591[»]
ProteinModelPortaliO95198
SMRiO95198
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116431, 75 interactors
ELMiO95198
IntActiO95198, 29 interactors
MINTiO95198
STRINGi9606.ENSP00000424198

PTM databases

iPTMnetiO95198
PhosphoSitePlusiO95198

Polymorphism and mutation databases

BioMutaiKLHL2

Proteomic databases

EPDiO95198
PaxDbiO95198
PeptideAtlasiO95198
PRIDEiO95198
ProteomicsDBi50705
50706 [O95198-2]

Protocols and materials databases

DNASUi11275
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000226725; ENSP00000226725; ENSG00000109466 [O95198-1]
ENST00000514860; ENSP00000424198; ENSG00000109466 [O95198-2]
ENST00000538127; ENSP00000437526; ENSG00000109466 [O95198-3]
GeneIDi11275
KEGGihsa:11275
UCSCiuc003irb.4 human [O95198-1]

Organism-specific databases

CTDi11275
DisGeNETi11275
EuPathDBiHostDB:ENSG00000109466.13
GeneCardsiKLHL2
H-InvDBiHIX0004470
HIX0022043
HGNCiHGNC:6353 KLHL2
HPAiHPA051637
MIMi605774 gene
neXtProtiNX_O95198
OpenTargetsiENSG00000109466
PharmGKBiPA30143
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00760000118931
HOGENOMiHOG000230814
HOVERGENiHBG014286
InParanoidiO95198
KOiK10443
OMAiNMQDRRS
OrthoDBiEOG091G04QJ
PhylomeDBiO95198
TreeFamiTF329218

Enzyme and pathway databases

ReactomeiR-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

ChiTaRSiKLHL2 human
EvolutionaryTraceiO95198
GenomeRNAii11275
PROiPR:O95198
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109466 Expressed in 223 organ(s), highest expression level in brain
CleanExiHS_KLHL2
ExpressionAtlasiO95198 baseline and differential
GenevisibleiO95198 HS

Family and domain databases

Gene3Di2.120.10.80, 1 hit
InterProiView protein in InterPro
IPR011705 BACK
IPR017096 BTB-kelch_protein
IPR000210 BTB/POZ_dom
IPR015915 Kelch-typ_b-propeller
IPR006652 Kelch_1
IPR011333 SKP1/BTB/POZ_sf
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits
PIRSFiPIRSF037037 Kelch-like_protein_gigaxonin, 1 hit
SMARTiView protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits
SUPFAMiSSF117281 SSF117281, 1 hit
SSF54695 SSF54695, 1 hit
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKLHL2_HUMAN
AccessioniPrimary (citable) accession number: O95198
Secondary accession number(s): A6NCM7
, B2RD18, B4DFH7, F5H6M3, Q8N484, Q8TBH5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: September 27, 2004
Last modified: November 7, 2018
This is version 157 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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