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Protein

Kelch-like protein 2

Gene

KLHL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Actin-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109466-MONOMER.
ReactomeiR-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

HGNCiHGNC:6353. KLHL2.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: UniProtKB
  • Cul3-RING ubiquitin ligase complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB-SubCell
  • lamellipodium Source: UniProtKB-SubCell
  • ruffle Source: UniProtKB-SubCell
Complete GO annotation...

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

PaxDbiO95198.
PRIDEiO95198.

PTM databases

iPTMnetiO95198.
PhosphoSitePlusiO95198.

Expressioni

Tissue specificityi

Ubiquitous. Detected throughout the brain.1 Publication

Gene expression databases

BgeeiENSG00000109466.
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

WithEntry#Exp.IntActNotes
itself3EBI-746999,EBI-746999
BCAMP508953EBI-746999,EBI-10212133
CCDC43Q86WV75EBI-746999,EBI-10260148
CCDC43Q96MW13EBI-746999,EBI-9247198
CLK2P497605EBI-746999,EBI-750020
CUL3Q136183EBI-746999,EBI-456129
KLHL12Q53G596EBI-746999,EBI-740929
SDCBPO005603EBI-746999,EBI-727004
TMA16Q96EY45EBI-746999,EBI-1045338
TNPO2O147873EBI-746999,EBI-431907
TXNDC12O958813EBI-746999,EBI-2564581
UBE2CQ5TZN33EBI-746999,EBI-10247554
ZNF114Q8NC265EBI-746999,EBI-10265237

GO - Molecular functioni

  • actin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116431. 68 interactors.
IntActiO95198. 26 interactors.
MINTiMINT-1463156.
STRINGi9606.ENSP00000424198.

Structurei

Secondary structure

1593
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi307 – 312Combined sources6
Beta strandi315 – 320Combined sources6
Beta strandi323 – 327Combined sources5
Turni328 – 331Combined sources4
Beta strandi332 – 335Combined sources4
Beta strandi343 – 345Combined sources3
Beta strandi347 – 351Combined sources5
Beta strandi354 – 358Combined sources5
Beta strandi363 – 366Combined sources4
Beta strandi370 – 374Combined sources5
Turni375 – 378Combined sources4
Beta strandi379 – 383Combined sources5
Beta strandi394 – 398Combined sources5
Beta strandi401 – 405Combined sources5
Beta strandi410 – 413Combined sources4
Beta strandi417 – 421Combined sources5
Turni422 – 425Combined sources4
Beta strandi426 – 430Combined sources5
Beta strandi441 – 445Combined sources5
Beta strandi448 – 452Combined sources5
Turni457 – 460Combined sources4
Beta strandi466 – 470Combined sources5
Turni471 – 474Combined sources4
Beta strandi475 – 478Combined sources4
Beta strandi490 – 494Combined sources5
Beta strandi497 – 501Combined sources5
Beta strandi504 – 509Combined sources6
Beta strandi513 – 516Combined sources4
Turni518 – 520Combined sources3
Beta strandi523 – 525Combined sources3
Beta strandi537 – 541Combined sources5
Beta strandi544 – 548Combined sources5
Beta strandi553 – 556Combined sources4
Beta strandi560 – 564Combined sources5
Turni565 – 568Combined sources4
Beta strandi569 – 572Combined sources4
Beta strandi585 – 590Combined sources6

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...

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

Sequence similaritiesi

Contains 1 BTB (POZ) domain.PROSITE-ProRule annotation
Contains 6 Kelch repeats.Curated

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di2.130.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015916. Gal_Oxidase_b-propeller.
IPR006652. Kelch_1.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 6 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 6 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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

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. 68 interactors.
IntActiO95198. 26 interactors.
MINTiMINT-1463156.
STRINGi9606.ENSP00000424198.

PTM databases

iPTMnetiO95198.
PhosphoSitePlusiO95198.

Polymorphism and mutation databases

BioMutaiKLHL2.

Proteomic databases

PaxDbiO95198.
PRIDEiO95198.

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.
GeneCardsiKLHL2.
H-InvDBHIX0004470.
HIX0022043.
HGNCiHGNC:6353. KLHL2.
HPAiHPA051637.
MIMi605774. gene.
neXtProtiNX_O95198.
OpenTargetsiENSG00000109466.
PharmGKBiPA30143.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109466-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

EvolutionaryTraceiO95198.
GenomeRNAii11275.
PROiO95198.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109466.
CleanExiHS_KLHL2.
ExpressionAtlasiO95198. baseline and differential.
GenevisibleiO95198. HS.

Family and domain databases

Gene3Di2.130.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015916. Gal_Oxidase_b-propeller.
IPR006652. Kelch_1.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 6 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 6 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKLHL2_HUMAN
AccessioniPrimary (citable) accession number: O95198
Secondary accession number(s): A6NCM7
, B2RD18, B4DFH7, F5H6M3, Q8N484, Q8TBH5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: September 27, 2004
Last modified: November 30, 2016
This is version 139 of the entry and version 2 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 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
  4. 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.