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Protein

Kelch-like protein 20

Gene

KLHL20

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

Functioni

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis (PubMed:20389280). The BCR(KLHL20) E3 ubiquitin ligase complex also specifically mediates 'Lys-33'-linked ubiquitination (PubMed:24768539). Involved in anterograde Golgi to endosome transport by mediating 'Lys-33'-linked ubiquitination of CORO7, promoting interaction between CORO7 and EPS15, thereby facilitating actin polymerization and post-Golgi trafficking (PubMed:24768539). Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. The BCR(KLHL20) E3 ubiquitin ligase complex acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11 (PubMed:21670212). In case of tumor, the BCR(KLHL20) E3 ubiquitin ligase complex is involved in tumor hypoxia: following hypoxia, the BCR(KLHL20)complex mediates ubiquitination and degradation of PML, potentiating HIF-1 signaling and cancer progression (PubMed:21840486).6 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • actin binding Source: UniProtKB-KW
  • interferon-gamma binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • cytoskeleton organization Source: ProtInc
  • Golgi to endosome transport Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • post-translational protein modification Source: Reactome
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein K33-linked ubiquitination Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • protein ubiquitination Source: UniProtKB
  • response to interferon-alpha Source: UniProtKB

Keywordsi

Molecular functionActin-binding
Biological processProtein transport, Transport, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like protein 20
Alternative name(s):
Kelch-like ECT2-interacting protein
Kelch-like protein X
Gene namesi
Name:KLHL20
Synonyms:KLEIP, KLHLX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000076321.10
HGNCiHGNC:25056 KLHL20
MIMi617679 gene
neXtProtiNX_Q9Y2M5

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, Golgi apparatus, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi109V → A in KLHL20m6; abolishes interaction with CUL3; when associated with A-111; A-113; A-146; A-148 and A-150. 4 Publications1
Mutagenesisi111I → A in KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-113; A-146; A-148 and A-150. 4 Publications1
Mutagenesisi113D → A in KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-111; A-146; A-148 and A-150. 4 Publications1
Mutagenesisi146C → A in KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-148 and A-150. 4 Publications1
Mutagenesisi148L → A in KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-146 and A-150. 4 Publications1
Mutagenesisi150L → A in KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-146 and A-148. 4 Publications1

Organism-specific databases

DisGeNETi27252
OpenTargetsiENSG00000076321
PharmGKBiPA134982126

Polymorphism and mutation databases

BioMutaiKLHL20
DMDMi257051084

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001191231 – 609Kelch-like protein 20Add BLAST609

Proteomic databases

EPDiQ9Y2M5
PaxDbiQ9Y2M5
PeptideAtlasiQ9Y2M5
PRIDEiQ9Y2M5

PTM databases

iPTMnetiQ9Y2M5
PhosphoSitePlusiQ9Y2M5

Expressioni

Inductioni

By hypoxia.1 Publication

Gene expression databases

BgeeiENSG00000076321
CleanExiHS_KLHL20
ExpressionAtlasiQ9Y2M5 baseline and differential
GenevisibleiQ9Y2M5 HS

Organism-specific databases

HPAiHPA025034
HPA053704

Interactioni

Subunit structurei

Component of the BCR(KLHL20) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL20 and RBX1. Interacts with PDZ-RhoGEF/ARHGEF11, DAPK1, PML and CORO7. Interacts with F-actin. Interacts with IFN-gamma (IFNG). Interacts (via kelch repeats) with IVNS1ABP (via kelch repeats); this interaction blocks the assembly of CUL3-KLHL20 complex (PubMed:25619834).7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin binding Source: UniProtKB-KW
  • interferon-gamma binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118100, 81 interactors
IntActiQ9Y2M5, 19 interactors
MINTiQ9Y2M5
STRINGi9606.ENSP00000209884

Structurei

3D structure databases

ProteinModelPortaliQ9Y2M5
SMRiQ9Y2M5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini68 – 135BTBPROSITE-ProRule annotationAdd BLAST68
Domaini170 – 272BACKAdd BLAST103
Repeati319 – 365Kelch 1Add BLAST47
Repeati367 – 413Kelch 2Add BLAST47
Repeati414 – 460Kelch 3Add BLAST47
Repeati462 – 507Kelch 4Add BLAST46
Repeati509 – 554Kelch 5Add BLAST46
Repeati556 – 601Kelch 6Add BLAST46

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00760000118931
HOGENOMiHOG000230814
HOVERGENiHBG014286
InParanoidiQ9Y2M5
KOiK10457
OMAiNSWSPIV
OrthoDBiEOG091G04QJ
PhylomeDBiQ9Y2M5
TreeFamiTF329218

Family and domain databases

Gene3Di2.120.10.80, 2 hits
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y2M5-1) [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
MEGKPMRRCT NIRPGETGMD VTSRCTLGDP NKLPEGVPQP ARMPYISDKH
60 70 80 90 100
PRQTLEVINL LRKHRELCDV VLVVGAKKIY AHRVILSACS PYFRAMFTGE
110 120 130 140 150
LAESRQTEVV IRDIDERAME LLIDFAYTSQ ITVEEGNVQT LLPAACLLQL
160 170 180 190 200
AEIQEACCEF LKRQLDPSNC LGIRAFADTH SCRELLRIAD KFTQHNFQEV
210 220 230 240 250
MESEEFMLLP ANQLIDIISS DELNVRSEEQ VFNAVMAWVK YSIQERRPQL
260 270 280 290 300
PQVLQHVRLP LLSPKFLVGT VGSDPLIKSD EECRDLVDEA KNYLLLPQER
310 320 330 340 350
PLMQGPRTRP RKPIRCGEVL FAVGGWCSGD AISSVERYDP QTNEWRMVAS
360 370 380 390 400
MSKRRCGVGV SVLDDLLYAV GGHDGSSYLN SVERYDPKTN QWSSDVAPTS
410 420 430 440 450
TCRTSVGVAV LGGFLYAVGG QDGVSCLNIV ERYDPKENKW TRVASMSTRR
460 470 480 490 500
LGVAVAVLGG FLYAVGGSDG TSPLNTVERY NPQENRWHTI APMGTRRKHL
510 520 530 540 550
GCAVYQDMIY AVGGRDDTTE LSSAERYNPR TNQWSPVVAM TSRRSGVGLA
560 570 580 590 600
VVNGQLMAVG GFDGTTYLKT IEVFDPDANT WRLYGGMNYR RLGGGVGVIK

MTHCESHIW
Length:609
Mass (Da):67,955
Last modified:September 1, 2009 - v4
Checksum:iFA05E3FE8341B422
GO
Isoform 2 (identifier: Q9Y2M5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MEGKPMRRCT → MVHGRKANAQ
     11-199: Missing.

Note: No experimental confirmation available.
Show »
Length:420
Mass (Da):46,490
Checksum:i87CFCA63FAB1F719
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti171L → Q in BAG50912 (PubMed:14702039).Curated1
Sequence conflicti321F → S in BAG50912 (PubMed:14702039).Curated1
Sequence conflicti334S → N in BAG50912 (PubMed:14702039).Curated1
Sequence conflicti396V → M in BAG50912 (PubMed:14702039).Curated1
Sequence conflicti593G → W in BAA77027 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0570261 – 10MEGKPMRRCT → MVHGRKANAQ in isoform 2. 1 Publication10
Alternative sequenceiVSP_05702711 – 199Missing in isoform 2. 1 PublicationAdd BLAST189

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ844466 mRNA Translation: CAH59617.1
AB026190 mRNA Translation: BAA77027.1
AK001430 mRNA Translation: BAG50912.1
AK300755 mRNA Translation: BAG62422.1
AL109921 Genomic DNA No translation available.
BX248409 Genomic DNA No translation available.
BC063418 mRNA Translation: AAH63418.1
CCDSiCCDS1310.1 [Q9Y2M5-1]
RefSeqiNP_055273.2, NM_014458.3 [Q9Y2M5-1]
XP_005245150.1, XM_005245093.3 [Q9Y2M5-1]
UniGeneiHs.495035

Genome annotation databases

EnsembliENST00000209884; ENSP00000209884; ENSG00000076321 [Q9Y2M5-1]
GeneIDi27252
KEGGihsa:27252
UCSCiuc001gjc.5 human [Q9Y2M5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKLH20_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2M5
Secondary accession number(s): B3KMA0
, B4DUR0, Q5TZF2, Q5ZF45, Q9H457
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: September 1, 2009
Last modified: May 23, 2018
This is version 152 of the entry and version 4 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

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