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Protein

Kelch-like protein 24

Gene

KLHL24

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

Functioni

Necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity (PubMed:27889062). As part of the BCR(KLHL24) E3 ubiquitin ligase complex, mediates ubiquitination of KRT14 and controls its levels during keratinocytes differentiation (PubMed:27798626). Specifically reduces kainate receptor-mediated currents in hippocampal neurons, most probably by modulating channel properties (By similarity).By similarity2 Publications

GO - Biological processi

  • intermediate filament organization Source: UniProtKB
  • protein autoubiquitination Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of kainate selective glutamate receptor activity Source: InterPro

Keywordsi

Biological processUbl conjugation pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like protein 24
Alternative name(s):
Kainate receptor-interacting protein for GluR6
Short name:
KRIP6
Protein DRE1
Gene namesi
Name:KLHL24
Synonyms:DRE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000114796.15.
HGNCiHGNC:25947. KLHL24.

Subcellular locationi

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Epidermolysis bullosa simplex, generalized, with scarring and hair loss (EBSSH)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. Gain-of-function mutations that lead to excessive ubiquitination and degradation of KRT14 result in compromised mechanical integrity of basal keratinocytes. Under this pathological condition, trivial mechanical stress can induce blister formation at the basal layer of skin.1 Publication
Disease descriptionA form of epidermolysis bullosa, a group of mechano-bullous disorders characterized by structural skin fragility, recurrent blister formation and erosion of the skin and mucous membranes occurring spontaneously or after mild trauma. Epidermolysis bullosa simplex is characterized by intraepidermal tissue separation that occurs within the basal keratinocytes at the bottom layer of epidermis. EBSSH is an autosomal dominant epidermolysis bullosa simplex, presenting at birth with extensive skin defects on the extremities, leaving behind hypopigmentation and atrophy with a whirled pattern. Cutaneous fragility and generalized blistering persist during childhood and decrease in adulthood. Adult patients have dyspigmentation and atrophy of the skin, scars, follicular atrophoderma, sparse body hair, progressive diffuse alopecia of the scalp, diffuse palmoplantar keratoderma, and nail changes.
See also OMIM:617294

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi32K → R: Increased protein stability. 1 Publication1
Mutagenesisi90Y → A: Weak interaction with CUL3. Weak autoubiquitination. 1 Publication1
Mutagenesisi175A → V: Weak interaction with CUL3. Weak autoubiquitination. 1 Publication1

Keywords - Diseasei

Epidermolysis bullosa

Organism-specific databases

MalaCardsiKLHL24.
MIMi617294. phenotype.
OpenTargetsiENSG00000114796.
PharmGKBiPA142671576.

Polymorphism and mutation databases

BioMutaiKLHL24.
DMDMi74722812.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002615941 – 600Kelch-like protein 24Add BLAST600

Post-translational modificationi

Autoubiquitinated. Autoubiquitination leads to proteasomal degradation and is necessary to control KLHL24 levels.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ6TFL4.
MaxQBiQ6TFL4.
PaxDbiQ6TFL4.
PeptideAtlasiQ6TFL4.
PRIDEiQ6TFL4.

PTM databases

iPTMnetiQ6TFL4.
PhosphoSitePlusiQ6TFL4.

Expressioni

Tissue specificityi

Expressed in the skin (PubMed:27889062, PubMed:27798626). Found in keratinocytes, dermal fibroblasts, and melanocytes (PubMed:27889062). Basal-layer keratinocytes have lower KLHL24 expression than suprabasal keratinocytes (PubMed:27798626).2 Publications

Gene expression databases

BgeeiENSG00000114796.
CleanExiHS_KLHL24.
ExpressionAtlasiQ6TFL4. baseline and differential.
GenevisibleiQ6TFL4. HS.

Organism-specific databases

HPAiHPA056337.

Interactioni

Subunit structurei

Forms homodimers. Interacts with GRIK2 (By similarity). Component of the BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and KLHL24. Interacts with CUL3. Interacts with KRT14 (PubMed:27798626).By similarity1 Publication

Protein-protein interaction databases

BioGridi120159. 26 interactors.
IntActiQ6TFL4. 6 interactors.
STRINGi9606.ENSP00000242810.

Structurei

3D structure databases

ProteinModelPortaliQ6TFL4.
SMRiQ6TFL4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini66 – 133BTBPROSITE-ProRule annotationAdd BLAST68
Domaini168 – 270BACKAdd BLAST103
Repeati314 – 363Kelch 1Add BLAST50
Repeati365 – 407Kelch 2Add BLAST43
Repeati408 – 454Kelch 3Add BLAST47
Repeati456 – 502Kelch 4Add BLAST47
Repeati504 – 544Kelch 5Add BLAST41
Repeati546 – 592Kelch 6Add BLAST47

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00900000140791.
HOGENOMiHOG000230817.
HOVERGENiHBG108068.
InParanoidiQ6TFL4.
KOiK10461.
OMAiEAMDCFL.
OrthoDBiEOG091G037V.
PhylomeDBiQ6TFL4.
TreeFamiTF351654.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
2.130.10.80. 1 hit.
InterProiView protein in InterPro
IPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR011043. Gal_Oxase/kelch_b-propeller.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR030596. KLHL24.
IPR011333. SKP1/BTB/POZ.
PANTHERiPTHR24412:SF215. PTHR24412:SF215. 1 hit.
PfamiView protein in Pfam
PF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 5 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: Q6TFL4-1) [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
MVLILGRRLN REDLGVRDSP ATKRKVFEMD PKSLTGHEFF DFSSGSSHAE
60 70 80 90 100
NILQIFNEFR DSRLFTDVII CVEGKEFPCH RAVLSACSSY FRAMFCNDHR
110 120 130 140 150
ESREMLVEIN GILAEAMECF LQYVYTGKVK ITTENVQYLF ETSSLFQISV
160 170 180 190 200
LRDACAKFLE EQLDPCNCLG IQRFADTHSL KTLFTKCKNF ALQTFEDVSQ
210 220 230 240 250
HEEFLELDKD ELIDYICSDE LVIGKEEMVF EAVMRWVYRA VDLRRPLLHE
260 270 280 290 300
LLTHVRLPLL HPNYFVQTVE VDQLIQNSPE CYQLLHEARR YHILGNEMMS
310 320 330 340 350
PRTRPRRSTG YSEVIVVVGG CERVGGFNLP YTECYDPVTG EWKSLAKLPE
360 370 380 390 400
FTKSEYAVCA LRNDILVSGG RINSRDVWIY NSQLNIWIRV ASLNKGRWRH
410 420 430 440 450
KMAVLLGKVY VVGGYDGQNR LSSVECYDSF SNRWTEVAPL KEAVSSPAVT
460 470 480 490 500
SCVGKLFVIG GGPDDNTCSD KVQSYDPETN SWLLRAAIPI AKRCITAVSL
510 520 530 540 550
NNLIYVAGGL TKAIYCYDPV EDYWMHVQNT FSRQENCGMS VCNGKIYILG
560 570 580 590 600
GRRENGEATD TILCYDPATS IITGVAAMPR PVSYHGCVTI HRYNEKCFKL
Length:600
Mass (Da):68,361
Last modified:July 5, 2004 - v1
Checksum:i54538E2BF447A56B
GO
Isoform 2 (identifier: Q6TFL4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     535-537: ENC → VIT
     538-600: Missing.

Note: No experimental confirmation available.
Show »
Length:537
Mass (Da):61,453
Checksum:i710C21C9D54A1E4E
GO

Sequence cautioni

Q6TFL4: The sequence BAA90921 differs from that shown. Reason: Erroneous initiation.Curated
Q6TFL4: The sequence BAB15447 differs from that shown. Aberrant splicing.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti489P → R in BAA90921 (PubMed:14702039).Curated1
Sequence conflicti515Y → C in BAB15447 (PubMed:14702039).Curated1
Sequence conflicti536N → D in AAI42994 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028644535 – 537ENC → VIT in isoform 2. 1 Publication3
Alternative sequenceiVSP_028645538 – 600Missing in isoform 2. 1 PublicationAdd BLAST63

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY422472 mRNA. Translation: AAR13703.1.
DQ925701 mRNA. Translation: ABI96896.1.
AK000066 mRNA. Translation: BAA90921.1. Different initiation.
AK026326 mRNA. Translation: BAB15447.1. Sequence problems.
BX648466 mRNA. Translation: CAI46031.1.
BX648812 mRNA. Translation: CAI46002.1.
BC142993 mRNA. Translation: AAI42994.1.
CCDSiCCDS3246.1. [Q6TFL4-1]
RefSeqiNP_060114.2. NM_017644.3. [Q6TFL4-1]
XP_005247609.1. XM_005247552.2. [Q6TFL4-1]
XP_005247610.1. XM_005247553.1.
XP_005247611.1. XM_005247554.2.
XP_005247612.1. XM_005247555.1.
XP_005247613.1. XM_005247556.1.
XP_011511240.1. XM_011512938.2.
XP_016862148.1. XM_017006659.1.
XP_016862149.1. XM_017006660.1.
UniGeneiHs.407709.

Genome annotation databases

EnsembliENST00000242810; ENSP00000242810; ENSG00000114796. [Q6TFL4-1]
ENST00000454652; ENSP00000395012; ENSG00000114796. [Q6TFL4-1]
ENST00000476808; ENSP00000419010; ENSG00000114796. [Q6TFL4-2]
GeneIDi54800.
KEGGihsa:54800.
UCSCiuc003flv.4. human. [Q6TFL4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKLH24_HUMAN
AccessioniPrimary (citable) accession number: Q6TFL4
Secondary accession number(s): A5PLN8, Q9H620, Q9NXT9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: July 5, 2004
Last modified: October 25, 2017
This is version 117 of the entry and version 1 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 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot