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Protein

Kelch-like protein 15

Gene

KLHL15

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

Functioni

Substrate-specific adapter for CUL3 E3 ubiquitin-protein ligase complex (PubMed:14528312). Acts as an adapter for CUL3 to target the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits (PubMed:23135275). Acts as an adapter for CUL3 to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:27561354).3 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 - Biological processi

  • negative regulation of double-strand break repair via homologous recombination Source: UniProtKB
  • nuclear protein quality control by the ubiquitin-proteasome system Source: UniProtKB
  • protein ubiquitination Source: UniProtKB-UniPathway
  • ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like protein 15
Gene namesi
Name:KLHL15
Synonyms:KIAA1677
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000174010.9
HGNCiHGNC:29347 KLHL15
MIMi300980 gene
neXtProtiNX_Q96M94

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

Nucleus

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked 103 (MRX103)2 Publications
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.
See also OMIM:300982

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi32D → A: Impaired homodimerization and PPP2R5B proteasomal degradation. No effect on PPP2R5B-binding. 1 Publication1
Mutagenesisi45H → L: No effect on homodimerization, PPP2R5B-binding, nor on PPP2R5B proteasomal degradation. 1 Publication1
Mutagenesisi72 – 75IHLK → AHAA: No effect on PPP2R5B-binding, nor on homodimerization, but loss of CUL3 recruitment to the KLHL15/PPP2R5B complex and impaired PPP2R5B proteasomal degradation. 1 Publication4
Mutagenesisi132N → A: Decreased interaction with CUL3, especially with the neddylated form of CUL3. 1 Publication1
Mutagenesisi136I → A: Decreased interaction with CUL3, especially with the neddylated form of CUL3. 1 Publication1
Mutagenesisi318R → E: Impaired PPP2R5B-binding and proteasomal degradation. 1 Publication1
Mutagenesisi335 – 337EEL → REA: Impaired PPP2R5B-binding and proteasomal degradation. 1 Publication3
Mutagenesisi371E → R: Impaired PPP2R5B-binding and proteasomal degradation. 1 Publication1
Mutagenesisi386G → C: Decreased interaction with RBBP8 and complete loss of nuclear localization, found exclusively in the cytoplasm. 1 Publication1
Mutagenesisi552Y → A: Decreased interaction with RBBP8 and increased DNA-end resection and homologous recombination frequency following DNA double-strand breaks compared to the wild-type protein. No significant change in subcellular location. 1 Publication1

Keywords - Diseasei

Mental retardation

Organism-specific databases

MalaCardsiKLHL15
MIMi300982 phenotype
OpenTargetsiENSG00000174010
PharmGKBiPA134934728

Polymorphism and mutation databases

BioMutaiKLHL15
DMDMi88909167

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002239491 – 604Kelch-like protein 15Add BLAST604

Proteomic databases

EPDiQ96M94
PaxDbiQ96M94
PeptideAtlasiQ96M94
PRIDEiQ96M94

PTM databases

iPTMnetiQ96M94
PhosphoSitePlusiQ96M94

Expressioni

Gene expression databases

BgeeiENSG00000174010
CleanExiHS_KLHL15
ExpressionAtlasiQ96M94 baseline and differential
GenevisibleiQ96M94 HS

Organism-specific databases

HPAiHPA065730

Interactioni

Subunit structurei

Homodimer. Dimerization does not affect PPP2R5B-binding, but is required for its proteasomal degradation (PubMed:23135275). Interacts with CUL3 (PubMed:27561354, PubMed:14528312, PubMed:23135275). Directly interacts with PPP2R5B; this interaction leads to PPP2R5B proteasomal degradation (PubMed:23135275). Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation (PubMed:27561354).3 Publications

Protein-protein interaction databases

BioGridi123224, 53 interactors
IntActiQ96M94, 7 interactors
STRINGi9606.ENSP00000332791

Structurei

3D structure databases

ProteinModelPortaliQ96M94
SMRiQ96M94
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 98BTBPROSITE-ProRule annotationAdd BLAST68
Domaini133 – 237BACKAdd BLAST105
Repeati328 – 379Kelch 1Add BLAST52
Repeati381 – 426Kelch 2Add BLAST46
Repeati428 – 473Kelch 3Add BLAST46
Repeati489 – 542Kelch 4Add BLAST54
Repeati544 – 590Kelch 5Add BLAST47

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00760000118825
HOGENOMiHOG000231204
HOVERGENiHBG096076
InParanoidiQ96M94
KOiK10452
OMAiMISHNGK
OrthoDBiEOG091G0333
PhylomeDBiQ96M94
TreeFamiTF328485

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
IPR030597 KLHL15
IPR011333 SKP1/BTB/POZ_sf
PANTHERiPTHR24412:SF61 PTHR24412:SF61, 1 hit
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 3 hits
PIRSFiPIRSF037037 Kelch-like_protein_gigaxonin, 1 hit
SMARTiView protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 5 hits
SUPFAMiSSF117281 SSF117281, 1 hit
SSF54695 SSF54695, 1 hit
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit

Sequencei

Sequence statusi: Complete.

Q96M94-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGDVEGFCS SIHDTSVSAG FRALYEEGLL LDVTLVIEDH QFQAHKALLA
60 70 80 90 100
TQSDYFRIMF TADMRERDQD KIHLKGLTAT GFSHVLQFMY YGTIELSMNT
110 120 130 140 150
VHEILQAAMY VQLIEVVKFC CSFLLAKICL ENCAEIMRLL DDFGVNIEGV
160 170 180 190 200
REKLDTFLLD NFVPLMSRPD FLSYLSFEKL MSYLDNDHLS RFPEIELYEA
210 220 230 240 250
VQSWLRHDRR RWRHTDTIIQ NIRFCLMTPT SVFEKVKTSE FYRYSRQLRY
260 270 280 290 300
EVDQALNYFQ NVHQQPLLDM KSSRIRSAKP QTTVFRGMIG HSMVNSKILL
310 320 330 340 350
LKKPRVWWEL EGPQVPLRPD CLAIVNNFVF LLGGEELGPD GEFHASSKVF
360 370 380 390 400
RYDPRQNSWL QMADMSVPRS EFAVGVIGKF IYAVAGRTRD ETFYSTERYD
410 420 430 440 450
ITNDKWEFVD PYPVNKYGHE GTVLNNKLFI TGGITSSSTS KQVCVFDPSK
460 470 480 490 500
EGTIEQRTRR TQVVTNCWEN KSKMNYARCF HKMISYNGKL YVFGGVCVIL
510 520 530 540 550
RASFESQGCP STEVYNPETD QWTILASMPI GRSGHGVTVL DKQIMVLGGL
560 570 580 590 600
CYNGHYSDSI LTFDPDENKW KEDEYPRMPC KLDGLQVCNL HFPDYVLDEV

RRCN
Length:604
Mass (Da):69,775
Last modified:February 21, 2006 - v2
Checksum:iE37606E8AE367C83
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti297K → E in BAB71415 (PubMed:14702039).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK057298 mRNA Translation: BAB71415.1
BC015415 mRNA Translation: AAH15415.1
BC109058 mRNA Translation: AAI09059.1
BC109059 mRNA Translation: AAI09060.1
AB051464 mRNA Translation: BAB21768.1
AL834313 mRNA Translation: CAD38983.1
CCDSiCCDS35217.1
RefSeqiNP_085127.2, NM_030624.2
XP_006724581.1, XM_006724518.1
UniGeneiHs.495854

Genome annotation databases

EnsembliENST00000328046; ENSP00000332791; ENSG00000174010
GeneIDi80311
KEGGihsa:80311

Similar proteinsi

Entry informationi

Entry nameiKLH15_HUMAN
AccessioniPrimary (citable) accession number: Q96M94
Secondary accession number(s): Q32MN3
, Q8NDA3, Q96BM6, Q9C0I6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: February 21, 2006
Last modified: May 23, 2018
This is version 135 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways

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