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Protein

Kelch-like protein 25

Gene

KLHL25

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for translational homeostasis. The BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination of hypophosphorylated EIF4EBP1 (4E-BP1): ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) probably serves as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. The BCR(KLHL25) complex does not target EIF4EBP1 (4E-BP1) when it is hyperphosphorylated or associated with eIF4E.1 Publication

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

  • protein ubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of translational initiation Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Translation regulation, Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like protein 25
Alternative name(s):
Ectoderm-neural cortex protein 2
Short name:
ENC-2
Gene namesi
Name:KLHL25
Synonyms:ENC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:25732. KLHL25.

Subcellular locationi

GO - Cellular componenti

  • Cul3-RING ubiquitin ligase complex Source: UniProtKB
  • cytoplasm Source: LIFEdb
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142671577.

Polymorphism and mutation databases

BioMutaiKLHL25.
DMDMi74733525.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 589589Kelch-like protein 25PRO_0000272308Add
BLAST

Proteomic databases

EPDiQ9H0H3.
MaxQBiQ9H0H3.
PaxDbiQ9H0H3.
PRIDEiQ9H0H3.

PTM databases

iPTMnetiQ9H0H3.
PhosphoSiteiQ9H0H3.

Expressioni

Gene expression databases

BgeeiQ9H0H3.
CleanExiHS_KLHL25.
GenevisibleiQ9H0H3. HS.

Organism-specific databases

HPAiHPA023450.

Interactioni

Subunit structurei

Component of the BCR(KLHL25) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL25 and RBX1. Interacts with EIF4EBP1 (when hypophosphorylated).1 Publication

Protein-protein interaction databases

BioGridi122162. 8 interactions.
IntActiQ9H0H3. 3 interactions.
MINTiMINT-4717137.
STRINGi9606.ENSP00000336800.

Structurei

3D structure databases

ProteinModelPortaliQ9H0H3.
SMRiQ9H0H3. Positions 3-275, 297-570.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini46 – 11469BTBPROSITE-ProRule annotationAdd
BLAST
Domaini149 – 250102BACKAdd
BLAST
Repeati296 – 34045Kelch 1Add
BLAST
Repeati341 – 38848Kelch 2Add
BLAST
Repeati389 – 44456Kelch 3Add
BLAST
Repeati446 – 49247Kelch 4Add
BLAST
Repeati494 – 53845Kelch 5Add
BLAST
Repeati539 – 58547Kelch 6Add
BLAST

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.
GeneTreeiENSGT00840000129689.
HOGENOMiHOG000232171.
HOVERGENiHBG000905.
InParanoidiQ9H0H3.
KOiK10462.
OMAiTSDTWNC.
OrthoDBiEOG7FJGZZ.
PhylomeDBiQ9H0H3.
TreeFamiTF329218.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR030565. KLHL25.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PANTHERiPTHR24410:SF10. PTHR24410:SF10. 1 hit.
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 4 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]

Sequencei

Sequence statusi: Complete.

Q9H0H3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSVSVHETRK SRSSTGSMNV TLFHKASHPD CVLAHLNTLR KHCMFTDVTL
60 70 80 90 100
WAGDRAFPCH RAVLAASSRY FEAMFSHGLR ESRDDTVNFQ DNLHPEVLEL
110 120 130 140 150
LLDFAYSSRI AINEENAESL LEAGDMLQFH DVRDAAAEFL EKNLFPSNCL
160 170 180 190 200
GMMLLSDAHQ CRRLYEFSWR MCLVHFETVR QSEDFNSLSK DTLLDLISSD
210 220 230 240 250
ELETEDERVV FEAILQWVKH DLEPRKVHLP ELLRSVRLAL LPSDCLQEAV
260 270 280 290 300
SSEALLMADE RTKLIMDEAL RCKTRILQND GVVTSPCARP RKAGHTLLIL
310 320 330 340 350
GGQTFMCDKI YQVDHKAKEI IPKADLPSPR KEFSASAIGC KVYVTGGRGS
360 370 380 390 400
ENGVSKDVWV YDTVHEEWSK AAPMLIARFG HGSAELENCL YVVGGHTSLA
410 420 430 440 450
GVFPASPSVS LKQVEKYDPG ANKWMMVAPL RDGVSNAAVV SAKLKLFVFG
460 470 480 490 500
GTSIHRDMVS KVQCYDPSEN RWTIKAECPQ PWRYTAAAVL GSQIFIMGGD
510 520 530 540 550
TEFTAASAYR FDCETNQWTR IGDMTAKRMS CHALASGNKL YVVGGYFGTQ
560 570 580
RCKTLDCYDP TSDTWNCITT VPYSLIPTAF VSTWKHLPA
Length:589
Mass (Da):65,923
Last modified:March 1, 2001 - v1
Checksum:i411795EF2C616BF4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti320 – 3201I → T in BAG37919 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti250 – 2501V → I.1 Publication
Corresponds to variant rs35582838 [ dbSNP | Ensembl ].
VAR_050041
Natural varianti257 – 2571M → L.
Corresponds to variant rs36031133 [ dbSNP | Ensembl ].
VAR_050042

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY764034 mRNA. Translation: AAV51405.1.
AL136796 mRNA. Translation: CAB66730.1.
AK092231 mRNA. Translation: BAG52499.1.
AK315541 mRNA. Translation: BAG37919.1.
AC021739 Genomic DNA. No translation available.
BC028100 mRNA. Translation: AAH28100.1.
CCDSiCCDS10339.1.
RefSeqiNP_071925.2. NM_022480.3.
UniGeneiHs.498371.

Genome annotation databases

EnsembliENST00000337975; ENSP00000336800; ENSG00000183655.
GeneIDi64410.
KEGGihsa:64410.
UCSCiuc002bly.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY764034 mRNA. Translation: AAV51405.1.
AL136796 mRNA. Translation: CAB66730.1.
AK092231 mRNA. Translation: BAG52499.1.
AK315541 mRNA. Translation: BAG37919.1.
AC021739 Genomic DNA. No translation available.
BC028100 mRNA. Translation: AAH28100.1.
CCDSiCCDS10339.1.
RefSeqiNP_071925.2. NM_022480.3.
UniGeneiHs.498371.

3D structure databases

ProteinModelPortaliQ9H0H3.
SMRiQ9H0H3. Positions 3-275, 297-570.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122162. 8 interactions.
IntActiQ9H0H3. 3 interactions.
MINTiMINT-4717137.
STRINGi9606.ENSP00000336800.

PTM databases

iPTMnetiQ9H0H3.
PhosphoSiteiQ9H0H3.

Polymorphism and mutation databases

BioMutaiKLHL25.
DMDMi74733525.

Proteomic databases

EPDiQ9H0H3.
MaxQBiQ9H0H3.
PaxDbiQ9H0H3.
PRIDEiQ9H0H3.

Protocols and materials databases

DNASUi64410.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000337975; ENSP00000336800; ENSG00000183655.
GeneIDi64410.
KEGGihsa:64410.
UCSCiuc002bly.5. human.

Organism-specific databases

CTDi64410.
GeneCardsiKLHL25.
HGNCiHGNC:25732. KLHL25.
HPAiHPA023450.
neXtProtiNX_Q9H0H3.
PharmGKBiPA142671577.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00840000129689.
HOGENOMiHOG000232171.
HOVERGENiHBG000905.
InParanoidiQ9H0H3.
KOiK10462.
OMAiTSDTWNC.
OrthoDBiEOG7FJGZZ.
PhylomeDBiQ9H0H3.
TreeFamiTF329218.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

GeneWikiiKLHL25.
GenomeRNAii64410.
NextBioi35468269.
PROiQ9H0H3.

Gene expression databases

BgeeiQ9H0H3.
CleanExiHS_KLHL25.
GenevisibleiQ9H0H3. HS.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR030565. KLHL25.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PANTHERiPTHR24410:SF10. PTHR24410:SF10. 1 hit.
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 4 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...

Publicationsi

« Hide 'large scale' publications
  1. "ENC2 a member of the BTB/POZ KELCH protein family."
    Corcoran M.M.
    Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-250.
    Tissue: Placenta.
  4. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH EIF4EBP1.

Entry informationi

Entry nameiKLH25_HUMAN
AccessioniPrimary (citable) accession number: Q9H0H3
Secondary accession number(s): B2RDH2, B3KRT7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: March 1, 2001
Last modified: May 11, 2016
This is version 116 of the entry and version 1 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. 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.