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Protein

Kelch repeat and BTB domain-containing protein 8

Gene

KBTBD8

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

Functioni

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification (PubMed:26399832). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1: monoubiquitination promotes the formation of a NOLC1-TCOF1 complex that acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832).1 Publication

GO - Biological processi

  • neural crest cell development Source: UniProtKB
  • neural crest formation Source: UniProtKB
  • post-translational protein modification Source: Reactome
  • protein monoubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • regulation of translation Source: UniProtKB-KW

Keywordsi

Biological processTranslation regulation, Ubl conjugation pathway

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch repeat and BTB domain-containing protein 8
Alternative name(s):
T-cell activation kelch repeat protein
Short name:
TA-KRP
Gene namesi
Name:KBTBD8
Synonyms:KIAA1842, TAKRP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:30691. KBTBD8.

Subcellular locationi

  • Cytoplasmcytoskeletonspindle 1 Publication
  • Golgi apparatus 1 Publication

  • Note: Translocates to the spindle apparatus during mitosis.1 Publication

GO - Cellular componenti

  • Cul3-RING ubiquitin ligase complex Source: UniProtKB
  • cytosol Source: Reactome
  • Golgi apparatus Source: UniProtKB-SubCell
  • spindle Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Golgi apparatus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi74Y → A: Abolishes CUL3-binding and ability to mediate monoubiquitination of NOLC1 and TCOF1. 1 Publication1
Mutagenesisi579W → A: Abolishes substrate-binding and ability to mediate monoubiquitination of NOLC1 and TCOF1. 1 Publication1

Organism-specific databases

DisGeNETi84541.
OpenTargetsiENSG00000163376.
PharmGKBiPA142671641.

Polymorphism and mutation databases

BioMutaiKBTBD8.
DMDMi126215728.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002782201 – 601Kelch repeat and BTB domain-containing protein 8Add BLAST601

Proteomic databases

EPDiQ8NFY9.
MaxQBiQ8NFY9.
PaxDbiQ8NFY9.
PeptideAtlasiQ8NFY9.
PRIDEiQ8NFY9.

PTM databases

iPTMnetiQ8NFY9.
PhosphoSitePlusiQ8NFY9.

Expressioni

Developmental stagei

Down-regulated in differentiating embryonic stem cells (ESCs) (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000163376.
CleanExiHS_KBTBD8.
ExpressionAtlasiQ8NFY9. baseline and differential.
GenevisibleiQ8NFY9. HS.

Organism-specific databases

HPAiHPA041285.
HPA069190.

Interactioni

Subunit structurei

Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD8 and RBX1 (PubMed:26399832).1 Publication

Protein-protein interaction databases

BioGridi124128. 11 interactors.
STRINGi9606.ENSP00000401878.

Structurei

3D structure databases

ProteinModelPortaliQ8NFY9.
SMRiQ8NFY9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini49 – 117BTBPROSITE-ProRule annotationAdd BLAST69
Domaini153 – 252BACKSequence analysisAdd BLAST100
Repeati336 – 390Kelch 1Sequence analysisAdd BLAST55
Repeati391 – 441Kelch 2Sequence analysisAdd BLAST51
Repeati443 – 481Kelch 3Sequence analysisAdd BLAST39
Repeati483 – 532Kelch 4Sequence analysisAdd BLAST50
Repeati542 – 588Kelch 5Sequence analysisAdd BLAST47

Sequence similaritiesi

Belongs to the KBTBD8 family.Curated

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00880000137845.
HOGENOMiHOG000113200.
HOVERGENiHBG100857.
InParanoidiQ8NFY9.
KOiK10475.
OMAiRWFEHEQ.
OrthoDBiEOG091G035Y.
PhylomeDBiQ8NFY9.
TreeFamiTF332672.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiView protein in InterPro
IPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR028764. KBTBD8.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR011333. SKP1/BTB/POZ.
PANTHERiPTHR24412:SF299. PTHR24412:SF299. 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. 3 hits.
SUPFAMiSSF54695. 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: Q8NFY9-1) [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
MAASADLSKS SPTPNGIPSS DPASDAMDPF HACSILKQLK TMYDEGQLTD
60 70 80 90 100
IVVEVDHGKT FSCHRNVLAA ISPYFRSMFT SGLTESTQKE VRIVGVEAES
110 120 130 140 150
MDLVLNYAYT SRVILTEANV QALFTAASIF QIPSIQDQCA KYMISHLDPQ
160 170 180 190 200
NSIGVFIFAD HYGHQELGDR SKEYIRKKFL CVTKEQEFLQ LTKDQLISIL
210 220 230 240 250
DSDDLNVDRE EHVYESIIRW FEHEQNEREV HLPEIFAKCI RFPLMEDTFI
260 270 280 290 300
EKIPPQFAQA IAKSCVEKGP SNTNGCTQRL GMTASEMIIC FDAAHKHSGK
310 320 330 340 350
KQTVPCLDIV TGRVFKLCKP PNDLREVGIL VSPDNDIYIA GGYRPSSSEV
360 370 380 390 400
SIDHKAENDF WMYDHSTNRW LSKPSLLRAR IGCKLVYCCG KMYAIGGRVY
410 420 430 440 450
EGDGRNSLKS VECYDSRENC WTTVCAMPVA MEFHNAVEYK EKIYVLQGEF
460 470 480 490 500
FLFYEPQKDY WGFLTPMTVP RIQGLAAVYK DSIYYIAGTC GNHQRMFTVE
510 520 530 540 550
AYDIELNKWT RKKDFPCDQS INPYLKLVLF QNKLHLFVRA TQVTVEEHVF
560 570 580 590 600
RTSRKNSLYQ YDDIADQWMK VYETPDRLWD LGRHFECAVA KLYPQCLQKV

L
Length:601
Mass (Da):68,823
Last modified:February 20, 2007 - v2
Checksum:iE5DC921FD9C10BBA
GO
Isoform 2 (identifier: Q8NFY9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     6-447: Missing.

Note: No experimental confirmation available.
Show »
Length:159
Mass (Da):18,827
Checksum:i951CFB969FFDE36E
GO

Sequence cautioni

The sequence AAI17488 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAM43839 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036082198S → C in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_036083405R → K in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_030694420C → R. Corresponds to variant dbSNP:rs13096789Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0561076 – 447Missing in isoform 2. 1 PublicationAdd BLAST442

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK096640 mRNA. No translation available.
AK300397 mRNA. Translation: BAG62128.1.
AC020655 Genomic DNA. No translation available.
AF385438 mRNA. Translation: AAM43839.1. Different initiation.
BC117487 mRNA. Translation: AAI17488.1. Different initiation.
AB058745 mRNA. Translation: BAB47471.1.
CCDSiCCDS2906.2. [Q8NFY9-1]
RefSeqiNP_115894.2. NM_032505.2. [Q8NFY9-1]
UniGeneiHs.116665.

Genome annotation databases

EnsembliENST00000417314; ENSP00000401878; ENSG00000163376. [Q8NFY9-1]
ENST00000460576; ENSP00000419738; ENSG00000163376. [Q8NFY9-2]
GeneIDi84541.
KEGGihsa:84541.
UCSCiuc003dmy.4. human. [Q8NFY9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKBTB8_HUMAN
AccessioniPrimary (citable) accession number: Q8NFY9
Secondary accession number(s): B4DTW6, Q96JI5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: August 30, 2017
This is version 114 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, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families