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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-046742
UUCD1 version UUC-HoS-00138
Ensembl Protein ID ENSP00000356230.3
UniProt Accession Q53G59; A6NEN8; B7Z7B8; Q9HBX5; KLH12_HUMAN
Genbank Protein ID AAG17175.1; BAB55271.1; BAH13554.1; BAD96792.1; AAH03183.1; AAH04175.1
Protein Name Kelch-like protein 12; CUL3-interacting protein 1; DKIR homolog
Genbank Nucleotide ID AF190900; AK027656; AK301791; AK223072; AC096632; BC004175
Gene Name KLHL12; C3IP1
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000117153.15 ENST00000367261.7 ENSP00000356230.3
ENSG00000117153.15 ENST00000367259.1 ENSP00000356228.1
ENSG00000117153.15 ENST00000367258.1 ENSP00000356227.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
TargetScanmiRecordsRepTarSomamiR
miRcodeRAID2
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Protein 3D Structure
PDBMMDB
Disease-associated Information
GWASdbGWAS CentralOMIM
Post-translational Modifications (PTMs)
CPLMdbPAFPhosphositePlusdbPTM
BioGRIDmUbiSiDa
DNA Methylation
TCGAICGCCOSMIC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
E3 adaptor/Cullin RING/BCR/BTB_3-box BTB_3-box 18303015; 19805045
Classification
Family E-value Score Start End
E3 adaptor/Cullin RING/BCR/BTB_3-box: BTB 7.60e-19 69.5 33 96
E3 adaptor/Cullin RING/BCR/BTB_3-box: 3-box 8.00e-14 50.6 132 163
Active Site
Position(s) Description Evidence
N/A N/A N/A
Domain Profile

   E3 adaptor/Cullin RING/BCR/BTB_3-box: BTB
   S: 1    aDvilvvggeeffahkivLaasSsvFyalflmeleesksklmveikdvqpevfrallkFlYtgkl 65
           +Dv+l v+++ f+ah+ivLaa+S++F a+f++el+e+  k+ v+i+++ ++ ++ ll+F+Yt ++
   Q: 33   CDVTLRVEQKDFPAHRIVLAACSDYFCAMFTSELSEKG-KPYVDIQGLTASTMEILLDFVYTETV 96
           9***********************************98.***********************987 PP
   

   E3 adaptor/Cullin RING/BCR/BTB_3-box: 3-box
   S: 1    leNclgilrfAdlydcpdLkdaaldfilkhFk 32
           ++Nclgi++fA++++c dL++aa+ f +khF+
   Q: 132  PSNCLGIRDFAETHNCVDLMQAAEVFSQKHFP 163
           89*****************************6 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is also involved in neural crest specification: in response to cytosolic calcium increase, interacts with the heterodimer formed with PEF1 and PDCD6/ALG-2, leading to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export (PubMed:27716508). As part of the BCR(KLHL12) complex, also acts as a negative regulator of the Wnt signaling pathway by mediating ubiquitination and subsequent proteolysis of DVL3 (PubMed:16547521). The BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and PEF1, without leading to degradation of these proteins (PubMed:18303015, PubMed:20100572, PubMed:27716508).
 Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is also involved in neural crest specification: in response to cytosolic calcium increase, interacts with the heterodimer formed with PEF1 and PDCD6/ALG-2, leading to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export (PubMed:27716508). As part of the BCR(KLHL12) complex, also acts as a negative regulator of the Wnt signaling pathway by mediating ubiquitination and subsequent proteolysis of DVL3 (PubMed:16547521). The BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and PEF1, without leading to degradation of these proteins (PubMed:18303015, PubMed:20100572, PubMed:27716508).
Protein Sequence
(Fasta)
MGGIMAPKDI MTNTHAKSIL NSMNSLRKSN TLCDVTLRVE QKDFPAHRIV LAACSDYFCA 60
MFTSELSEKG KPYVDIQGLT ASTMEILLDF VYTETVHVTV ENVQELLPAA CLLQLKGVKQ 120
It may take some time, please wait.

Protein Fasta Sequence


>IUUC-Hsa-046742|E3,BTB_3-box|Homo sapiens
Please wait for a moment...
Nucleotide Sequence
(Fasta)
GCAGAGTATA TACTGAGGTC TGTGGATCCT AAGGCTCAGA GGATTCTCGC CGCAGCGTTG 60
TTCGGCCCGA AAAGGCCATT GTGGACAATG GACGTGAATA AATTTGAGGC CTCTGTGGGT 120
It may take some time, please wait.

Nucleotide Fasta Sequence


>IUUC-Hsa-046742|E3,BTB_3-box|Homo sapiens
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-0025--Alternative splicing
KW-0181--Complete proteome
KW-0968--Cytoplasmic vesicle
KW-0931--ER-Golgi transport
KW-0880--Kelch repeat
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0677--Repeat
KW-0813--Transport
KW-0833--Ubl conjugation pathway
KW-0879--Wnt signaling pathway
Interpro

IPR011705--BACK
IPR017096--BTB-kelch_protein
IPR000210--BTB/POZ_dom
IPR015915--Kelch-typ_b-propeller
IPR006652--Kelch_1
IPR011333--SKP1/BTB/POZ
PROSITE

PS50097--BTB
Pfam

PF07707--BACK
PF00651--BTB
PF01344--Kelch_1
SMART

SM00875--BACK
SM00225--BTB
SM00612--Kelch
Gene Ontology

GO:0031463--C:Cul3-RING ubiquitin ligase complex
GO:0005829--C:cytosol
GO:0030134--C:ER to Golgi transport vesicle
GO:0000139--C:Golgi membrane
GO:0043231--C:intracellular membrane-bounded organelle
GO:0005815--C:microtubule organizing center
GO:0042802--F:identical protein binding
GO:0048208--P:COPII vesicle coating
GO:0006888--P:ER to Golgi vesicle-mediated transport
GO:0090090--P:negative regulation of canonical Wnt signaling pathway
GO:0006513--P:protein monoubiquitination
GO:0016055--P:Wnt signaling pathway
KEGG hsa:59349
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-002301 Ailuropoda melanoleuca 99.29 0.00e+00 1126.00
IUUC-Apl-003339 Anas platyrhynchos 96.92 0.00e+00 1028.00
IUUC-Aca-004418 Anolis carolinensis 96.28 0.00e+00 1114.00
IUUC-Ath-007066 Arabidopsis thaliana 32.98 1.00e-39 157.00
IUUC-Ame-011906 Astyanax mexicanus 75.70 0.00e+00 878.00
IUUC-Bta-012979 Bos taurus 97.36 0.00e+00 1125.00
IUUC-Cja-019582 Callithrix jacchus 99.12 0.00e+00 1145.00
IUUC-Cfa-020716 Canis familiaris 99.82 0.00e+00 1154.00
IUUC-Cpo-022013 Cavia porcellus 99.65 0.00e+00 1152.00
IUUC-Cre-022752 Chlamydomonas reinhardtii 28.76 9.00e-16 80.10
IUUC-Csa-023424 Chlorocebus sabaeus 100.00 0.00e+00 1071.00
IUUC-Cho-024586 Choloepus hoffmanni 81.51 0.00e+00 900.00
IUUC-Dre-028344 Danio rerio 88.67 1.00e-167 581.00
IUUC-Dno-028854 Dasypus novemcinctus 99.82 0.00e+00 1154.00
IUUC-Dor-030403 Dipodomys ordii 99.65 0.00e+00 1150.00
IUUC-Ete-032963 Echinops telfairi 97.81 0.00e+00 991.00
IUUC-Eca-033282 Equus caballus 99.65 0.00e+00 1154.00
IUUC-Eeu-034933 Erinaceus europaeus 98.82 1.00e-142 499.00
IUUC-Fca-035487 Felis catus 99.82 0.00e+00 1154.00
IUUC-Fal-037059 Ficedula albicollis 95.76 0.00e+00 1107.00
IUUC-Gmo-039564 Gadus morhua 89.73 0.00e+00 1086.00
IUUC-Gga-040629 Gallus gallus 96.44 0.00e+00 1113.00
IUUC-Gac-042526 Gasterosteus aculeatus 90.28 0.00e+00 1087.00
IUUC-Ggo-044839 Gorilla gorilla 100.00 0.00e+00 1157.00
IUUC-Itr-048958 Ictidomys tridecemlineatus 99.65 0.00e+00 1152.00
IUUC-Lch-049540 Latimeria chalumnae 93.62 0.00e+00 1120.00
IUUC-Loc-051923 Lepisosteus oculatus 92.91 0.00e+00 1087.00
IUUC-Laf-054370 Loxodonta africana 99.30 0.00e+00 1150.00
IUUC-Mcc-054852 Macaca mulatta 100.00 0.00e+00 1157.00
IUUC-Mga-059486 Meleagris gallopavo 95.30 0.00e+00 1018.00
IUUC-Mmr-061777 Microcebus murinus 99.65 0.00e+00 1150.00
IUUC-Mdo-061990 Monodelphis domestica 97.88 0.00e+00 1134.00
IUUC-Mmu-064053 Mus musculus 99.30 0.00e+00 1151.00
IUUC-Mac-064654 Musa acuminata 33.33 2.00e-40 160.00
IUUC-Mpu-066623 Mustela putorius furo 85.86 0.00e+00 821.00
IUUC-Mlu-067648 Myotis lucifugus 98.94 0.00e+00 1173.00
IUUC-Nle-069714 Nomascus leucogenys 99.82 0.00e+00 1155.00
IUUC-Opr-071143 Ochotona princeps 92.96 0.00e+00 1055.00
IUUC-Ont-071848 Oreochromis niloticus 90.96 0.00e+00 1093.00
IUUC-Oan-073041 Ornithorhynchus anatinus 97.51 5.00e-165 573.00
IUUC-Ocu-074379 Oryctolagus cuniculus 99.12 0.00e+00 1147.00
IUUC-Oin-079973 Oryza indica 32.05 1.00e-33 138.00
IUUC-Osa-085891 Oryza sativa 32.05 3.00e-35 143.00
IUUC-Ola-087469 Oryzias latipes 90.96 0.00e+00 1093.00
IUUC-Oga-088004 Otolemur garnettii 99.16 7.00e-142 496.00
IUUC-Oar-090144 Ovis aries 98.42 0.00e+00 1137.00
IUUC-Ptr-091406 Pan troglodytes 100.00 0.00e+00 1157.00
IUUC-Pan-092762 Papio anubis 98.95 0.00e+00 1138.00
IUUC-Psi-093391 Pelodiscus sinensis 95.92 0.00e+00 1114.00
IUUC-Pma-094134 Petromyzon marinus 74.36 0.00e+00 833.00
IUUC-Pfo-096404 Poecilia formosa 91.01 0.00e+00 1096.00
IUUC-Pab-098425 Pongo abelii 99.12 0.00e+00 1142.00
IUUC-Pop-099216 Populus trichocarpa 33.74 1.00e-30 127.00
IUUC-Pca-101093 Procavia capensis 99.66 2.00e-173 602.00
IUUC-Pva-102239 Pteropus vampyrus 89.08 0.00e+00 1032.00
IUUC-Rno-104921 Rattus norvegicus 99.47 0.00e+00 1154.00
IUUC-Sha-106625 Sarcophilus harrisii 98.77 0.00e+00 1144.00
IUUC-Sly-111189 Solanum lycopersicum 35.87 2.00e-27 115.00
IUUC-Sar-113468 Sorex araneus 87.56 0.00e+00 717.00
IUUC-Ssc-116106 Sus scrofa 99.47 0.00e+00 1149.00
IUUC-Tgu-117402 Taeniopygia guttata 74.58 0.00e+00 749.00
IUUC-Tru-117546 Takifugu rubripes 90.43 0.00e+00 1088.00
IUUC-Tsy-118802 Tarsius syrichta 89.75 0.00e+00 1000.00
IUUC-Tni-119999 Tetraodon nigroviridis 90.09 0.00e+00 1083.00
IUUC-Tca-121074 Theobroma cacao 30.96 7.00e-38 152.00
IUUC-Tbe-127987 Tupaia belangeri 99.57 0.00e+00 966.00
IUUC-Ttr-128613 Tursiops truncatus 92.42 0.00e+00 1047.00
IUUC-Xtr-132401 Xenopus tropicalis 92.23 8.00e-175 605.00
Created Date 25-Jun-2017

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