Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - Q53G59 (KLH12_HUMAN)

(max 400 entries)x

Your basket is currently empty. i

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Kelch-like protein 12

Gene

KLHL12

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

Functioni

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).6 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 - Molecular functioni

  • identical protein binding Source: IntAct
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • COPII vesicle coating Source: UniProtKB
  • ER to Golgi vesicle-mediated transport Source: UniProtKB
  • negative regulation of canonical Wnt signaling pathway Source: Reactome
  • neural crest cell development Source: UniProtKB
  • neural crest formation Source: UniProtKB
  • protein monoubiquitination Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Biological processER-Golgi transport, Transport, Ubl conjugation pathway, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-4641258 Degradation of DVL
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like protein 12
Alternative name(s):
CUL3-interacting protein 11 Publication
DKIR homolog1 Publication
Short name:
hDKIR1 Publication
Gene namesi
Name:KLHL12
Synonyms:C3IP11 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000117153.15
HGNCiHGNC:19360 KLHL12
MIMi614522 gene
neXtProtiNX_Q53G59

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

Cytoplasmic vesicle

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi289 – 290FG → AA: Abolishes interaction with SEC31A and subsequent monoubiquitination of SEC31A. Abolishes ubiquitination of PEF1. 2 Publications2

Organism-specific databases

DisGeNETi59349
OpenTargetsiENSG00000117153
PharmGKBiPA134952416

Polymorphism and mutation databases

BioMutaiKLHL12
DMDMi97054498

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002343491 – 568Kelch-like protein 12Add BLAST568

Proteomic databases

EPDiQ53G59
MaxQBiQ53G59
PaxDbiQ53G59
PeptideAtlasiQ53G59
PRIDEiQ53G59
ProteomicsDBi62474
62475 [Q53G59-2]

PTM databases

iPTMnetiQ53G59
PhosphoSitePlusiQ53G59

Expressioni

Tissue specificityi

Ubiquitously expressed. Highly expressed in testis and at lower levels in the submandibular salivary gland.2 Publications

Gene expression databases

BgeeiENSG00000117153
CleanExiHS_KLHL12
ExpressionAtlasiQ53G59 baseline and differential
GenevisibleiQ53G59 HS

Organism-specific databases

HPAiHPA071324

Interactioni

Subunit structurei

Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1 (PubMed:22358839). This complex interacts with DVL3 upon activation of the Wnt signaling pathway by WNT3A (PubMed:16547521). Interacts with DRD4, KLHL2 and SEC31A (PubMed:15383316,PubMed:18303015, PubMed:22358839). Interacts with PEF1 and PDCD6/ALG-2; interaction takes place in response to cytosolic calcium increase and leads to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B) (PubMed:27716508).5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi121890, 67 interactors
CORUMiQ53G59
IntActiQ53G59, 77 interactors
MINTiQ53G59
STRINGi9606.ENSP00000356230

Structurei

Secondary structure

1568
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi281 – 286Combined sources6
Turni291 – 293Combined sources3
Beta strandi299 – 303Combined sources5
Turni304 – 307Combined sources4
Beta strandi308 – 311Combined sources4
Beta strandi323 – 327Combined sources5
Beta strandi330 – 334Combined sources5
Beta strandi346 – 350Combined sources5
Beta strandi360 – 362Combined sources3
Beta strandi373 – 377Combined sources5
Beta strandi380 – 384Combined sources5
Beta strandi395 – 400Combined sources6
Turni401 – 404Combined sources4
Beta strandi405 – 411Combined sources7
Beta strandi420 – 424Combined sources5
Beta strandi427 – 431Combined sources5
Beta strandi443 – 446Combined sources4
Turni448 – 450Combined sources3
Beta strandi453 – 456Combined sources4
Beta strandi467 – 471Combined sources5
Beta strandi474 – 478Combined sources5
Beta strandi483 – 486Combined sources4
Beta strandi490 – 494Combined sources5
Turni495 – 498Combined sources4
Beta strandi499 – 503Combined sources5
Beta strandi514 – 518Combined sources5
Beta strandi521 – 525Combined sources5
Beta strandi530 – 541Combined sources12
Turni542 – 545Combined sources4
Beta strandi546 – 559Combined sources14
Beta strandi561 – 566Combined sources6

3D structure databases

ProteinModelPortaliQ53G59
SMRiQ53G59
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ53G59

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 100BTBPROSITE-ProRule annotationAdd BLAST68
Domaini135 – 236BACKAdd BLAST102
Repeati282 – 329Kelch 1Add BLAST48
Repeati331 – 379Kelch 2Add BLAST49
Repeati380 – 426Kelch 3Add BLAST47
Repeati427 – 473Kelch 4Add BLAST47
Repeati475 – 520Kelch 5Add BLAST46
Repeati522 – 567Kelch 6Add BLAST46

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni405 – 568Interaction with DVL31 PublicationAdd BLAST164

Domaini

The BTB domain is required for interaction with CUL3.

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00760000118931
HOGENOMiHOG000230814
HOVERGENiHBG014286
InParanoidiQ53G59
KOiK10450
OMAiTEPFIRC
OrthoDBiEOG091G04QJ
PhylomeDBiQ53G59
TreeFamiTF329218

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
IPR011333 SKP1/BTB/POZ_sf
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 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: Q53G59-1) [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
MGGIMAPKDI MTNTHAKSIL NSMNSLRKSN TLCDVTLRVE QKDFPAHRIV 
        60         70         80         90        100
LAACSDYFCA MFTSELSEKG KPYVDIQGLT ASTMEILLDF VYTETVHVTV 
       110        120        130        140        150
ENVQELLPAA CLLQLKGVKQ ACCEFLESQL DPSNCLGIRD FAETHNCVDL 
       160        170        180        190        200
MQAAEVFSQK HFPEVVQHEE FILLSQGEVE KLIKCDEIQV DSEEPVFEAV 
       210        220        230        240        250
INWVKHAKKE REESLPNLLQ YVRMPLLTPR YITDVIDAEP FIRCSLQCRD 
       260        270        280        290        300
LVDEAKKFHL RPELRSQMQG PRTRARLGAN EVLLVVGGFG SQQSPIDVVE 
       310        320        330        340        350
KYDPKTQEWS FLPSITRKRR YVASVSLHDR IYVIGGYDGR SRLSSVECLD 
       360        370        380        390        400
YTADEDGVWY SVAPMNVRRG LAGATTLGDM IYVSGGFDGS RRHTSMERYD 
       410        420        430        440        450
PNIDQWSMLG DMQTAREGAG LVVASGVIYC LGGYDGLNIL NSVEKYDPHT 
       460        470        480        490        500
GHWTNVTPMA TKRSGAGVAL LNDHIYVVGG FDGTAHLSSV EAYNIRTDSW 
       510        520        530        540        550
TTVTSMTTPR CYVGATVLRG RLYAIAGYDG NSLLSSIECY DPIIDSWEVV 
       560 
TSMGTQRCDA GVCVLREK
Length:568
Mass (Da):63,277
Last modified:May 16, 2006 - v2
Checksum:i4EB1BC33B6351B5D
GO
Isoform 2 (identifier: Q53G59-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MDVNKFEASVGFLDVKKFLSTWKLQNPRTHFVLSPHCFM

Show »
Length:606
Mass (Da):67,727
Checksum:i47F91BE5B8ED7C33
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti122C → R in BAD96792 (Ref. 3) Curated1
Sequence conflicti197 – 198FE → LG in BAD96792 (Ref. 3) Curated2
Sequence conflicti394T → A in BAD96792 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05004972P → L. Corresponds to variant dbSNP:rs12569087Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0429751M → MDVNKFEASVGFLDVKKFLS TWKLQNPRTHFVLSPHCFM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190900 mRNA Translation: AAG17175.1
AK027656 mRNA Translation: BAB55271.1
AK301791 mRNA Translation: BAH13554.1
AK223072 mRNA Translation: BAD96792.1
AC096632 Genomic DNA No translation available.
BC003183 mRNA Translation: AAH03183.1
BC004175 mRNA Translation: AAH04175.1
CCDSiCCDS1429.1 [Q53G59-1]
RefSeqiNP_001289980.1, NM_001303051.1 [Q53G59-2]
NP_001290038.1, NM_001303109.1
NP_067646.1, NM_021633.3 [Q53G59-1]
UniGeneiHs.706793

Genome annotation databases

EnsembliENST00000367261; ENSP00000356230; ENSG00000117153 [Q53G59-1]
GeneIDi59349
KEGGihsa:59349
UCSCiuc001gyo.2 human [Q53G59-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKLH12_HUMAN
AccessioniPrimary (citable) accession number: Q53G59
Secondary accession number(s): A6NEN8, B7Z7B8, Q9HBX5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: July 18, 2018
This is version 133 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health