Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q53G59 (KLH12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kelch-like protein 12
Alternative name(s):
CUL3-interacting protein 1
DKIR homolog
Short name=hDKIR
Gene names
Name:KLHL12
Synonyms:C3IP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length568 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. 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). 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. The BCR(KLHL12) complex also mediates polyubiquitination of DRD4, without leading to degradation of DRD4. Ref.8 Ref.9 Ref.10 Ref.11

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1. This complex interacts with DVL3 upon activation of the Wnt signaling pathway by WNT3A. Interacts with DRD4, KLHL12 and SEC31A. Ref.6 Ref.8 Ref.9 Ref.11

Subcellular location

Cytoplasmic vesicleCOPII-coated vesicle Ref.11.

Tissue specificity

Ubiquitously expressed. Highly expressed in testis and at lower levels in the submandibular salivary gland. Ref.6 Ref.7

Domain

The BTB domain is required for interaction with CUL3.

Sequence similarities

Contains 1 BACK (BTB/Kelch associated) domain.

Contains 1 BTB (POZ) domain.

Contains 6 Kelch repeats.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ATXN1P542532EBI-740929,EBI-930964
PEF1Q9UBV82EBI-740929,EBI-724639

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q53G59-1)

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.
Isoform 2 (identifier: Q53G59-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 568568Kelch-like protein 12
PRO_0000234349

Regions

Domain33 – 10068BTB
Domain135 – 236102BACK
Repeat282 – 32948Kelch 1
Repeat331 – 37949Kelch 2
Repeat380 – 42647Kelch 3
Repeat427 – 47347Kelch 4
Repeat475 – 52046Kelch 5
Repeat522 – 56746Kelch 6
Region405 – 568164Interaction with DVL3

Natural variations

Alternative sequence11M → MDVNKFEASVGFLDVKKFLS TWKLQNPRTHFVLSPHCFM in isoform 2.
VSP_042975
Natural variant721P → L.
Corresponds to variant rs12569087 [ dbSNP | Ensembl ].
VAR_050049

Experimental info

Mutagenesis289 – 2902FG → AA: Abolishes interaction with SEC31A and subsequent monoubiquitination of SEC31A. Ref.11
Sequence conflict1221C → R in BAD96792. Ref.3
Sequence conflict197 – 1982FE → LG in BAD96792. Ref.3
Sequence conflict3941T → A in BAD96792. Ref.3

Secondary structure

....................................................... 568
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 16, 2006. Version 2.
Checksum: 4EB1BC33B6351B5D

FASTA56863,277
        10         20         30         40         50         60 
MGGIMAPKDI MTNTHAKSIL NSMNSLRKSN TLCDVTLRVE QKDFPAHRIV LAACSDYFCA 

        70         80         90        100        110        120 
MFTSELSEKG KPYVDIQGLT ASTMEILLDF VYTETVHVTV ENVQELLPAA CLLQLKGVKQ 

       130        140        150        160        170        180 
ACCEFLESQL DPSNCLGIRD FAETHNCVDL MQAAEVFSQK HFPEVVQHEE FILLSQGEVE 

       190        200        210        220        230        240 
KLIKCDEIQV DSEEPVFEAV INWVKHAKKE REESLPNLLQ YVRMPLLTPR YITDVIDAEP 

       250        260        270        280        290        300 
FIRCSLQCRD LVDEAKKFHL RPELRSQMQG PRTRARLGAN EVLLVVGGFG SQQSPIDVVE 

       310        320        330        340        350        360 
KYDPKTQEWS FLPSITRKRR YVASVSLHDR IYVIGGYDGR SRLSSVECLD YTADEDGVWY 

       370        380        390        400        410        420 
SVAPMNVRRG LAGATTLGDM IYVSGGFDGS RRHTSMERYD PNIDQWSMLG DMQTAREGAG 

       430        440        450        460        470        480 
LVVASGVIYC LGGYDGLNIL NSVEKYDPHT GHWTNVTPMA TKRSGAGVAL LNDHIYVVGG 

       490        500        510        520        530        540 
FDGTAHLSSV EAYNIRTDSW TTVTSMTTPR CYVGATVLRG RLYAIAGYDG NSLLSSIECY 

       550        560 
DPIIDSWEVV TSMGTQRCDA GVCVLREK 

« Hide

Isoform 2 [UniParc].

Checksum: 47F91BE5B8ED7C33
Show »

FASTA60667,727

References

« Hide 'large scale' references
[1]"Sequence of a novel kelch-like protein, C3IP1."
Du M., Zu Z., Liou J.-Y., Chu K.-Y., Sansores Garcia L., Yeh E., Wu K.K.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"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. expand/collapse author list , 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] (ISOFORMS 1 AND 2).
Tissue: Teratocarcinoma, Testis and Thyroid.
[3]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(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] (ISOFORM 1).
Tissue: Kidney adenocarcinoma.
[6]"hDKIR, a human homologue of the Drosophila kelch protein, involved in a ring-like structure."
Mai A., Jung S.K., Yonehara S.
Exp. Cell Res. 300:72-83(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INTERACTION WITH KLHL2.
[7]"Identification of specific autoantigens in Sjoegren's syndrome by SEREX."
Uchida K., Akita Y., Matsuo K., Fujiwara S., Nakagawa A., Kazaoka Y., Hachiya H., Naganawa Y., Oh-Iwa I., Ohura K., Saga S., Kawai T., Matsumoto Y., Shimozato K., Kozaki K.
Immunology 116:53-63(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"The KLHL12-cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation."
Angers S., Thorpe C.J., Biechele T.L., Goldenberg S.J., Zheng N., Maccoss M.J., Moon R.T.
Nat. Cell Biol. 8:348-357(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH CUL3 AND DVL3.
[9]"BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase."
Rondou P., Haegeman G., Vanhoenacker P., Van Craenenbroeck K.
J. Biol. Chem. 283:11083-11096(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DRD4.
[10]"KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation."
Rondou P., Skieterska K., Packeu A., Lintermans B., Vanhoenacker P., Vauquelin G., Haegeman G., Van Craenenbroeck K.
Cell. Signal. 22:900-913(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Ubiquitin-dependent regulation of COPII coat size and function."
Jin L., Pahuja K.B., Wickliffe K.E., Gorur A., Baumgartel C., Schekman R., Rape M.
Nature 482:495-500(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE BCR(KLHL12) COMPLEX, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC31A, MUTAGENESIS OF 289-PHE-GLY-290.
[12]"Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases."
Canning P., Cooper C.D., Krojer T., Murray J.W., Pike A.C., Chaikuad A., Keates T., Thangaratnarajah C., Hojzan V., Marsden B.D., Gileadi O., Knapp S., von Delft F., Bullock A.N.
J. Biol. Chem. 288:7803-7814(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 268-567.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS1429.1. [Q53G59-1]
RefSeqNP_067646.1. NM_021633.2. [Q53G59-1]
XP_005245460.1. XM_005245403.1. [Q53G59-2]
UniGeneHs.706793.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VPJX-ray1.85A268-567[»]
ProteinModelPortalQ53G59.
SMRQ53G59. Positions 5-567.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121890. 27 interactions.
IntActQ53G59. 20 interactions.
MINTMINT-1434520.
STRING9606.ENSP00000356230.

PTM databases

PhosphoSiteQ53G59.

Polymorphism databases

DMDM97054498.

Proteomic databases

MaxQBQ53G59.
PaxDbQ53G59.
PRIDEQ53G59.

Protocols and materials databases

DNASU59349.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367261; ENSP00000356230; ENSG00000117153. [Q53G59-1]
ENST00000435533; ENSP00000416886; ENSG00000117153. [Q53G59-2]
GeneID59349.
KEGGhsa:59349.
UCSCuc001gyn.1. human. [Q53G59-1]
uc010pqc.1. human. [Q53G59-2]

Organism-specific databases

CTD59349.
GeneCardsGC01M202860.
HGNCHGNC:19360. KLHL12.
MIM614522. gene.
neXtProtNX_Q53G59.
PharmGKBPA134952416.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG73120.
HOGENOMHOG000230814.
HOVERGENHBG014286.
InParanoidQ53G59.
KOK10450.
OMARYDPHTG.
OrthoDBEOG7HTHGF.
PhylomeDBQ53G59.
TreeFamTF329218.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ53G59.
BgeeQ53G59.
CleanExHS_KLHL12.
GenevestigatorQ53G59.

Family and domain databases

Gene3D2.130.10.80. 1 hit.
3.30.710.10. 1 hit.
InterProIPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR015916. Gal_Oxidase_b-propeller.
IPR017096. Kelch-like_gigaxonin-typ.
IPR006652. Kelch_1.
[Graphical view]
PfamPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 6 hits.
[Graphical view]
PIRSFPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 6 hits.
[Graphical view]
SUPFAMSSF54695. SSF54695. 1 hit.
PROSITEPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSKLHL12. human.
EvolutionaryTraceQ53G59.
GeneWikiKLHL12.
GenomeRNAi59349.
NextBio65257.
PROQ53G59.
SOURCESearch...

Entry information

Entry nameKLH12_HUMAN
AccessionPrimary (citable) accession number: Q53G59
Secondary accession number(s): A6NEN8, B7Z7B8, Q9HBX5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: July 9, 2014
This is version 92 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM