KLHL12 kelch like family member 12 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KLHL12provided by HGNC
Official Full Name: kelch like family member 12provided by HGNC
Primary source: HGNC:HGNC:19360
See related: Ensembl:ENSG00000117153 MIM:614522; AllianceGenome:HGNC:19360
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DKIR; C3IP1
Summary: This gene encodes a member of the KLHL (Kelch-like) family of proteins. This protein has been identified as an autoantigen in the autoimmune disease Sjogren's syndrome and as a potential biomarker in primary biliary cirrhosis. This protein may act as a substrate adaptor of the Cullin-3 ubiquitin ligase complex to promote substrate-specific ubiquitylation. Ubiquitylation by this complex has been shown to regulate the Wnt signaling pathway as well as COPII vesicle coat size. A pseudogene has been identified on chromosome 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
Expression: Ubiquitous expression in testis (RPKM 23.4), brain (RPKM 11.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q32.1

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (202891120..202928599, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (202153802..202191306, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (202860248..202897727, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3(KLHL12) Ubiquitin Ligase Complex.
Title: Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3(KLHL12) Ubiquitin Ligase Complex.
Identification of a PGXPP degron motif in dishevelled and structural basis for its binding to the E3 ligase KLHL12.
Title: Identification of a PGXPP degron motif in dishevelled and structural basis for its binding to the E3 ligase KLHL12.
The interaction between the KLHL12 and the C-terminal domain of KHSRP contributed to KHSRP ubiquitination, leading to downregulation of enterovirus internal ribosome entry sites-mediated translation in infected cells.
Title: Control of the negative IRES trans-acting factor KHSRP by ubiquitination.
p44/42 MAPK phosphorylation, the signaling pathway which is often regulated by beta-arrestins is not influenced by KLHL12, but seems to be exclusively mediated by Galphai protein upon dopamine D4 receptor stimulation.
Title: Characterization of the interaction between the dopamine D4 receptor, KLHL12 and β-arrestins.
KLHL12 promotes ubiquitination of the dopamine D4 receptor on non-lysine residues.
Title: KLHL12 Promotes Non-Lysine Ubiquitination of the Dopamine Receptors D4.2 and D4.4, but Not of the ADHD-Associated D4.7 Variant.
Observational study of gene-disease association. (HuGE Navigator)
Title: Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study.
KLHL12 specifically interacts with the D4 polymorphism, thereby building up a Cul3-E3 ligase complex with substrate specificity toward the D4 receptor
Title: BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase.
molecular cloning and characterization of a novel gene, encoded a human kelch protein containing 568 amino acid residues, termed hDKIR.
Title: hDKIR, a human homologue of the Drosophila kelch protein, involved in a ring-like structure.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH38852 (e-PCR)
- UniSTS:91684

RH123350 (e-PCR)
- UniSTS:135727

AL034249 (e-PCR)
- UniSTS:94067

SHGC-76168 (e-PCR)
- UniSTS:68605

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-like ligase-substrate adaptor activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in COPII vesicle coating	IBA Inferred from Biological aspect of Ancestor more info
involved_in COPII vesicle coating	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endoplasmic reticulum to Golgi vesicle-mediated transport	IDA Inferred from Direct Assay more info	PubMed
involved_in endoplasmic reticulum to Golgi vesicle-mediated transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neural crest cell development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neural crest formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein monoubiquitination	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of COPII vesicle coat	IDA Inferred from Direct Assay more info	PubMed
is_active_in COPII-coated ER to Golgi transport vesicle	IBA Inferred from Biological aspect of Ancestor more info
located_in COPII-coated ER to Golgi transport vesicle	IDA Inferred from Direct Assay more info	PubMed
part_of Cul3-RING ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of Cul3-RING ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
located_in centriolar satellite	IDA Inferred from Direct Assay more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: kelch-like protein 12

Names: CUL3-interacting protein 1; DKIR homolog; kelch-like protein C3IP1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001303051.2 → NP_001289980.1 kelch-like protein 12 isoform 1

See identical proteins and their annotated locations for NP_001289980.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AK024412, AK027656, AK301791

UniProtKB/Swiss-Prot

Q53G59

UniProtKB/TrEMBL

Q9H7R2

Conserved Domains (5) summary

smart00612
Location:512 → 558

Kelch; Kelch domain

PHA03098
Location:84 → 539

PHA03098; kelch-like protein; Provisional

sd00038
Location:454 → 497

Kelch; KELCH repeat [structural motif]

pfam00651
Location:61 → 164

BTB; BTB/POZ domain

pfam07707
Location:173 → 274

BACK; BTB And C-terminal Kelch
NM_001303109.2 → NP_001290038.1 kelch-like protein 12 isoform 3

See identical proteins and their annotated locations for NP_001290038.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate 5' terminal exon, resulting in a distinct 5' UTR and an in-frame downstream translational start site, and lacks two alternate internal exons in the 3' coding region, compared to variant 1. This results in isoform 3, which is shorter compared to isoform 1.

Source sequence(s)

AF306689, AK024412, AK027656, AK301791

UniProtKB/Swiss-Prot

Q53G59

UniProtKB/TrEMBL

Q9H7R2

Conserved Domains (5) summary

smart00612
Location:373 → 419

Kelch; Kelch domain

PLN02193
Location:317 → 461

PLN02193; nitrile-specifier protein

sd00038
Location:315 → 358

Kelch; KELCH repeat [structural motif]

cd18242
Location:12 → 135

BTB_POZ_KLHL12_C3IP1_DKIR; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 12 (KLHL12)

cd18452
Location:130 → 265

BACK_KLHL12; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 12 (KLHL12)
NM_021633.4 → NP_067646.1 kelch-like protein 12 isoform 2

See identical proteins and their annotated locations for NP_067646.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate 5' terminal exon, resulting in a distinct 5' UTR and an in-frame downstream translational start site, compared to variant 1. This results in isoform 2, which has a shorter N-terminus compared to isoform 1.

Source sequence(s)

AK024412, AK027656, AK301791

Consensus CDS

CCDS1429.1

UniProtKB/Swiss-Prot

A6NEN8, B7Z7B8, Q53G59, Q9HBX5

Related

ENSP00000356230.3, ENST00000367261.8

Conserved Domains (5) summary

smart00612
Location:521 → 565

Kelch; Kelch domain

PHA03098
Location:46 → 501

PHA03098; kelch-like protein; Provisional

sd00038
Location:416 → 459

Kelch; KELCH repeat [structural motif]

cd18242
Location:12 → 135

BTB_POZ_KLHL12_C3IP1_DKIR; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 12 (KLHL12)

cd18452
Location:130 → 265

BACK_KLHL12; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 12 (KLHL12)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

202891120..202928599 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047426918.1 → XP_047282874.1 kelch-like protein 12 isoform X5
XM_011509837.3 → XP_011508139.1 kelch-like protein 12 isoform X3

Conserved Domains (5) summary

smart00612
Location:428 → 474

Kelch; Kelch domain

smart00225
Location:89 → 185

BTB; Broad-Complex, Tramtrack and Bric a brac

sd00038
Location:370 → 413

Kelch; KELCH repeat [structural motif]

pfam00651
Location:78 → 181

BTB; BTB/POZ domain

pfam07707
Location:190 → 291

BACK; BTB And C-terminal Kelch
XM_011509836.3 → XP_011508138.1 kelch-like protein 12 isoform X2

Conserved Domains (6) summary

smart00612
Location:436 → 481

Kelch; Kelch domain

smart00225
Location:89 → 185

BTB; Broad-Complex, Tramtrack and Bric a brac

sd00038
Location:374 → 420

Kelch; KELCH repeat [structural motif]

pfam00651
Location:78 → 181

BTB; BTB/POZ domain

pfam01344
Location:470 → 514

Kelch_1; Kelch motif

pfam07707
Location:190 → 291

BACK; BTB And C-terminal Kelch
XM_011509835.3 → XP_011508137.1 kelch-like protein 12 isoform X1

See identical proteins and their annotated locations for XP_011508137.1

Conserved Domains (5) summary

smart00612
Location:529 → 575

Kelch; Kelch domain

PHA03098
Location:101 → 556

PHA03098; kelch-like protein; Provisional

sd00038
Location:471 → 514

Kelch; KELCH repeat [structural motif]

pfam00651
Location:78 → 181

BTB; BTB/POZ domain

pfam07707
Location:190 → 291

BACK; BTB And C-terminal Kelch
XM_047426919.1 → XP_047282875.1 kelch-like protein 12 isoform X6
XM_017001995.3 → XP_016857484.1 kelch-like protein 12 isoform X4

Conserved Domains (5) summary

smart00612
Location:381 → 426

Kelch; Kelch domain

PLN02193
Location:269 → 468

PLN02193; nitrile-specifier protein

sd00038
Location:319 → 365

Kelch; KELCH repeat [structural motif]

cd18242
Location:12 → 135

BTB_POZ_KLHL12_C3IP1_DKIR; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 12 (KLHL12)

cd18452
Location:130 → 265

BACK_KLHL12; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 12 (KLHL12)