LRWD1 leucine rich repeats and WD repeat domain containing 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LRWD1provided by HGNC
Official Full Name: leucine rich repeats and WD repeat domain containing 1provided by HGNC
Primary source: HGNC:HGNC:21769
See related: Ensembl:ENSG00000161036 MIM:615167; AllianceGenome:HGNC:21769
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: ORCA; CENP-33
Summary: The protein encoded by this gene interacts with components of the origin recognition complex (ORC) and regulates the formation of the prereplicative complex. The encoded protein stabilizes the ORC and therefore aids in DNA replication. This protein is required for the G1/S phase transition of the cell cycle. In addition, the encoded protein binds to trimethylated histone H3 in heterochromatin and recruits the ORC and lysine methyltransferases, which help maintain the repressive heterochromatic state. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]
Expression: Biased expression in testis (RPKM 101.1) and bone marrow (RPKM 5.9) See more
Orthologs: mouse all
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Genomic context

Location:: 7q22.1

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (102464984..102473168)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (103782613..103790767)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (102105431..102113615)

Chromosome 7 - NC_000007.14 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?

MicroRNA-320a enhances LRWD1 expression through the AGO2/FXR1-dependent pathway to affect cell behaviors and the oxidative stress response in human testicular embryonic carcinoma cells.
Title: MicroRNA-320a enhances LRWD1 expression through the AGO2/FXR1-dependent pathway to affect cell behaviors and the oxidative stress response in human testicular embryonic carcinoma cells.
Nuclear factor erythroid-2-related factor regulates LRWD1 expression and cellular adaptation to oxidative stress in human embryonal carcinoma cells
Title: Nuclear factor erythroid-2-related factor regulates LRWD1 expression and cellular adaptation to oxidative stress in human embryonal carcinoma cells.
a novel function of LRWD1 in controlling microtubule nucleation and cell cycle progression in the human testicular embryonic carcinoma cells.
Title: LRWD1 Regulates Microtubule Nucleation and Proper Cell Cycle Progression in the Human Testicular Embryonic Carcinoma Cells.
LRWD1 is a novel regulator of EWS-FLI1 driven cell proliferation in Ewing sarcoma cells. EWS-FLI1 regulates LRWD1 expression and LRWD1 may contribute to EWS-FLI1 mediated transcriptional repression.
Title: High-throughput RNAi screen in Ewing sarcoma cells identifies leucine rich repeats and WD repeat domain containing 1 (LRWD1) as a regulator of EWS-FLI1 driven cell viability.
Data show that ORCA acts as a scaffold for the establishment of H3K9 KMT complex.
Title: The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin.
This is the first study showing that the expression of the testis-enriched LRWD1 gene is regulated by NF-kappaB.
Title: Nuclear factor-κB (NF-κB) regulates the expression of human testis-enriched Leucine-rich repeats and WD repeat domain containing 1 (LRWD1) gene.
Data (from studies using recombinant proteins) suggest that deletion of leucine rich (LRR) domain significantly down-regulates expression of LRWD1 protein; LRR domain is significantly correlated with stability of LRWD1 protein.
Title: Correlation between leucine rich domain and the stability of LRWD1 protein in human NT2/D1 cells.
three coding single-nucleotide polymorphisms (SNP1-SNP3) could be detected in Japanese patients with Sertoli cell-only syndrome
Title: Single-nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.
Orc2 protects ORCA from ubiquitin-mediated degradation in vivo.
Title: Orc2 protects ORCA from ubiquitin-mediated degradation.
propose that the dynamic association of ORCA with pre-RC components modulates the assembly of its interacting partners on chromatin and facilitates DNA replication initiation
Title: Dynamic association of ORCA with prereplicative complex components regulates DNA replication initiation.

Submit: New GeneRIF Correction See all GeneRIFs (12)

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

STS-H73947 (e-PCR)
- UniSTS:5192

D1S1423 (e-PCR)
- UniSTS:149619

D1S1425 (e-PCR)
- UniSTS:149621

STS-L37127 (e-PCR)
- UniSTS:6631

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chromatin binding	IBA Inferred from Biological aspect of Ancestor more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables methyl-CpG binding	IDA Inferred from Direct Assay more info	PubMed
enables methylated histone binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA replication initiation	TAS Traceable Author Statement more info	PubMed
involved_in chromatin organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in chromatin organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of protein localization to chromatin	IBA Inferred from Biological aspect of Ancestor more info
involved_in establishment of protein localization to chromatin	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in centrosome	IEA Inferred from Electronic Annotation more info
located_in chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in kinetochore	IDA Inferred from Direct Assay more info	PubMed
part_of nuclear origin of replication recognition complex	IBA Inferred from Biological aspect of Ancestor more info
part_of nuclear origin of replication recognition complex	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in pericentric heterochromatin	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: leucine-rich repeat and WD repeat-containing protein 1

Names: ORC-associated protein; centromere protein 33; origin recognition complex-associated protein; testicular tissue protein Li 4

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_001317721.2 → NP_001304650.1 leucine-rich repeat and WD repeat-containing protein 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice junction at the 3' end of the first exon compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

BC009436, BC030547, HY051509

UniProtKB/Swiss-Prot

Q9UFC0

Conserved Domains (3) summary

COG2319
Location:157 → 432

WD40; WD40 repeat [General function prediction only]

sd00039
Location:206 → 238

7WD40; WD40 repeat [structural motif]

cl02567
Location:156 → 429

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
NM_152892.3 → NP_690852.1 leucine-rich repeat and WD repeat-containing protein 1 isoform 1

See identical proteins and their annotated locations for NP_690852.1

Status: REVIEWED

Description

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

Source sequence(s)

BC009436, BC030547

Consensus CDS

CCDS34715.1

UniProtKB/Swiss-Prot

A8K4K2, B2R9G2, Q8N0T9, Q8WV43, Q96GJ2, Q9UFC0

UniProtKB/TrEMBL

A0A140VJD0

Related

ENSP00000292616.5, ENST00000292616.10

Conserved Domains (6) summary

COG2319
Location:309 → 584

WD40; WD40 repeat [General function prediction only]

sd00031
Location:23 → 48

LRR_1; leucine-rich repeat [structural motif]

pfam12799
Location:47 → 87

LRR_4; Leucine Rich repeats (2 copies)

pfam13855
Location:47 → 103

LRR_8; Leucine rich repeat

sd00039
Location:295 → 337

7WD40; WD40 repeat [structural motif]

cl02567
Location:308 → 581

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...