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UniProtKB - Q9UFC0 (LRWD1_HUMAN)

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Protein

Leucine-rich repeat and WD repeat-containing protein 1

Gene

LRWD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for G1/S transition. Recruits and stabilizes the origin recognition complex (ORC) onto chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative manner with DNA methylation. Required for silencing of major satellite repeats. May be important ORC2, ORC3 and ORC4 stability.5 Publications

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • methylated histone binding Source: UniProtKB
  • methyl-CpG binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  • chromatin organization Source: UniProtKB
  • covalent chromatin modification Source: UniProtKB-KW
  • DNA replication initiation Source: UniProtKB
  • establishment of protein localization to chromatin Source: UniProtKB
Complete GO annotation...

Keywordsi

Molecular functionChromatin regulator
Biological processDNA replication

Enzyme and pathway databases

SignaLinkiQ9UFC0.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat and WD repeat-containing protein 1
Alternative name(s):
Centromere protein 33
Short name:
CENP-33
Origin recognition complex-associated protein
Short name:
ORC-associated protein
Short name:
ORCA
Gene namesi
Name:LRWD1
Synonyms:CENP-331 Publication, ORCA
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 7

Organism-specific databases

HGNCiHGNC:21769. LRWD1.

Subcellular locationi

GO - Cellular componenti

  • condensed chromosome kinetochore Source: UniProtKB-SubCell
  • cytosol Source: HPA
  • kinetochore Source: UniProtKB
  • microtubule organizing center Source: UniProtKB-SubCell
  • nuclear origin of replication recognition complex Source: UniProtKB
  • nucleolus Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • pericentric heterochromatin Source: UniProtKB
  • telomeric heterochromatin Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus, Telomere

Pathology & Biotechi

Organism-specific databases

DisGeNETi222229.
OpenTargetsiENSG00000161036.
PharmGKBiPA162394694.

Polymorphism and mutation databases

BioMutaiLRWD1.
DMDMi74761931.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003109941 – 647Leucine-rich repeat and WD repeat-containing protein 1Add BLAST647

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei212PhosphoserineCombined sources1
Modified residuei243PhosphoserineCombined sources1
Modified residuei251PhosphoserineCombined sources1
Modified residuei259PhosphoserineCombined sources1
Modified residuei264PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination leading to proteasomal degradation. Ubiquitination occurs within the WD repeats at the end of the G1 phase. Ubiquitination may be catalyzed by the CUL4-DDB1 E3 ubiquitin-protein ligase complex and other E3 ligases.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UFC0.
MaxQBiQ9UFC0.
PaxDbiQ9UFC0.
PeptideAtlasiQ9UFC0.
PRIDEiQ9UFC0.

PTM databases

iPTMnetiQ9UFC0.
PhosphoSitePlusiQ9UFC0.

Expressioni

Tissue specificityi

Testis-specific. Drastically down-regulated in testis from patients with Sertoli cell-only syndrome (SCOS).1 Publication

Developmental stagei

Regulated in a cell-cycle dependent manner. Highest expression in G1 phase. Expression decreases during S phase, rises again during G2 and drops during mitosis (at protein level). In contrast to protein levels, transcript levels do not show any significant variation during different stages of the cell cycle (PubMed:22935713).2 Publications

Gene expression databases

BgeeiENSG00000161036.
CleanExiHS_LRWD1.
ExpressionAtlasiQ9UFC0. baseline and differential.
GenevisibleiQ9UFC0. HS.

Organism-specific databases

HPAiHPA021320.
HPA029916.

Interactioni

Subunit structurei

Integral component of the ORC complex. Directly interacts with CDT1, GMNN and ORC2. Interacts with ORC2 only when non-ubiquitinated; this interaction prevents LRWD1 ubiquitination and degradation. Some of these interactions are regulated in a cell-cycle dependent manner. Interaction with ORC1 occurs predominantly during G1. Association with phosphorylated ORC1 during mitosis is not efficient. Interaction with CDT1 occurs during G1 phase, as well as during mitosis with phosphorylated CDT1. Interaction with GMNN occurs from G1/S to mitosis. Interaction with ORC2 is observed throughout the cell cycle. The stoichiometry of the ORCA/ORC/CDT1/GMNN complex is 1:1:1:2. Interacts with CUL4A and DDB1; this interaction may lead to ubiquitination.5 Publications

GO - Molecular functioni

  • methylated histone binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi128790. 45 interactors.
IntActiQ9UFC0. 28 interactors.
MINTiMINT-7944578.
STRINGi9606.ENSP00000292616.

Structurei

3D structure databases

ProteinModelPortaliQ9UFC0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati22 – 43LRR 1Add BLAST22
Repeati48 – 69LRR 2Add BLAST22
Repeati70 – 91LRR 3Add BLAST22
Repeati92 – 113LRR 4Add BLAST22
Repeati282 – 335WD 1Add BLAST54
Repeati341 – 379WD 2Add BLAST39
Repeati383 – 422WD 3Add BLAST40
Repeati426 – 472WD 4Add BLAST47
Repeati484 – 526WD 5Add BLAST43
Repeati542 – 582WD 6Add BLAST41
Repeati598 – 646WD 7Add BLAST49

Domaini

The entire WD repeat region is required for the interaction with ORC, CDT1 and GMNN, as well as for association with chromatin and for binding to histone H3 and H4 trimethylation marks H3K9me3 and H4K20me3.3 Publications

Sequence similaritiesi

Belongs to the LRWD1 family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00390000008446.
HOGENOMiHOG000113393.
HOVERGENiHBG076949.
InParanoidiQ9UFC0.
OMAiRRVCEVE.
OrthoDBiEOG091G0I17.
PhylomeDBiQ9UFC0.
TreeFamiTF329554.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
3.80.10.10. 1 hit.
InterProiView protein in InterPro
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
PfamiView protein in Pfam
PF12799. LRR_4. 1 hit.
SMARTiView protein in SMART
SM00369. LRR_TYP. 1 hit.
SM00320. WD40. 3 hits.
SUPFAMiSSF50978. SSF50978. 1 hit.
SSF52058. SSF52058. 1 hit.
PROSITEiView protein in PROSITE
PS51450. LRR. 3 hits.
PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9UFC0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPLSARLLM QRGRPKSDRL GKIRSLDLSG LELLSEHLDP KLLCRLTQLQ 
        60         70         80         90        100
ELDLSNNHLE TLPDNLGLSH LRVLRCANNQ LGDVTALCQF PKLEELSLEG 
       110        120        130        140        150
NPFLTVNDNL KVSFLLPTLR KVNGKDASST YSQVENLNRE LTSRVTAHWE 
       160        170        180        190        200
KFMATLGPEE EAEKAQADFV KSAVRDVRYG PESLSEFTQW RVRMISEELV 
       210        220        230        240        250
AASRTQVQKA NSPEKPPEAG AAHKPRARLA ALKRPDDVPL SLSPSKRACA 
       260        270        280        290        300
SPSAQVEGSP VAGSDGSQPA VKLEPLHFLQ CHSKNNSPQD LETQLWACAF 
       310        320        330        340        350
EPAWEEGATS QTVATCGGEA VCVIDCQTGI VLHKYKAPGE EFFSVAWTAL 
       360        370        380        390        400
MVVTQAGHKK RWSVLAAAGL RGLVRLLHVR AGFCCGVIRA HKKAIATLCF 
       410        420        430        440        450
SPAHETHLFT ASYDKRIILW DIGVPNQDYE FQASQLLTLD TTSIPLRLCP 
       460        470        480        490        500
VASCPDARLL AGCEGGCCCW DVRLDQPQKR RVCEVEFVFS EGSEASGRRV 
       510        520        530        540        550
DGLAFVNEDI VASKGSGLGT ICLWSWRQTW GGRGSQSTVA VVVLARLQWS 
       560        570        580        590        600
STELAYFSLS ACPDKGIVLC GDEEGNVWLY DVSNILKQPP LLPAALQAPT 
       610        620        630        640 
QILKWPQPWA LGQVVTKTMV NTVVANASFT YLTALTDSNI VAIWGRM
Length:647
Mass (Da):70,861
Last modified:October 25, 2004 - v2
Checksum:i59C6ABF57A957D9F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti629F → S in BAF83656 (PubMed:14702039).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK290967 mRNA. Translation: BAF83656.1.
AK313771 mRNA. Translation: BAG36509.1.
AL133057 mRNA. Translation: CAB61382.2.
AC093668 Genomic DNA. No translation available.
CH471197 Genomic DNA. Translation: EAW50250.1.
BC009436 mRNA. Translation: AAH09436.1.
BC018769 mRNA. Translation: AAH18769.1.
BC030547 mRNA. Translation: AAH30547.1.
CCDSiCCDS34715.1.
PIRiT42659.
RefSeqiNP_001304650.1. NM_001317721.1.
NP_690852.1. NM_152892.2.
UniGeneiHs.274135.

Genome annotation databases

EnsembliENST00000292616; ENSP00000292616; ENSG00000161036.
GeneIDi222229.
KEGGihsa:222229.
UCSCiuc003uzn.4. human.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiLRWD1_HUMAN
AccessioniPrimary (citable) accession number: Q9UFC0
Secondary accession number(s): A8K4K2
, B2R9G2, Q8N0T9, Q8WV43, Q96GJ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: October 25, 2004
Last modified: June 7, 2017
This is version 140 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families