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Protein

Leucine-rich repeat and WD repeat-containing protein 1

Gene

LRWD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

  • chromatin organization Source: UniProtKB
  • DNA replication initiation Source: UniProtKB
  • establishment of protein localization to chromatin Source: UniProtKB

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000161036.10
HGNCiHGNC:21769 LRWD1
MIMi615167 gene
neXtProtiNX_Q9UFC0

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

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
ProteomicsDBi84177

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

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

Protein-protein interaction databases

BioGridi128790, 49 interactors
IntActiQ9UFC0, 29 interactors
MINTiQ9UFC0
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
IPR001611 Leu-rich_rpt
IPR025875 Leu-rich_rpt_4
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
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
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

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 20, 2018
This is version 148 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

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