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
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
- covalent chromatin modification Source: UniProtKB-KW
- DNA replication initiation Source: UniProtKB
- establishment of protein localization to chromatin Source: UniProtKB
Keywordsi
Molecular function | Chromatin regulator |
Biological process | DNA replication |
Enzyme and pathway databases
SignaLinki | Q9UFC0. |
Names & Taxonomyi
Protein namesi | Recommended name: Leucine-rich repeat and WD repeat-containing protein 1Alternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000161036.10. |
HGNCi | HGNC:21769. LRWD1. |
MIMi | 615167. gene. |
neXtProti | NX_Q9UFC0. |
Subcellular locationi
Keywords - Cellular componenti
Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus, TelomerePathology & Biotechi
Organism-specific databases
DisGeNETi | 222229. |
OpenTargetsi | ENSG00000161036. |
PharmGKBi | PA162394694. |
Polymorphism and mutation databases
BioMutai | LRWD1. |
DMDMi | 74761931. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000310994 | 1 – 647 | Leucine-rich repeat and WD repeat-containing protein 1Add BLAST | 647 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 212 | PhosphoserineCombined sources | 1 | |
Modified residuei | 243 | PhosphoserineCombined sources | 1 | |
Modified residuei | 251 | PhosphoserineCombined sources | 1 | |
Modified residuei | 259 | PhosphoserineCombined sources | 1 | |
Modified residuei | 264 | PhosphoserineCombined sources | 1 |
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 conjugationProteomic databases
EPDi | Q9UFC0. |
MaxQBi | Q9UFC0. |
PaxDbi | Q9UFC0. |
PeptideAtlasi | Q9UFC0. |
PRIDEi | Q9UFC0. |
PTM databases
iPTMneti | Q9UFC0. |
PhosphoSitePlusi | Q9UFC0. |
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
Bgeei | ENSG00000161036. |
CleanExi | HS_LRWD1. |
ExpressionAtlasi | Q9UFC0. baseline and differential. |
Genevisiblei | Q9UFC0. HS. |
Organism-specific databases
HPAi | HPA021320. 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
Protein-protein interaction databases
BioGridi | 128790. 49 interactors. |
IntActi | Q9UFC0. 28 interactors. |
MINTi | Q9UFC0. |
STRINGi | 9606.ENSP00000292616. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 22 – 43 | LRR 1Add BLAST | 22 | |
Repeati | 48 – 69 | LRR 2Add BLAST | 22 | |
Repeati | 70 – 91 | LRR 3Add BLAST | 22 | |
Repeati | 92 – 113 | LRR 4Add BLAST | 22 | |
Repeati | 282 – 335 | WD 1Add BLAST | 54 | |
Repeati | 341 – 379 | WD 2Add BLAST | 39 | |
Repeati | 383 – 422 | WD 3Add BLAST | 40 | |
Repeati | 426 – 472 | WD 4Add BLAST | 47 | |
Repeati | 484 – 526 | WD 5Add BLAST | 43 | |
Repeati | 542 – 582 | WD 6Add BLAST | 41 | |
Repeati | 598 – 646 | WD 7Add BLAST | 49 |
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 repeatPhylogenomic databases
eggNOGi | KOG0619. Eukaryota. COG4886. LUCA. |
GeneTreei | ENSGT00390000008446. |
HOGENOMi | HOG000113393. |
HOVERGENi | HBG076949. |
InParanoidi | Q9UFC0. |
OMAi | RRVCEVE. |
OrthoDBi | EOG091G0I17. |
PhylomeDBi | Q9UFC0. |
TreeFami | TF329554. |
Family and domain databases
Gene3Di | 2.130.10.10. 1 hit. 3.80.10.10. 1 hit. |
InterProi | View 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. |
Pfami | View protein in Pfam PF12799. LRR_4. 1 hit. |
SMARTi | View protein in SMART SM00369. LRR_TYP. 1 hit. SM00320. WD40. 3 hits. |
SUPFAMi | SSF50978. SSF50978. 1 hit. |
PROSITEi | View 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. |
i Sequence
Sequence statusi: Complete.
Q9UFC0-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 629 | F → S in BAF83656 (PubMed:14702039).Curated | 1 |
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. |
CCDSi | CCDS34715.1. |
PIRi | T42659. |
RefSeqi | NP_001304650.1. NM_001317721.1. NP_690852.1. NM_152892.2. |
UniGenei | Hs.274135. |
Genome annotation databases
Ensembli | ENST00000292616; ENSP00000292616; ENSG00000161036. |
GeneIDi | 222229. |
KEGGi | hsa:222229. |
UCSCi | uc003uzn.4. human. |
Similar proteinsi
Entry informationi
Entry namei | LRWD1_HUMAN | |
Accessioni | Q9UFC0Primary (citable) accession number: Q9UFC0 Secondary accession number(s): A8K4K2 Q96GJ2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 13, 2007 |
Last sequence update: | October 25, 2004 | |
Last modified: | February 28, 2018 | |
This is version 145 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |