Q9UFC0 (LRWD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leucine-rich repeat and WD repeat-containing protein 1

Alternative name(s):
ORC-associated protein
Short name=ORCA
Origin recognition complex-associated protein

Gene names

Name:	LRWD1
Synonyms:	ORCA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	647 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Associated component of the origin recognition complex (ORC) required to recruit and stabilize the ORC complex to chromatin. Probably required for the association of ORC on 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. It is unclear whether it recognizes and binds these repressive marks by itself or needs additional factors. Ref.10 Ref.11 Ref.12
Subunit structure	Component of the ORC complex. Ref.10 Ref.11 Ref.12
Subcellular location	Nucleus. Chromosome › centromere. Chromosome › telomere. Note: Localizes to heterochromatin during G1 phase. Restricted to centromeres or telomeres as cells progress though S phase. When cells enter mitosis, relocalizes to centromeres. Ref.11 Ref.12
Domain	The WD repeats are required for the interaction with ORC components. Ref.12
Sequence similarities	Belongs to the LRWD1 family. Contains 4 LRR (leucine-rich) repeats. Contains 5 WD repeats.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Centromere Chromosome Nucleus Telomere
Domain	Leucine-rich repeat Repeat WD repeat
Molecular function	Chromatin regulator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication initiation Traceable author statement Ref.12. Source: UniProtKB G1 phase of mitotic cell cycle Inferred from mutant phenotype Ref.12. Source: UniProtKB chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW chromatin organization Inferred from mutant phenotype Ref.12. Source: UniProtKB establishment of protein localization to chromatin Inferred from direct assay Ref.12. Source: UniProtKB
Cellular_component	centromeric heterochromatin Inferred from direct assay Ref.12. Source: UniProtKB nuclear origin of replication recognition complex Inferred from direct assay Ref.12Ref.11. Source: UniProtKB telomeric heterochromatin Inferred from direct assay Ref.12. Source: UniProtKB
Molecular_function	chromatin binding Inferred from direct assay Ref.12Ref.11. Source: UniProtKB methyl-CpG binding Inferred from direct assay Ref.11. Source: UniProtKB methylated histone residue binding Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 647	647	Leucine-rich repeat and WD repeat-containing protein 1		PRO_0000310994
Regions
	Repeat	22 – 43	22	LRR 1
	Repeat	48 – 69	22	LRR 2
	Repeat	70 – 91	22	LRR 3
	Repeat	92 – 113	22	LRR 4
	Repeat	390 – 430	41	WD 1
	Repeat	441 – 480	40	WD 2
	Repeat	495 – 534	40	WD 3
	Repeat	551 – 590	40	WD 4
	Repeat	615 – 647	33	WD 5
Amino acid modifications
	Modified residue	212	1	Phosphoserine Ref.6 Ref.9 Ref.13 Ref.14
	Modified residue	243	1	Phosphoserine Ref.8 Ref.9 Ref.13 Ref.14
	Modified residue	251	1	Phosphoserine Ref.8
	Modified residue	259	1	Phosphoserine Ref.7 Ref.8 Ref.9
Experimental info
	Sequence conflict	629	1	F → S in BAF83656. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UFC0 [UniParc]. Last modified October 25, 2004. Version 2. Checksum: 59C6ABF57A957D9F	FASTA	647	70,861
	10 20 30 40 50 60 MGPLSARLLM QRGRPKSDRL GKIRSLDLSG LELLSEHLDP KLLCRLTQLQ ELDLSNNHLE 70 80 90 100 110 120 TLPDNLGLSH LRVLRCANNQ LGDVTALCQF PKLEELSLEG NPFLTVNDNL KVSFLLPTLR 130 140 150 160 170 180 KVNGKDASST YSQVENLNRE LTSRVTAHWE KFMATLGPEE EAEKAQADFV KSAVRDVRYG 190 200 210 220 230 240 PESLSEFTQW RVRMISEELV AASRTQVQKA NSPEKPPEAG AAHKPRARLA ALKRPDDVPL 250 260 270 280 290 300 SLSPSKRACA SPSAQVEGSP VAGSDGSQPA VKLEPLHFLQ CHSKNNSPQD LETQLWACAF 310 320 330 340 350 360 EPAWEEGATS QTVATCGGEA VCVIDCQTGI VLHKYKAPGE EFFSVAWTAL MVVTQAGHKK 370 380 390 400 410 420 RWSVLAAAGL RGLVRLLHVR AGFCCGVIRA HKKAIATLCF SPAHETHLFT ASYDKRIILW 430 440 450 460 470 480 DIGVPNQDYE FQASQLLTLD TTSIPLRLCP VASCPDARLL AGCEGGCCCW DVRLDQPQKR 490 500 510 520 530 540 RVCEVEFVFS EGSEASGRRV DGLAFVNEDI VASKGSGLGT ICLWSWRQTW GGRGSQSTVA 550 560 570 580 590 600 VVVLARLQWS STELAYFSLS ACPDKGIVLC GDEEGNVWLY DVSNILKQPP LLPAALQAPT 610 620 630 640 QILKWPQPWA LGQVVTKTMV NTVVANASFT YLTALTDSNI VAIWGRM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Eye.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-243; SER-251 AND SER-259, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212; SER-243 AND SER-259, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers." Vermeulen M., Eberl H.C., Matarese F., Marks H., Denissov S., Butter F., Lee K.K., Olsen J.V., Hyman A.A., Stunnenberg H.G., Mann M. Cell 142:967-980(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE ORC COMPLEX, FUNCTION.
[11]	"Nucleosome-interacting proteins regulated by DNA and histone methylation." Bartke T., Vermeulen M., Xhemalce B., Robson S.C., Mann M., Kouzarides T. Cell 143:470-484(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN THE ORC COMPLEX, FUNCTION.
[12]	"A WD-repeat protein stabilizes ORC binding to chromatin." Shen Z., Sathyan K.M., Geng Y., Zheng R., Chakraborty A., Freeman B., Wang F., Prasanth K.V., Prasanth S.G. Mol. Cell 40:99-111(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DOMAIN WD REPEATS, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE ORC COMPLEX.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212 AND SER-243, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212 AND SER-243, MASS SPECTROMETRY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00069309.
PIR	T42659.
RefSeq	NP_690852.1. NM_152892.1.
UniGene	Hs.274135.
3D structure databases
ProteinModelPortal	Q9UFC0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UFC0. 1 interaction.
MINT	MINT-7944578.
STRING	9606.ENSP00000292616.
PTM databases
PhosphoSite	Q9UFC0.
Polymorphism databases
DMDM	74761931.
Proteomic databases
PaxDb	Q9UFC0.
PeptideAtlas	Q9UFC0.
PRIDE	Q9UFC0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000292616; ENSP00000292616; ENSG00000161036.
GeneID	222229.
KEGG	hsa:222229.
UCSC	uc003uzn.3. human.
Organism-specific databases
CTD	222229.
GeneCards	GC07P102105.
HGNC	HGNC:21769. LRWD1.
HPA	HPA021320. HPA029916.
neXtProt	NX_Q9UFC0.
PharmGKB	PA162394694.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG304996.
HOGENOM	HOG000113393.
HOVERGEN	HBG076949.
InParanoid	Q9UFC0.
OMA	EFTQWRV.
OrthoDB	EOG4X97GT.
Enzyme and pathway databases
SignaLink	Q9UFC0.
Gene expression databases
ArrayExpress	Q9UFC0.
Bgee	Q9UFC0.
CleanEx	HS_LRWD1.
Genevestigator	Q9UFC0.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR001611. Leu-rich_rpt. IPR003591. Leu-rich_rpt_typical-subtyp. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF00400. WD40. 1 hit. [Graphical view]
SMART	SM00369. LRR_TYP. 1 hit. SM00320. WD40. 3 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS51450. LRR. 3 hits. PS00678. WD_REPEATS_1. 1 hit. PS50082. WD_REPEATS_2. 1 hit. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	222229.
NextBio	91575.

Entry information

Entry name

LRWD1_HUMAN

Accession

Primary (citable) accession number: Q9UFC0
Secondary accession number(s): A8K4K2 , B2R9G2, Q8N0T9, Q8WV43, Q96GJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 13, 2007
Last sequence update:	October 25, 2004
Last modified:	May 29, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.