P18754 (RCC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Regulator of chromosome condensation

Alternative name(s):
Cell cycle regulatory protein
Chromosome condensation protein 1

Gene names

Name:	RCC1
Synonyms:	CHC1

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	421 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Guanine-nucleotide releasing factor that promotes the exchange of Ran-bound GDP by GTP. Involved in the regulation of onset of chromosome condensation in the S phase. Binds both to the nucleosomes and double-stranded DNA. RCC1-Ran complex (together with other proteins) acts as a component of a signal transmission pathway that detects unreplicated DNA. Plays a key role in nucleo-cytoplasmic transport, mitosis and nuclear-envelope assembly. Ref.7
Subunit structure	Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation. Ref.9 Ref.10
Subcellular location	Nucleus. Cytoplasm. Note: Becomes dispersed throughout the cytoplasm during mitosis. Ref.10
Post-translational modification	N-terminal methylation by METTL11A/NTM1 is required for binding double-stranded DNA and stable chromatin association. Di- and trimethylation produce a permanent positive charge on the amino group, which facilitate electrostatic binding to the phosphate groups on DNA, while inhibiting histone-binding. Methylated tail helps retain RCC1 on chromosomes during nucleotide exchange on Ran. Ref.10 Ref.11 Ref.13
Miscellaneous	Patients with Raynaud disease produce antibodies that bind to RCC1.
Sequence similarities	Contains 7 RCC1 repeats.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	DNA-binding
Molecular function	Guanine-nucleotide releasing factor
PTM	Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from mutant phenotype Ref.1. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW chromosome segregation Inferred from mutant phenotype Ref.10. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic spindle organization Inferred from direct assay PubMed 15014043. Source: UniProtKB regulation of S phase of mitotic cell cycle Inferred from mutant phenotype Ref.1. Source: UniProtKB regulation of mitosis Inferred from direct assay PubMed 15014043. Source: UniProtKB spindle assembly Inferred from mutant phenotype Ref.10. Source: UniProtKB viral reproduction Traceable author statement. Source: Reactome
Cellular_component	condensed nuclear chromosome Inferred from direct assay PubMed 15014043. Source: UniProtKB cytoplasm Inferred from direct assay Ref.10. Source: UniProtKB nuclear chromatin Inferred from direct assay PubMed 15014043. Source: UniProtKB nuclear membrane Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	Ran guanyl-nucleotide exchange factor activity Inferred from direct assay Ref.7. Source: UniProtKB histone binding Inferred from direct assay PubMed 11375490. Source: UniProtKB nucleosomal DNA binding Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RAN	P62826	6	EBI-992720,EBI-286642
RANBP3	Q9H6Z4	2	EBI-992720,EBI-992681

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P18754-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P18754-2)

Also known as: RCC1-I;

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: K → KDTRAAASRRVPGARSCQGACGPSPPDQKTRP

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.10 Ref.13

Chain

2 – 421

420

Regulator of chromosome condensation

PRO_0000206628

Regions

Repeat

34 – 84

51

RCC1 1

Repeat

85 – 136

52

RCC1 2

Repeat

138 – 189

52

RCC1 3

Repeat

191 – 257

67

RCC1 4

Repeat

258 – 311

54

RCC1 5

Repeat

312 – 362

51

RCC1 6

Repeat

363 – 416

54

RCC1 7

Amino acid modifications

Modified residue

2

1

N,N,N-trimethylserine; alternate Ref.10 Ref.11 Ref.13

Modified residue

2

1

N,N-dimethylserine; alternate Ref.10 Ref.11 Ref.13

Modified residue

2

1

N-methylserine; alternate Ref.10 Ref.11 Ref.13

Modified residue

2

1

Phosphoserine Ref.10

Modified residue

11

1

Phosphoserine Ref.8 Ref.14 Ref.16

Natural variations

Alternative sequence

24

1

K → KDTRAAASRRVPGARSCQGA CGPSPPDQKTRP in isoform 2.

VSP_041122

Experimental info

Mutagenesis

2

1

S → A: Does not abolish N-terminal methylation. Ref.10

Mutagenesis

2

1

S → Q: Does not abolish N-terminal methylation. Ref.10

Mutagenesis

3

1

P → Q: Abolishes N-terminal methylation. Ref.10

Mutagenesis

4

1

K → Q: Abolishes N-terminal methylation. Ref.10 Ref.13

Mutagenesis

4

1

K → R: Stongly impairs N-terminal methylation and subcellular localization. Ref.10 Ref.13

Mutagenesis

182

1

D → A: Abolishes interaction with Ran and chromosome localization. Ref.10

Secondary structure

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421

Helix Strand Turn

Details...

Beta strand

35 – 42

8

Beta strand

56 – 63

8

Beta strand

69 – 74

6

Beta strand

76 – 83

8

Beta strand

88 – 92

5

Helix

108 – 110

3

Beta strand

121 – 126

6

Beta strand

128 – 135

8

Beta strand

140 – 144

5

Beta strand

146 – 148

3

Beta strand

151 – 158

8

Beta strand

162 – 168

7

Beta strand

174 – 179

6

Beta strand

181 – 188

8

Beta strand

193 – 197

5

Beta strand

205 – 207

3

Helix

208 – 210

3

Beta strand

212 – 214

3

Helix

216 – 219

4

Helix

220 – 224

5

Beta strand

242 – 248

7

Beta strand

251 – 256

6

Beta strand

261 – 265

5

Beta strand

280 – 285

6

Helix

287 – 289

3

Beta strand

296 – 301

6

Beta strand

303 – 310

8

Beta strand

315 – 319

5

Helix

322 – 324

3

Beta strand

335 – 340

6

Beta strand

343 – 352

10

Beta strand

354 – 361

8

Beta strand

366 – 370

5

Beta strand

379 – 381

3

Beta strand

385 – 390

6

Turn

394 – 398

5

Beta strand

399 – 406

8

Beta strand

408 – 417

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: F6D225AF81928305	FASTA	421	44,969
	10 20 30 40 50 60 MSPKRIAKRR SPPADAIPKS KKVKVSHRSH STEPGLVLTL GQGDVGQLGL GENVMERKKP 70 80 90 100 110 120 ALVSIPEDVV QAEAGGMHTV CLSKSGQVYS FGCNDEGALG RDTSVEGSEM VPGKVELQEK 130 140 150 160 170 180 VVQVSAGDSH TAALTDDGRV FLWGSFRDNN GVIGLLEPMK KSMVPVQVQL DVPVVKVASG 190 200 210 220 230 240 NDHLVMLTAD GDLYTLGCGE QGQLGRVPEL FANRGGRQGL ERLLVPKCVM LKSRGSRGHV 250 260 270 280 290 300 RFQDAFCGAY FTFAISHEGH VYGFGLSNYH QLGTPGTESC FIPQNLTSFK NSTKSWVGFS 310 320 330 340 350 360 GGQHHTVCMD SEGKAYSLGR AEYGRLGLGE GAEEKSIPTL ISRLPAVSSV ACGASVGYAV 370 380 390 400 410 420 TKDGRVFAWG MGTNYQLGTG QDEDAWSPVE MMGKQLENRV VLSVSSGGQH TVLLVKDKEQ S
	Isoform 2 (RCC1-I) [UniParc]. Checksum: A31255E99A01A25F	FASTA	452	48,146
	10 20 30 40 50 60 MSPKRIAKRR SPPADAIPKS KKVKDTRAAA SRRVPGARSC QGACGPSPPD QKTRPVSHRS 70 80 90 100 110 120 HSTEPGLVLT LGQGDVGQLG LGENVMERKK PALVSIPEDV VQAEAGGMHT VCLSKSGQVY 130 140 150 160 170 180 SFGCNDEGAL GRDTSVEGSE MVPGKVELQE KVVQVSAGDS HTAALTDDGR VFLWGSFRDN 190 200 210 220 230 240 NGVIGLLEPM KKSMVPVQVQ LDVPVVKVAS GNDHLVMLTA DGDLYTLGCG EQGQLGRVPE 250 260 270 280 290 300 LFANRGGRQG LERLLVPKCV MLKSRGSRGH VRFQDAFCGA YFTFAISHEG HVYGFGLSNY 310 320 330 340 350 360 HQLGTPGTES CFIPQNLTSF KNSTKSWVGF SGGQHHTVCM DSEGKAYSLG RAEYGRLGLG 370 380 390 400 410 420 EGAEEKSIPT LISRLPAVSS VACGASVGYA VTKDGRVFAW GMGTNYQLGT GQDEDAWSPV 430 440 450 EMMGKQLENR VVLSVSSGGQ HTVLLVKDKE QS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation." Ohtsubo M., Kai R., Furuno N., Sekiguchi T., Sekiguchi M., Hayashida H., Kuma K., Miyata T., Fukushige S., Murotsu T., Matsubara K., Nishimoto T. Genes Dev. 1:585-593(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete nucleotide sequence of the human RCC1 gene involved in coupling between DNA replication and mitosis." Furuno N., Nakagawa K., Eguchi U., Ohtsubo M., Nishimoto T., Soeda E. Genomics 11:459-461(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[4]	"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] (ISOFORMS 1 AND 2). Tissue: Eye, Mammary gland, Muscle and Testis.
[5]	"Mammalian cells have two functional RCC1 proteins produced by alternative splicing." Miyabashira J., Sekiguchi T., Nishimoto T. J. Cell Sci. 107:2203-2208(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-33 (ISOFORM 2), ALTERNATIVE SPLICING.
[6]	"A 47-kDa human nuclear protein recognized by antikinetochore autoimmune sera is homologous with the protein encoded by RCC1, a gene implicated in onset of chromosome condensation." Bischoff F.R., Maier G., Tilz G., Ponstingl H. Proc. Natl. Acad. Sci. U.S.A. 87:8617-8621(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[7]	"Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1." Bischoff F.R., Ponstingl H. Nature 354:80-82(1991) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"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-11, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Novel function of beta-arrestin2 in the nucleus of mature spermatozoa." Neuhaus E.M., Mashukova A., Barbour J., Wolters D., Hatt H. J. Cell Sci. 119:3047-3056(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB2.
[10]	"N-terminal alpha-methylation of RCC1 is necessary for stable chromatin association and normal mitosis." Chen T., Muratore T.L., Schaner-Tooley C.E., Shabanowitz J., Hunt D.F., Macara I.G. Nat. Cell Biol. 9:596-603(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE OF INITIATOR METHIONINE, SUBCELLULAR LOCATION, HISTONE-BINDING, INTERACTION WITH RAN, PHOSPHORYLATION AT SER-2, METHYLATION AT SER-2, MUTAGENESIS OF SER-2; PRO-3; LYS-4 AND ASP-182.
[11]	"Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1." Hao Y., Macara I.G. J. Cell Biol. 182:827-836(2008) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT SER-2.
[12]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[13]	"NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein." Tooley C.E., Petkowski J.J., Muratore-Schroeder T.L., Balsbaugh J.L., Shabanowitz J., Sabat M., Minor W., Hunt D.F., Macara I.G. Nature 466:1125-1128(2010) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE OF INITIATOR METHIONINE, METHYLATION AT SER-2, MUTAGENESIS OF LYS-4.
[14]	"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-11, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"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-11, MASS SPECTROMETRY.
[17]	"The 1.7-A crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller." Renault L., Nassar N., Vetter I., Becker J., Klebe C., Roth M., Wittinghofer A. Nature 392:97-101(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 21-421.
[18]	"Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1)." Renault L., Kuhlmann J., Henkel A., Wittinghofer A. Cell 105:245-255(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 20-421 IN COMPLEX WITH RAN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X12654 mRNA. Translation: CAA31182.1.
X06130 mRNA. Translation: CAA29496.1.
D00591 Genomic DNA. Translation: BAA00469.1.
AF498924 mRNA. Translation: AAM21072.1.
BC007300 mRNA. Translation: AAH07300.1.
BC010067 mRNA. Translation: AAH10067.1.
BC036903 mRNA. Translation: AAH36903.1.
BC069198 mRNA. Translation: AAH69198.1.
S75708 mRNA. Translation: AAB32653.1.

IPI

IPI00001661.
IPI00747309.

PIR

A26691.

RefSeq

NP_001041659.1. NM_001048194.2.
NP_001041660.1. NM_001048195.2.
NP_001041664.1. NM_001048199.2.
NP_001260.1. NM_001269.4.

UniGene

Hs.469723.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A12	X-ray	1.70	A/B/C	9-421	[»]
1I2M	X-ray	1.76	B/D	20-421	[»]

ProteinModelPortal

P18754.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35416N.

IntAct

P18754. 8 interactions.

MINT

MINT-240062.

STRING

9606.ENSP00000362937.

PTM databases

PhosphoSite

P18754.

Polymorphism databases

DMDM

132170.

Proteomic databases

PaxDb

P18754.

PRIDE

P18754.

Protocols and materials databases

DNASU

1104.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373831; ENSP00000362937; ENSG00000180198.
ENST00000373832; ENSP00000362938; ENSG00000180198.
ENST00000373833; ENSP00000362939; ENSG00000180198.
ENST00000398958; ENSP00000381931; ENSG00000180198.

GeneID

1104.

KEGG

hsa:1104.

UCSC

uc001bqa.2. human.
uc001bqf.2. human.

Organism-specific databases

CTD

1104.

GeneCards

GC01P028834.

HGNC

HGNC:1913. RCC1.

HPA

CAB015413.
HPA027573.
HPA027574.

MIM

179710. gene.

neXtProt

NX_P18754.

PharmGKB

PA26449.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5184.

HOGENOM

HOG000234341.

HOVERGEN

HBG017712.

KO

K11493.

OMA

RETTEEG.

PhylomeDB

P18754.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

P18754.

Bgee

P18754.

CleanEx

HS_RCC1.

Genevestigator

P18754.

GermOnline

ENSG00000180198. Homo sapiens.

Family and domain databases

Gene3D

2.130.10.30. 1 hit.

InterPro

IPR009091. RCC1/BLIP-II.
IPR000408. Reg_chr_condens.
[Graphical view]

Pfam

PF00415. RCC1. 7 hits.
[Graphical view]

PRINTS

PR00633. RCCNDNSATION.

SUPFAM

SSF50985. RCC1/BLIP-II. 1 hit.

PROSITE

PS00625. RCC1_1. 1 hit.
PS00626. RCC1_2. 4 hits.
PS50012. RCC1_3. 7 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P18754.

GenomeRNAi

1104.

NextBio

4572.

SOURCE

Search...

Entry information

Entry name

RCC1_HUMAN

Accession

Primary (citable) accession number: P18754
Secondary accession number(s): Q16269, Q6NT97

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	May 1, 2013
This is version 144 of the entry and version 1 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.