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O75496 (GEMI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Geminin
Gene names
Name:GMNN
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length209 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle. Ref.1 Ref.5 Ref.15 Ref.16

Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control. Ref.1 Ref.5 Ref.15 Ref.16

Subunit structure

Homotetramer. Interacts with CDT1; this inhibits binding of the MCM complex to origins of replication. The complex with CDT1 exists in two forms, a "permissive" heterotrimer and an "inhibitory" heterohexamer. Interacts (via coiled-coil domain) with IDAS (via coiled-coil domain); this targets GMNN to the nucleus. The heterodimer formed by GMNN and MCIDAS has much lower affinity for CDT1 than the GMNN homodimer. Interacts with a subset of Hox proteins, affinity increasing from anterior to posterior types, the strongest interaction being with HOXB1, HOXC9 and HOXD10. Interacts with LRWD1 from G1/S to mitosis. Ref.5 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16

Subcellular location

Cytoplasm. Nucleus. Note: Mainly cytoplasmic but can be relocalized to the nucleus.

Developmental stage

Absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase-anaphase transition. Ref.1

Post-translational modification

Phosphorylated during mitosis. Phosphorylation at Ser-184 by CK2 results in enhanced binding to Hox proteins and more potent inhibitory effect on Hox transcriptional activity. Ref.10 Ref.15

Sequence similarities

Belongs to the geminin family.

Sequence caution

The sequence CAC21511.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDT1Q9H21111EBI-371669,EBI-456953
MCIDASD6RGH67EBI-371669,EBI-3954372

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 209209Geminin
PRO_0000148729

Regions

Region82 – 16180Necessary and sufficient for interaction with IDAS and CDT1
Region170 – 19021Homeodomain binding
Coiled coil94 – 14451 Ref.11 Ref.12 Ref.13 Ref.16

Amino acid modifications

Modified residue271N6-acetyllysine Ref.7
Modified residue631Phosphoserine Ref.6
Modified residue641Phosphoserine Ref.6
Modified residue1841Phosphoserine; by CK2 Ref.15

Natural variations

Natural variant151N → H.
Corresponds to variant rs34891389 [ dbSNP | Ensembl ].
VAR_033959
Natural variant181N → T. Ref.2
Corresponds to variant rs1923185 [ dbSNP | Ensembl ].
VAR_024233
Natural variant481L → F.
Corresponds to variant rs2307307 [ dbSNP | Ensembl ].
VAR_033960
Natural variant541R → W.
Corresponds to variant rs2307306 [ dbSNP | Ensembl ].
VAR_033961
Natural variant601S → P.
Corresponds to variant rs2307302 [ dbSNP | Ensembl ].
VAR_053107
Natural variant2031T → M.
Corresponds to variant rs2307303 [ dbSNP | Ensembl ].
VAR_053108

Secondary structure

..... 209
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O75496 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 0BABE60F6F5AC252

FASTA20923,565
        10         20         30         40         50         60 
MNPSMKQKQE EIKENIKNSS VPRRTLKMIQ PSASGSLVGR ENELSAGLSK RKHRNDHLTS 

        70         80         90        100        110        120 
TTSSPGVIVP ESSENKNLGG VTQESFDLMI KENPSSQYWK EVAEKRRKAL YEALKENEKL 

       130        140        150        160        170        180 
HKEIEQKDNE IARLKKENKE LAEVAEHVQY MAELIERLNG EPLDNFESLD NQEFDSEEET 

       190        200 
VEDSLVEDSE IGTCAEGTVS SSTDAKPCI 

« Hide

References

« Hide 'large scale' references
[1]"Geminin, an inhibitor of DNA replication, is degraded during mitosis."
McGarry T.J., Kirschner M.W.
Cell 93:1043-1053(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE.
[2]"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. expand/collapse author list , 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], VARIANT THR-18.
Tissue: Embryo.
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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].
Tissue: Lung and Urinary bladder.
[5]"Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding."
Sugimoto N., Tatsumi Y., Tsurumi T., Matsukage A., Kiyono T., Nishitani H., Fujita M.
J. Biol. Chem. 279:19691-19697(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CDT1.
[6]"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-63 AND SER-64, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-27, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Idas, a novel phylogenetically conserved geminin-related protein, binds to geminin and is required for cell cycle progression."
Pefani D.E., Dimaki M., Spella M., Karantzelis N., Mitsiki E., Kyrousi C., Symeonidou I.E., Perrakis A., Taraviras S., Lygerou Z.
J. Biol. Chem. 286:23234-23246(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IDAS AND CDT1.
[10]"Dynamic association of ORCA with prereplicative complex components regulates DNA replication initiation."
Shen Z., Chakraborty A., Jain A., Giri S., Ha T., Prasanth K.V., Prasanth S.G.
Mol. Cell. Biol. 32:3107-3120(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRWD1 AND CDT1, PHOSPHORYLATION DURING MITOSIS.
[11]"Crystal structure of the coiled-coil dimerization motif of geminin: structural and functional insights on DNA replication regulation."
Thepaut M., Maiorano D., Guichou J.-F., Auge M.-T., Dumas C., Mechali M., Padilla A.
J. Mol. Biol. 342:275-287(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF 110-145, SUBUNIT, COILED-COIL DOMAIN.
[12]"A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition."
Saxena S., Yuan P., Dhar S.K., Senga T., Takeda D., Robinson H., Kornbluth S., Swaminathan K., Dutta A.
Mol. Cell 15:245-258(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 70-152, SUBUNIT, INTERACTION WITH CDT1, COILED-COIL DOMAIN.
[13]"Molecular structure of human geminin."
Okorokov A.L., Orlova E.V., Kingsbury S.R., Bagneris C., Gohlke U., Williams G.H., Stoeber K.
Nat. Struct. Mol. Biol. 11:1021-1022(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ELECTRON MICROSCOPY (17.5 ANGSTROMS), SUBUNIT, COILED-COIL DOMAIN.
[14]"Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensing."
De Marco V., Gillespie P.J., Li A., Karantzelis N., Christodoulou E., Klompmaker R., van Gerwen S., Fish A., Petoukhov M.V., Iliou M.S., Lygerou Z., Medema R.H., Blow J.J., Svergun D.I., Taraviras S., Perrakis A.
Proc. Natl. Acad. Sci. U.S.A. 106:19807-19812(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS), SUBUNIT.
[15]"Structural basis for homeodomain recognition by the cell-cycle regulator Geminin."
Zhou B., Liu C., Xu Z., Zhu G.
Proc. Natl. Acad. Sci. U.S.A. 109:8931-8936(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 171-190 IN COMPLEX WITH HOXC9, FUNCTION, PHOSPHORYLATION AT SER-184.
[16]"The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing."
Caillat C., Pefani E.D., Gillespie P.J., Taraviras S., Blow J.J., Lygerou Z., Perrakis A.
J. Biol. Chem. 288:31624-31634(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 83-160 IN COMPLEX WITH MCIDAS, SUBUNIT, FUNCTION, COILED-COIL DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF067855 mRNA. Translation: AAC39787.1.
AK021685 mRNA. Translation: BAG51040.1.
AL133264 Genomic DNA. Translation: CAC21511.1. Different initiation.
BC005185 mRNA. Translation: AAH05185.1.
BC005389 mRNA. Translation: AAH05389.1.
RefSeqNP_001238918.1. NM_001251989.1.
NP_001238919.1. NM_001251990.1.
NP_001238920.1. NM_001251991.1.
NP_056979.1. NM_015895.4.
XP_005249216.1. XM_005249159.1.
UniGeneHs.234896.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1T6FX-ray1.47A/B110-145[»]
1UIIX-ray2.00A/B70-152[»]
2LP0NMR-B171-190[»]
2WVRX-ray3.30A/B1-209[»]
4BRYX-ray2.89A83-160[»]
ProteinModelPortalO75496.
SMRO75496. Positions 92-152.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119246. 25 interactions.
DIPDIP-31088N.
IntActO75496. 9 interactions.
MINTMINT-1201770.
STRING9606.ENSP00000230056.

Chemistry

ChEMBLCHEMBL1293278.

PTM databases

PhosphoSiteO75496.

Proteomic databases

PaxDbO75496.
PRIDEO75496.

Protocols and materials databases

DNASU51053.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000230056; ENSP00000230056; ENSG00000112312.
ENST00000356509; ENSP00000348902; ENSG00000112312.
GeneID51053.
KEGGhsa:51053.
UCSCuc003nem.3. human.

Organism-specific databases

CTD51053.
GeneCardsGC06P024779.
HGNCHGNC:17493. GMNN.
HPACAB011458.
CAB047327.
CAB047328.
HPA049977.
HPA054597.
MIM602842. gene.
neXtProtNX_O75496.
PharmGKBPA38455.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39688.
HOGENOMHOG000112711.
HOVERGENHBG002965.
InParanoidO75496.
KOK10749.
OMAVPEHSEN.
OrthoDBEOG7RFTJX.
PhylomeDBO75496.
TreeFamTF101171.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpressO75496.
BgeeO75496.
CleanExHS_GMNN.
GenevestigatorO75496.

Family and domain databases

InterProIPR022786. Geminin_fam.
[Graphical view]
PANTHERPTHR13372. PTHR13372. 1 hit.
PfamPF07412. Geminin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO75496.
GeneWikiGeminin.
GenomeRNAi51053.
NextBio53616.
PMAP-CutDBO75496.
PROO75496.
SOURCESearch...

Entry information

Entry nameGEMI_HUMAN
AccessionPrimary (citable) accession number: O75496
Secondary accession number(s): B3KMM8, Q9H1Z1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM