O75496 (GEMI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Geminin

Gene names

Name:

GMNN

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	209 AA.
Sequence status	Complete.
Protein existence	Evidence 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.14 Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control. Ref.1 Ref.5 Ref.14
Subunit structure	Homotetramer. Interacts with CDT1; inhibits binding of the MCM complex to origins of replication, the complex exists in two forms, a "permissive" heterotrimer and an "inhibitory" heterohexamer. Interacts with IDAS; which targets GMNN to the nucleus, prevents GMNN interaction with CDT1 and competes with IDAS homodimerization. Interacts with a subset of Hox proteins, affinity increasing from anterior to posterior types, the strongest interaction being with HOXB1, HOXC9 and HOXD10. Ref.5 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
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	Phosphorylation at Ser-184 by CK2 results in enhanced binding to Hox proteins and more potent inhibitory effect on Hox transcriptional activity.
Sequence similarities	Belongs to the geminin family.
Sequence caution	The sequence CAC21511.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Molecular function	DNA replication inhibitor
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mitotic cell cycle Traceable author statement. Source: Reactome negative regulation of DNA replication Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of cell cycle Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 16924111. Source: UniProtKB organ morphogenesis Inferred from electronic annotation. Source: Compara protein complex assembly Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	transcription corepressor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDT1	Q9H211	8	EBI-371669,EBI-456953
MCIN	D6RGH6	7	EBI-371669,EBI-3954372

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 209

209

Geminin

PRO_0000148729

Regions

Region

82 – 161

80

Necessary and sufficient for interaction with IDAS

Region

170 – 190

21

Homeodomain binding

Coiled coil

94 – 144

51

Ref.10 Ref.11 Ref.12

Amino acid modifications

Modified residue

27

1

N6-acetyllysine Ref.7

Modified residue

63

1

Phosphoserine Ref.6

Modified residue

64

1

Phosphoserine Ref.6

Modified residue

184

1

Phosphoserine; by CK2 Ref.14

Natural variations

Natural variant

15

1

N → H.
Corresponds to variant rs34891389 [ dbSNP | Ensembl ].

VAR_033959

Natural variant

18

1

N → T. Ref.2
Corresponds to variant rs1923185 [ dbSNP | Ensembl ].

VAR_024233

Natural variant

48

1

L → F.
Corresponds to variant rs2307307 [ dbSNP | Ensembl ].

VAR_033960

Natural variant

54

1

R → W.
Corresponds to variant rs2307306 [ dbSNP | Ensembl ].

VAR_033961

Natural variant

60

1

S → P.
Corresponds to variant rs2307302 [ dbSNP | Ensembl ].

VAR_053107

Natural variant

203

1

T → M.
Corresponds to variant rs2307303 [ dbSNP | Ensembl ].

VAR_053108

Secondary structure

1

.

.

.

.

.

209

Helix Strand Turn

Details...

Helix

110 – 142

33

Turn

177 – 179

3

Sequences

	Sequence		Length	Mass (Da)
	O75496 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 0BABE60F6F5AC252	FASTA	209	23,565
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
+	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.

IPI

IPI00026309.

RefSeq

NP_001238918.1. NM_001251989.1.
NP_001238919.1. NM_001251990.1.
NP_001238920.1. NM_001251991.1.
NP_056979.1. NM_015895.4.

UniGene

Hs.234896.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T6F	X-ray	1.47	A/B	110-145	[»]
1UII	X-ray	2.00	A/B	70-152	[»]
2LP0	NMR	-	B	171-190	[»]
2WVR	X-ray	3.30	A/B	1-209	[»]

ProteinModelPortal

O75496.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31088N.

IntAct

O75496. 9 interactions.

MINT

MINT-1201770.

STRING

9606.ENSP00000230056.

PTM databases

PhosphoSite

O75496.

Proteomic databases

PaxDb

O75496.

PRIDE

O75496.

Protocols and materials databases

DNASU

51053.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000230056; ENSP00000230056; ENSG00000112312.
ENST00000356509; ENSP00000348902; ENSG00000112312.

GeneID

51053.

KEGG

hsa:51053.

UCSC

uc003nem.3. human.

Organism-specific databases

CTD

51053.

GeneCards

GC06P024779.

HGNC

HGNC:17493. GMNN.

HPA

CAB011458.
CAB047327.
HPA049977.

MIM

602842. gene.

neXtProt

NX_O75496.

PharmGKB

PA38455.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39688.

HOGENOM

HOG000112711.

HOVERGEN

HBG002965.

InParanoid

O75496.

KO

K10749.

OMA

NLGGVTQ.

OrthoDB

EOG4JDH85.

PhylomeDB

O75496.

Enzyme and pathway databases

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpress

O75496.

Bgee

O75496.

CleanEx

HS_GMNN.

Genevestigator

O75496.

GermOnline

ENSG00000112312. Homo sapiens.

Family and domain databases

InterPro

IPR022786. Geminin_fam.
[Graphical view]

PANTHER

PTHR13372. PTHR13372. 1 hit.

Pfam

PF07412. Geminin. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1293278.

EvolutionaryTrace

O75496.

GenomeRNAi

51053.

NextBio

53616.

PMAP-CutDB

O75496.

SOURCE

Search...

Entry information

Entry name

GEMI_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 110 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.