UniProt functional annotation for O75496



	UniProt functional annotation for O75496

UniProt code: O75496.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC) (PubMed:9635433, PubMed:14993212, PubMed:20129055, PubMed:24064211). It is degraded during the mitotic phase of the cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Its destruction at the metaphase- anaphase transition permits replication in the succeeding cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Inhibits histone acetyltransferase activity of KAT7/HBO1 in a CDT1-dependent manner, inhibiting histone H4 acetylation and DNA replication licensing (PubMed:20129055). Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (PubMed:22615398). {ECO:0000269|PubMed:14993212, ECO:0000269|PubMed:20129055, ECO:0000269|PubMed:22615398, ECO:0000269|PubMed:24064211, ECO:0000269|PubMed:9635433}.

Subunit: Homotetramer (PubMed:15313623, PubMed:15260975, PubMed:15378034, PubMed:19906994). Interacts with CDT1; this inhibits binding of the MCM complex to origins of replication (PubMed:14993212, PubMed:21543332, PubMed:15260975, PubMed:19906994). The complex with CDT1 exists in two forms, a 'permissive' heterotrimer and an 'inhibitory' heterohexamer (PubMed:14993212, PubMed:15260975, PubMed:19906994). Interacts (via coiled-coil domain) with IDAS (via coiled-coil domain); this targets GMNN to the nucleus (PubMed:21543332). The heterodimer formed by GMNN and MCIDAS has much lower affinity for CDT1 than the GMNN homodimer (PubMed:24064211). Interacts with a subset of Hox proteins, affinity increasing from anterior to posterior types, the strongest interaction being with HOXB1, HOXC9 and HOXD10 (PubMed:22615398). Interacts with LRWD1 from G1/S to mitosis (PubMed:22645314). {ECO:0000269|PubMed:14993212, ECO:0000269|PubMed:15260975, ECO:0000269|PubMed:15313623, ECO:0000269|PubMed:15378034, ECO:0000269|PubMed:19906994, ECO:0000269|PubMed:21543332, ECO:0000269|PubMed:22615398, ECO:0000269|PubMed:22645314, ECO:0000269|PubMed:24064211}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:21543332}. Nucleus {ECO:0000269|PubMed:21543332}. Note=Mainly cytoplasmic but can be relocalized to the nucleus. {ECO:0000269|PubMed:21543332}.

Developmental stage: Absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase-anaphase transition. {ECO:0000269|PubMed:9635433}.

Ptm: 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. {ECO:0000269|PubMed:22615398, ECO:0000269|PubMed:22645314}.

Disease: Meier-Gorlin syndrome 6 (MGORS6) [MIM:616835]: A form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. {ECO:0000269|PubMed:26637980}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the geminin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC) (PubMed:9635433, PubMed:14993212, PubMed:20129055, PubMed:24064211). It is degraded during the mitotic phase of the cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Its destruction at the metaphase- anaphase transition permits replication in the succeeding cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Inhibits histone acetyltransferase activity of KAT7/HBO1 in a CDT1-dependent manner, inhibiting histone H4 acetylation and DNA replication licensing (PubMed:20129055). Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (PubMed:22615398). {ECO:0000269\|PubMed:14993212, ECO:0000269\|PubMed:20129055, ECO:0000269\|PubMed:22615398, ECO:0000269\|PubMed:24064211, ECO:0000269\|PubMed:9635433}.


Subunit:		Homotetramer (PubMed:15313623, PubMed:15260975, PubMed:15378034, PubMed:19906994). Interacts with CDT1; this inhibits binding of the MCM complex to origins of replication (PubMed:14993212, PubMed:21543332, PubMed:15260975, PubMed:19906994). The complex with CDT1 exists in two forms, a 'permissive' heterotrimer and an 'inhibitory' heterohexamer (PubMed:14993212, PubMed:15260975, PubMed:19906994). Interacts (via coiled-coil domain) with IDAS (via coiled-coil domain); this targets GMNN to the nucleus (PubMed:21543332). The heterodimer formed by GMNN and MCIDAS has much lower affinity for CDT1 than the GMNN homodimer (PubMed:24064211). Interacts with a subset of Hox proteins, affinity increasing from anterior to posterior types, the strongest interaction being with HOXB1, HOXC9 and HOXD10 (PubMed:22615398). Interacts with LRWD1 from G1/S to mitosis (PubMed:22645314). {ECO:0000269\|PubMed:14993212, ECO:0000269\|PubMed:15260975, ECO:0000269\|PubMed:15313623, ECO:0000269\|PubMed:15378034, ECO:0000269\|PubMed:19906994, ECO:0000269\|PubMed:21543332, ECO:0000269\|PubMed:22615398, ECO:0000269\|PubMed:22645314, ECO:0000269\|PubMed:24064211}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:21543332}. Nucleus {ECO:0000269\|PubMed:21543332}. Note=Mainly cytoplasmic but can be relocalized to the nucleus. {ECO:0000269\|PubMed:21543332}.
Developmental stage:		Absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase-anaphase transition. {ECO:0000269\|PubMed:9635433}.
Ptm:		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. {ECO:0000269\|PubMed:22615398, ECO:0000269\|PubMed:22645314}.
Disease:		Meier-Gorlin syndrome 6 (MGORS6) [MIM:616835]: A form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. {ECO:0000269\|PubMed:26637980}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the geminin family. {ECO:0000305}.