GANP_HUMAN
ID GANP_HUMAN Reviewed; 1980 AA.
AC O60318; C9JL56; Q2M3C1; Q6PJP6; Q9BSY5; Q9UMT4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Germinal-center associated nuclear protein;
DE Short=GANP;
DE EC=2.3.1.48 {ECO:0000269|PubMed:23652018};
DE AltName: Full=80 kDa MCM3-associated protein;
DE AltName: Full=MCM3 acetylating protein;
DE Short=MCM3AP;
DE EC=2.3.1.-;
DE AltName: Full=MCM3 acetyltransferase;
GN Name=MCM3AP; Synonyms=GANP, KIAA0572, MAP80;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11024281; DOI=10.1016/s0378-1119(00)00336-x;
RA Abe E., Kuwahara K., Yoshida M., Suzuki M., Terasaki H., Matsuo Y.,
RA Takahashi E., Sakaguchi N.;
RT "Structure, expression, and chromosomal localization of the human gene
RT encoding a germinal center-associated nuclear protein (GANP) that
RT associates with MCM3 involved in the initiation of DNA replication.";
RL Gene 255:219-227(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-102; VAL-288; LEU-333;
RP LEU-413; LEU-1051; MET-1062; TRP-1314; GLU-1449; ILE-1576; THR-1795;
RP ARG-1870 AND VAL-1941.
RG NIEHS SNPs program;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-102.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 109-1980.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1260-1980, AND INTERACTION WITH MCM3.
RX PubMed=9712829; DOI=10.1074/jbc.273.35.22177;
RA Takei Y., Tsujimoto G.;
RT "Identification of a novel MCM3-associated protein that facilitates MCM3
RT nuclear localization.";
RL J. Biol. Chem. 273:22177-22180(1998).
RN [7]
RP FUNCTION (ISOFORM MCM3AP), INTERACTION WITH MCM3, AND MUTAGENESIS OF
RP 1730-HIS--GLY-1733.
RX PubMed=11258703; DOI=10.1093/embo-reports/kve026;
RA Takei Y., Swietlik M., Tanoue A., Tsujimoto G., Kouzarides T., Laskey R.;
RT "MCM3AP, a novel acetyltransferase that acetylates replication protein
RT MCM3.";
RL EMBO Rep. 2:119-123(2001).
RN [8]
RP FUNCTION (ISOFORM MCM3AP), INTERACTION WITH MCM3, SUBCELLULAR LOCATION
RP (ISOFORM MCM3AP), AND MUTAGENESIS OF 1496-LEU--LEU-1501 AND
RP 1730-HIS--GLY-1733.
RX PubMed=12226073; DOI=10.1074/jbc.c200442200;
RA Takei Y., Assenberg M., Tsujimoto G., Laskey R.;
RT "The MCM3 acetylase MCM3AP inhibits initiation, but not elongation, of DNA
RT replication via interaction with MCM3.";
RL J. Biol. Chem. 277:43121-43125(2002).
RN [9]
RP INTERACTION WITH NR3C1.
RX PubMed=16914116; DOI=10.1016/j.bbrc.2006.07.182;
RA Osman W., Laine S., Zilliacus J.;
RT "Functional interaction between the glucocorticoid receptor and
RT GANP/MCM3AP.";
RL Biochem. Biophys. Res. Commun. 348:1239-1244(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-538, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-538, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP FUNCTION (ISOFORM GANP), SUBCELLULAR LOCATION, FG-REPEATS, AND INTERACTION
RP WITH NUP153; NXF1 AND RANBP2.
RX PubMed=20005110; DOI=10.1016/j.cub.2009.10.078;
RA Wickramasinghe V.O., McMurtrie P.I., Mills A.D., Takei Y., Penrhyn-Lowe S.,
RA Amagase Y., Main S., Marr J., Stewart M., Laskey R.A.;
RT "mRNA export from mammalian cell nuclei is dependent on GANP.";
RL Curr. Biol. 20:25-31(2010).
RN [14]
RP FUNCTION (ISOFORM GANP).
RX PubMed=20384790; DOI=10.1111/j.1365-2443.2010.01396.x;
RA Okamoto N., Kuwahara K., Ohta K., Kitabatake M., Takagi K., Mizuta H.,
RA Kondo E., Sakaguchi N.;
RT "Germinal center-associated nuclear protein (GANP) is involved in mRNA
RT export of Shugoshin-1 required for centromere cohesion and in sister-
RT chromatid exchange.";
RL Genes Cells 15:471-484(2010).
RN [15]
RP INTERACTION WITH AICDA.
RX PubMed=20507984; DOI=10.1074/jbc.m110.131441;
RA Maeda K., Singh S.K., Eda K., Kitabatake M., Pham P., Goodman M.F.,
RA Sakaguchi N.;
RT "GANP-mediated recruitment of activation-induced cytidine deaminase to cell
RT nuclei and to immunoglobulin variable region DNA.";
RL J. Biol. Chem. 285:23945-23953(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-538, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP ALTERNATIVE PROMOTER USAGE, AND SUBCELLULAR LOCATION.
RX PubMed=21195085; DOI=10.1016/j.jmb.2010.12.035;
RA Wickramasinghe V.O., McMurtrie P.I., Marr J., Amagase Y., Main S.,
RA Mills A.D., Laskey R.A., Takei Y.;
RT "MCM3AP is transcribed from a promoter within an intron of the overlapping
RT gene for GANP.";
RL J. Mol. Biol. 406:355-361(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP FUNCTION (ISOFORM GANP), IDENTIFICATION IN THE TREX-2 COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23591820; DOI=10.1242/jcs.118000;
RA Umlauf D., Bonnet J., Waharte F., Fournier M., Stierle M., Fischer B.,
RA Brino L., Devys D., Tora L.;
RT "The human TREX-2 complex is stably associated with the nuclear pore
RT basket.";
RL J. Cell Sci. 126:2656-2667(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-430; SER-538 AND SER-557, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP FUNCTION, INTERACTION WITH DDX21; DDX39A; DHX9; NUP62; NUP153; POLR2A;
RP SUPT5H AND TOP2A, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=23652018; DOI=10.1038/ncomms2823;
RA Singh S.K., Maeda K., Eid M.M., Almofty S.A., Ono M., Pham P.,
RA Goodman M.F., Sakaguchi N.;
RT "GANP regulates recruitment of AID to immunoglobulin variable regions by
RT modulating transcription and nucleosome occupancy.";
RL Nat. Commun. 4:1830-1830(2013).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1163-1235 IN COMPLEX WITH ENY2,
RP FUNCTION (ISOFORM GANP), IDENTIFICATION IN THE TREX-2 COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=22307388; DOI=10.1093/nar/gks059;
RA Jani D., Lutz S., Hurt E., Laskey R.A., Stewart M., Wickramasinghe V.O.;
RT "Functional and structural characterization of the mammalian TREX-2 complex
RT that links transcription with nuclear messenger RNA export.";
RL Nucleic Acids Res. 40:4562-4573(2012).
RN [23]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-409 AND ILE-1576.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [24]
RP INVOLVEMENT IN PNRIID, AND VARIANT PNRIID LYS-915.
RX PubMed=24123876; DOI=10.1136/jmedgenet-2013-101644;
RA Schuurs-Hoeijmakers J.H., Vulto-van Silfhout A.T., Vissers L.E.,
RA van de Vondervoort I.I., van Bon B.W., de Ligt J., Gilissen C.,
RA Hehir-Kwa J.Y., Neveling K., del Rosario M., Hira G., Reitano S.,
RA Vitello A., Failla P., Greco D., Fichera M., Galesi O., Kleefstra T.,
RA Greally M.T., Ockeloen C.W., Willemsen M.H., Bongers E.M., Janssen I.M.,
RA Pfundt R., Veltman J.A., Romano C., Willemsen M.A., van Bokhoven H.,
RA Brunner H.G., de Vries B.B., de Brouwer A.P.;
RT "Identification of pathogenic gene variants in small families with
RT intellectually disabled siblings by exome sequencing.";
RL J. Med. Genet. 50:802-811(2013).
RN [25]
RP INVOLVEMENT IN PNRIID, VARIANTS PNRIID THR-762; ASP-867; 889-TYR--ILE-1980
RP DEL; MET-1272; 1478-SER--ILE-1980 DEL AND LYS-1577, AND SUBCELLULAR
RP LOCATION.
RX PubMed=28633435; DOI=10.1093/brain/awx138;
RA Ylikallio E., Woldegebriel R., Tumiati M., Isohanni P., Ryan M.M.,
RA Stark Z., Walsh M., Sawyer S.L., Bell K.M., Oshlack A., Lockhart P.J.,
RA Shcherbii M., Estrada-Cuzcano A., Atkinson D., Hartley T., Tetreault M.,
RA Cuppen I., van der Pol W.L., Candayan A., Battaloglu E., Parman Y.,
RA van Gassen K.L.I., van den Boogaard M.H., Boycott K.M., Kauppi L.,
RA Jordanova A., Loennqvist T., Tyynismaa H.;
RT "MCM3AP in recessive Charcot-Marie-Tooth neuropathy and mild intellectual
RT disability.";
RL Brain 140:2093-2103(2017).
RN [26]
RP INVOLVEMENT IN PNRIID, AND VARIANTS PNRIID HIS-878; PRO-951 AND
RP 1804-GLN--ILE-1980 DEL.
RX PubMed=28969388; DOI=10.1093/brain/awx222;
RA Karakaya M., Mazaheri N., Polat I., Bharucha-Goebel D., Donkervoort S.,
RA Maroofian R., Shariati G., Hoelker I., Monaghan K., Winchester S., Zori R.,
RA Galehdari H., Boennemann C.G., Yis U., Wirth B.;
RT "Biallelic MCM3AP mutations cause Charcot-Marie-Tooth neuropathy with
RT variable clinical presentation.";
RL Brain 140:E65-E65(2017).
RN [27]
RP INVOLVEMENT IN PNRIID, AND VARIANT PNRIID SER-870.
RX PubMed=29982295; DOI=10.1093/brain/awy184;
RA Kennerson M.L., Corbett A.C., Ellis M., Perez-Siles G., Nicholson G.A.;
RT "A novel MCM3AP mutation in a Lebanese family with recessive Charcot-Marie-
RT Tooth neuropathy.";
RL Brain 141:E66-E66(2018).
CC -!- FUNCTION: [Isoform GANP]: As a component of the TREX-2 complex,
CC involved in the export of mRNAs to the cytoplasm through the nuclear
CC pores (PubMed:20005110, PubMed:20384790, PubMed:23591820,
CC PubMed:22307388). Through the acetylation of histones, affects the
CC assembly of nucleosomes at immunoglobulin variable region genes and
CC promotes the recruitment and positioning of transcription complex to
CC favor DNA cytosine deaminase AICDA/AID targeting, hence promoting
CC somatic hypermutations (PubMed:23652018). {ECO:0000269|PubMed:20005110,
CC ECO:0000269|PubMed:20384790, ECO:0000269|PubMed:22307388,
CC ECO:0000269|PubMed:23591820, ECO:0000269|PubMed:23652018}.
CC -!- FUNCTION: [Isoform MCM3AP]: Binds to and acetylates the replication
CC protein MCM3. Plays a role in the initiation of DNA replication and
CC participates in controls that ensure that DNA replication initiates
CC only once per cell cycle (PubMed:11258703, PubMed:12226073). Through
CC the acetylation of histones, affects the assembly of nucleosomes at
CC immunoglobulin variable region genes and promotes the recruitment and
CC positioning of transcription complex to favor DNA cytosine deaminase
CC AICDA/AID targeting, hence promoting somatic hypermutations
CC (PubMed:23652018). {ECO:0000269|PubMed:11258703,
CC ECO:0000269|PubMed:12226073, ECO:0000269|PubMed:23652018}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-lysyl-[histone] = CoA + H(+) + N(6)-acetyl-L-
CC lysyl-[histone]; Xref=Rhea:RHEA:21992, Rhea:RHEA-COMP:9845,
CC Rhea:RHEA-COMP:11338, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48;
CC Evidence={ECO:0000269|PubMed:23652018};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21993;
CC Evidence={ECO:0000269|PubMed:23652018};
CC -!- SUBUNIT: Isoform GANP: Component of the nuclear pore complex (NPC)-
CC associated TREX-2 complex (transcription and export complex 2),
CC composed of at least GANP, 2 copies of ENY2, PCID2, SEM1/DSS1, and
CC either centrin CETN2 or centrin CETN3. The TREX-2 complex also
CC associates with ALYREF/ALY (PubMed:23591820, PubMed:22307388).
CC Interacts with RNA polymerase II subunit POLR2A and with the
CC transcription elongation factor SUPT5H/SPT5 (PubMed:23652018,
CC PubMed:22307388). Interacts (via FG-repeats) with NXF1; this
CC interaction is not mediated by RNA (PubMed:20005110). Isoform GANP
CC interacts with nuclear envelope proteins NUP62, NUP153 and
CC RANBP2/NUP358; interaction with NUP153 is required for full
CC localization at the nuclear pore complex (PubMed:20005110,
CC PubMed:23652018). Interacts with several RNA helicases, including DHX9,
CC DDX21, and DDX39A/DDX39, and with DNA topoisomerase TOP2A
CC (PubMed:23652018). Directly interacts with AICDA/AID (PubMed:20507984).
CC Interacts with the glucocorticoid receptor NR3C1 (PubMed:16914116).
CC Isoform MCM3AP: Interacts with the glucocorticoid receptor NR3C1
CC (PubMed:16914116). Interacts with MCM3; this interaction leads to MCM3
CC acetylation (PubMed:9712829, PubMed:11258703, PubMed:12226073).
CC {ECO:0000269|PubMed:11258703, ECO:0000269|PubMed:12226073,
CC ECO:0000269|PubMed:16914116, ECO:0000269|PubMed:20005110,
CC ECO:0000269|PubMed:20507984, ECO:0000269|PubMed:22307388,
CC ECO:0000269|PubMed:23591820, ECO:0000269|PubMed:23652018,
CC ECO:0000269|PubMed:9712829}.
CC -!- SUBCELLULAR LOCATION: [Isoform GANP]: Nucleus envelope
CC {ECO:0000269|PubMed:20005110, ECO:0000269|PubMed:21195085,
CC ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:23591820,
CC ECO:0000269|PubMed:28633435}. Nucleus, nuclear pore complex
CC {ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:23591820}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:20005110}. Chromosome
CC {ECO:0000269|PubMed:23652018}. Note=Predominantly located at the
CC nuclear envelope, facing the nucleus interior (PubMed:20005110,
CC PubMed:21195085, PubMed:23591820). Localization at the nuclear pore
CC complex requires NUP153, TPR and ALYREF/ALY (PubMed:23591820,
CC PubMed:22307388). Also found associated with chromatin
CC (PubMed:23652018). In B-cells, targeted to the immunoglobulin variable
CC region genes (PubMed:23652018). {ECO:0000269|PubMed:20005110,
CC ECO:0000269|PubMed:21195085, ECO:0000269|PubMed:22307388,
CC ECO:0000269|PubMed:23591820, ECO:0000269|PubMed:23652018}.
CC -!- SUBCELLULAR LOCATION: [Isoform MCM3AP]: Cytoplasm
CC {ECO:0000269|PubMed:12226073, ECO:0000269|PubMed:21195085}. Nucleus
CC {ECO:0000269|PubMed:12226073, ECO:0000269|PubMed:21195085}.
CC Note=Translocates into the nucleus in the presence of MCM3
CC (PubMed:12226073). Associates with chromatin possibly through
CC interaction with MCM3 (PubMed:12226073). {ECO:0000269|PubMed:12226073}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=GANP;
CC IsoId=O60318-1; Sequence=Displayed;
CC Name=MCM3AP; Synonyms=80 kDa MCM3-associated protein;
CC IsoId=O60318-2; Sequence=VSP_053438;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:11024281). Up-regulated in
CC germinal center B-cells in tonsils (at protein level)
CC (PubMed:11024281). {ECO:0000269|PubMed:11024281}.
CC -!- DISEASE: Peripheral neuropathy, autosomal recessive, with or without
CC impaired intellectual development (PNRIID) [MIM:618124]: An autosomal
CC recessive disorder characterized by early childhood-onset of peripheral
CC sensorimotor neuropathy, progressive distal muscle weakness, atrophy in
CC hands and feet, and gait difficulties, often with loss of ambulation.
CC Most affected individuals also have impaired intellectual development,
CC although some have normal cognition. Additional features may include
CC eye movement abnormalities, claw hands, foot deformities, and
CC scoliosis. {ECO:0000269|PubMed:24123876, ECO:0000269|PubMed:28633435,
CC ECO:0000269|PubMed:28969388, ECO:0000269|PubMed:29982295}. Note=The
CC disease is caused by variants affecting distinct genetic loci,
CC including the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform MCM3AP]: Produced via an alternative promoter
CC within an intron of GANP. MCM3AP promoter elements are poorly conserved
CC in mice, suggesting that the regulation of MCM3AP may be human
CC specific. {ECO:0000269|PubMed:21195085}.
CC -!- SIMILARITY: Belongs to the SAC3 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mcm3ap/";
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DR EMBL; AJ010089; CAB52687.1; -; mRNA.
DR EMBL; AY590469; AAS89300.1; -; Genomic_DNA.
DR EMBL; AP000471; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013285; AAH13285.2; -; mRNA.
DR EMBL; BC004497; AAH04497.2; -; mRNA.
DR EMBL; BC104958; AAI04959.1; -; mRNA.
DR EMBL; BC104960; AAI04961.1; -; mRNA.
DR EMBL; AB011144; BAA25498.1; -; mRNA.
DR EMBL; AB005543; BAA25170.1; -; mRNA.
DR CCDS; CCDS13734.1; -. [O60318-1]
DR PIR; T00339; T00339.
DR RefSeq; NP_003897.2; NM_003906.4. [O60318-1]
DR RefSeq; XP_005261260.1; XM_005261203.4. [O60318-1]
DR RefSeq; XP_005261261.1; XM_005261204.4. [O60318-1]
DR RefSeq; XP_005261262.1; XM_005261205.3. [O60318-1]
DR PDB; 4DHX; X-ray; 2.10 A; A/D=1163-1235.
DR PDBsum; 4DHX; -.
DR AlphaFoldDB; O60318; -.
DR SMR; O60318; -.
DR BioGRID; 114406; 122.
DR DIP; DIP-31696N; -.
DR IntAct; O60318; 47.
DR MINT; O60318; -.
DR STRING; 9606.ENSP00000380820; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyGen; O60318; 12 sites, 2 O-linked glycans (12 sites).
DR iPTMnet; O60318; -.
DR PhosphoSitePlus; O60318; -.
DR BioMuta; MCM3AP; -.
DR EPD; O60318; -.
DR jPOST; O60318; -.
DR MassIVE; O60318; -.
DR MaxQB; O60318; -.
DR PaxDb; O60318; -.
DR PeptideAtlas; O60318; -.
DR PRIDE; O60318; -.
DR ProteomicsDB; 10659; -.
DR ProteomicsDB; 49343; -. [O60318-1]
DR Antibodypedia; 10636; 250 antibodies from 33 providers.
DR DNASU; 8888; -.
DR Ensembl; ENST00000291688.6; ENSP00000291688.1; ENSG00000160294.11. [O60318-1]
DR Ensembl; ENST00000397708.1; ENSP00000380820.1; ENSG00000160294.11. [O60318-1]
DR GeneID; 8888; -.
DR KEGG; hsa:8888; -.
DR MANE-Select; ENST00000291688.6; ENSP00000291688.1; NM_003906.5; NP_003897.2.
DR UCSC; uc002zir.3; human. [O60318-1]
DR CTD; 8888; -.
DR DisGeNET; 8888; -.
DR GeneCards; MCM3AP; -.
DR GeneReviews; MCM3AP; -.
DR HGNC; HGNC:6946; MCM3AP.
DR HPA; ENSG00000160294; Low tissue specificity.
DR MalaCards; MCM3AP; -.
DR MIM; 603294; gene.
DR MIM; 618124; phenotype.
DR neXtProt; NX_O60318; -.
DR OpenTargets; ENSG00000160294; -.
DR PharmGKB; PA30692; -.
DR VEuPathDB; HostDB:ENSG00000160294; -.
DR eggNOG; KOG1860; Eukaryota.
DR GeneTree; ENSGT00940000156322; -.
DR HOGENOM; CLU_001842_1_0_1; -.
DR InParanoid; O60318; -.
DR OMA; RRHGHET; -.
DR OrthoDB; 1593971at2759; -.
DR PhylomeDB; O60318; -.
DR TreeFam; TF105948; -.
DR PathwayCommons; O60318; -.
DR SignaLink; O60318; -.
DR SIGNOR; O60318; -.
DR BioGRID-ORCS; 8888; 781 hits in 1092 CRISPR screens.
DR ChiTaRS; MCM3AP; human.
DR GeneWiki; MCM3AP; -.
DR GenomeRNAi; 8888; -.
DR Pharos; O60318; Tbio.
DR PRO; PR:O60318; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; O60318; protein.
DR Bgee; ENSG00000160294; Expressed in tendon of biceps brachii and 200 other tissues.
DR ExpressionAtlas; O60318; baseline and differential.
DR Genevisible; O60318; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0044615; C:nuclear pore nuclear basket; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0070390; C:transcription export complex 2; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0010484; F:H3 histone acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004402; F:histone acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0006406; P:mRNA export from nucleus; IBA:GO_Central.
DR GO; GO:0034728; P:nucleosome organization; IDA:UniProtKB.
DR GO; GO:0016973; P:poly(A)+ mRNA export from nucleus; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IDA:UniProtKB.
DR CDD; cd12443; RRM_MCM3A_like; 1.
DR InterPro; IPR031910; GANP_CID_dom.
DR InterPro; IPR031907; MCM3AP_GANP.
DR InterPro; IPR034265; MCM3AP_RRM.
DR InterPro; IPR031908; NupH_GANP.
DR InterPro; IPR000717; PCI_dom.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR045107; SAC3/GANP/THP3.
DR InterPro; IPR005062; SAC3/GANP/THP3_conserved.
DR PANTHER; PTHR12436; PTHR12436; 1.
DR Pfam; PF16766; CID_GANP; 1.
DR Pfam; PF16769; MCM3AP_GANP; 1.
DR Pfam; PF16768; NupH_GANP; 1.
DR Pfam; PF03399; SAC3_GANP; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50250; PCI; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Acyltransferase; Alternative promoter usage;
KW Chromosome; Coiled coil; Cytoplasm; Immunity; Intellectual disability;
KW Methylation; mRNA transport; Neuropathy; Nuclear pore complex; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome; Transferase;
KW Translocation; Transport.
FT CHAIN 1..1980
FT /note="Germinal-center associated nuclear protein"
FT /id="PRO_0000096284"
FT DOMAIN 775..958
FT /note="PCI"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01185"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 33..340
FT /note="FG-repeats"
FT REGION 212..247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..432
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 511..557
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..1003
FT /note="Interaction with PCID2 and SEM1"
FT /evidence="ECO:0000269|PubMed:22307388"
FT REGION 998..1038
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1162..1256
FT /note="CID"
FT REGION 1162..1200
FT /note="Interaction with ENY2"
FT /evidence="ECO:0000269|PubMed:22307388"
FT REGION 1207..1235
FT /note="Interaction with ENY2"
FT /evidence="ECO:0000269|PubMed:22307388"
FT REGION 1236..1256
FT /note="Interaction with Centrin"
FT /evidence="ECO:0000269|PubMed:22307388"
FT REGION 1658..1790
FT /note="Acetyltransferase"
FT COILED 1133..1170
FT /evidence="ECO:0000255"
FT COMPBIAS 1..26
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..330
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 351..369
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 393..412
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..432
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 511..526
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 32
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9WUU9"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 489
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WUU9"
FT MOD_RES 490
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WUU9"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WUU9"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..1259
FT /note="Missing (in isoform MCM3AP)"
FT /evidence="ECO:0000305"
FT /id="VSP_053438"
FT VARIANT 102
FT /note="S -> L (in dbSNP:rs9975588)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_019240"
FT VARIANT 288
FT /note="M -> V (in dbSNP:rs17182545)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019241"
FT VARIANT 333
FT /note="R -> L (in dbSNP:rs17182552)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019242"
FT VARIANT 409
FT /note="L -> V (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs773228537)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035472"
FT VARIANT 413
FT /note="P -> L (in dbSNP:rs17182566)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019243"
FT VARIANT 762
FT /note="M -> T (in PNRIID; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28633435"
FT /id="VAR_081543"
FT VARIANT 867
FT /note="A -> D (in PNRIID; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28633435"
FT /id="VAR_081544"
FT VARIANT 870
FT /note="L -> S (in PNRIID; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29982295"
FT /id="VAR_081545"
FT VARIANT 878
FT /note="R -> H (in PNRIID; unknown pathological
FT significance; dbSNP:rs373674344)"
FT /evidence="ECO:0000269|PubMed:28969388"
FT /id="VAR_081546"
FT VARIANT 889..1980
FT /note="Missing (in PNRIID)"
FT /evidence="ECO:0000269|PubMed:28633435"
FT /id="VAR_081547"
FT VARIANT 915
FT /note="E -> K (in PNRIID; unknown pathological
FT significance; dbSNP:rs483352869)"
FT /evidence="ECO:0000269|PubMed:24123876"
FT /id="VAR_070560"
FT VARIANT 951
FT /note="S -> P (in PNRIID; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28969388"
FT /id="VAR_081548"
FT VARIANT 1051
FT /note="P -> L (in dbSNP:rs17182850)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019244"
FT VARIANT 1062
FT /note="V -> M (in dbSNP:rs17182857)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019245"
FT VARIANT 1272
FT /note="V -> M (in PNRIID; unknown pathological
FT significance; dbSNP:rs779248881)"
FT /evidence="ECO:0000269|PubMed:28633435"
FT /id="VAR_081549"
FT VARIANT 1314
FT /note="R -> W (in dbSNP:rs17176709)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019246"
FT VARIANT 1449
FT /note="D -> E (in dbSNP:rs17183220)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019247"
FT VARIANT 1478..1980
FT /note="Missing (in PNRIID; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28633435"
FT /id="VAR_081550"
FT VARIANT 1576
FT /note="V -> I (in dbSNP:rs17183248)"
FT /evidence="ECO:0000269|PubMed:16959974, ECO:0000269|Ref.2"
FT /id="VAR_019248"
FT VARIANT 1577
FT /note="E -> K (in PNRIID; unknown pathological
FT significance; dbSNP:rs779630101)"
FT /evidence="ECO:0000269|PubMed:28633435"
FT /id="VAR_081551"
FT VARIANT 1795
FT /note="A -> T (in dbSNP:rs17183290)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019249"
FT VARIANT 1804..1980
FT /note="Missing (in PNRIID; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28969388"
FT /id="VAR_081552"
FT VARIANT 1831
FT /note="R -> C (in dbSNP:rs2298697)"
FT /id="VAR_053973"
FT VARIANT 1870
FT /note="L -> R (in dbSNP:rs17176933)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019250"
FT VARIANT 1941
FT /note="A -> V (in dbSNP:rs17183403)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019251"
FT MUTAGEN 1496..1501
FT /note="LPLVVL->APLAAA: Loss of i nteraction with MCM3, loss
FT of nuclear localization, loss of chromatin-binding."
FT /evidence="ECO:0000269|PubMed:12226073"
FT MUTAGEN 1730..1733
FT /note="HGAG->AAAA: Severely decreased acetylase activity,
FT loss of DNA replication inhibition. Does not affect
FT chromatin-binding."
FT /evidence="ECO:0000269|PubMed:11258703,
FT ECO:0000269|PubMed:12226073"
FT HELIX 1168..1232
FT /evidence="ECO:0007829|PDB:4DHX"
SQ SEQUENCE 1980 AA; 218405 MW; 503D192686FC38A8 CRC64;
MNPTNPFSGQ QPSAFSASSS NVGTLPSKPP FRFGQPSLFG QNSTLSGKSS GFSQVSSFPA
SSGVSHSSSV QTLGFTQTSS VGPFSGLEHT STFVATSGPS SSSVLGNTGF SFKSPTSVGA
FPSTSAFGQE AGEIVNSGFG KTEFSFKPLE NAVFKPILGA ESEPEKTQSQ IASGFFTFSH
PISSAPGGLA PFSFPQVTSS SATTSNFTFS KPVSSNNSLS AFTPALSNQN VEEEKRGPKS
IFGSSNNSFS SFPVSSAVLG EPFQASKAGV RQGCEEAVSQ VEPLPSLMKG LKRKEDQDRS
PRRHGHEPAE DSDPLSRGDH PPDKRPVRLN RPRGGTLFGR TIQDVFKSNK EVGRLGNKEA
KKETGFVESA ESDHMAIPGG NQSVLAPSRI PGVNKEEETE SREKKEDSLR GTPARQSNRS
ESTDSLGGLS PSEVTAIQCK NIPDYLNDRT ILENHFGKIA KVQRIFTRRS KKLAVVHFFD
HASAALARKK GKSLHKDMAI FWHRKKISPN KKPFSLKEKK PGDGEVSPST EDAPFQHSPL
GKAAGRTGAS SLLNKSSPVK KPSLLKAHQF EGDSFDSASE GSEGLGPCVL SLSTLIGTVA
ETSKEKYRLL DQRDRIMRQA RVKRTDLDKA RTFVGTCLDM CPEKERYMRE TRSQLSVFEV
VPGTDQVDHA AAVKEYSRSS ADQEEPLPHE LRPLPVLSRT MDYLVTQIMD QKEGSLRDWY
DFVWNRTRGI RKDITQQHLC DPLTVSLIEK CTRFHIHCAH FMCEEPMSSF DAKINNENMT
KCLQSLKEMY QDLRNKGVFC ASEAEFQGYN VLLSLNKGDI LREVQQFHPA VRNSSEVKFA
VQAFAALNSN NFVRFFKLVQ SASYLNACLL HCYFSQIRKD ALRALNFAYT VSTQRSTIFP
LDGVVRMLLF RDCEEATDFL TCHGLTVSDG CVELNRSAFL EPEGLSKTRK SVFITRKLTV
SVGEIVNGGP LPPVPRHTPV CSFNSQNKYI GESLAAELPV STQRPGSDTV GGGRGEECGV
EPDAPLSSLP QSLPAPAPSP VPLPPVLALT PSVAPSLFQL SVQPEPPPPE PVPMYSDEDL
AQVVDELIQE ALQRDCEEVG SAGAAYAAAA LGVSNAAMED LLTAATTGIL RHIAAEEVSK
ERERREQERQ RAEEERLKQE RELVLSELSQ GLAVELMERV MMEFVRETCS QELKNAVETD
QRVRVARCCE DVCAHLVDLF LVEEIFQTAK ETLQELQCFC KYLQRWREAV TARKKLRRQM
RAFPAAPCCV DVSDRLRALA PSAECPIAEE NLARGLLDLG HAGRLGISCT RLRRLRNKTA
HQMKVQHFYQ QLLSDVAWAS LDLPSLVAEH LPGRQEHVFW KLVLVLPDVE EQSPESCGRI
LANWLKVKFM GDEGSVDDTS SDAGGIQTLS LFNSLSSKGD QMISVNVCIK VAHGALSDGA
IDAVETQKDL LGASGLMLLL PPKMKSEDMA EEDVYWLSAL LQLKQLLQAK PFQPALPLVV
LVPSPGGDAV EKEVEDGLML QDLVSAKLIS DYTVTEIPDT INDLQGSTKV LQAVQWLVSH
CPHSLDLCCQ TLIQYVEDGI GHEFSGRFFH DRRERRLGGL ASQEPGAIIE LFNSVLQFLA
SVVSSEQLCD LSWPVTEFAE AGGSRLLPHL HWNAPEHLAW LKQAVLGFQL PQMDLPPLGA
PWLPVCSMVV QYASQIPSSR QTQPVLQSQV ENLLHRTYCR WKSKSPSPVH GAGPSVMEIP
WDDLIALCIN HKLRDWTPPR LPVTSEALSE DGQICVYFFK NDLKKYDVPL SWEQARLQTQ
KELQLREGRL AIKPFHPSAN NFPIPLLHMH RNWKRSTECA QEGRIPSTED LMRGASAEEL
LAQCLSSSLL LEKEENKRFE DQLQQWLSED SGAFTDLTSL PLYLPQTLVS LSHTIEPVMK
TSVTTSPQSD MMREQLQLSE ATGTCLGERL KHLERLIRSS REEEVASELH LSALLDMVDI
