G2Cdb::Gene report

Gene id
Gene symbol
Homo sapiens
microtubule-actin crosslinking factor 1
G00000548 (Mus musculus)

Databases (8)

Curated Gene
OTTHUMG00000007754 (Vega human gene)
ENSG00000127603 (Ensembl human gene)
23499 (Entrez Gene)
965 (G2Cdb plasticity & disease)
MACF1 (GeneCards)
608271 (OMIM)
Marker Symbol
HGNC:13664 (HGNC)
Protein Sequence
Q96PK2 (UniProt)

Synonyms (7)

  • ABP620
  • ACF7
  • FLJ45612
  • FLJ46776
  • KIAA0465
  • KIAA1251
  • MACF

Literature (26)

Pubmed - other

  • Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation.

    Martins-de-Souza D, Gattaz WF, Schmitt A, Novello JC, Marangoni S, Turck CW and Dias-Neto E

    Laboratório de Neurociências, Instituto de Psiquiatria, Faculdade de Medicina da USP, Rua Dr, Ovídio Pires de Campos, no 785, São Paulo, SP, CEP 05403-010, Brazil. martins@mpipsykl.mpg.de

    Background: Schizophrenia is likely to be a consequence of DNA alterations that, together with environmental factors, will lead to protein expression differences and the ultimate establishment of the illness. The superior temporal gyrus is implicated in schizophrenia and executes functions such as the processing of speech, language skills and sound processing.

    Methods: We performed an individual comparative proteome analysis using two-dimensional gel electrophoresis of 9 schizophrenia and 6 healthy control patients' left posterior superior temporal gyrus (Wernicke's area - BA22p) identifying by mass spectrometry several protein expression alterations that could be related to the disease.

    Results: Our analysis revealed 11 downregulated and 14 upregulated proteins, most of them related to energy metabolism. Whereas many of the identified proteins have been previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C, creatine kinase and neuron-specific enolase, new putative disease markers were also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and phosphate carrier protein, mitochondrial precursor. Besides, the differential expression of peroxiredoxin 6 (PRDX6) and glial fibrillary acidic protein (GFAP) were confirmed by western blot in schizophrenia prefrontal cortex.

    Conclusion: Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease.

    BMC psychiatry 2009;9;17

  • Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia.

    Camargo LM, Collura V, Rain JC, Mizuguchi K, Hermjakob H, Kerrien S, Bonnert TP, Whiting PJ and Brandon NJ

    Merck Research Labs, Merck & Co., Boston, MA 02115, USA. miguel_camargo@merck.com

    Disrupted in Schizophrenia 1 (DISC1) is a schizophrenia risk gene associated with cognitive deficits in both schizophrenics and the normal ageing population. In this study, we have generated a network of protein-protein interactions (PPIs) around DISC1. This has been achieved by utilising iterative yeast-two hybrid (Y2H) screens, combined with detailed pathway and functional analysis. This so-called 'DISC1 interactome' contains many novel PPIs and provides a molecular framework to explore the function of DISC1. The network implicates DISC1 in processes of cytoskeletal stability and organisation, intracellular transport and cell-cycle/division. In particular, DISC1 looks to have a PPI profile consistent with that of an essential synaptic protein, which fits well with the underlying molecular pathology observed at the synaptic level and the cognitive deficits seen behaviourally in schizophrenics. Utilising a similar approach with dysbindin (DTNBP1), a second schizophrenia risk gene, we show that dysbindin and DISC1 share common PPIs suggesting they may affect common biological processes and that the function of schizophrenia risk genes may converge.

    Molecular psychiatry 2007;12;1;74-86

  • Role of CLASP2 in microtubule stabilization and the regulation of persistent motility.

    Drabek K, van Ham M, Stepanova T, Draegestein K, van Horssen R, Sayas CL, Akhmanova A, Ten Hagen T, Smits R, Fodde R, Grosveld F and Galjart N

    Department of Cell Biology and Genetics, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.

    In motile fibroblasts, stable microtubules (MTs) are oriented toward the leading edge of cells. How these polarized MT arrays are established and maintained, and the cellular processes they control, have been the subject of many investigations. Several MT "plus-end-tracking proteins," or +TIPs, have been proposed to regulate selective MT stabilization, including the CLASPs, a complex of CLIP-170, IQGAP1, activated Cdc42 or Rac1, a complex of APC, EB1, and mDia1, and the actin-MT crosslinking factor ACF7. By using mouse embryonic fibroblasts (MEFs) in a wound-healing assay, we show here that CLASP2 is required for the formation of a stable, polarized MT array but that CLIP-170 and an APC-EB1 interaction are not essential. Persistent motility is also hampered in CLASP2-deficient MEFs. We find that ACF7 regulates cortical CLASP localization in HeLa cells, indicating it acts upstream of CLASP2. Fluorescence-based approaches show that GFP-CLASP2 is immobilized in a bimodal manner in regions near cell edges. Our results suggest that the regional immobilization of CLASP2 allows MT stabilization and promotes directionally persistent motility in fibroblasts.

    Current biology : CB 2006;16;22;2259-64

  • Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

    Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P and Mann M

    Center for Experimental BioInformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.

    Cell signaling mechanisms often transmit information via posttranslational protein modifications, most importantly reversible protein phosphorylation. Here we develop and apply a general mass spectrometric technology for identification and quantitation of phosphorylation sites as a function of stimulus, time, and subcellular location. We have detected 6,600 phosphorylation sites on 2,244 proteins and have determined their temporal dynamics after stimulating HeLa cells with epidermal growth factor (EGF) and recorded them in the Phosida database. Fourteen percent of phosphorylation sites are modulated at least 2-fold by EGF, and these were classified by their temporal profiles. Surprisingly, a majority of proteins contain multiple phosphorylation sites showing different kinetics, suggesting that they serve as platforms for integrating signals. In addition to protein kinase cascades, the targets of reversible phosphorylation include ubiquitin ligases, guanine nucleotide exchange factors, and at least 46 different transcriptional regulators. The dynamic phosphoproteome provides a missing link in a global, integrative view of cellular regulation.

    Cell 2006;127;3;635-48

  • The DNA sequence and biological annotation of human chromosome 1.

    Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM and Prigmore E

    The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. sgregory@chg.duhs.duke.edu

    The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

    Funded by: Medical Research Council: G0000107; Wellcome Trust

    Nature 2006;441;7091;315-21

  • Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC.

    Gevaert K, Staes A, Van Damme J, De Groot S, Hugelier K, Demol H, Martens L, Goethals M and Vandekerckhove J

    Department of Medical Protein Research, Flanders Interuniversity Institute for Biotechnology, Ghent University, Ghent, Belgium.

    We present a phosphoproteomics approach using diagonal RP chromatography as the basic isolation principle. Phosphopeptides present in a tryptic digest of total cellular lysates were first enriched by Fe3+-immobilized metal ion affinity chromatography. Further sorting of the phosphopeptides took place in three steps. First, the resulting peptide mixture was fractionated over reversed-phase chromatography. Second, peptides present in each fraction were treated with phosphatases. Third, the dephosphorylated peptides were then more hydrophobic and shifted towards a later elution interval from the contaminating non-phosphopeptides eluting at the same position as during the primary run. Since the phosphopeptides are isolated as their dephosphorylated form, additional proof for their original phosphorylation state was obtained by split-differential 16O-18O labeling. The method was validated with alpha-casein phosphopeptides and consecutively applied on HepG2 cells. We identified 190 phosphorylated peptides from 152 different proteins. This dataset includes 38 novel protein phosphorylation sites.

    Proteomics 2005;5;14;3589-99

  • Microtubule actin crosslinking factor 1b: a novel plakin that localizes to the Golgi complex.

    Lin CM, Chen HJ, Leung CL, Parry DA and Liem RK

    Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

    MACF1 (microtubule actin crosslinking factor), also called ACF7 (actin crosslinking family 7) is a cytoskeletal linker protein that can associate with both actin filaments and microtubules. We have identified a novel alternatively spliced isoform of MACF1. We named this isoform MACF1b and renamed the original isoform MACF1a. MACF1b is identical to MACF1a, except that it has a region containing plakin (or plectin) repeats in the middle of the molecule. MACF1b is ubiquitously expressed in adult tissues with especially high levels in the lung. We studied the subcellular localization of MACF1b proteins in mammalian cell lines. In two lung cell lines, MACF1b was chiefly localized to the Golgi complex. Upon treatments that disrupt the Golgi complex, MACF1b redistributed into the cytosol, but remained co-localized with the dispersed Golgi ministacks. MACF1b proteins can be detected in the enriched Golgi fraction by western blotting. The domain of MACF1b that targets it to the Golgi was found at the N-terminal part of the region that contains the plakin repeats. Reducing the level of MACF1 proteins by small-interfering RNA resulted in the dispersal of the Golgi complex.

    Funded by: NINDS NIH HHS: NS040784

    Journal of cell science 2005;118;Pt 16;3727-38

  • Automated yeast two-hybrid screening for nuclear receptor-interacting proteins.

    Albers M, Kranz H, Kober I, Kaiser C, Klink M, Suckow J, Kern R and Koegl M

    PheneX Pharmaceuticals AG, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.

    High throughput analysis of protein-protein interactions is an important sector of hypothesis-generating research. Using an improved and automated version of the yeast two-hybrid system, we completed a large interaction screening project with a focus on nuclear receptors and their cofactors. A total of 425 independent yeast two-hybrid cDNA library screens resulted in 6425 potential interacting protein fragments involved in 1613 different interaction pairs. We show that simple statistical parameters can be used to narrow down the data set to a high confidence set of 377 interaction pairs where validated interactions are enriched to 61% of all pairs. Within the high confidence set, there are 64 novel proteins potentially binding to nuclear receptors or their cofactors. We discuss several examples of high interest, and we expect that communication of this huge data set will help to complement our knowledge of the protein interaction repertoire of this family of transcription factors and instigate the characterization of the various novel candidate interactors.

    Molecular & cellular proteomics : MCP 2005;4;2;205-13

  • Interaction between p230 and MACF1 is associated with transport of a glycosyl phosphatidyl inositol-anchored protein from the Golgi to the cell periphery.

    Kakinuma T, Ichikawa H, Tsukada Y, Nakamura T and Toh BH

    Department of Orthopaedic Surgery, Kyoto University, Kyoto, Japan. t-kak@umin.ac.jp

    The molecular basis by which proteins are transported along cytoskeletal tracts from the trans-Golgi network (TGN) to the cell periphery remains poorly understood. Previously, using human autoimmune sera, we identified and characterized a TGN protein, p230/Golgin-245, an extensively coiled-coil protein with flexible amino- and carboxyl-terminal ends, that is anchored to TGN membranes and TGN-derived vesicles by its carboxyl-terminal GRIP domain. To identify molecules that interact with the flexible amino-terminal end of p230, we used this domain as bait to screen a human brain cDNA library in a yeast two-hybrid assay. We found that this domain interacts with the carboxyl-terminal domain of MACF1, a protein that cross-links microtubules to the actin cytoskeleton. The interaction was confirmed by co-immunoprecipitation, an in vitro binding assay, double immunofluorescence images demonstrating overlapped localization in HeLa cells, and co-localization of FLAG-tagged constructs containing the interacting domains of these two proteins with their endogenous partners. Expression in HeLa cells of FLAG-tagged constructs containing the interacting domains of p230 and MACF1 disrupted transport of the glycosyl phosphatidyl inositol-anchored marker protein conjugated with yellow fluorescent protein (YFP-SP-GPI), while trafficking of the transmembrane marker protein, vesicular stomatitis virus glycoprotein conjugated with YFP (VSVG3-GL-YFP), was unaffected. Our results suggest that p230, through its interaction with MACF1, provides the molecular link for transport of GPI-anchored proteins along the microtubule and actin cytoskeleton from the TGN to the cell periphery.

    Experimental cell research 2004;298;2;388-98

  • Functional proteomics mapping of a human signaling pathway.

    Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P and Gauthier JM

    Hybrigenics SA, 75014 Paris, France. fcolland@hybrigenics.fr

    Access to the human genome facilitates extensive functional proteomics studies. Here, we present an integrated approach combining large-scale protein interaction mapping, exploration of the interaction network, and cellular functional assays performed on newly identified proteins involved in a human signaling pathway. As a proof of principle, we studied the Smad signaling system, which is regulated by members of the transforming growth factor beta (TGFbeta) superfamily. We used two-hybrid screening to map Smad signaling protein-protein interactions and to establish a network of 755 interactions, involving 591 proteins, 179 of which were poorly or not annotated. The exploration of such complex interaction databases is improved by the use of PIMRider, a dedicated navigation tool accessible through the Web. The biological meaning of this network is illustrated by the presence of 18 known Smad-associated proteins. Functional assays performed in mammalian cells including siRNA knock-down experiments identified eight novel proteins involved in Smad signaling, thus validating this integrated functional proteomics approach.

    Genome research 2004;14;7;1324-32

  • 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 TO, 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 and Sugano S

    Helix Research Institute, 1532-3 Yana, Kisarazu, Chiba 292-0812, Japan.

    As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.

    Nature genetics 2004;36;1;40-5

  • ACF7: an essential integrator of microtubule dynamics.

    Kodama A, Karakesisoglou I, Wong E, Vaezi A and Fuchs E

    Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021, USA.

    ACF7 is a member of the spectraplakin family of cytoskeletal crosslinking proteins possessing actin and microtubule binding domains. Here, we show that ACF7 is an essential integrator of MT-actin dynamics. In endodermal cells, ACF7 binds along microtubules but concentrates at their distal ends and at cell borders when polarized. In ACF7's absence, microtubules still bind EB1 and CLIP170, but they no longer grow along polarized actin bundles, nor do they pause and tether to actin-rich cortical sites. The consequences are less stable, long microtubules with skewed cytoplasmic trajectories and altered dynamic instability. In response to wounding, ACF7 null cultures activate polarizing signals, but fail to maintain them and coordinate migration. Rescue of these defects requires ACF7's actin and microtubule binding domains. Thus, spectraplakins are important for controlling microtubule dynamics and reinforcing links between microtubules and polarized F-actin, so that cellular polarization and coordinated cell movements can be sustained.

    Funded by: NIAMS NIH HHS: R01 AR027883-28

    Cell 2003;115;3;343-54

  • Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs.

    Nakayama M, Kikuno R and Ohara O

    Department of Human Gene Research, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan. nmanabu@kazusa.or.jp

    Large proteins have multiple domains that are potentially capable of binding many kinds of partners. It is conceivable, therefore, that such proteins could function as an intricate framework of assembly protein complexes. To comprehensively study protein-protein interactions between large KIAA proteins, we have constructed a library composed of 1087 KIAA cDNA clones based on prior functional classifications done in silico. We were guided by two principles that raise the success rate for detecting interactions per tested combination: we avoided testing low-probability combinations, and reduced the number of potential false negatives that arise from the fact that large proteins cannot reliably be expressed in yeast. The latter was addressed by constructing a cDNA library comprised of random fragments encoding large proteins. Cytoplasmic domains of KIAA transmembrane proteins (>1000 amino acids) were used as bait for yeast two-hybrid screening. Our analyses reveal that several KIAA proteins bearing a transmembrane region have the capability of binding to other KIAA proteins containing domains (e.g., PDZ, SH3, rhoGEF, and spectrin) known to be localized to highly specialized submembranous sites, indicating that they participate in cellular junction formation, receptor or channel clustering, and intracellular signaling events. Our representative library should be a very useful resource for detecting previously unidentified interactions because it complements conventional expression libraries, which seldom contain large cDNAs.

    Genome research 2002;12;11;1773-84

  • Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.

    Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O and Nagase T

    Kazusa DNA Research Institute, Kisarazu, Chiba, Japan.

    We have accumulated information on protein-coding sequences of uncharacterized human genes, which are known as KIAA genes, through cDNA sequencing. For comprehensive functional analysis of the KIAA genes, it is necessary to prepare a set of cDNA clones which direct the synthesis of functional KIAA gene products. However, since the KIAA cDNAs were derived from long mRNAs (> 4 kb), it was not expected that all of them were full-length. Thus, as the first step toward preparing these clones, we evaluated the integrity of protein-coding sequences of KIAA cDNA clones through comparison with homologous protein entries in the public database. As a result, 1141 KIAA cDNAs had at least one homologous entry in the database, and 619 of them (54%) were found to be truncated at the 5' and/or 3' ends. In this study, 290 KIAA cDNA clones were tailored to be full-length or have considerably longer sequences than the original clones by isolating additional cDNA clones and/or connected parts of additional cDNAs or PCR products of the missing portion to the original cDNA clone. Consequently, 265, 8, and 17 predicted CDSs of KIAA cDNA clones were increased in the amino-, carboxy-, and both terminal sequences, respectively. In addition, 40 cDNA clones were modified to remove spurious interruption of protein-coding sequences. The total length of the resultant extensions at amino- and carboxy-terminals of KIAA gene products reached 97,000 and 7,216 amino acid residues, respectively, and various protein domains were found in these extended portions.

    DNA research : an international journal for rapid publication of reports on genes and genomes 2002;9;3;99-106

  • MACF1 gene structure: a hybrid of plectin and dystrophin.

    Gong TW, Besirli CG and Lomax MI

    Kresge Hearing Research Institute, Department of Otolaryngology/Head Neck Surgery, 9301E MSRB III, 1150 W. Medical Center Dr., Box 0648, University of Michigan, Ann Arbor, MI 48109-0648, USA.

    Mammalian MACF1 (Macrophin1; previously named ACF7) is a giant cytoskeletal linker protein with three known isoforms that arise by alternative splicing. We isolated a 19.1-kb cDNA encoding a fourth isoform (MACF1-4) with a unique N-terminus. Instead of an N-terminal actin-binding domain found in the other three isoforms, MACF1-4 has eight plectin repeats. The MACF1 gene is located on human Chr 1p32, contains at least 102 exons, spans over 270 kb, and gives rise to four major isoforms with different N-termini. The genomic organization of the actin-binding domain is highly conserved in mammalian genes for both plectin and BPAG1. All eight plectin repeats are encoded by one large exon; this feature is similar to the genomic structure of plectin. The intron positions within spectrin repeats in MACF1 are very similar to those in the dystrophin gene. This demonstrates that MACF1 has characteristic features of genes for two classes of cytoskeletal proteins, i.e., plectin and dystrophin.

    Funded by: NIDCD NIH HHS: P01 DC02982, R01 DC02492

    Mammalian genome : official journal of the International Mammalian Genome Society 2001;12;11;852-61

  • Identification and characterization of RRM-containing coactivator activator (CoAA) as TRBP-interacting protein, and its splice variant as a coactivator modulator (CoAM).

    Iwasaki T, Chin WW and Ko L

    Lilly Research Laboratories, Department of Gene Regulation, Bone and Inflammation Research, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.

    We previously cloned and characterized thyroid hormone receptor-binding protein (TRBP) as an LXXLL-containing general coactivator that associates with coactivator complexes through its C terminus. To identify protein cofactors for TRBP action, a Sos-Ras yeast two-hybrid cDNA library was screened using TRBP C terminus as bait. A novel coactivator was isolated, coactivator activator (CoAA), that specifically associates with TRBP. Human CoAA is composed of 669 amino acids with a TRBP-interacting domain and two highly conserved RNA recognition motifs (RRM) commonly found in ribonucleoproteins. A splice variant lacking the entire TRBP-interacting domain was also isolated as a coactivator modulator (CoAM), a 156-amino acid protein containing only the RRM region. Human CoAA and CoAM mRNAs are encoded by a single gene located on chromosome 11q13; alternative splicing in exon 2 of CoAA yields CoAM. CoAA interacts with both TRBP and p300 in vitro. In addition, CoAA potently coactivates transcription mediated by multiple hormone-response elements and acts synergistically with TRBP and CREB-binding protein (CBP). Furthermore, CoAA is associated with the DNA-dependent protein kinase-poly(ADP-ribose) polymerase complex. Strikingly, CoAM, which lacks a TRBP-interacting domain, strongly represses both TRBP and CBP action suggesting that CoAM may modulate endogenous CoAA function. These data suggest that CoAA may serve as a mediator of coactivators such as TRBP in gene activation.

    The Journal of biological chemistry 2001;276;36;33375-83

  • Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins.

    Sun D, Leung CL and Liem RK

    Departments of Pathology and Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

    MACF (microtubule actin cross-linking factor) is a large, 608-kDa protein that can associate with both actin microfilaments and microtubules (MTs). Structurally, MACF can be divided into 3 domains: an N-terminal domain that contains both a calponin type actin-binding domain and a plakin domain; a rod domain that is composed of 23 dystrophin-like spectrin repeats; and a C-terminal domain that includes two EF-hand calcium-binding motifs, as well as a region that is homologous to two related proteins, GAR22 and Gas2. We have previously demonstrated that the C-terminal domain of MACF binds to MTs, although no homology was observed between this domain and other known microtubule-binding proteins. In this report, we describe the characterization of this microtubule-binding domain of MACF by transient transfection studies and in vitro binding assays. We found that the C-terminus of MACF contains at least two microtubule-binding regions, a GAR domain and a domain containing glycine-serine-arginine (GSR) repeats. In transfected cells, the GAR domain bound to and partially stabilized MTs to depolymerization by nocodazole. The GSR-containing domain caused MTs to form bundles that are still sensitive to nocodazole-induced depolymerization. When present together, these two domains acted in concert to bundle MTs and render them stable to nocodazole treatment. Recently, a study has shown that the N-terminal half of the plakin domain (called the M1 domain) of MACF also binds MTs. We therefore examined the microtubule binding ability of the M1 domain in the context of the entire plakin domain with and without the remaining N-terminal regions of two different MACF isoforms. Interestingly, in the presence of the surrounding sequences, the M1 domain did not bind MTs. In addition to MACF, cDNA sequences encoding the GAR and GSR-containing domains are also found in the partial human EST clone KIAA0728, which has high sequence homology to the 3' end of the MACF cDNA; hence, we refer to it as MACF2. The C-terminal domain of mouse MACF2 was cloned and characterized. The microtubule-binding properties of MACF2 C-terminal domain are similar to that of MACF. The GAR domain was originally found in Gas 2 protein and here we show that it can associate with MTs in transfected cells. Plectin and desmoplakin have GSR-containing domains at their C-termini and we further demonstrate that the GSR-containing domain of plectin, but not desmoplakin, can bind to MTs in vivo.

    Funded by: NIA NIH HHS: AG00189; NINDS NIH HHS: NS15182

    Journal of cell science 2001;114;Pt 1;161-172

  • An epidermal plakin that integrates actin and microtubule networks at cellular junctions.

    Karakesisoglou I, Yang Y and Fuchs E

    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA.

    Plakins are cytoskeletal linker proteins initially thought to interact exclusively with intermediate filaments (IFs), but recently were found to associate additionally with actin and microtubule networks. Here, we report on ACF7, a mammalian orthologue of the Drosophila kakapo plakin genetically involved in epidermal-muscle adhesion and neuromuscular junctions. While ACF7/kakapo is divergent from other plakins in its IF-binding domain, it has at least one actin (K(d) = 0.35 microM) and one microtubule (K(d) approximately 6 microM) binding domain. Similar to its fly counterpart, ACF7 is expressed in the epidermis. In well spread epidermal keratinocytes, ACF7 discontinuously decorates the cytoskeleton at the cell periphery, including microtubules (MTs) and actin filaments (AFs) that are aligned in parallel converging at focal contacts. Upon calcium induction of intercellular adhesion, ACF7 and the cytoskeleton reorganize at cell-cell borders but with different kinetics from adherens junctions and desmosomes. Treatments with cytoskeletal depolymerizing drugs reveal that ACF7's cytoskeletal association is dependent upon the microtubule network, but ACF7 also appears to stabilize actin at sites where microtubules and microfilaments meet. We posit that ACF7 may function in microtubule dynamics to facilitate actin-microtubule interactions at the cell periphery and to couple the microtubule network to cellular junctions. These attributes provide a clear explanation for the kakapo mutant phenotype in flies.

    Funded by: NIAMS NIH HHS: R01 AR027883, R01-AR27883

    The Journal of cell biology 2000;149;1;195-208

  • Microtubule actin cross-linking factor (MACF): a hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons.

    Leung CL, Sun D, Zheng M, Knowles DR and Liem RK

    Department of Pathology and Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

    We cloned and characterized a full-length cDNA of mouse actin cross-linking family 7 (mACF7) by sequential rapid amplification of cDNA ends-PCR. The completed mACF7 cDNA is 17 kb and codes for a 608-kD protein. The closest relative of mACF7 is the Drosophila protein Kakapo, which shares similar architecture with mACF7. mACF7 contains a putative actin-binding domain and a plakin-like domain that are highly homologous to dystonin (BPAG1-n) at its NH(2) terminus. However, unlike dystonin, mACF7 does not contain a coiled-coil rod domain; instead, the rod domain of mACF7 is made up of 23 dystrophin-like spectrin repeats. At its COOH terminus, mACF7 contains two putative EF-hand calcium-binding motifs and a segment homologous to the growth arrest-specific protein, Gas2. In this paper, we demonstrate that the NH(2)-terminal actin-binding domain of mACF7 is functional both in vivo and in vitro. More importantly, we found that the COOH-terminal domain of mACF7 interacts with and stabilizes microtubules. In transfected cells full-length mACF7 can associate not only with actin but also with microtubules. Hence, we suggest a modified name: MACF (microtubule actin cross-linking factor). The properties of MACF are consistent with the observation that mutations in kakapo cause disorganization of microtubules in epidermal muscle attachment cells and some sensory neurons.

    Funded by: NIA NIH HHS: AG00189, T32 AG000189; NINDS NIH HHS: NS15182, R01 NS015182

    The Journal of cell biology 1999;147;6;1275-86

  • Molecular cloning and characterization of human trabeculin-alpha, a giant protein defining a new family of actin-binding proteins.

    Sun Y, Zhang J, Kraeft SK, Auclair D, Chang MS, Liu Y, Sutherland R, Salgia R, Griffin JD, Ferland LH and Chen LB

    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

    We describe the molecular cloning and characterization of a novel giant human cytoplasmic protein, trabeculin-alpha (M(r) = 614,000). Analysis of the deduced amino acid sequence reveals homologies with several putative functional domains, including a pair of alpha-actinin-like actin binding domains; regions of homology to plakins at either end of the giant polypeptide; 29 copies of a spectrin-like motif in the central region of the protein; two potential Ca(2+)-binding EF-hand motifs; and a Ser-rich region containing a repeated GSRX motif. With similarities to both plakins and spectrins, trabeculin-alpha appears to have evolved as a hybrid of these two families of proteins. The functionality of the actin binding domains located near the N terminus was confirmed with an F-actin binding assay using glutathione S-transferase fusion proteins comprising amino acids 9-486 of the deduced peptide. Northern and Western blotting and immunofluorescence studies suggest that trabeculin is ubiquitously expressed and is distributed throughout the cytoplasm, though the protein was found to be greatly up-regulated upon differentiation of myoblasts into myotubes. Finally, the presence of cDNAs similar to, yet distinct from, trabeculin-alpha in both human and mouse suggests that trabeculins may form a new subfamily of giant actin-binding/cytoskeletal cross-linking proteins.

    The Journal of biological chemistry 1999;274;47;33522-30

  • Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

    Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N and Ohara O

    Kazusa DNA Research Institute, Kisarazu, Chiba, Japan. nagase@kazusa.or.jp

    In order to obtain information on the coding sequences of unidentified human genes, we newly determined the sequences of 100 cDNA clones of unknown human genes, which we named KIAA1193 to KIAA1292, from two sets of size-fractionated human adult and fetal brain cDNA libraries. The results of our particular strategy to select cDNA clones which have the potentiality of coding for large proteins in vitro revealed that the average sizes of the inserts and the corresponding open reading frames reached 5.2 kb and 2.8 kb (933 amino acid residues), respectively. By the computational analysis of the predicted amino acid sequences against the OWL and Pfam databases, 58 predicted gene products were classified into the following five functional categories: cell signaling/communication, cell structure/motility, nucleic acid management, protein management and metabolism. It was also found that 30 gene products had homologues in the public databases which were similar in sequence throughout almost their entire regions to the newly identified genes. The chromosomal loci of the genes were assigned by using human-rodent hybrid panels unless their mapping data were already available in the public databases. The expression profiles of the genes were studied in 10 human tissues, 8 brain regions, spinal cord, fetal brain and fetal liver by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay.

    DNA research : an international journal for rapid publication of reports on genes and genomes 1999;6;5;337-45

  • Molecular cloning of macrophin, a human homologue of Drosophila kakapo with a close structural similarity to plectin and dystrophin.

    Okuda T, Matsuda S, Nakatsugawa S, Ichigotani Y, Iwahashi N, Takahashi M, Ishigaki T and Hamaguchi M

    Department of Radiology, Department of Molecular Pathogenesis, Pathology II, Nagoya University School of Medicine, 65 Turumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

    We have determined the complete cDNA coding sequence of a novel cytoskeletal protein by the degenerative primer-mediated PCR strategy. This novel gene, named as macrophin (microfilament and actin filament cross-linker protein related to plectin and dystrophin, Accession No. AB029290), appears to be a human homologue of a Drosophila gene, kakapo, and shows close similarity to plectin and dystrophin on the search of BLAST homology-computed database. Comparison of the deduced protein sequences for macrophin and kakapo revealed that they were 66% similar, and both of them have an NH2-terminal actin-binding domain, a central rod region composed of spectrin-like repeats, and COOH-terminal Gas2-related region. The predicted sequences for macrophin are 5430 amino acids in length with a calculated molecular mass of 620 kDa, which is one of the largest size idenfied in human cytoskeletal proteins. High expression of macrophin was observed in brain, heart, lung, placenta, liver, kidney, and pancreas. In pancreas, we found that macrophin was specifically expressed in acinar cells than islet cells by in situ hybridization. By using radiation hybrid panel, we have mapped the macrophin gene to the chromosome 1p31-32.

    Biochemical and biophysical research communications 1999;264;2;568-74

  • Characterization of cDNA clones in size-fractionated cDNA libraries from human brain.

    Seki N, Ohira M, Nagase T, Ishikawa K, Miyajima N, Nakajima D, Nomura N and Ohara O

    Kazusa DNA Research Institute, Chiba, Japan. nseki@kazusa.or.jp

    To evaluate the size-fractionated cDNA libraries of human brain previously constructed (O. O'hara et al. DNA Research, 4, 53-59, 1997), the occurrence of chimeric clones and the content of clones with coding potentiality were analyzed using the randomly sampled clones with insert sizes of 5 to 7 kb. When the chromosomal location of 30 clones was determined by the radiation-hybrid mapping method, the map positions assigned from the 3'- and 5'-end sequences separately were coincident for 29 clones, suggesting that the occurrence of chimeric clones is at most 1/30. Using 91 clones mapped to chromosome 1, the content of clones that have the potentiality coding for proteins larger than 100 amino acid residues was estimated to be approximately 50% (46 out of 91 clones) on the basis of nucleotide sequence analysis and coding potentiality assay in vitro. No significant open reading frames were detected in the remaining clones. Although the clones coding for short peptides may not have been included in the above estimation, the libraries constructed from the whole brain mRNA fraction appear to contain a considerable amount of clones corresponding to the 5'-truncated transcripts in an unprocessed form and/or those with long 3'-untranslated regions.

    DNA research : an international journal for rapid publication of reports on genes and genomes 1997;4;5;345-9

  • Novel actin crosslinker superfamily member identified by a two step degenerate PCR procedure.

    Byers TJ, Beggs AH, McNally EM and Kunkel LM

    Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202, USA.

    Actin-crosslinking proteins link F-actin into the bundles and networks that constitute the cytoskeleton. Dystrophin, beta-spectrin, alpha-actinin, ABP-120, ABP-280, and fimbrin share homologous actin-binding domains and comprise an actin crosslinker superfamily. We have identified a novel member of this superfamily (ACF7) using a degenerate primer-mediated PCR strategy that was optimized to resolve less-abundant superfamily sequences. The ACF7 gene is on human chromosome 1 and hybridizes to high molecular weight bands on northern blots. Sequence comparisons argue that ACF7 does not fit into one of the existing families, but represents a new class within the superfamily.

    Funded by: NINDS NIH HHS: NS 23740

    FEBS letters 1995;368;3;500-4

  • My franchise was a teen-age lion's den.

    Caccamise DA

    Dental economics - oral hygiene 1976;66;11;36-43

Gene lists (6)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000061 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus (ortho) 984
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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