Full text data of GOLPH3
GOLPH3
(GPP34)
[Confidence: low (only semi-automatic identification from reviews)]
Golgi phosphoprotein 3 (Coat protein GPP34; Mitochondrial DNA absence factor; MIDAS)
Golgi phosphoprotein 3 (Coat protein GPP34; Mitochondrial DNA absence factor; MIDAS)
UniProt
Q9H4A6
ID GOLP3_HUMAN Reviewed; 298 AA.
AC Q9H4A6; Q9UIW5;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 88.
DE RecName: Full=Golgi phosphoprotein 3;
DE AltName: Full=Coat protein GPP34;
DE AltName: Full=Mitochondrial DNA absence factor;
DE Short=MIDAS;
GN Name=GOLPH3; Synonyms=GPP34;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11042173; DOI=10.1074/jbc.M006143200;
RA Bell A.W., Ward M.A., Blackstock W.P., Freeman H.N.M., Choudhary J.S.,
RA Lewis A.P., Chotai D., Fazel A., Gushue J.N., Paiement J., Palcy S.,
RA Chevet E., Lafreniere-Roula M., Solari R., Thomas D.Y., Rowley A.,
RA Bergeron J.J.M.;
RT "Proteomics characterization of abundant Golgi membrane proteins.";
RL J. Biol. Chem. 276:5152-5165(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, Placenta, and Prostate;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 91-298.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16263763; DOI=10.1242/jcs.02645;
RA Nakashima-Kamimura N., Asoh S., Ishibashi Y., Mukai Y., Shidara Y.,
RA Oda H., Munakata K., Goto Y., Ohta S.;
RT "MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial
RT mass in response to mitochondrial dysfunction.";
RL J. Cell Sci. 118:5357-5367(2005).
RN [7]
RP FUNCTION IN GOLGI MEMBRANE BUDDING, INTERACTION WITH MYO18A,
RP LIPID-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-90;
RP ARG-171 AND ARG-174.
RX PubMed=19837035; DOI=10.1016/j.cell.2009.07.052;
RA Dippold H.C., Ng M.M., Farber-Katz S.E., Lee S.K., Kerr M.L.,
RA Peterman M.C., Sim R., Wiharto P.A., Galbraith K.A., Madhavarapu S.,
RA Fuchs G.J., Meerloo T., Farquhar M.G., Zhou H., Field S.J.;
RT "GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to
RT stretch and shape the Golgi to promote budding.";
RL Cell 139:337-351(2009).
RN [8]
RP FUNCTION IN MTOR SIGNALING, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP VPS35.
RX PubMed=19553991; DOI=10.1038/nature08109;
RA Scott K.L., Kabbarah O., Liang M.C., Ivanova E., Anagnostou V., Wu J.,
RA Dhakal S., Wu M., Chen S., Feinberg T., Huang J., Saci A.,
RA Widlund H.R., Fisher D.E., Xiao Y., Rimm D.L., Protopopov A.,
RA Wong K.K., Chin L.;
RT "GOLPH3 modulates mTOR signalling and rapamycin sensitivity in
RT cancer.";
RL Nature 459:1085-1090(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
RP FUNCTION IN SECRETION.
RX PubMed=22745132; DOI=10.1074/jbc.M112.346569;
RA Bishe B., Syed G.H., Field S.J., Siddiqui A.;
RT "Role of phosphatidylinositol 4-phosphate (PI4P) and its binding
RT protein GOLPH3 in hepatitis C virus secretion.";
RL J. Biol. Chem. 287:27637-27647(2012).
RN [12]
RP FUNCTION, INTERACTION WITH GCNT1, AND SUBCELLULAR LOCATION.
RX PubMed=23027862; DOI=10.1074/jbc.M112.346528;
RA Ali M.F., Chachadi V.B., Petrosyan A., Cheng P.W.;
RT "Golgi phosphoprotein 3 determines cell binding properties under
RT dynamic flow by controlling Golgi localization of core 2 N-
RT acetylglucosaminyltransferase 1.";
RL J. Biol. Chem. 287:39564-39577(2012).
RN [13]
RP MUTAGENESIS OF ARG-7 AND 14-ARG--ARG-15, AND COATOMER-BINDING.
RX PubMed=22889169; DOI=10.1111/j.1600-0854.2012.01403.x;
RA Tu L., Chen L., Banfield D.K.;
RT "A conserved N-terminal arginine-motif in GOLPH3-family proteins
RT mediates binding to coatomer.";
RL Traffic 13:1496-1507(2012).
RN [14]
RP FUNCTION IN CELL MIGRATION.
RX PubMed=23500462; DOI=10.1016/j.bbrc.2013.03.003;
RA Zhou X., Zhan W., Bian W., Hua L., Shi Q., Xie S., Yang D., Li Y.,
RA Zhang X., Liu G., Yu R.;
RT "GOLPH3 regulates the migration and invasion of glioma cells though
RT RhoA.";
RL Biochem. Biophys. Res. Commun. 433:338-344(2013).
RN [15]
RP INTERACTION WITH MYO18A.
RX PubMed=23990465; DOI=10.1074/jbc.M113.497180;
RA Taft M.H., Behrmann E., Munske-Weidemann L.C., Thiel C., Raunser S.,
RA Manstein D.J.;
RT "Functional Characterization of Human Myosin-18A and its Interaction
RT with F-actin and GOLPH3.";
RL J. Biol. Chem. 288:30029-30041(2013).
RN [16]
RP FUNCTION, INTERACTION WITH MYO18A, SUBCELLULAR LOCATION, AND
RP LIPID-BINDING.
RX PubMed=23345592; DOI=10.1091/mbc.E12-07-0525;
RA Ng M.M., Dippold H.C., Buschman M.D., Noakes C.J., Field S.J.;
RT "GOLPH3L antagonizes GOLPH3 to determine Golgi morphology.";
RL Mol. Biol. Cell 24:796-808(2013).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 52-298, LIPID-BINDING,
RP OLIGOMERIZATION, DISULFIDE BOND, AND MUTAGENESIS OF TRP-81; ARG-90;
RP ARG-171 AND ARG-174.
RX PubMed=20026658; DOI=10.1083/jcb.200909063;
RA Wood C.S., Schmitz K.R., Bessman N.J., Setty T.G., Ferguson K.M.,
RA Burd C.G.;
RT "PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling
RT to retrograde Golgi trafficking.";
RL J. Cell Biol. 187:967-975(2009).
CC -!- FUNCTION: Phosphatidylinositol-4-phosphate-binding protein that
CC links Golgi membranes to the cytoskeleton and may participate in
CC the tensile force required for vesicle budding from the Golgi.
CC Thereby, may play a role in Golgi membrane trafficking and could
CC indirectly give its flattened shape to the Golgi apparatus. May
CC also bind to the coatomer to regulate Golgi membrane trafficking.
CC May play a role in anterograde transport from the Golgi to the
CC plasma membrane and regulate secretion. Has also been involved in
CC the control of the localization of Golgi enzymes through
CC interaction with their cytoplasmic part. May play an indirect role
CC in cell migration. Has also been involved in the modulation of
CC mTOR signaling. May also be involved in the regulation of
CC mitochondrial lipids biosynthesis.
CC -!- SUBUNIT: Homodimer. Interacts with the coatomer complex. Interacts
CC with MYO18A; the interaction is direct and may link Golgi
CC membranes to the actin cytoskeleton. Interacts with GCNT1; may
CC control its retention in the Golgi. Interacts with VPS35.
CC -!- INTERACTION:
CC Q02742:GCNT1; NbExp=6; IntAct=EBI-2465479, EBI-8766035;
CC Q92614:MYO18A; NbExp=4; IntAct=EBI-2465479, EBI-949059;
CC P12520:vpr (xeno); NbExp=3; IntAct=EBI-2465479, EBI-6164519;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane;
CC Peripheral membrane protein; Cytoplasmic side. Golgi apparatus,
CC trans-Golgi network membrane; Peripheral membrane protein;
CC Cytoplasmic side. Mitochondrion intermembrane space. Cell membrane
CC (By similarity). Endosome (By similarity).
CC Note=Phosphatidylinositol 4-phosphate-binding and oligomerization
CC participate in the recruitment onto Golgi membranes (Probable).
CC -!- TISSUE SPECIFICITY: Detected in muscle fibers of patients with
CC mitochondrial diseases; not detected in normal muscle fibers.
CC -!- INDUCTION: Activated by depletion of mitochondrial DNA.
CC -!- PTM: Phosphorylated (By similarity).
CC -!- MISCELLANEOUS: Modulates sensitivity to rapamycin. Tumors
CC expressing this protein are more sensitive to rapamycin in vivo.
CC -!- SIMILARITY: Belongs to the GOLPH3/VPS74 family.
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DR EMBL; AJ296152; CAC13124.1; -; mRNA.
DR EMBL; AK075156; BAC11438.1; -; mRNA.
DR EMBL; AL356292; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356356; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012123; AAH12123.1; -; mRNA.
DR EMBL; BC033725; AAH33725.1; -; mRNA.
DR EMBL; BC063586; AAH63586.1; -; mRNA.
DR EMBL; AL133078; CAB61398.1; -; mRNA.
DR PIR; T42677; T42677.
DR RefSeq; NP_071413.1; NM_022130.3.
DR UniGene; Hs.408909; -.
DR PDB; 3KN1; X-ray; 2.90 A; A=52-298.
DR PDBsum; 3KN1; -.
DR ProteinModelPortal; Q9H4A6; -.
DR SMR; Q9H4A6; 59-297.
DR IntAct; Q9H4A6; 3.
DR MINT; MINT-5001986; -.
DR STRING; 9606.ENSP00000265070; -.
DR PhosphoSite; Q9H4A6; -.
DR DMDM; 50400651; -.
DR PaxDb; Q9H4A6; -.
DR PRIDE; Q9H4A6; -.
DR Ensembl; ENST00000265070; ENSP00000265070; ENSG00000113384.
DR GeneID; 64083; -.
DR KEGG; hsa:64083; -.
DR UCSC; uc003jhp.1; human.
DR CTD; 64083; -.
DR GeneCards; GC05M032124; -.
DR H-InvDB; HIX0032097; -.
DR HGNC; HGNC:15452; GOLPH3.
DR HPA; HPA044564; -.
DR MIM; 612207; gene.
DR neXtProt; NX_Q9H4A6; -.
DR PharmGKB; PA28812; -.
DR eggNOG; NOG79916; -.
DR HOGENOM; HOG000209848; -.
DR HOVERGEN; HBG059607; -.
DR InParanoid; Q9H4A6; -.
DR KO; K15620; -.
DR OMA; DYELAMR; -.
DR OrthoDB; EOG7ZKSBV; -.
DR PhylomeDB; Q9H4A6; -.
DR ChiTaRS; GOLPH3; human.
DR EvolutionaryTrace; Q9H4A6; -.
DR GenomeRNAi; 64083; -.
DR NextBio; 65876; -.
DR PRO; PR:Q9H4A6; -.
DR ArrayExpress; Q9H4A6; -.
DR Bgee; Q9H4A6; -.
DR CleanEx; HS_GOLPH3; -.
DR Genevestigator; Q9H4A6; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031985; C:Golgi cisterna; IDA:UniProtKB.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
DR GO; GO:0060352; P:cell adhesion molecule production; IMP:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IMP:UniProtKB.
DR GO; GO:0010467; P:gene expression; IMP:UniProtKB.
DR GO; GO:0009101; P:glycoprotein biosynthetic process; IMP:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; IMP:UniProtKB.
DR GO; GO:0048194; P:Golgi vesicle budding; IMP:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IMP:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling cascade; IMP:UniProtKB.
DR GO; GO:0045053; P:protein retention in Golgi apparatus; IMP:UniProtKB.
DR GO; GO:0009306; P:protein secretion; IMP:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IDA:UniProtKB.
DR InterPro; IPR008628; GPP34.
DR PANTHER; PTHR12704; PTHR12704; 1.
DR Pfam; PF05719; GPP34; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Complete proteome; Disulfide bond;
KW Endosome; Golgi apparatus; Lipid-binding; Membrane; Mitochondrion;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1 298 Golgi phosphoprotein 3.
FT /FTId=PRO_0000123819.
FT REGION 190 201 Beta-hairpin required for oligomerization
FT (By similarity).
FT COMPBIAS 48 51 Poly-Asp.
FT BINDING 81 81 PtdIns4P (Probable).
FT BINDING 90 90 PtdIns4P (Probable).
FT BINDING 171 171 PtdIns4P (Probable).
FT BINDING 174 174 PtdIns4P (Probable).
FT MOD_RES 36 36 Phosphoserine.
FT DISULFID 84 108
FT MUTAGEN 7 7 R->A: Altered binding to coatomer.
FT MUTAGEN 14 15 RR->AA: Loss of binding to coatomer.
FT MUTAGEN 81 81 W->A: Abolishes phosphoinositide binding
FT and localization to the Golgi apparatus;
FT when associated with A-90.
FT MUTAGEN 90 90 R->A: Abolishes phosphoinositide binding
FT and localization to the Golgi apparatus;
FT when associated with A-81.
FT MUTAGEN 90 90 R->L: Loss of function in vesicle
FT budding, abolishes phosphoinositide
FT binding and localization to the Golgi
FT apparatus.
FT MUTAGEN 171 171 R->A,L: Abolishes phosphoinositide
FT binding and localization to the Golgi
FT apparatus; when associated with A-174.
FT MUTAGEN 174 174 R->A: Abolishes phosphoinositide binding
FT and localization to the Golgi apparatus;
FT when associated with A-171 or L-171.
FT HELIX 62 69
FT STRAND 73 75
FT HELIX 83 99
FT STRAND 102 105
FT TURN 110 112
FT TURN 115 117
FT STRAND 118 123
FT HELIX 131 142
FT HELIX 149 156
FT HELIX 163 166
FT HELIX 173 183
FT STRAND 190 194
FT STRAND 197 201
FT HELIX 207 220
FT TURN 221 224
FT HELIX 229 231
FT HELIX 234 245
FT HELIX 250 253
FT HELIX 258 273
FT HELIX 276 279
FT STRAND 282 284
FT HELIX 287 295
SQ SEQUENCE 298 AA; 33811 MW; 34FAD78155CC214A CRC64;
MTSLTQRSSG LVQRRTEASR NAADKERAAG GGAGSSEDDA QSRRDEQDDD DKGDSKETRL
TLMEEVLLLG LKDREGYTSF WNDCISSGLR GCMLIELALR GRLQLEACGM RRKSLLTRKV
ICKSDAPTGD VLLDEALKHV KETQPPETVQ NWIELLSGET WNPLKLHYQL RNVRERLAKN
LVEKGVLTTE KQNFLLFDMT THPLTNNNIK QRLIKKVQEA VLDKWVNDPH RMDRRLLALI
YLAHASDVLE NAFAPLLDEQ YDLATKRVRQ LLDLDPEVEC LKANTNEVLW AVVAAFTK
//
ID GOLP3_HUMAN Reviewed; 298 AA.
AC Q9H4A6; Q9UIW5;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 88.
DE RecName: Full=Golgi phosphoprotein 3;
DE AltName: Full=Coat protein GPP34;
DE AltName: Full=Mitochondrial DNA absence factor;
DE Short=MIDAS;
GN Name=GOLPH3; Synonyms=GPP34;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11042173; DOI=10.1074/jbc.M006143200;
RA Bell A.W., Ward M.A., Blackstock W.P., Freeman H.N.M., Choudhary J.S.,
RA Lewis A.P., Chotai D., Fazel A., Gushue J.N., Paiement J., Palcy S.,
RA Chevet E., Lafreniere-Roula M., Solari R., Thomas D.Y., Rowley A.,
RA Bergeron J.J.M.;
RT "Proteomics characterization of abundant Golgi membrane proteins.";
RL J. Biol. Chem. 276:5152-5165(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, Placenta, and Prostate;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 91-298.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16263763; DOI=10.1242/jcs.02645;
RA Nakashima-Kamimura N., Asoh S., Ishibashi Y., Mukai Y., Shidara Y.,
RA Oda H., Munakata K., Goto Y., Ohta S.;
RT "MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial
RT mass in response to mitochondrial dysfunction.";
RL J. Cell Sci. 118:5357-5367(2005).
RN [7]
RP FUNCTION IN GOLGI MEMBRANE BUDDING, INTERACTION WITH MYO18A,
RP LIPID-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-90;
RP ARG-171 AND ARG-174.
RX PubMed=19837035; DOI=10.1016/j.cell.2009.07.052;
RA Dippold H.C., Ng M.M., Farber-Katz S.E., Lee S.K., Kerr M.L.,
RA Peterman M.C., Sim R., Wiharto P.A., Galbraith K.A., Madhavarapu S.,
RA Fuchs G.J., Meerloo T., Farquhar M.G., Zhou H., Field S.J.;
RT "GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to
RT stretch and shape the Golgi to promote budding.";
RL Cell 139:337-351(2009).
RN [8]
RP FUNCTION IN MTOR SIGNALING, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP VPS35.
RX PubMed=19553991; DOI=10.1038/nature08109;
RA Scott K.L., Kabbarah O., Liang M.C., Ivanova E., Anagnostou V., Wu J.,
RA Dhakal S., Wu M., Chen S., Feinberg T., Huang J., Saci A.,
RA Widlund H.R., Fisher D.E., Xiao Y., Rimm D.L., Protopopov A.,
RA Wong K.K., Chin L.;
RT "GOLPH3 modulates mTOR signalling and rapamycin sensitivity in
RT cancer.";
RL Nature 459:1085-1090(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
RP FUNCTION IN SECRETION.
RX PubMed=22745132; DOI=10.1074/jbc.M112.346569;
RA Bishe B., Syed G.H., Field S.J., Siddiqui A.;
RT "Role of phosphatidylinositol 4-phosphate (PI4P) and its binding
RT protein GOLPH3 in hepatitis C virus secretion.";
RL J. Biol. Chem. 287:27637-27647(2012).
RN [12]
RP FUNCTION, INTERACTION WITH GCNT1, AND SUBCELLULAR LOCATION.
RX PubMed=23027862; DOI=10.1074/jbc.M112.346528;
RA Ali M.F., Chachadi V.B., Petrosyan A., Cheng P.W.;
RT "Golgi phosphoprotein 3 determines cell binding properties under
RT dynamic flow by controlling Golgi localization of core 2 N-
RT acetylglucosaminyltransferase 1.";
RL J. Biol. Chem. 287:39564-39577(2012).
RN [13]
RP MUTAGENESIS OF ARG-7 AND 14-ARG--ARG-15, AND COATOMER-BINDING.
RX PubMed=22889169; DOI=10.1111/j.1600-0854.2012.01403.x;
RA Tu L., Chen L., Banfield D.K.;
RT "A conserved N-terminal arginine-motif in GOLPH3-family proteins
RT mediates binding to coatomer.";
RL Traffic 13:1496-1507(2012).
RN [14]
RP FUNCTION IN CELL MIGRATION.
RX PubMed=23500462; DOI=10.1016/j.bbrc.2013.03.003;
RA Zhou X., Zhan W., Bian W., Hua L., Shi Q., Xie S., Yang D., Li Y.,
RA Zhang X., Liu G., Yu R.;
RT "GOLPH3 regulates the migration and invasion of glioma cells though
RT RhoA.";
RL Biochem. Biophys. Res. Commun. 433:338-344(2013).
RN [15]
RP INTERACTION WITH MYO18A.
RX PubMed=23990465; DOI=10.1074/jbc.M113.497180;
RA Taft M.H., Behrmann E., Munske-Weidemann L.C., Thiel C., Raunser S.,
RA Manstein D.J.;
RT "Functional Characterization of Human Myosin-18A and its Interaction
RT with F-actin and GOLPH3.";
RL J. Biol. Chem. 288:30029-30041(2013).
RN [16]
RP FUNCTION, INTERACTION WITH MYO18A, SUBCELLULAR LOCATION, AND
RP LIPID-BINDING.
RX PubMed=23345592; DOI=10.1091/mbc.E12-07-0525;
RA Ng M.M., Dippold H.C., Buschman M.D., Noakes C.J., Field S.J.;
RT "GOLPH3L antagonizes GOLPH3 to determine Golgi morphology.";
RL Mol. Biol. Cell 24:796-808(2013).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 52-298, LIPID-BINDING,
RP OLIGOMERIZATION, DISULFIDE BOND, AND MUTAGENESIS OF TRP-81; ARG-90;
RP ARG-171 AND ARG-174.
RX PubMed=20026658; DOI=10.1083/jcb.200909063;
RA Wood C.S., Schmitz K.R., Bessman N.J., Setty T.G., Ferguson K.M.,
RA Burd C.G.;
RT "PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling
RT to retrograde Golgi trafficking.";
RL J. Cell Biol. 187:967-975(2009).
CC -!- FUNCTION: Phosphatidylinositol-4-phosphate-binding protein that
CC links Golgi membranes to the cytoskeleton and may participate in
CC the tensile force required for vesicle budding from the Golgi.
CC Thereby, may play a role in Golgi membrane trafficking and could
CC indirectly give its flattened shape to the Golgi apparatus. May
CC also bind to the coatomer to regulate Golgi membrane trafficking.
CC May play a role in anterograde transport from the Golgi to the
CC plasma membrane and regulate secretion. Has also been involved in
CC the control of the localization of Golgi enzymes through
CC interaction with their cytoplasmic part. May play an indirect role
CC in cell migration. Has also been involved in the modulation of
CC mTOR signaling. May also be involved in the regulation of
CC mitochondrial lipids biosynthesis.
CC -!- SUBUNIT: Homodimer. Interacts with the coatomer complex. Interacts
CC with MYO18A; the interaction is direct and may link Golgi
CC membranes to the actin cytoskeleton. Interacts with GCNT1; may
CC control its retention in the Golgi. Interacts with VPS35.
CC -!- INTERACTION:
CC Q02742:GCNT1; NbExp=6; IntAct=EBI-2465479, EBI-8766035;
CC Q92614:MYO18A; NbExp=4; IntAct=EBI-2465479, EBI-949059;
CC P12520:vpr (xeno); NbExp=3; IntAct=EBI-2465479, EBI-6164519;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane;
CC Peripheral membrane protein; Cytoplasmic side. Golgi apparatus,
CC trans-Golgi network membrane; Peripheral membrane protein;
CC Cytoplasmic side. Mitochondrion intermembrane space. Cell membrane
CC (By similarity). Endosome (By similarity).
CC Note=Phosphatidylinositol 4-phosphate-binding and oligomerization
CC participate in the recruitment onto Golgi membranes (Probable).
CC -!- TISSUE SPECIFICITY: Detected in muscle fibers of patients with
CC mitochondrial diseases; not detected in normal muscle fibers.
CC -!- INDUCTION: Activated by depletion of mitochondrial DNA.
CC -!- PTM: Phosphorylated (By similarity).
CC -!- MISCELLANEOUS: Modulates sensitivity to rapamycin. Tumors
CC expressing this protein are more sensitive to rapamycin in vivo.
CC -!- SIMILARITY: Belongs to the GOLPH3/VPS74 family.
CC -----------------------------------------------------------------------
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DR EMBL; AJ296152; CAC13124.1; -; mRNA.
DR EMBL; AK075156; BAC11438.1; -; mRNA.
DR EMBL; AL356292; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356356; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012123; AAH12123.1; -; mRNA.
DR EMBL; BC033725; AAH33725.1; -; mRNA.
DR EMBL; BC063586; AAH63586.1; -; mRNA.
DR EMBL; AL133078; CAB61398.1; -; mRNA.
DR PIR; T42677; T42677.
DR RefSeq; NP_071413.1; NM_022130.3.
DR UniGene; Hs.408909; -.
DR PDB; 3KN1; X-ray; 2.90 A; A=52-298.
DR PDBsum; 3KN1; -.
DR ProteinModelPortal; Q9H4A6; -.
DR SMR; Q9H4A6; 59-297.
DR IntAct; Q9H4A6; 3.
DR MINT; MINT-5001986; -.
DR STRING; 9606.ENSP00000265070; -.
DR PhosphoSite; Q9H4A6; -.
DR DMDM; 50400651; -.
DR PaxDb; Q9H4A6; -.
DR PRIDE; Q9H4A6; -.
DR Ensembl; ENST00000265070; ENSP00000265070; ENSG00000113384.
DR GeneID; 64083; -.
DR KEGG; hsa:64083; -.
DR UCSC; uc003jhp.1; human.
DR CTD; 64083; -.
DR GeneCards; GC05M032124; -.
DR H-InvDB; HIX0032097; -.
DR HGNC; HGNC:15452; GOLPH3.
DR HPA; HPA044564; -.
DR MIM; 612207; gene.
DR neXtProt; NX_Q9H4A6; -.
DR PharmGKB; PA28812; -.
DR eggNOG; NOG79916; -.
DR HOGENOM; HOG000209848; -.
DR HOVERGEN; HBG059607; -.
DR InParanoid; Q9H4A6; -.
DR KO; K15620; -.
DR OMA; DYELAMR; -.
DR OrthoDB; EOG7ZKSBV; -.
DR PhylomeDB; Q9H4A6; -.
DR ChiTaRS; GOLPH3; human.
DR EvolutionaryTrace; Q9H4A6; -.
DR GenomeRNAi; 64083; -.
DR NextBio; 65876; -.
DR PRO; PR:Q9H4A6; -.
DR ArrayExpress; Q9H4A6; -.
DR Bgee; Q9H4A6; -.
DR CleanEx; HS_GOLPH3; -.
DR Genevestigator; Q9H4A6; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031985; C:Golgi cisterna; IDA:UniProtKB.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
DR GO; GO:0060352; P:cell adhesion molecule production; IMP:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IMP:UniProtKB.
DR GO; GO:0010467; P:gene expression; IMP:UniProtKB.
DR GO; GO:0009101; P:glycoprotein biosynthetic process; IMP:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; IMP:UniProtKB.
DR GO; GO:0048194; P:Golgi vesicle budding; IMP:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IMP:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling cascade; IMP:UniProtKB.
DR GO; GO:0045053; P:protein retention in Golgi apparatus; IMP:UniProtKB.
DR GO; GO:0009306; P:protein secretion; IMP:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IDA:UniProtKB.
DR InterPro; IPR008628; GPP34.
DR PANTHER; PTHR12704; PTHR12704; 1.
DR Pfam; PF05719; GPP34; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Complete proteome; Disulfide bond;
KW Endosome; Golgi apparatus; Lipid-binding; Membrane; Mitochondrion;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1 298 Golgi phosphoprotein 3.
FT /FTId=PRO_0000123819.
FT REGION 190 201 Beta-hairpin required for oligomerization
FT (By similarity).
FT COMPBIAS 48 51 Poly-Asp.
FT BINDING 81 81 PtdIns4P (Probable).
FT BINDING 90 90 PtdIns4P (Probable).
FT BINDING 171 171 PtdIns4P (Probable).
FT BINDING 174 174 PtdIns4P (Probable).
FT MOD_RES 36 36 Phosphoserine.
FT DISULFID 84 108
FT MUTAGEN 7 7 R->A: Altered binding to coatomer.
FT MUTAGEN 14 15 RR->AA: Loss of binding to coatomer.
FT MUTAGEN 81 81 W->A: Abolishes phosphoinositide binding
FT and localization to the Golgi apparatus;
FT when associated with A-90.
FT MUTAGEN 90 90 R->A: Abolishes phosphoinositide binding
FT and localization to the Golgi apparatus;
FT when associated with A-81.
FT MUTAGEN 90 90 R->L: Loss of function in vesicle
FT budding, abolishes phosphoinositide
FT binding and localization to the Golgi
FT apparatus.
FT MUTAGEN 171 171 R->A,L: Abolishes phosphoinositide
FT binding and localization to the Golgi
FT apparatus; when associated with A-174.
FT MUTAGEN 174 174 R->A: Abolishes phosphoinositide binding
FT and localization to the Golgi apparatus;
FT when associated with A-171 or L-171.
FT HELIX 62 69
FT STRAND 73 75
FT HELIX 83 99
FT STRAND 102 105
FT TURN 110 112
FT TURN 115 117
FT STRAND 118 123
FT HELIX 131 142
FT HELIX 149 156
FT HELIX 163 166
FT HELIX 173 183
FT STRAND 190 194
FT STRAND 197 201
FT HELIX 207 220
FT TURN 221 224
FT HELIX 229 231
FT HELIX 234 245
FT HELIX 250 253
FT HELIX 258 273
FT HELIX 276 279
FT STRAND 282 284
FT HELIX 287 295
SQ SEQUENCE 298 AA; 33811 MW; 34FAD78155CC214A CRC64;
MTSLTQRSSG LVQRRTEASR NAADKERAAG GGAGSSEDDA QSRRDEQDDD DKGDSKETRL
TLMEEVLLLG LKDREGYTSF WNDCISSGLR GCMLIELALR GRLQLEACGM RRKSLLTRKV
ICKSDAPTGD VLLDEALKHV KETQPPETVQ NWIELLSGET WNPLKLHYQL RNVRERLAKN
LVEKGVLTTE KQNFLLFDMT THPLTNNNIK QRLIKKVQEA VLDKWVNDPH RMDRRLLALI
YLAHASDVLE NAFAPLLDEQ YDLATKRVRQ LLDLDPEVEC LKANTNEVLW AVVAAFTK
//
MIM
612207
*RECORD*
*FIELD* NO
612207
*FIELD* TI
*612207 GOLGI PHOSPHOPROTEIN 3; GOLPH3
;;GOLGI-ASSOCIATED PROTEIN, 34-KD; GPP34;;
MITOCHONDRIAL DNA ABSENCE-SENSITIVE FACTOR; MIDAS
read more*FIELD* TX
DESCRIPTION
GOLPH3 forms a complex with myosin-18A (MYO18A; 610067) that regulates
Golgi architecture and participates in vesicle budding for anterograde
trafficking (Ng et al., 2013).
CLONING
Following the purification and characterization of rat Golgi-associated
proteins, Bell et al. (2001) cloned rat Golph3, which they called Gpp34.
By EST database analysis, they identified human GOLPH3, which encodes a
deduced 298-amino acid protein. Immunogold electron microscopy localized
rat Golph3 at the periphery of Golgi stacks, on the cis and trans sides,
as well as at the lateral edges of stacked cisternae. Scanning confocal
microscopy of cultured rat hippocampal neurons and a rat fibroblast cell
line confirmed the Golgi localization and more diffuse cytosolic
labeling.
Nakashima-Kamimura et al. (2005) determined that GOLPH3, which they
called MIDAS, has an N-terminal acidic region and a C-terminal leucine
zipper motif. Immunohistochemical analysis and density gradient
fractionation, followed by Western blot analysis, showed that the
majority of GOLPH3 localized to mitochondria in HeLa cells and only a
small proportion distributed to the Golgi apparatus. Protease and
membrane permeability studies indicated that GOLPH3 localized to inner
mitochondria or was embedded in the outer membrane.
Using Western blot analysis, Ng et al. (2013) detected high GOLPH3
expression in all mouse tissues and human and other mammalian cell lines
examined. Fluorescence-tagged human GOLPH3 and the related protein
GOLPH3L (612208) colocalized with Golgi-resident proteins following
expression in HeLa cells. Orthologs of GOLPH3 were detected in
vertebrates, invertebrates, and yeast.
GENE FUNCTION
Nakashima-Kamimura et al. (2005) found that expression of MIDAS was
increased in muscle fibers of patients with mitochondrial diseases such
as CPEO (see KSS; 530000) and MELAS (540000). Upregulation of MIDAS in
HeLa cells caused an increase in mitochondria number, redistributed
mitochondria to the perinuclear region, and prevented cell growth. MIDAS
had no effect on mitochondria membrane potential, cytoskeletal
structure, or mitochondrial DNA, RNA or protein, but the amount of the
mitochondria-specific phospholipid cardiolipin was increased almost
2-fold following MIDAS overexpression. Nakashima-Kamimura et al. (2005)
concluded that MIDAS regulates mitochondrial lipids leading to increased
total mitochondrial mass in response to mitochondrial dysfunction.
Tu et al. (2008) found that yeast Vps74, a homolog of human GOLPH3 and
GOLPH3L, binds to a pentameric motif present in the cytoplasmic tails of
the majority of yeast Golgi-localized glycosyltransferases, as well as
to coat protein complex I (COPI). Tu et al. (2008) proposed that Vps74p
maintains a steady-state localization of Golgi glycosyltransferases
dynamically, by promoting their incorporation into COPI-coated vesicles.
Genomewide copy number analyses of human cancers identified a frequent
5p13 amplification in several solid tumor types, including lung (56%),
ovarian (38%), breast (32%), prostate (37%), and melanoma (32%). Using
integrative analysis of a genomic profile of the region, Scott et al.
(2009) identified a Golgi protein, GOLPH3, as a candidate targeted for
amplification. Gain- and loss-of-function studies in vitro and in vivo
validated GOLPH3 as a potent oncogene. Physically, GOLPH3 localizes to
the trans-Golgi network and interacts with components of the retromer
complex, which in yeast has been linked to TOR signaling.
Mechanistically, GOLPH3 regulates cell size, enhances growth
factor-induced mTOR (601231) signaling in human cancer cells, and alters
the response of an mTOR inhibitor in vivo. Thus, Scott et al. (2009)
concluded that genomic and genetic, biologic, functional, and
biochemical data in yeast and humans establishes GOLPH3 as a novel
oncogene that is commonly targeted for amplification in human cancer,
and is capable of modulating the response to rapamycin, a cancer drug in
clinical use.
Ng et al. (2013) found that GOLPH3 and GOLPH3L interacted with
phosphitidylinositol-4-phosphate (PI4P), but not with each other. Both
proteins independently localized to the Golgi in a PI4P-dependent
manner. GOLPH3, but not GOLPH3L, also interacted with MYO18A.
Overexpression of GOLPH3 in HEK293 cells resulted in dispersal of Golgi,
whereas overexpression of GOLPH3L resulted in compaction of Golgi.
Knockdown of GOLPH3 or MYO18A via small interfering RNA resulted in a
compact Golgi, and knockdown of GOLPH3L had the opposite effect.
However, knockdown of GOLPH3L had no effect on Golgi morphology in the
absence of GOLPH3 and MYO18A, suggesting that the effect of GOLPH3L on
Golgi is indirect and that GOLPH3L may function as an inhibitor of
GOLPH3 and MYO18A. Knockdown of GOLPH3, MYO18A, or GOLPH3L impaired
secretion from HEK293 cells.
MAPPING
Hartz (2013) mapped the GOLPH3 gene to chromosome 5p13.3 based on an
alignment of the GOLPH3 sequence (GenBank GENBANK AJ296152) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Bell, A. W.; Ward, M. A.; Blackstock, W. P.; Freeman, H. N. M.;
Choudhary, J. S.; Lewis, A. P.; Chotai, D.; Fazel, A.; Gushue, J.
N.; Paiement, J.; Palcy, S.; Chevet, E.; Lafreniere-Roula, M.; Solari,
R.; Thomas, D. Y.; Rowley, A.; Bergeron, J. J. M.: Proteomics characterization
of abundant Golgi membrane proteins. J. Biol. Chem. 276: 5152-5165,
2001.
2. Hartz, P. A.: Personal Communication. Baltimore, Md. 11/11/2013.
3. Nakashima-Kamimura, N.; Asoh, S.; Ishibashi, Y.; Mukai, Y.; Shidara,
Y.; Oda, H.; Munakata, K.; Goto, Y.; Ohta, S.: MIDAS/GPP34, a nuclear
gene product, regulates total mitochondrial mass in response to mitochondrial
dysfunction. J. Cell Sci. 118: 5357-5367, 2005.
4. Ng, M. M.; Dippold, H. C.; Buschman, M. D.; Noakes, C. J.; Field,
S. J.: GOLPH3L antagonizes GOLPH3 to determine Golgi morphology. Molec.
Biol. Cell 24: 796-808, 2013.
5. Scott, K. L.; Kabbarah, O.; Liang, M.-C.; Ivanova, E.; Anagnostou,
V.; Wu, J.; Dhakal, S.; Wu, M.; Chen, S.; Feinberg, T.; Huang, J.;
Saci, A.; Widlund, H. R.; Fisher, D. E.; Xiao, Y.; Rimm, D. L.; Protopopov,
A.; Wong, K.-K.; Chin, L.: GOLPH3 modulates mTOR signalling and rapamycin
sensitivity in cancer. Nature 459: 1085-1090, 2009.
6. Tu, L.; Tai, W. C. S.; Chen, L.; Banfield, D. K.: Signal-mediated
dynamic retention of glycosyltransferases in the Golgi. Science 321:
404-407, 2008.
*FIELD* CN
Patricia A. Hartz - updated: 11/11/2013
Ada Hamosh - updated: 7/9/2009
Ada Hamosh - updated: 8/13/2008
*FIELD* CD
Patricia A. Hartz: 7/30/2008
*FIELD* ED
mgross: 11/15/2013
mcolton: 11/12/2013
mcolton: 11/11/2013
alopez: 7/15/2009
terry: 7/9/2009
alopez: 8/18/2008
terry: 8/13/2008
wwang: 7/30/2008
*RECORD*
*FIELD* NO
612207
*FIELD* TI
*612207 GOLGI PHOSPHOPROTEIN 3; GOLPH3
;;GOLGI-ASSOCIATED PROTEIN, 34-KD; GPP34;;
MITOCHONDRIAL DNA ABSENCE-SENSITIVE FACTOR; MIDAS
read more*FIELD* TX
DESCRIPTION
GOLPH3 forms a complex with myosin-18A (MYO18A; 610067) that regulates
Golgi architecture and participates in vesicle budding for anterograde
trafficking (Ng et al., 2013).
CLONING
Following the purification and characterization of rat Golgi-associated
proteins, Bell et al. (2001) cloned rat Golph3, which they called Gpp34.
By EST database analysis, they identified human GOLPH3, which encodes a
deduced 298-amino acid protein. Immunogold electron microscopy localized
rat Golph3 at the periphery of Golgi stacks, on the cis and trans sides,
as well as at the lateral edges of stacked cisternae. Scanning confocal
microscopy of cultured rat hippocampal neurons and a rat fibroblast cell
line confirmed the Golgi localization and more diffuse cytosolic
labeling.
Nakashima-Kamimura et al. (2005) determined that GOLPH3, which they
called MIDAS, has an N-terminal acidic region and a C-terminal leucine
zipper motif. Immunohistochemical analysis and density gradient
fractionation, followed by Western blot analysis, showed that the
majority of GOLPH3 localized to mitochondria in HeLa cells and only a
small proportion distributed to the Golgi apparatus. Protease and
membrane permeability studies indicated that GOLPH3 localized to inner
mitochondria or was embedded in the outer membrane.
Using Western blot analysis, Ng et al. (2013) detected high GOLPH3
expression in all mouse tissues and human and other mammalian cell lines
examined. Fluorescence-tagged human GOLPH3 and the related protein
GOLPH3L (612208) colocalized with Golgi-resident proteins following
expression in HeLa cells. Orthologs of GOLPH3 were detected in
vertebrates, invertebrates, and yeast.
GENE FUNCTION
Nakashima-Kamimura et al. (2005) found that expression of MIDAS was
increased in muscle fibers of patients with mitochondrial diseases such
as CPEO (see KSS; 530000) and MELAS (540000). Upregulation of MIDAS in
HeLa cells caused an increase in mitochondria number, redistributed
mitochondria to the perinuclear region, and prevented cell growth. MIDAS
had no effect on mitochondria membrane potential, cytoskeletal
structure, or mitochondrial DNA, RNA or protein, but the amount of the
mitochondria-specific phospholipid cardiolipin was increased almost
2-fold following MIDAS overexpression. Nakashima-Kamimura et al. (2005)
concluded that MIDAS regulates mitochondrial lipids leading to increased
total mitochondrial mass in response to mitochondrial dysfunction.
Tu et al. (2008) found that yeast Vps74, a homolog of human GOLPH3 and
GOLPH3L, binds to a pentameric motif present in the cytoplasmic tails of
the majority of yeast Golgi-localized glycosyltransferases, as well as
to coat protein complex I (COPI). Tu et al. (2008) proposed that Vps74p
maintains a steady-state localization of Golgi glycosyltransferases
dynamically, by promoting their incorporation into COPI-coated vesicles.
Genomewide copy number analyses of human cancers identified a frequent
5p13 amplification in several solid tumor types, including lung (56%),
ovarian (38%), breast (32%), prostate (37%), and melanoma (32%). Using
integrative analysis of a genomic profile of the region, Scott et al.
(2009) identified a Golgi protein, GOLPH3, as a candidate targeted for
amplification. Gain- and loss-of-function studies in vitro and in vivo
validated GOLPH3 as a potent oncogene. Physically, GOLPH3 localizes to
the trans-Golgi network and interacts with components of the retromer
complex, which in yeast has been linked to TOR signaling.
Mechanistically, GOLPH3 regulates cell size, enhances growth
factor-induced mTOR (601231) signaling in human cancer cells, and alters
the response of an mTOR inhibitor in vivo. Thus, Scott et al. (2009)
concluded that genomic and genetic, biologic, functional, and
biochemical data in yeast and humans establishes GOLPH3 as a novel
oncogene that is commonly targeted for amplification in human cancer,
and is capable of modulating the response to rapamycin, a cancer drug in
clinical use.
Ng et al. (2013) found that GOLPH3 and GOLPH3L interacted with
phosphitidylinositol-4-phosphate (PI4P), but not with each other. Both
proteins independently localized to the Golgi in a PI4P-dependent
manner. GOLPH3, but not GOLPH3L, also interacted with MYO18A.
Overexpression of GOLPH3 in HEK293 cells resulted in dispersal of Golgi,
whereas overexpression of GOLPH3L resulted in compaction of Golgi.
Knockdown of GOLPH3 or MYO18A via small interfering RNA resulted in a
compact Golgi, and knockdown of GOLPH3L had the opposite effect.
However, knockdown of GOLPH3L had no effect on Golgi morphology in the
absence of GOLPH3 and MYO18A, suggesting that the effect of GOLPH3L on
Golgi is indirect and that GOLPH3L may function as an inhibitor of
GOLPH3 and MYO18A. Knockdown of GOLPH3, MYO18A, or GOLPH3L impaired
secretion from HEK293 cells.
MAPPING
Hartz (2013) mapped the GOLPH3 gene to chromosome 5p13.3 based on an
alignment of the GOLPH3 sequence (GenBank GENBANK AJ296152) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Bell, A. W.; Ward, M. A.; Blackstock, W. P.; Freeman, H. N. M.;
Choudhary, J. S.; Lewis, A. P.; Chotai, D.; Fazel, A.; Gushue, J.
N.; Paiement, J.; Palcy, S.; Chevet, E.; Lafreniere-Roula, M.; Solari,
R.; Thomas, D. Y.; Rowley, A.; Bergeron, J. J. M.: Proteomics characterization
of abundant Golgi membrane proteins. J. Biol. Chem. 276: 5152-5165,
2001.
2. Hartz, P. A.: Personal Communication. Baltimore, Md. 11/11/2013.
3. Nakashima-Kamimura, N.; Asoh, S.; Ishibashi, Y.; Mukai, Y.; Shidara,
Y.; Oda, H.; Munakata, K.; Goto, Y.; Ohta, S.: MIDAS/GPP34, a nuclear
gene product, regulates total mitochondrial mass in response to mitochondrial
dysfunction. J. Cell Sci. 118: 5357-5367, 2005.
4. Ng, M. M.; Dippold, H. C.; Buschman, M. D.; Noakes, C. J.; Field,
S. J.: GOLPH3L antagonizes GOLPH3 to determine Golgi morphology. Molec.
Biol. Cell 24: 796-808, 2013.
5. Scott, K. L.; Kabbarah, O.; Liang, M.-C.; Ivanova, E.; Anagnostou,
V.; Wu, J.; Dhakal, S.; Wu, M.; Chen, S.; Feinberg, T.; Huang, J.;
Saci, A.; Widlund, H. R.; Fisher, D. E.; Xiao, Y.; Rimm, D. L.; Protopopov,
A.; Wong, K.-K.; Chin, L.: GOLPH3 modulates mTOR signalling and rapamycin
sensitivity in cancer. Nature 459: 1085-1090, 2009.
6. Tu, L.; Tai, W. C. S.; Chen, L.; Banfield, D. K.: Signal-mediated
dynamic retention of glycosyltransferases in the Golgi. Science 321:
404-407, 2008.
*FIELD* CN
Patricia A. Hartz - updated: 11/11/2013
Ada Hamosh - updated: 7/9/2009
Ada Hamosh - updated: 8/13/2008
*FIELD* CD
Patricia A. Hartz: 7/30/2008
*FIELD* ED
mgross: 11/15/2013
mcolton: 11/12/2013
mcolton: 11/11/2013
alopez: 7/15/2009
terry: 7/9/2009
alopez: 8/18/2008
terry: 8/13/2008
wwang: 7/30/2008