COG2_HUMAN
ID COG2_HUMAN Reviewed; 738 AA.
AC Q14746; Q86U99;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Conserved oligomeric Golgi complex subunit 2;
DE Short=COG complex subunit 2;
DE AltName: Full=Component of oligomeric Golgi complex 2;
DE AltName: Full=Low density lipoprotein receptor defect C-complementing protein;
GN Name=COG2; Synonyms=LDLC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7962052; DOI=10.1083/jcb.127.3.679;
RA Podos S.D., Reddy P., Ashkenas J., Krieger M.;
RT "LDLC encodes a brefeldin A-sensitive, peripheral Golgi protein required
RT for normal Golgi function.";
RL J. Cell Biol. 127:679-691(1994).
RN [2]
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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Retinal pigment epithelium, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP 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., Buerckstuemmer T.,
RA 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 [6]
RP INVOLVEMENT IN CDG2Q, AND VARIANT CDG2Q GLY-634.
RX PubMed=24784932; DOI=10.1111/cge.12417;
RA Kodera H., Ando N., Yuasa I., Wada Y., Tsurusaki Y., Nakashima M.,
RA Miyake N., Saitoh S., Matsumoto N., Saitsu H.;
RT "Mutations in COG2 encoding a subunit of the conserved oligomeric golgi
RT complex cause a congenital disorder of glycosylation.";
RL Clin. Genet. 87:455-460(2015).
CC -!- FUNCTION: Required for normal Golgi morphology and function.
CC -!- SUBUNIT: Component of the conserved oligomeric Golgi complex which is
CC composed of eight different subunits and is required for normal Golgi
CC morphology and localization.
CC -!- INTERACTION:
CC Q14746; Q76N32-2: CEP68; NbExp=3; IntAct=EBI-389449, EBI-11975967;
CC Q14746; Q9H9E3: COG4; NbExp=2; IntAct=EBI-389449, EBI-368382;
CC Q14746; Q96PV6: LENG8; NbExp=3; IntAct=EBI-389449, EBI-739546;
CC Q14746; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-389449, EBI-1216080;
CC Q14746; Q5JR59-3: MTUS2; NbExp=4; IntAct=EBI-389449, EBI-11522433;
CC Q14746-2; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-10233912, EBI-742948;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14746-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14746-2; Sequence=VSP_042942;
CC -!- DISEASE: Congenital disorder of glycosylation 2Q (CDG2Q) [MIM:617395]:
CC A form of congenital disorder of glycosylation, a genetically
CC heterogeneous group of autosomal recessive, multisystem disorders
CC caused by a defect in glycoprotein biosynthesis and characterized by
CC under-glycosylated serum glycoproteins. Congenital disorders of
CC glycosylation result in a wide variety of clinical features, such as
CC defects in the nervous system development, psychomotor retardation,
CC dysmorphic features, hypotonia, coagulation disorders, and
CC immunodeficiency. The broad spectrum of features reflects the critical
CC role of N-glycoproteins during embryonic development, differentiation,
CC and maintenance of cell functions. The transmission pattern of CDG2Q is
CC consistent with autosomal recessive inheritance.
CC {ECO:0000269|PubMed:24784932}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the COG2 family. {ECO:0000305}.
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DR EMBL; Z34975; CAA84427.1; -; mRNA.
DR EMBL; AL158214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW69916.1; -; Genomic_DNA.
DR EMBL; BC014960; AAH14960.1; -; mRNA.
DR EMBL; BC051906; AAH51906.1; -; mRNA.
DR CCDS; CCDS1584.1; -. [Q14746-1]
DR CCDS; CCDS44329.1; -. [Q14746-2]
DR PIR; A53542; A53542.
DR RefSeq; NP_001138508.1; NM_001145036.1. [Q14746-2]
DR RefSeq; NP_031383.1; NM_007357.2. [Q14746-1]
DR AlphaFoldDB; Q14746; -.
DR SMR; Q14746; -.
DR BioGRID; 116477; 81.
DR ComplexPortal; CPX-6199; COG tethering complex.
DR CORUM; Q14746; -.
DR IntAct; Q14746; 35.
DR STRING; 9606.ENSP00000355629; -.
DR iPTMnet; Q14746; -.
DR PhosphoSitePlus; Q14746; -.
DR BioMuta; COG2; -.
DR DMDM; 2498512; -.
DR EPD; Q14746; -.
DR jPOST; Q14746; -.
DR MassIVE; Q14746; -.
DR MaxQB; Q14746; -.
DR PaxDb; Q14746; -.
DR PeptideAtlas; Q14746; -.
DR PRIDE; Q14746; -.
DR ProteomicsDB; 60153; -. [Q14746-1]
DR ProteomicsDB; 60154; -. [Q14746-2]
DR TopDownProteomics; Q14746-1; -. [Q14746-1]
DR Antibodypedia; 34680; 211 antibodies from 26 providers.
DR DNASU; 22796; -.
DR Ensembl; ENST00000366668.7; ENSP00000355628.3; ENSG00000135775.14. [Q14746-2]
DR Ensembl; ENST00000366669.9; ENSP00000355629.4; ENSG00000135775.14. [Q14746-1]
DR GeneID; 22796; -.
DR KEGG; hsa:22796; -.
DR MANE-Select; ENST00000366669.9; ENSP00000355629.4; NM_007357.3; NP_031383.1.
DR UCSC; uc001htw.4; human. [Q14746-1]
DR CTD; 22796; -.
DR DisGeNET; 22796; -.
DR GeneCards; COG2; -.
DR GeneReviews; COG2; -.
DR HGNC; HGNC:6546; COG2.
DR HPA; ENSG00000135775; Tissue enhanced (parathyroid).
DR MalaCards; COG2; -.
DR MIM; 606974; gene.
DR MIM; 617395; phenotype.
DR neXtProt; NX_Q14746; -.
DR OpenTargets; ENSG00000135775; -.
DR Orphanet; 435934; COG2-CDG.
DR PharmGKB; PA26697; -.
DR VEuPathDB; HostDB:ENSG00000135775; -.
DR eggNOG; KOG2307; Eukaryota.
DR GeneTree; ENSGT00390000012040; -.
DR HOGENOM; CLU_005470_0_0_1; -.
DR InParanoid; Q14746; -.
DR OMA; CWAEGVY; -.
DR PhylomeDB; Q14746; -.
DR TreeFam; TF105824; -.
DR PathwayCommons; Q14746; -.
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR Reactome; R-HSA-6811438; Intra-Golgi traffic.
DR Reactome; R-HSA-6811440; Retrograde transport at the Trans-Golgi-Network.
DR SignaLink; Q14746; -.
DR BioGRID-ORCS; 22796; 373 hits in 1081 CRISPR screens.
DR GeneWiki; COG2; -.
DR GenomeRNAi; 22796; -.
DR Pharos; Q14746; Tbio.
DR PRO; PR:Q14746; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q14746; protein.
DR Bgee; ENSG00000135775; Expressed in rectum and 197 other tissues.
DR ExpressionAtlas; Q14746; baseline and differential.
DR Genevisible; Q14746; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005795; C:Golgi stack; IDA:UniProtKB.
DR GO; GO:0017119; C:Golgi transport complex; IDA:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0070085; P:glycosylation; IMP:ComplexPortal.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0006891; P:intra-Golgi vesicle-mediated transport; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0000301; P:retrograde transport, vesicle recycling within Golgi; IMP:ComplexPortal.
DR InterPro; IPR009316; COG2.
DR InterPro; IPR024603; COG_complex_COG2_C.
DR InterPro; IPR024602; COG_su2_N.
DR PANTHER; PTHR12961; PTHR12961; 1.
DR Pfam; PF06148; COG2; 1.
DR Pfam; PF12022; DUF3510; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Congenital disorder of glycosylation;
KW Disease variant; Golgi apparatus; Membrane; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..738
FT /note="Conserved oligomeric Golgi complex subunit 2"
FT /id="PRO_0000213495"
FT REGION 474..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 668..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 482..504
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 551
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042942"
FT VARIANT 288
FT /note="R -> H (in dbSNP:rs34796217)"
FT /id="VAR_048757"
FT VARIANT 304
FT /note="N -> K (in dbSNP:rs6681346)"
FT /id="VAR_029274"
FT VARIANT 589
FT /note="V -> I (in dbSNP:rs34109129)"
FT /id="VAR_048758"
FT VARIANT 634
FT /note="W -> G (in CDG2Q; dbSNP:rs1085307117)"
FT /evidence="ECO:0000269|PubMed:24784932"
FT /id="VAR_078769"
SQ SEQUENCE 738 AA; 83208 MW; 8E393CBE1114DB28 CRC64;
MEKSRMNLPK GPDTLCFDKD EFMKEDFDVD HFVSDCRKRV QLEELRDDLE LYYKLLKTAM
VELINKDYAD FVNLSTNLVG MDKALNQLSV PLGQLREEVL SLRSSVSEGI RAVDERMSKQ
EDIRKKKMCV LRLIQVIRSV EKIEKILNSQ SSKETSALEA SSPLLTGQIL ERIATEFNQL
QFHAVQSKGM PLLDKVRPRI AGITAMLQQS LEGLLLEGLQ TSDVDIIRHC LRTYATIDKT
RDAEALVGQV LVKPYIDEVI IEQFVESHPN GLQVMYNKLL EFVPHHCRLL REVTGGAISS
EKGNTVPGYD FLVNSVWPQI VQGLEEKLPS LFNPGNPDAF HEKYTISMDF VRRLERQCGS
QASVKRLRAH PAYHSFNKKW NLPVYFQIRF REIAGSLEAA LTDVLEDAPA ESPYCLLASH
RTWSSLRRCW SDEMFLPLLV HRLWRLTLQI LARYSVFVNE LSLRPISNES PKEIKKPLVT
GSKEPSITQG NTEDQGSGPS ETKPVVSISR TQLVYVVADL DKLQEQLPEL LEIIKPKLEM
IGFKNFSSIS AALEDSQSSF SACVPSLSSK IIQDLSDSCF GFLKSALEVP RLYRRTNKEV
PTTASSYVDS ALKPLFQLQS GHKDKLKQAI IQQWLEGTLS ESTHKYYETV SDVLNSVKKM
EESLKRLKQA RKTTPANPVG PSGGMSDDDK IRLQLALDVE YLGEQIQKLG LQASDIKSFS
ALAELVAAAK DQATAEQP
