PGAP4_HUMAN
ID PGAP4_HUMAN Reviewed; 403 AA.
AC Q9BRR3; Q49AQ4;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Post-GPI attachment to proteins factor 4 {ECO:0000305};
DE AltName: Full=Post-GPI attachment to proteins GalNAc transferase 4 {ECO:0000312|HGNC:HGNC:28180};
DE AltName: Full=Transmembrane protein 246;
GN Name=PGAP4 {ECO:0000312|HGNC:HGNC:28180}; Synonyms=C9orf125, TMEM246;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, 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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [4]
RP FUNCTION, DOMAIN, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-87, AND
RP MUTAGENESIS OF ASN-87; VAL-109; GLU-211; ASP-213; HIS-247; GLU-249;
RP MET-260; MET-270; PHE-283; MET-302; HIS-311; PHE-313; ARG-317; THR-334;
RP PRO-335; THR-347; LYS-362 AND ASP-363.
RX PubMed=29374258; DOI=10.1038/s41467-017-02799-0;
RA Hirata T., Mishra S.K., Nakamura S., Saito K., Motooka D., Takada Y.,
RA Kanzawa N., Murakami Y., Maeda Y., Fujita M., Yamaguchi Y., Kinoshita T.;
RT "Identification of a Golgi GPI-N-acetylgalactosamine transferase with
RT tandem transmembrane regions in the catalytic domain.";
RL Nat. Commun. 9:405-405(2018).
CC -!- FUNCTION: Golgi-resident glycosylphosphatidylinositol (GPI)-N-
CC acetylgalactosamine transferase involved in the lipid remodeling steps
CC of GPI-anchor maturation. Lipid remodeling steps consist in the
CC generation of 2 saturated fatty chains at the sn-2 position of GPI-
CC anchors proteins (PubMed:29374258). Required for the initial step of
CC GPI-GalNAc biosynthesis, transfers GalNAc to GPI in the Golgi after
CC fatty acid remodeling by PGAP2 (PubMed:29374258).
CC {ECO:0000269|PubMed:29374258}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:29374258}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29374258}.
CC -!- DOMAIN: Contains three transmembrane domains, including a tandem
CC transmembrane domain insertion into its glycosyltransferase-A fold
CC (PubMed:29374258). Transmembrane domain 1 functions as a signal for
CC Golgi targeting (PubMed:29374258). {ECO:0000269|PubMed:29374258}.
CC -!- DOMAIN: The conserved DXD motif is involved in enzyme activity.
CC {ECO:0000269|PubMed:29374258}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:29374258}.
CC -!- SIMILARITY: Belongs to the PGAP4 family. {ECO:0000305}.
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DR EMBL; AL353621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006115; AAH06115.1; -; mRNA.
DR EMBL; BC033550; AAH33550.1; -; mRNA.
DR CCDS; CCDS6757.1; -.
DR RefSeq; NP_001290036.1; NM_001303107.1.
DR RefSeq; NP_001290037.1; NM_001303108.1.
DR RefSeq; NP_115718.1; NM_032342.2.
DR RefSeq; XP_016870695.1; XM_017015206.1.
DR AlphaFoldDB; Q9BRR3; -.
DR BioGRID; 124028; 101.
DR IntAct; Q9BRR3; 6.
DR STRING; 9606.ENSP00000363984; -.
DR GlyGen; Q9BRR3; 1 site.
DR iPTMnet; Q9BRR3; -.
DR PhosphoSitePlus; Q9BRR3; -.
DR BioMuta; TMEM246; -.
DR DMDM; 71152417; -.
DR EPD; Q9BRR3; -.
DR jPOST; Q9BRR3; -.
DR MassIVE; Q9BRR3; -.
DR MaxQB; Q9BRR3; -.
DR PaxDb; Q9BRR3; -.
DR PeptideAtlas; Q9BRR3; -.
DR PRIDE; Q9BRR3; -.
DR ProteomicsDB; 78811; -.
DR Antibodypedia; 54396; 21 antibodies from 9 providers.
DR DNASU; 84302; -.
DR Ensembl; ENST00000374847.5; ENSP00000363980.1; ENSG00000165152.9.
DR Ensembl; ENST00000374848.8; ENSP00000363981.3; ENSG00000165152.9.
DR Ensembl; ENST00000374851.1; ENSP00000363984.1; ENSG00000165152.9.
DR GeneID; 84302; -.
DR KEGG; hsa:84302; -.
DR MANE-Select; ENST00000374848.8; ENSP00000363981.3; NM_032342.3; NP_115718.1.
DR UCSC; uc004bbm.4; human.
DR CTD; 84302; -.
DR GeneCards; PGAP4; -.
DR HGNC; HGNC:28180; PGAP4.
DR HPA; ENSG00000165152; Low tissue specificity.
DR neXtProt; NX_Q9BRR3; -.
DR OpenTargets; ENSG00000165152; -.
DR VEuPathDB; HostDB:ENSG00000165152; -.
DR eggNOG; ENOG502QT3K; Eukaryota.
DR GeneTree; ENSGT00500000045018; -.
DR HOGENOM; CLU_049086_0_0_1; -.
DR InParanoid; Q9BRR3; -.
DR OMA; RDYVFCL; -.
DR OrthoDB; 864176at2759; -.
DR PhylomeDB; Q9BRR3; -.
DR TreeFam; TF313998; -.
DR PathwayCommons; Q9BRR3; -.
DR SignaLink; Q9BRR3; -.
DR BioGRID-ORCS; 84302; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; TMEM246; human.
DR GenomeRNAi; 84302; -.
DR Pharos; Q9BRR3; Tdark.
DR PRO; PR:Q9BRR3; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9BRR3; protein.
DR Bgee; ENSG00000165152; Expressed in pons and 183 other tissues.
DR ExpressionAtlas; Q9BRR3; baseline and differential.
DR Genevisible; Q9BRR3; HS.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016757; F:glycosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006506; P:GPI anchor biosynthetic process; IMP:UniProtKB.
DR InterPro; IPR029675; PGAP4.
DR PANTHER; PTHR31410; PTHR31410; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Golgi apparatus; Membrane; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..403
FT /note="Post-GPI attachment to proteins factor 4"
FT /id="PRO_0000089731"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29374258"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..259
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:29374258"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..287
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29374258"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..403
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:29374258"
FT MOTIF 211..213
FT /note="DXD motif"
FT /evidence="ECO:0000269|PubMed:29374258"
FT CARBOHYD 87
FT /note="N-linked (GalNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 87
FT /note="N->A: Loss of glycosylation. Not glycosylated; when
FT associated with N-283. Glycosylated; when associated with
FT N-347."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 109
FT /note="V->A: Reduces GPI-GalNAc transferase activity. No
FT effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 211
FT /note="E->A: Loss of GPI-GalNAc transferase activity."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 213
FT /note="D->A: Loss of GPI-GalNAc transferase activity."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 247
FT /note="H->A: Reduces GPI-GalNAc transferase activity. No
FT effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 249
FT /note="E->A: Slightly reduces GPI-GalNAc transferase
FT activity. No effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 260
FT /note="M->A: No effect on GPI-GalNAc transferase activity.
FT No effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 270
FT /note="M->A: No effect on GPI-GalNAc transferase activity.
FT No effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 283
FT /note="F->N: Not glycosylated; when associated with A-87."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 302
FT /note="M->A: No effect on GPI-GalNAc transferase activity.
FT No effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 311
FT /note="H->A: No effect on GPI-GalNAc transferase activity.
FT No effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 313
FT /note="F->A: Reduces GPI-GalNAc transferase activity. No
FT effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 317
FT /note="R->A: Strongly reduces GPI-GalNAc transferase
FT activity. Accumulates in the endoplasmic reticulum."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 334
FT /note="T->A: Almost abolishes GPI-GalNAc transferase
FT activity. No effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 335
FT /note="P->A: Reduces GPI-GalNAc transferase activity. No
FT effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 347
FT /note="T->N: Glycosylated; when associated with A-87."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 362
FT /note="K->A: Reduces GPI-GalNAc transferase activity. No
FT effect on Golgi apparatus membrane location."
FT /evidence="ECO:0000269|PubMed:29374258"
FT MUTAGEN 363
FT /note="D->A: Loss of GPI-GalNAc transferase activity."
FT /evidence="ECO:0000269|PubMed:29374258"
SQ SEQUENCE 403 AA; 46588 MW; 82987435CDE27216 CRC64;
MSTSTSPAAM LLRRLRRLSW GSTAVQLFIL TVVTFGLLAP LACHRLLHSY FYLRHWHLNQ
MSQEFLQQSL KEGEAALHYF EELPSANGSV PIVWQATPRP WLVITIITVD RQPGFHYVLQ
VVSQFHRLLQ QCGPQCEGHQ LFLCNVERSV SHFDAKLLSK YVPVANRYEG TEDDYGDDPS
TNSFEKEKQD YVYCLESSLQ TYNPDYVLMV EDDAVPEEQI FPVLEHLLRA RFSEPHLRDA
LYLKLYHPER LQHYINPEPM RILEWVGVGM LLGPLLTWIY MRFASRPGFS WPVMLFFSLY
SMGLVELVGR HYFLELRRLS PSLYSVVPAS QCCTPAMLFP APAARRTLTY LSQVYCHKGF
GKDMALYSLL RAKGERAYVV EPNLVKHIGL FSSLRYNFHP SLL
