ID   D19L3_HUMAN             Reviewed;         716 AA.
AC   Q6ZPD9; Q68DC7; Q6ZTB7; Q6ZTS2;
DT   04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 134.
DE   RecName: Full=Protein C-mannosyl-transferase DPY19L3;
DE            EC=2.4.1.- {ECO:0000269|PubMed:26764097, ECO:0000269|PubMed:29405629};
DE   AltName: Full=Dpy-19-like protein 3;
DE   AltName: Full=Protein dpy-19 homolog 3;
GN   Name=DPY19L3;
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 MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 235-716 (ISOFORM 2).
RC   TISSUE=Brain, Cerebellum, and Trachea;
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., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., 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., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 203-716 (ISOFORM 1).
RC   TISSUE=Prostate;
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., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   TISSUE SPECIFICITY.
RX   PubMed=16526957; DOI=10.1186/1471-2164-7-45;
RA   Carson A.R., Cheung J., Scherer S.W.;
RT   "Duplication and relocation of the functional DPY19L2 gene within low copy
RT   repeats.";
RL   BMC Genomics 7:45-45(2006).
RN   [5]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=26764097; DOI=10.1091/mbc.e15-06-0373;
RA   Niwa Y., Suzuki T., Dohmae N., Simizu S.;
RT   "Identification of DPY19L3 as the C-mannosyltransferase of R-spondin1 in
RT   human cells.";
RL   Mol. Biol. Cell 27:744-756(2016).
RN   [6]
RP   FUNCTION (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY, TOPOLOGY, SUBCELLULAR
RP   LOCATION (ISOFORMS 1 AND 2), GLYCOSYLATION AT ASN-118 AND ASN-704, AND
RP   MUTAGENESIS OF ASN-118 AND ASN-704.
RX   PubMed=29405629; DOI=10.1111/febs.14398;
RA   Niwa Y., Nakano Y., Suzuki T., Yamagishi M., Otani K., Dohmae N.,
RA   Simizu S.;
RT   "Topological analysis of DPY19L3, a human C-mannosyltransferase.";
RL   FEBS J. 285:1162-1174(2018).
CC   -!- FUNCTION: C-mannosyltransferase that mediates C-mannosylation of
CC       tryptophan residues on target proteins. The reaction occurs on the
CC       luminal side of the endoplasmic reticulum and involves the transfer of
CC       a mannose unit from a dolichylphosphate mannose (Dol-P-Man) donor to an
CC       acceptor protein containing a WxxW or WxxC consensus sequence
CC       (PubMed:26764097, PubMed:29405629). C-mannosylates RSPO1, a Wnt
CC       signaling regulator, preferentially at the first Trp residue in the
CC       sequence WxxW (PubMed:26764097, PubMed:29405629). C-mannosylates the
CC       netrin receptor UNC5A, preferentially at the third tryptophan of
CC       WxxWxxWxxC sequence (By similarity). {ECO:0000250|UniProtKB:Q71B07,
CC       ECO:0000269|PubMed:26764097, ECO:0000269|PubMed:29405629}.
CC   -!- FUNCTION: [Isoform 2]: Has no C-mannosyltransferase activity.
CC       {ECO:0000269|PubMed:29405629}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a dolichyl beta-D-mannosyl phosphate + L-tryptophyl-[protein]
CC         = a dolichyl phosphate + C-alpha-D-mannosyl-L-tryptophyl-[protein] +
CC         H(+); Xref=Rhea:RHEA:77219, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527,
CC         Rhea:RHEA-COMP:15365, Rhea:RHEA-COMP:18864, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:29954, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211,
CC         ChEBI:CHEBI:195646; Evidence={ECO:0000269|PubMed:26764097,
CC         ECO:0000269|PubMed:29405629};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77220;
CC         Evidence={ECO:0000305|PubMed:26764097, ECO:0000305|PubMed:29405629};
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC       {ECO:0000269|PubMed:26764097, ECO:0000269|PubMed:29405629}.
CC   -!- INTERACTION:
CC       Q6ZPD9-2; Q92876: KLK6; NbExp=3; IntAct=EBI-25888224, EBI-2432309;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:29405629}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:29405629}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:29405629}; Multi-pass membrane protein
CC       {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6ZPD9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6ZPD9-2; Sequence=VSP_029634, VSP_029635;
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:16526957}.
CC   -!- DOMAIN: The C-terminal luminal region is essential for C-
CC       mannosyltransferase activity. {ECO:0000269|PubMed:29405629}.
CC   -!- SIMILARITY: Belongs to the dpy-19 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAC86508.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AK126264; BAC86508.1; ALT_INIT; mRNA.
DR   EMBL; AK126757; BAC86676.1; -; mRNA.
DR   EMBL; AK129497; BAC85166.1; -; mRNA.
DR   EMBL; BC131725; AAI31726.1; -; mRNA.
DR   EMBL; CR749459; CAH18293.1; -; mRNA.
DR   CCDS; CCDS12422.1; -. [Q6ZPD9-1]
DR   RefSeq; NP_001166245.1; NM_001172774.1. [Q6ZPD9-1]
DR   RefSeq; NP_997208.2; NM_207325.2. [Q6ZPD9-1]
DR   RefSeq; XP_011524828.1; XM_011526526.2. [Q6ZPD9-1]
DR   AlphaFoldDB; Q6ZPD9; -.
DR   SMR; Q6ZPD9; -.
DR   BioGRID; 127110; 28.
DR   IntAct; Q6ZPD9; 14.
DR   STRING; 9606.ENSP00000344937; -.
DR   CAZy; GT98; Glycosyltransferase Family 98.
DR   GlyGen; Q6ZPD9; 4 sites.
DR   iPTMnet; Q6ZPD9; -.
DR   PhosphoSitePlus; Q6ZPD9; -.
DR   SwissPalm; Q6ZPD9; -.
DR   BioMuta; DPY19L3; -.
DR   DMDM; 74710923; -.
DR   EPD; Q6ZPD9; -.
DR   jPOST; Q6ZPD9; -.
DR   MassIVE; Q6ZPD9; -.
DR   MaxQB; Q6ZPD9; -.
DR   PaxDb; 9606-ENSP00000344937; -.
DR   PeptideAtlas; Q6ZPD9; -.
DR   ProteomicsDB; 68077; -. [Q6ZPD9-1]
DR   ProteomicsDB; 68078; -. [Q6ZPD9-2]
DR   Pumba; Q6ZPD9; -.
DR   Antibodypedia; 2035; 121 antibodies from 15 providers.
DR   DNASU; 147991; -.
DR   Ensembl; ENST00000342179.9; ENSP00000344937.4; ENSG00000178904.19. [Q6ZPD9-1]
DR   Ensembl; ENST00000392250.7; ENSP00000376081.2; ENSG00000178904.19. [Q6ZPD9-1]
DR   GeneID; 147991; -.
DR   KEGG; hsa:147991; -.
DR   MANE-Select; ENST00000392250.7; ENSP00000376081.2; NM_001172774.2; NP_001166245.1.
DR   UCSC; uc002ntg.4; human. [Q6ZPD9-1]
DR   AGR; HGNC:27120; -.
DR   CTD; 147991; -.
DR   DisGeNET; 147991; -.
DR   GeneCards; DPY19L3; -.
DR   HGNC; HGNC:27120; DPY19L3.
DR   HPA; ENSG00000178904; Low tissue specificity.
DR   MIM; 613894; gene.
DR   neXtProt; NX_Q6ZPD9; -.
DR   OpenTargets; ENSG00000178904; -.
DR   PharmGKB; PA142671954; -.
DR   VEuPathDB; HostDB:ENSG00000178904; -.
DR   eggNOG; KOG4587; Eukaryota.
DR   GeneTree; ENSGT00530000063023; -.
DR   HOGENOM; CLU_014404_1_0_1; -.
DR   InParanoid; Q6ZPD9; -.
DR   OMA; FSLAWQF; -.
DR   OrthoDB; 242062at2759; -.
DR   PhylomeDB; Q6ZPD9; -.
DR   TreeFam; TF313376; -.
DR   BRENDA; 2.4.1.B72; 2681.
DR   PathwayCommons; Q6ZPD9; -.
DR   SignaLink; Q6ZPD9; -.
DR   UniPathway; UPA00378; -.
DR   BioGRID-ORCS; 147991; 12 hits in 1156 CRISPR screens.
DR   ChiTaRS; DPY19L3; human.
DR   GenomeRNAi; 147991; -.
DR   Pharos; Q6ZPD9; Tbio.
DR   PRO; PR:Q6ZPD9; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q6ZPD9; Protein.
DR   Bgee; ENSG00000178904; Expressed in tibia and 179 other cell types or tissues.
DR   ExpressionAtlas; Q6ZPD9; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR   GO; GO:0005637; C:nuclear inner membrane; IBA:GO_Central.
DR   GO; GO:0000030; F:mannosyltransferase activity; IDA:UniProtKB.
DR   CDD; cd20181; Dpy19L3; 1.
DR   InterPro; IPR018732; Dpy-19/Dpy-19-like.
DR   InterPro; IPR047465; Dpy19L3.
DR   PANTHER; PTHR31488:SF4; C-MANNOSYLTRANSFERASE DPY19L3-RELATED; 1.
DR   PANTHER; PTHR31488; DPY-19-LIKE 1, LIKE (H. SAPIENS); 1.
DR   Pfam; PF10034; Dpy19; 1.
DR   Genevisible; Q6ZPD9; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW   Glycosyltransferase; Membrane; Reference proteome; Transferase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..716
FT                   /note="Protein C-mannosyl-transferase DPY19L3"
FT                   /id="PRO_0000311901"
FT   TOPO_DOM        1..43
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TRANSMEM        44..64
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        65..154
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        155..182
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        183..184
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   INTRAMEM        185..197
FT                   /note="Name=3"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        198..215
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   INTRAMEM        216..230
FT                   /note="Name=4"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        231..239
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        240..256
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        257..262
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        263..279
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        280..289
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        290..306
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        307..308
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        309..323
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        324..338
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        339..359
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        360..414
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        415..437
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        438..465
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        466..485
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        486..487
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        488..499
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        500..522
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   TRANSMEM        523..539
FT                   /note="Helical; Name=13"
FT                   /evidence="ECO:0000303|PubMed:29405629"
FT   TOPO_DOM        540..716
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   CARBOHYD        118
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   CARBOHYD        704
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   VAR_SEQ         539..542
FT                   /note="FWPG -> NQKS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_029634"
FT   VAR_SEQ         543..716
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_029635"
FT   VARIANT         350
FT                   /note="M -> V (in dbSNP:rs8105178)"
FT                   /id="VAR_037336"
FT   MUTAGEN         118
FT                   /note="N->Q: Does not affect endoplasmic reticulum membrane
FT                   localization. Does not affect mannosyltransferase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   MUTAGEN         704
FT                   /note="N->Q: Does not affect endoplasmic reticulum membrane
FT                   localization. Does not affect mannosyltransferase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:29405629"
FT   CONFLICT        482
FT                   /note="R -> G (in Ref. 1; BAC86676)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   716 AA;  83197 MW;  EE76B5A54024A8CC CRC64;
     MMSIRQRREI RATEVSEDFP AQEENVKLEN KLPSGCTSRR LWKILSLTIG GTIALCIGLL
     TSVYLATLHE NDLWFSNIKE VEREISFRTE CGLYYSYYKQ MLQAPTLVQG FHGLIYDNKT
     ESMKTINLLQ RMNIYQEVFL SILYRVLPIQ KYLEPVYFYI YTLFGLQAIY VTALYITSWL
     LSGTWLSGLL AAFWYVTNRI DTTRVEFTIP LRENWALPFF AIQIAAITYF LRPNLQPLSE
     RLTLLAIFIS TFLFSLTWQF NQFMMLMQAL VLFTLDSLDM LPAVKATWLY GIQITSLLLV
     CILQFFNSMI LGSLLISFNL SVFIARKLQK NLKTGSFLNR LGKLLLHLFM VLCLTLFLNN
     IIKKILNLKS DEHIFKFLKA KFGLGATRDF DANLYLCEEA FGLLPFNTFG RLSDTLLFYA
     YIFVLSITVI VAFVVAFHNL SDSTNQQSVG KMEKGTVDLK PETAYNLIHT ILFGFLALST
     MRMKYLWTSH MCVFASFGLC SPEIWELLLK SVHLYNPKRI CIMRYSVPIL ILLYLCYKFW
     PGMMDELSEL REFYDPDTVE LMNWINSNTP RKAVFAGSMQ LLAGVKLCTG RTLTNHPHYE
     DSSLRERTRA VYQIYAKRAP EEVHALLRSF GTDYVILEDS ICYERRHRRG CRLRDLLDIA
     NGHMMDGPGE NDPDLKPADH PRFCEEIKRN LPPYVAYFTR VFQNKTFHVY KLSRNK
//