UN13D_HUMAN
ID UN13D_HUMAN Reviewed; 1090 AA.
AC Q70J99; B4DWG9; Q9H7K5;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Protein unc-13 homolog D;
DE AltName: Full=Munc13-4;
GN Name=UNC13D;
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), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND INVOLVEMENT IN FHL3.
RC TISSUE=Blood;
RX PubMed=14622600; DOI=10.1016/s0092-8674(03)00855-9;
RA Feldmann J., Callebaut I., Raposo G., Certain S., Bacq D., Dumont C.,
RA Lambert N., Ouachee-Chardin M., Chedville G., Tamary H., Minard-Colin V.,
RA Vilmer E., Blanche S., Le Deist F., Fischer A., de Saint Basile G.;
RT "Munc13-4 is essential for cytolytic granules fusion and is mutated in a
RT form of familial hemophagocytic lymphohistiocytosis (FHL3).";
RL Cell 115:461-473(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
RX PubMed=11214971; DOI=10.1093/dnares/7.6.357;
RA Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen.";
RL DNA Res. 7:357-366(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Synovium;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB27A, TISSUE
RP SPECIFICITY, DOMAIN, AND MUTAGENESIS OF 608-VAL--ALA-611.
RX PubMed=15548590; DOI=10.1091/mbc.e04-10-0923;
RA Neeft M., Wieffer M., de Jong A.S., Negroiu G., Metz C.H., van Loon A.,
RA Griffith J., Krijgsveld J., Wulffraat N., Koch H., Heck A.J.R., Brose N.,
RA Kleijmeer M., van der Sluijs P.;
RT "Munc13-4 is an effector of rab27a and controls secretion of lysosomes in
RT hematopoietic cells.";
RL Mol. Biol. Cell 16:731-741(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB27A, AND DOMAIN.
RX PubMed=17237785; DOI=10.1038/ni1431;
RA Menager M.M., Menasche G., Romao M., Knapnougel P., Ho C.-H., Garfa M.,
RA Raposo G., Feldmann J., Fischer A., de Saint Basile G.;
RT "Secretory cytotoxic granule maturation and exocytosis require the effector
RT protein hMunc13-4.";
RL Nat. Immunol. 8:257-267(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Plays a role in cytotoxic granule exocytosis in lymphocytes.
CC Required for both granule maturation and granule docking and priming at
CC the immunologic synapse. Regulates assembly of recycling and late
CC endosomal structures, leading to the formation of an endosomal exocytic
CC compartment that fuses with perforin-containing granules at the
CC immunologic synapse and licences them for exocytosis. Regulates Ca(2+)-
CC dependent secretory lysosome exocytosis in mast cells.
CC {ECO:0000269|PubMed:15548590, ECO:0000269|PubMed:17237785}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with DOC2A (By similarity). Interacts with RAB27A.
CC {ECO:0000250, ECO:0000269|PubMed:15548590,
CC ECO:0000269|PubMed:17237785}.
CC -!- INTERACTION:
CC Q70J99; P51159: RAB27A; NbExp=3; IntAct=EBI-11479429, EBI-716881;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein.
CC Late endosome. Recycling endosome. Lysosome. Note=Colocalizes with
CC cytotoxic granules at the plasma membrane. Localizes to endosomal
CC exocytic vesicles.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q70J99-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q70J99-2; Sequence=VSP_011385, VSP_011386, VSP_011387;
CC Name=3;
CC IsoId=Q70J99-3; Sequence=VSP_037949;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in spleen, thymus and
CC leukocytes. Also expressed in lung and placenta, and at very low levels
CC in brain, heart, skeletal muscle and kidney. Expressed in cytotoxic T-
CC lymphocytes (CTL) and mast cells. {ECO:0000269|PubMed:14622600,
CC ECO:0000269|PubMed:15548590}.
CC -!- DOMAIN: The MHD1 and MHD2 domains mediate localization on recycling
CC endosomes and lysosome. {ECO:0000269|PubMed:15548590,
CC ECO:0000269|PubMed:17237785}.
CC -!- DISEASE: Hemophagocytic lymphohistiocytosis, familial, 3 (FHL3)
CC [MIM:608898]: A rare disorder characterized by immune dysregulation
CC with hypercytokinemia, defective function of natural killer cell, and
CC massive infiltration of several organs by activated lymphocytes and
CC macrophages. The clinical features of the disease include fever,
CC hepatosplenomegaly, cytopenia, and less frequently neurological
CC abnormalities ranging from irritability and hypotonia to seizures,
CC cranial nerve deficits and ataxia. {ECO:0000269|PubMed:14622600}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the unc-13 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15764.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=UNC13Dbase; Note=UNC13D mutation db;
CC URL="http://structure.bmc.lu.se/idbase/UNC13Dbase/";
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DR EMBL; AJ578444; CAE17516.1; -; mRNA.
DR EMBL; AK024474; BAB15764.1; ALT_INIT; mRNA.
DR EMBL; AK301529; BAG63031.1; -; mRNA.
DR EMBL; AC087289; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC067084; AAH67084.1; -; mRNA.
DR CCDS; CCDS11730.1; -. [Q70J99-1]
DR RefSeq; NP_954712.1; NM_199242.2. [Q70J99-1]
DR AlphaFoldDB; Q70J99; -.
DR SMR; Q70J99; -.
DR BioGRID; 128383; 16.
DR IntAct; Q70J99; 3.
DR STRING; 9606.ENSP00000207549; -.
DR GlyGen; Q70J99; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q70J99; -.
DR MetOSite; Q70J99; -.
DR PhosphoSitePlus; Q70J99; -.
DR BioMuta; UNC13D; -.
DR DMDM; 51316668; -.
DR EPD; Q70J99; -.
DR jPOST; Q70J99; -.
DR MassIVE; Q70J99; -.
DR MaxQB; Q70J99; -.
DR PaxDb; Q70J99; -.
DR PeptideAtlas; Q70J99; -.
DR PRIDE; Q70J99; -.
DR ProteomicsDB; 68558; -. [Q70J99-1]
DR ProteomicsDB; 68559; -. [Q70J99-2]
DR ProteomicsDB; 68560; -. [Q70J99-3]
DR Antibodypedia; 32273; 230 antibodies from 36 providers.
DR DNASU; 201294; -.
DR Ensembl; ENST00000207549.9; ENSP00000207549.3; ENSG00000092929.12. [Q70J99-1]
DR Ensembl; ENST00000412096.6; ENSP00000388093.1; ENSG00000092929.12. [Q70J99-3]
DR GeneID; 201294; -.
DR KEGG; hsa:201294; -.
DR MANE-Select; ENST00000207549.9; ENSP00000207549.3; NM_199242.3; NP_954712.1.
DR UCSC; uc002jpp.5; human. [Q70J99-1]
DR CTD; 201294; -.
DR DisGeNET; 201294; -.
DR GeneCards; UNC13D; -.
DR GeneReviews; UNC13D; -.
DR HGNC; HGNC:23147; UNC13D.
DR HPA; ENSG00000092929; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; UNC13D; -.
DR MIM; 608897; gene.
DR MIM; 608898; phenotype.
DR neXtProt; NX_Q70J99; -.
DR OpenTargets; ENSG00000092929; -.
DR Orphanet; 540; Familial hemophagocytic lymphohistiocytosis.
DR PharmGKB; PA134919958; -.
DR VEuPathDB; HostDB:ENSG00000092929; -.
DR eggNOG; KOG1328; Eukaryota.
DR GeneTree; ENSGT00730000110939; -.
DR HOGENOM; CLU_003295_1_0_1; -.
DR InParanoid; Q70J99; -.
DR OMA; ICKTKAF; -.
DR OrthoDB; 72416at2759; -.
DR PhylomeDB; Q70J99; -.
DR TreeFam; TF315526; -.
DR PathwayCommons; Q70J99; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q70J99; -.
DR BioGRID-ORCS; 201294; 18 hits in 1079 CRISPR screens.
DR ChiTaRS; UNC13D; human.
DR GeneWiki; UNC13D; -.
DR GenomeRNAi; 201294; -.
DR Pharos; Q70J99; Tbio.
DR PRO; PR:Q70J99; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q70J99; protein.
DR Bgee; ENSG00000092929; Expressed in granulocyte and 132 other tissues.
DR ExpressionAtlas; Q70J99; baseline and differential.
DR Genevisible; Q70J99; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070382; C:exocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0099503; C:secretory vesicle; IBA:GO_Central.
DR GO; GO:0033093; C:Weibel-Palade body; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:Ensembl.
DR GO; GO:0002467; P:germinal center formation; IEA:Ensembl.
DR GO; GO:0002432; P:granuloma formation; IEA:Ensembl.
DR GO; GO:0043320; P:natural killer cell degranulation; IEA:Ensembl.
DR GO; GO:0006909; P:phagocytosis; IEA:Ensembl.
DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:UniProtKB.
DR GO; GO:1903307; P:positive regulation of regulated secretory pathway; IGI:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0043304; P:regulation of mast cell degranulation; IMP:UniProtKB.
DR GO; GO:0046903; P:secretion; IBA:GO_Central.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR010439; MUN_dom.
DR InterPro; IPR014770; Munc13_1.
DR InterPro; IPR014772; Munc13_dom-2.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF06292; MUN; 1.
DR SMART; SM00239; C2; 2.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
DR PROSITE; PS51258; MHD1; 1.
DR PROSITE; PS51259; MHD2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cytoplasm; Endosome; Exocytosis;
KW Familial hemophagocytic lymphohistiocytosis; Lysosome; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..1090
FT /note="Protein unc-13 homolog D"
FT /id="PRO_0000188581"
FT DOMAIN 92..239
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 557..677
FT /note="MHD1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00587"
FT DOMAIN 788..895
FT /note="MHD2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00588"
FT DOMAIN 910..1035
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 240..543
FT /note="Interaction with RAB27A"
FT REGION 1026..1048
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 133
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 940
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 941
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 941
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 947
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1005
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1005
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1007
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1007
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1013
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 286
FT /note="R -> RVGRVLGQWPCPALAAVCWVAGLAAPSVRPCLLTEASLQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_011385"
FT VAR_SEQ 318..325
FT /note="AGSTSWDG -> VLPSWGWA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_011386"
FT VAR_SEQ 326..1090
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_011387"
FT VAR_SEQ 1081..1090
FT /note="ASQHALRPAP -> GIGPSVSWPWPICLLAFLFQPLGWGPGSLGPGLQAQSL
FT LEKGEGTLPKMRLQLPWGEGGGHY (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037949"
FT VARIANT 59
FT /note="A -> T (in dbSNP:rs9904366)"
FT /id="VAR_052469"
FT VARIANT 858
FT /note="H -> Q (in dbSNP:rs17496835)"
FT /id="VAR_029771"
FT VARIANT 867
FT /note="K -> E (in dbSNP:rs1135688)"
FT /id="VAR_029772"
FT MUTAGEN 608..611
FT /note="Missing: Abolishes localization to lysosomes and
FT interaction with RAB27A."
FT /evidence="ECO:0000269|PubMed:15548590"
FT CONFLICT 137
FT /note="L -> P (in Ref. 3; BAG63031)"
FT /evidence="ECO:0000305"
FT CONFLICT 476
FT /note="H -> R (in Ref. 3; BAG63031)"
FT /evidence="ECO:0000305"
FT CONFLICT 590
FT /note="Q -> R (in Ref. 3; BAG63031)"
FT /evidence="ECO:0000305"
FT CONFLICT 796
FT /note="K -> E (in Ref. 3; BAG63031)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1090 AA; 123282 MW; A71AD7A4E32C940C CRC64;
MATLLSHPQQ RPPFLRQAIK IRRRRVRDLQ DPPPQMAPEI QPPSHHFSPE QRALLYEDAL
YTVLHRLGHP EPNHVTEASE LLRYLQEAFH VEPEEHQQTL QRVRELEKPI FCLKATVKQA
KGILGKDVSG FSDPYCLLGI EQGVGVPGGS PGSRHRQKAV VRHTIPEEET HRTQVITQTL
NPVWDETFIL EFEDITNASF HLDMWDLDTV ESVRQKLGEL TDLHGLRRIF KEARKDKGQD
DFLGNVVLRL QDLRCREDQW YPLEPRTETY PDRGQCHLQF QLIHKRRATS ASRSQPSYTV
HLHLLQQLVS HEVTQHEAGS TSWDGSLSPQ AATVLFLHAT QKDLSDFHQS MAQWLAYSRL
YQSLEFPSSC LLHPITSIEY QWIQGRLKAE QQEELAASFS SLLTYGLSLI RRFRSVFPLS
VSDSPARLQS LLRVLVQMCK MKAFGELCPN TAPLPQLVTE ALQTGTTEWF HLKQQHHQPM
VQGIPEAGKA LLGLVQDVIG DLHQCQRTWD KIFHNTLKIH LFSMAFRELQ WLVAKRVQDH
TTVVGDVVSP EMGESLFQLY ISLKELCQLR MSSSERDGVL ALDNFHRWFQ PAIPSWLQKT
YNEALARVQR AVQMDELVPL GELTKHSTSA VDLSTCFAQI SHTARQLDWP DPEEAFMITV
KFVEDTCRLA LVYCSLIKAR ARELSSGQKD QGQAANMLCV VVNDMEQLRL VIGKLPAQLA
WEALEQRVGA VLEQGQLQNT LHAQLQSALA GLGHEIRTGV RTLAEQLEVG IAKHIQKLVG
VRESVLPEDA ILPLMKFLEV ELCYMNTNLV QENFSSLLTL LWTHTLTVLV EAAASQRSSS
LASNRLKIAL QNLEICFHAE GCGLPPKALH TATFQALQRD LELQAASSRE LIRKYFCSRI
QQQAETTSEE LGAVTVKASY RASEQKLRVE LLSASSLLPL DSNGSSDPFV QLTLEPRHEF
PELAARETQK HKKDLHPLFD ETFEFLVPAE PCRKAGACLL LTVLDYDTLG ADDLEGEAFL
PLREVPGLSG SEEPGEVPQT RLPLTYPAPN GDPILQLLEG RKGDREAQVF VRLRRHRAKQ
ASQHALRPAP
