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 27-MAR-2024, entry version 160. 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). RN [15] RP INTERACTION WITH RHOG. RX PubMed=33513601; DOI=10.1182/blood.2020008738; RA Kalinichenko A., Perinetti Casoni G., Dupre L., Trotta L., Huemer J., RA Galgano D., German Y., Haladik B., Pazmandi J., Thian M., RA Yuece Petronczki O., Chiang S.C., Taskinen M., Hekkala A., Kauppila S., RA Lindgren O., Tapiainen T., Kraakman M.J., Vettenranta K., Lomakin A.J., RA Saarela J., Seppaenen M.R.J., Bryceson Y.T., Boztug K.; RT "RhoG deficiency abrogates cytotoxicity of human lymphocytes and causes RT hemophagocytic lymphohistiocytosis."; RL Blood 137:2033-2045(2021). 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; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00041}; CC -!- SUBUNIT: Interacts with DOC2A (By similarity). Interacts with RAB27A CC (PubMed:15548590, PubMed:17237785). Interacts with RHOG; the CC interaction increases RhoG affinity to the membrane lipids, targets CC UNC13D to membrane lipids and facilitates cytotoxic granule (CG) CC docking to the plasma membrane (PubMed:33513601). CC {ECO:0000250|UniProtKB:B2RUP2, ECO:0000269|PubMed:15548590, CC ECO:0000269|PubMed:17237785, ECO:0000269|PubMed:33513601}. CC -!- INTERACTION: CC Q70J99; P51159: RAB27A; NbExp=3; IntAct=EBI-11479429, EBI-716881; CC Q70J99; P84095: RHOG; NbExp=6; IntAct=EBI-11479429, EBI-446579; 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 25. DR IntAct; Q70J99; 4. DR STRING; 9606.ENSP00000207549; -. DR GlyCosmos; Q70J99; 1 site, 2 glycans. 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; 9606-ENSP00000207549; -. DR PeptideAtlas; Q70J99; -. DR ProteomicsDB; 68558; -. [Q70J99-1] DR ProteomicsDB; 68559; -. [Q70J99-2] DR ProteomicsDB; 68560; -. [Q70J99-3] DR Pumba; Q70J99; -. DR Antibodypedia; 32273; 244 antibodies from 36 providers. DR DNASU; 201294; -. DR Ensembl; ENST00000207549.9; ENSP00000207549.3; ENSG00000092929.13. [Q70J99-1] DR Ensembl; ENST00000412096.6; ENSP00000388093.1; ENSG00000092929.13. [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 AGR; HGNC:23147; -. 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; 3059697at2759; -. DR PhylomeDB; Q70J99; -. DR TreeFam; TF315526; -. DR PathwayCommons; Q70J99; -. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; Q70J99; -. DR BioGRID-ORCS; 201294; 24 hits in 1159 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 133 other cell types or tissues. DR ExpressionAtlas; Q70J99; baseline and differential. 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: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 CDD; cd08676; C2A_Munc13-like; 1. DR CDD; cd04009; C2B_Munc13-like; 1. DR Gene3D; 1.10.357.50; -; 1. DR Gene3D; 1.20.58.1100; -; 1. DR Gene3D; 2.60.40.150; C2 domain; 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 PANTHER; PTHR45999:SF3; PROTEIN UNC-13 HOMOLOG D; 1. DR PANTHER; PTHR45999; UNC-13-4A, ISOFORM B; 1. DR Pfam; PF00168; C2; 2. DR Pfam; PF06292; MUN; 1. DR SMART; SM00239; C2; 2. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 2. DR PROSITE; PS50004; C2; 2. DR PROSITE; PS51258; MHD1; 1. DR PROSITE; PS51259; MHD2; 1. DR Genevisible; Q70J99; HS. 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 //