Q70J99 · UN13D_HUMAN
- ProteinProtein unc-13 homolog D
- GeneUNC13D
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1090 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis. Regulates Ca2+-dependent secretory lysosome exocytosis in mast cells.
Cofactor
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 127 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 133 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 206 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 208 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 940 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 941 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 941 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 947 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1005 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1005 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1007 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1007 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1013 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspect | Term | |
---|---|---|
Cellular Component | azurophil granule lumen | |
Cellular Component | cytosol | |
Cellular Component | exocytic vesicle | |
Cellular Component | extracellular region | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | late endosome | |
Cellular Component | lysosome | |
Cellular Component | membrane | |
Cellular Component | recycling endosome | |
Cellular Component | Weibel-Palade body | |
Molecular Function | metal ion binding | |
Molecular Function | small GTPase binding | |
Biological Process | defense response to virus | |
Biological Process | germinal center formation | |
Biological Process | granuloma formation | |
Biological Process | natural killer cell degranulation | |
Biological Process | phagocytosis | |
Biological Process | positive regulation of exocytosis | |
Biological Process | positive regulation of regulated secretory pathway | |
Biological Process | positive regulation of substrate adhesion-dependent cell spreading | |
Biological Process | regulation of mast cell degranulation | |
Biological Process | secretion |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein unc-13 homolog D
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ70J99
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Peripheral membrane protein
Note: Colocalizes with cytotoxic granules at the plasma membrane. Localizes to endosomal exocytic vesicles.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Hemophagocytic lymphohistiocytosis, familial, 3 (FHL3)
- Note
- DescriptionA rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia.
- See alsoMIM:608898
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_052469 | 59 | in dbSNP:rs9904366 | |||
Sequence: A → T | ||||||
Mutagenesis | 608-611 | Abolishes localization to lysosomes and interaction with RAB27A. | ||||
Sequence: Missing | ||||||
Natural variant | VAR_029771 | 858 | in dbSNP:rs17496835 | |||
Sequence: H → Q | ||||||
Natural variant | VAR_029772 | 867 | in dbSNP:rs1135688 | |||
Sequence: K → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,410 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000188581 | 1-1090 | UniProt | Protein unc-13 homolog D | |||
Sequence: MATLLSHPQQRPPFLRQAIKIRRRRVRDLQDPPPQMAPEIQPPSHHFSPEQRALLYEDALYTVLHRLGHPEPNHVTEASELLRYLQEAFHVEPEEHQQTLQRVRELEKPIFCLKATVKQAKGILGKDVSGFSDPYCLLGIEQGVGVPGGSPGSRHRQKAVVRHTIPEEETHRTQVITQTLNPVWDETFILEFEDITNASFHLDMWDLDTVESVRQKLGELTDLHGLRRIFKEARKDKGQDDFLGNVVLRLQDLRCREDQWYPLEPRTETYPDRGQCHLQFQLIHKRRATSASRSQPSYTVHLHLLQQLVSHEVTQHEAGSTSWDGSLSPQAATVLFLHATQKDLSDFHQSMAQWLAYSRLYQSLEFPSSCLLHPITSIEYQWIQGRLKAEQQEELAASFSSLLTYGLSLIRRFRSVFPLSVSDSPARLQSLLRVLVQMCKMKAFGELCPNTAPLPQLVTEALQTGTTEWFHLKQQHHQPMVQGIPEAGKALLGLVQDVIGDLHQCQRTWDKIFHNTLKIHLFSMAFRELQWLVAKRVQDHTTVVGDVVSPEMGESLFQLYISLKELCQLRMSSSERDGVLALDNFHRWFQPAIPSWLQKTYNEALARVQRAVQMDELVPLGELTKHSTSAVDLSTCFAQISHTARQLDWPDPEEAFMITVKFVEDTCRLALVYCSLIKARARELSSGQKDQGQAANMLCVVVNDMEQLRLVIGKLPAQLAWEALEQRVGAVLEQGQLQNTLHAQLQSALAGLGHEIRTGVRTLAEQLEVGIAKHIQKLVGVRESVLPEDAILPLMKFLEVELCYMNTNLVQENFSSLLTLLWTHTLTVLVEAAASQRSSSLASNRLKIALQNLEICFHAEGCGLPPKALHTATFQALQRDLELQAASSRELIRKYFCSRIQQQAETTSEELGAVTVKASYRASEQKLRVELLSASSLLPLDSNGSSDPFVQLTLEPRHEFPELAARETQKHKKDLHPLFDETFEFLVPAEPCRKAGACLLLTVLDYDTLGADDLEGEAFLPLREVPGLSGSEEPGEVPQTRLPLTYPAPNGDPILQLLEGRKGDREAQVFVRLRRHRAKQASQHALRPAP | |||||||
Modified residue (large scale data) | 135 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 150 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 150 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 153 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 784 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1029 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed at high levels in spleen, thymus and leukocytes. Also expressed in lung and placenta, and at very low levels in brain, heart, skeletal muscle and kidney. Expressed in cytotoxic T-lymphocytes (CTL) and mast cells.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with DOC2A (By similarity).
Interacts with RAB27A (PubMed:15548590, PubMed:17237785).
Interacts with RHOG; the interaction increases RhoG affinity to the membrane lipids, targets UNC13D to membrane lipids and facilitates cytotoxic granule (CG) docking to the plasma membrane (PubMed:33513601).
Interacts with RAB27A (PubMed:15548590, PubMed:17237785).
Interacts with RHOG; the interaction increases RhoG affinity to the membrane lipids, targets UNC13D to membrane lipids and facilitates cytotoxic granule (CG) docking to the plasma membrane (PubMed:33513601).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q70J99 | RAB27A P51159 | 3 | EBI-11479429, EBI-716881 | |
BINARY | Q70J99 | RHOG P84095 | 6 | EBI-11479429, EBI-446579 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 92-239 | C2 1 | ||||
Sequence: EPEEHQQTLQRVRELEKPIFCLKATVKQAKGILGKDVSGFSDPYCLLGIEQGVGVPGGSPGSRHRQKAVVRHTIPEEETHRTQVITQTLNPVWDETFILEFEDITNASFHLDMWDLDTVESVRQKLGELTDLHGLRRIFKEARKDKGQ | ||||||
Region | 240-543 | Interaction with RAB27A | ||||
Sequence: DDFLGNVVLRLQDLRCREDQWYPLEPRTETYPDRGQCHLQFQLIHKRRATSASRSQPSYTVHLHLLQQLVSHEVTQHEAGSTSWDGSLSPQAATVLFLHATQKDLSDFHQSMAQWLAYSRLYQSLEFPSSCLLHPITSIEYQWIQGRLKAEQQEELAASFSSLLTYGLSLIRRFRSVFPLSVSDSPARLQSLLRVLVQMCKMKAFGELCPNTAPLPQLVTEALQTGTTEWFHLKQQHHQPMVQGIPEAGKALLGLVQDVIGDLHQCQRTWDKIFHNTLKIHLFSMAFRELQWLVAKRVQDHTTV | ||||||
Domain | 557-677 | MHD1 | ||||
Sequence: FQLYISLKELCQLRMSSSERDGVLALDNFHRWFQPAIPSWLQKTYNEALARVQRAVQMDELVPLGELTKHSTSAVDLSTCFAQISHTARQLDWPDPEEAFMITVKFVEDTCRLALVYCSLI | ||||||
Domain | 788-895 | MHD2 | ||||
Sequence: EDAILPLMKFLEVELCYMNTNLVQENFSSLLTLLWTHTLTVLVEAAASQRSSSLASNRLKIALQNLEICFHAEGCGLPPKALHTATFQALQRDLELQAASSRELIRKY | ||||||
Domain | 910-1035 | C2 2 | ||||
Sequence: ELGAVTVKASYRASEQKLRVELLSASSLLPLDSNGSSDPFVQLTLEPRHEFPELAARETQKHKKDLHPLFDETFEFLVPAEPCRKAGACLLLTVLDYDTLGADDLEGEAFLPLREVPGLSGSEEPG | ||||||
Region | 1026-1048 | Disordered | ||||
Sequence: PGLSGSEEPGEVPQTRLPLTYPA |
Domain
The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome.
Sequence similarities
Belongs to the unc-13 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q70J99-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length1,090
- Mass (Da)123,282
- Last updated2004-07-05 v1
- ChecksumA71AD7A4E32C940C
Q70J99-2
- Name2
Q70J99-3
- Name3
- Differences from canonical
- 1081-1090: ASQHALRPAP → GIGPSVSWPWPICLLAFLFQPLGWGPGSLGPGLQAQSLLEKGEGTLPKMRLQLPWGEGGGHY
Computationally mapped potential isoform sequences
There are 13 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
K7EIH3 | K7EIH3_HUMAN | UNC13D | 169 | ||
A0A8V8TPN4 | A0A8V8TPN4_HUMAN | UNC13D | 183 | ||
A0A8V8TPP8 | A0A8V8TPP8_HUMAN | UNC13D | 299 | ||
A0A8V8TQ40 | A0A8V8TQ40_HUMAN | UNC13D | 190 | ||
A0A8V8TNE8 | A0A8V8TNE8_HUMAN | UNC13D | 320 | ||
A0A8V8TNG5 | A0A8V8TNG5_HUMAN | UNC13D | 712 | ||
A0A8V8TNT8 | A0A8V8TNT8_HUMAN | UNC13D | 136 | ||
K7ELN2 | K7ELN2_HUMAN | UNC13D | 68 | ||
K7EMK8 | K7EMK8_HUMAN | UNC13D | 188 | ||
K7EN29 | K7EN29_HUMAN | UNC13D | 146 | ||
K7EM66 | K7EM66_HUMAN | UNC13D | 147 | ||
K7EN81 | K7EN81_HUMAN | UNC13D | 311 | ||
K7EQ37 | K7EQ37_HUMAN | UNC13D | 267 |
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 137 | in Ref. 3; BAG63031 | ||||
Sequence: L → P | ||||||
Alternative sequence | VSP_011385 | 286 | in isoform 2 | |||
Sequence: R → RVGRVLGQWPCPALAAVCWVAGLAAPSVRPCLLTEASLQ | ||||||
Alternative sequence | VSP_011386 | 318-325 | in isoform 2 | |||
Sequence: AGSTSWDG → VLPSWGWA | ||||||
Alternative sequence | VSP_011387 | 326-1090 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 476 | in Ref. 3; BAG63031 | ||||
Sequence: H → R | ||||||
Sequence conflict | 590 | in Ref. 3; BAG63031 | ||||
Sequence: Q → R | ||||||
Sequence conflict | 796 | in Ref. 3; BAG63031 | ||||
Sequence: K → E | ||||||
Alternative sequence | VSP_037949 | 1081-1090 | in isoform 3 | |||
Sequence: ASQHALRPAP → GIGPSVSWPWPICLLAFLFQPLGWGPGSLGPGLQAQSLLEKGEGTLPKMRLQLPWGEGGGHY |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ578444 EMBL· GenBank· DDBJ | CAE17516.1 EMBL· GenBank· DDBJ | mRNA | ||
AK024474 EMBL· GenBank· DDBJ | BAB15764.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK301529 EMBL· GenBank· DDBJ | BAG63031.1 EMBL· GenBank· DDBJ | mRNA | ||
AC087289 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC067084 EMBL· GenBank· DDBJ | AAH67084.1 EMBL· GenBank· DDBJ | mRNA |