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Protein

Protein unc-13 homolog D

Gene

UNC13D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  • Rab GTPase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processExocytosis

Enzyme and pathway databases

ReactomeiR-HSA-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
Protein unc-13 homolog D
Alternative name(s):
Munc13-4
Gene namesi
Name:UNC13D
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000092929.11
HGNCiHGNC:23147 UNC13D
MIMi608897 gene
neXtProtiNX_Q70J99

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Familial hemophagocytic lymphohistiocytosis 3 (FHL3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:608898

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi608 – 611Missing : Abolishes localization to lysosomes and interaction with RAB27A. 1 Publication4

Keywords - Diseasei

Familial hemophagocytic lymphohistiocytosis

Organism-specific databases

DisGeNETi201294
GeneReviewsiUNC13D
MalaCardsiUNC13D
MIMi608898 phenotype
OpenTargetsiENSG00000092929
Orphaneti540 Familial hemophagocytic lymphohistiocytosis
PharmGKBiPA134919958

Polymorphism and mutation databases

BioMutaiUNC13D
DMDMi51316668

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001885811 – 1090Protein unc-13 homolog DAdd BLAST1090

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei150PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ70J99
MaxQBiQ70J99
PaxDbiQ70J99
PeptideAtlasiQ70J99
PRIDEiQ70J99
ProteomicsDBi68558
68559 [Q70J99-2]
68560 [Q70J99-3]

PTM databases

iPTMnetiQ70J99
PhosphoSitePlusiQ70J99

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000092929 Expressed in 163 organ(s), highest expression level in blood
CleanExiHS_UNC13D
ExpressionAtlasiQ70J99 baseline and differential
GenevisibleiQ70J99 HS

Organism-specific databases

HPAiHPA067117
HPA073525

Interactioni

Subunit structurei

Interacts with DOC2A (By similarity). Interacts with RAB27A.By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi128383, 10 interactors
IntActiQ70J99, 1 interactor
STRINGi9606.ENSP00000207549

Structurei

3D structure databases

ProteinModelPortaliQ70J99
SMRiQ70J99
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini98 – 221C2 1PROSITE-ProRule annotationAdd BLAST124
Domaini557 – 677MHD1PROSITE-ProRule annotationAdd BLAST121
Domaini788 – 895MHD2PROSITE-ProRule annotationAdd BLAST108
Domaini912 – 1019C2 2PROSITE-ProRule annotationAdd BLAST108

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni240 – 543Interaction with RAB27AAdd BLAST304

Domaini

The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome.2 Publications

Sequence similaritiesi

Belongs to the unc-13 family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1328 Eukaryota
ENOG410Z3Q9 LUCA
GeneTreeiENSGT00730000110939
HOGENOMiHOG000060231
HOVERGENiHBG104909
InParanoidiQ70J99
KOiK19728
OMAiHQCQRTW
OrthoDBiEOG091G024N
PhylomeDBiQ70J99
TreeFamiTF315526

Family and domain databases

Gene3Di2.60.40.150, 2 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR014770 Munc13_1
IPR014772 Munc13_dom-2
IPR019558 Munc13_subgr_dom-2
PfamiView protein in Pfam
PF00168 C2, 2 hits
PF10540 Membr_traf_MHD, 1 hit
SMARTiView protein in SMART
SM00239 C2, 2 hits
PROSITEiView protein in PROSITE
PS50004 C2, 2 hits
PS51258 MHD1, 1 hit
PS51259 MHD2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q70J99-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MATLLSHPQQ RPPFLRQAIK IRRRRVRDLQ DPPPQMAPEI QPPSHHFSPE
60 70 80 90 100
QRALLYEDAL YTVLHRLGHP EPNHVTEASE LLRYLQEAFH VEPEEHQQTL
110 120 130 140 150
QRVRELEKPI FCLKATVKQA KGILGKDVSG FSDPYCLLGI EQGVGVPGGS
160 170 180 190 200
PGSRHRQKAV VRHTIPEEET HRTQVITQTL NPVWDETFIL EFEDITNASF
210 220 230 240 250
HLDMWDLDTV ESVRQKLGEL TDLHGLRRIF KEARKDKGQD DFLGNVVLRL
260 270 280 290 300
QDLRCREDQW YPLEPRTETY PDRGQCHLQF QLIHKRRATS ASRSQPSYTV
310 320 330 340 350
HLHLLQQLVS HEVTQHEAGS TSWDGSLSPQ AATVLFLHAT QKDLSDFHQS
360 370 380 390 400
MAQWLAYSRL YQSLEFPSSC LLHPITSIEY QWIQGRLKAE QQEELAASFS
410 420 430 440 450
SLLTYGLSLI RRFRSVFPLS VSDSPARLQS LLRVLVQMCK MKAFGELCPN
460 470 480 490 500
TAPLPQLVTE ALQTGTTEWF HLKQQHHQPM VQGIPEAGKA LLGLVQDVIG
510 520 530 540 550
DLHQCQRTWD KIFHNTLKIH LFSMAFRELQ WLVAKRVQDH TTVVGDVVSP
560 570 580 590 600
EMGESLFQLY ISLKELCQLR MSSSERDGVL ALDNFHRWFQ PAIPSWLQKT
610 620 630 640 650
YNEALARVQR AVQMDELVPL GELTKHSTSA VDLSTCFAQI SHTARQLDWP
660 670 680 690 700
DPEEAFMITV KFVEDTCRLA LVYCSLIKAR ARELSSGQKD QGQAANMLCV
710 720 730 740 750
VVNDMEQLRL VIGKLPAQLA WEALEQRVGA VLEQGQLQNT LHAQLQSALA
760 770 780 790 800
GLGHEIRTGV RTLAEQLEVG IAKHIQKLVG VRESVLPEDA ILPLMKFLEV
810 820 830 840 850
ELCYMNTNLV QENFSSLLTL LWTHTLTVLV EAAASQRSSS LASNRLKIAL
860 870 880 890 900
QNLEICFHAE GCGLPPKALH TATFQALQRD LELQAASSRE LIRKYFCSRI
910 920 930 940 950
QQQAETTSEE LGAVTVKASY RASEQKLRVE LLSASSLLPL DSNGSSDPFV
960 970 980 990 1000
QLTLEPRHEF PELAARETQK HKKDLHPLFD ETFEFLVPAE PCRKAGACLL
1010 1020 1030 1040 1050
LTVLDYDTLG ADDLEGEAFL PLREVPGLSG SEEPGEVPQT RLPLTYPAPN
1060 1070 1080 1090
GDPILQLLEG RKGDREAQVF VRLRRHRAKQ ASQHALRPAP
Length:1,090
Mass (Da):123,282
Last modified:July 5, 2004 - v1
Checksum:iA71AD7A4E32C940C
GO
Isoform 2 (identifier: Q70J99-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     286-286: R → RVGRVLGQWPCPALAAVCWVAGLAAPSVRPCLLTEASLQ
     318-325: AGSTSWDG → VLPSWGWA
     326-1090: Missing.

Note: No experimental confirmation available.
Show »
Length:363
Mass (Da):41,642
Checksum:i0B16EF1B686C51CE
GO
Isoform 3 (identifier: Q70J99-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1081-1090: ASQHALRPAP → GIGPSVSWPWPICLLAFLFQPLGWGPGSLGPGLQAQSLLEKGEGTLPKMRLQLPWGEGGGHY

Note: No experimental confirmation available.
Show »
Length:1,142
Mass (Da):128,819
Checksum:i69183E35C9BB1AAF
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EMK8K7EMK8_HUMAN
Protein unc-13 homolog D
UNC13D
188Annotation score:
K7EN81K7EN81_HUMAN
Protein unc-13 homolog D
UNC13D
310Annotation score:
K7EQ37K7EQ37_HUMAN
Protein unc-13 homolog D
UNC13D
267Annotation score:
K7EN29K7EN29_HUMAN
Protein unc-13 homolog D
UNC13D
146Annotation score:
K7EIH3K7EIH3_HUMAN
Protein unc-13 homolog D
UNC13D
169Annotation score:
K7EM66K7EM66_HUMAN
Protein unc-13 homolog D
UNC13D
147Annotation score:
K7ELN2K7ELN2_HUMAN
Protein unc-13 homolog D
UNC13D
68Annotation score:

Sequence cautioni

The sequence BAB15764 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti137L → P in BAG63031 (PubMed:14702039).Curated1
Sequence conflicti476H → R in BAG63031 (PubMed:14702039).Curated1
Sequence conflicti590Q → R in BAG63031 (PubMed:14702039).Curated1
Sequence conflicti796K → E in BAG63031 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05246959A → T. Corresponds to variant dbSNP:rs9904366EnsemblClinVar.1
Natural variantiVAR_029771858H → Q. Corresponds to variant dbSNP:rs17496835Ensembl.1
Natural variantiVAR_029772867K → E. Corresponds to variant dbSNP:rs1135688EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011385286R → RVGRVLGQWPCPALAAVCWV AGLAAPSVRPCLLTEASLQ in isoform 2. 1 Publication1
Alternative sequenceiVSP_011386318 – 325AGSTSWDG → VLPSWGWA in isoform 2. 1 Publication8
Alternative sequenceiVSP_011387326 – 1090Missing in isoform 2. 1 PublicationAdd BLAST765
Alternative sequenceiVSP_0379491081 – 1090ASQHALRPAP → GIGPSVSWPWPICLLAFLFQ PLGWGPGSLGPGLQAQSLLE KGEGTLPKMRLQLPWGEGGG HY in isoform 3. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ578444 mRNA Translation: CAE17516.1
AK024474 mRNA Translation: BAB15764.1 Different initiation.
AK301529 mRNA Translation: BAG63031.1
AC087289 Genomic DNA No translation available.
BC067084 mRNA Translation: AAH67084.1
CCDSiCCDS11730.1 [Q70J99-1]
RefSeqiNP_954712.1, NM_199242.2 [Q70J99-1]
UniGeneiHs.41045

Genome annotation databases

EnsembliENST00000207549; ENSP00000207549; ENSG00000092929 [Q70J99-1]
ENST00000412096; ENSP00000388093; ENSG00000092929 [Q70J99-3]
GeneIDi201294
KEGGihsa:201294
UCSCiuc002jpp.5 human [Q70J99-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

UNC13Dbase

UNC13D mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ578444 mRNA Translation: CAE17516.1
AK024474 mRNA Translation: BAB15764.1 Different initiation.
AK301529 mRNA Translation: BAG63031.1
AC087289 Genomic DNA No translation available.
BC067084 mRNA Translation: AAH67084.1
CCDSiCCDS11730.1 [Q70J99-1]
RefSeqiNP_954712.1, NM_199242.2 [Q70J99-1]
UniGeneiHs.41045

3D structure databases

ProteinModelPortaliQ70J99
SMRiQ70J99
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128383, 10 interactors
IntActiQ70J99, 1 interactor
STRINGi9606.ENSP00000207549

PTM databases

iPTMnetiQ70J99
PhosphoSitePlusiQ70J99

Polymorphism and mutation databases

BioMutaiUNC13D
DMDMi51316668

Proteomic databases

EPDiQ70J99
MaxQBiQ70J99
PaxDbiQ70J99
PeptideAtlasiQ70J99
PRIDEiQ70J99
ProteomicsDBi68558
68559 [Q70J99-2]
68560 [Q70J99-3]

Protocols and materials databases

DNASUi201294
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000207549; ENSP00000207549; ENSG00000092929 [Q70J99-1]
ENST00000412096; ENSP00000388093; ENSG00000092929 [Q70J99-3]
GeneIDi201294
KEGGihsa:201294
UCSCiuc002jpp.5 human [Q70J99-1]

Organism-specific databases

CTDi201294
DisGeNETi201294
EuPathDBiHostDB:ENSG00000092929.11
GeneCardsiUNC13D
GeneReviewsiUNC13D
HGNCiHGNC:23147 UNC13D
HPAiHPA067117
HPA073525
MalaCardsiUNC13D
MIMi608897 gene
608898 phenotype
neXtProtiNX_Q70J99
OpenTargetsiENSG00000092929
Orphaneti540 Familial hemophagocytic lymphohistiocytosis
PharmGKBiPA134919958
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1328 Eukaryota
ENOG410Z3Q9 LUCA
GeneTreeiENSGT00730000110939
HOGENOMiHOG000060231
HOVERGENiHBG104909
InParanoidiQ70J99
KOiK19728
OMAiHQCQRTW
OrthoDBiEOG091G024N
PhylomeDBiQ70J99
TreeFamiTF315526

Enzyme and pathway databases

ReactomeiR-HSA-6798695 Neutrophil degranulation

Miscellaneous databases

ChiTaRSiUNC13D human
GeneWikiiUNC13D
GenomeRNAii201294
PROiPR:Q70J99
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000092929 Expressed in 163 organ(s), highest expression level in blood
CleanExiHS_UNC13D
ExpressionAtlasiQ70J99 baseline and differential
GenevisibleiQ70J99 HS

Family and domain databases

Gene3Di2.60.40.150, 2 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR014770 Munc13_1
IPR014772 Munc13_dom-2
IPR019558 Munc13_subgr_dom-2
PfamiView protein in Pfam
PF00168 C2, 2 hits
PF10540 Membr_traf_MHD, 1 hit
SMARTiView protein in SMART
SM00239 C2, 2 hits
PROSITEiView protein in PROSITE
PS50004 C2, 2 hits
PS51258 MHD1, 1 hit
PS51259 MHD2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUN13D_HUMAN
AccessioniPrimary (citable) accession number: Q70J99
Secondary accession number(s): B4DWG9, Q9H7K5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: November 7, 2018
This is version 131 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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