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Protein

Protein unc-13 homolog D

Gene

UNC13D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • defense response to virus Source: Ensembl
  • germinal center formation Source: Ensembl
  • granuloma formation Source: Ensembl
  • natural killer cell degranulation Source: Ensembl
  • phagocytosis Source: Ensembl
  • positive regulation of exocytosis Source: UniProtKB
  • positive regulation of regulated secretory pathway Source: UniProtKB
  • positive regulation of substrate adhesion-dependent cell spreading Source: Ensembl
  • regulation of mast cell degranulation Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Exocytosis

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

HGNCiHGNC:23147. UNC13D.

Subcellular locationi

GO - Cellular componenti

  • exocytic vesicle Source: UniProtKB
  • late endosome Source: UniProtKB-SubCell
  • lysosome Source: UniProtKB
  • membrane Source: UniProtKB-SubCell
  • recycling endosome Source: UniProtKB-SubCell
  • Weibel-Palade body Source: UniProtKB
Complete GO annotation...

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.
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.

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.
CleanExiHS_UNC13D.
ExpressionAtlasiQ70J99. baseline and differential.
GenevisibleiQ70J99. HS.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • Rab GTPase binding Source: UniProtKB

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
Contains 2 C2 domains.PROSITE-ProRule annotation
Contains 1 MHD1 (MUNC13 homology domain 1) domain.PROSITE-ProRule annotation
Contains 1 MHD2 (MUNC13 homology domain 2) domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.40.150. 2 hits.
InterProiIPR000008. C2_dom.
IPR014770. Munc13_1.
IPR014772. Munc13_dom-2.
IPR019558. Munc13_subgr_dom-2.
[Graphical view]
PfamiPF00168. C2. 2 hits.
PF10540. Membr_traf_MHD. 1 hit.
[Graphical view]
SMARTiSM00239. C2. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 4 hits.
PROSITEiPS50004. C2. 2 hits.
PS51258. MHD1. 1 hit.
PS51259. MHD2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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 rs9904366dbSNPEnsembl.1
Natural variantiVAR_029771858H → Q.Corresponds to variant rs17496835dbSNPEnsembl.1
Natural variantiVAR_029772867K → E.Corresponds to variant rs1135688dbSNPEnsembl.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

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.

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.
GeneCardsiUNC13D.
GeneReviewsiUNC13D.
HGNCiHGNC:23147. UNC13D.
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.
OMAiPYCLLGI.
OrthoDBiEOG091G024N.
PhylomeDBiQ70J99.
TreeFamiTF315526.

Enzyme and pathway databases

ReactomeiR-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

ChiTaRSiUNC13D. human.
GeneWikiiUNC13D.
GenomeRNAii201294.
PROiQ70J99.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000092929.
CleanExiHS_UNC13D.
ExpressionAtlasiQ70J99. baseline and differential.
GenevisibleiQ70J99. HS.

Family and domain databases

Gene3Di2.60.40.150. 2 hits.
InterProiIPR000008. C2_dom.
IPR014770. Munc13_1.
IPR014772. Munc13_dom-2.
IPR019558. Munc13_subgr_dom-2.
[Graphical view]
PfamiPF00168. C2. 2 hits.
PF10540. Membr_traf_MHD. 1 hit.
[Graphical view]
SMARTiSM00239. C2. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 4 hits.
PROSITEiPS50004. C2. 2 hits.
PS51258. MHD1. 1 hit.
PS51259. MHD2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUN13D_HUMAN
AccessioniPrimary (citable) accession number: Q70J99
Secondary accession number(s): B4DWG9, Q9H7K5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 122 of the entry and version 1 of the sequence. [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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.