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Q70J99 (UN13D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein unc-13 homolog D
Alternative name(s):
Munc13-4
Gene names
Name:UNC13D
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1090 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6 Ref.9

Subunit structure

Interacts with DOC2A By similarity. Interacts with RAB27A. Ref.6 Ref.9

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein. Late endosome. Recycling endosome. Lysosome. Note: Colocalizes with cytotoxic granules at the plasma membrane. Localizes to endosomal exocytic vesicles. Ref.1 Ref.6 Ref.9

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. Ref.1 Ref.6

Domain

The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome. Ref.6 Ref.9

Involvement in disease

Familial hemophagocytic lymphohistiocytosis 3 (FHL3) [MIM:608898]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence similarities

Belongs to the unc-13 family.

Contains 2 C2 domains.

Contains 1 MHD1 (MUNC13 homology domain 1) domain.

Contains 1 MHD2 (MUNC13 homology domain 2) domain.

Sequence caution

The sequence BAB15764.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: 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.
Isoform 2 (identifier: Q70J99-2)

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.
Isoform 3 (identifier: Q70J99-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1081-1090: ASQHALRPAP → GIGPSVSWPWPICLLAFLFQPLGWGPGSLGPGLQAQSLLEKGEGTLPKMRLQLPWGEGGGHY
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10901090Protein unc-13 homolog D
PRO_0000188581

Regions

Domain98 – 221124C2 1
Domain557 – 677121MHD1
Domain788 – 895108MHD2
Domain912 – 1019108C2 2
Region240 – 543304Interaction with RAB27A

Amino acid modifications

Modified residue1501Phosphoserine Ref.10

Natural variations

Alternative sequence2861R → RVGRVLGQWPCPALAAVCWV AGLAAPSVRPCLLTEASLQ in isoform 2.
VSP_011385
Alternative sequence318 – 3258AGSTSWDG → VLPSWGWA in isoform 2.
VSP_011386
Alternative sequence326 – 1090765Missing in isoform 2.
VSP_011387
Alternative sequence1081 – 109010ASQHALRPAP → GIGPSVSWPWPICLLAFLFQ PLGWGPGSLGPGLQAQSLLE KGEGTLPKMRLQLPWGEGGG HY in isoform 3.
VSP_037949
Natural variant591A → T.
Corresponds to variant rs9904366 [ dbSNP | Ensembl ].
VAR_052469
Natural variant8581H → Q.
Corresponds to variant rs17496835 [ dbSNP | Ensembl ].
VAR_029771
Natural variant8671K → E.
Corresponds to variant rs1135688 [ dbSNP | Ensembl ].
VAR_029772

Experimental info

Mutagenesis608 – 6114Missing: Abolishes localization to lysosomes and interaction with RAB27A. Ref.6
Sequence conflict1371L → P in BAG63031. Ref.3
Sequence conflict4761H → R in BAG63031. Ref.3
Sequence conflict5901Q → R in BAG63031. Ref.3
Sequence conflict7961K → E in BAG63031. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: A71AD7A4E32C940C

FASTA1,090123,282
        10         20         30         40         50         60 
MATLLSHPQQ RPPFLRQAIK IRRRRVRDLQ DPPPQMAPEI QPPSHHFSPE QRALLYEDAL 

        70         80         90        100        110        120 
YTVLHRLGHP EPNHVTEASE LLRYLQEAFH VEPEEHQQTL QRVRELEKPI FCLKATVKQA 

       130        140        150        160        170        180 
KGILGKDVSG FSDPYCLLGI EQGVGVPGGS PGSRHRQKAV VRHTIPEEET HRTQVITQTL 

       190        200        210        220        230        240 
NPVWDETFIL EFEDITNASF HLDMWDLDTV ESVRQKLGEL TDLHGLRRIF KEARKDKGQD 

       250        260        270        280        290        300 
DFLGNVVLRL QDLRCREDQW YPLEPRTETY PDRGQCHLQF QLIHKRRATS ASRSQPSYTV 

       310        320        330        340        350        360 
HLHLLQQLVS HEVTQHEAGS TSWDGSLSPQ AATVLFLHAT QKDLSDFHQS MAQWLAYSRL 

       370        380        390        400        410        420 
YQSLEFPSSC LLHPITSIEY QWIQGRLKAE QQEELAASFS SLLTYGLSLI RRFRSVFPLS 

       430        440        450        460        470        480 
VSDSPARLQS LLRVLVQMCK MKAFGELCPN TAPLPQLVTE ALQTGTTEWF HLKQQHHQPM 

       490        500        510        520        530        540 
VQGIPEAGKA LLGLVQDVIG DLHQCQRTWD KIFHNTLKIH LFSMAFRELQ WLVAKRVQDH 

       550        560        570        580        590        600 
TTVVGDVVSP EMGESLFQLY ISLKELCQLR MSSSERDGVL ALDNFHRWFQ PAIPSWLQKT 

       610        620        630        640        650        660 
YNEALARVQR AVQMDELVPL GELTKHSTSA VDLSTCFAQI SHTARQLDWP DPEEAFMITV 

       670        680        690        700        710        720 
KFVEDTCRLA LVYCSLIKAR ARELSSGQKD QGQAANMLCV VVNDMEQLRL VIGKLPAQLA 

       730        740        750        760        770        780 
WEALEQRVGA VLEQGQLQNT LHAQLQSALA GLGHEIRTGV RTLAEQLEVG IAKHIQKLVG 

       790        800        810        820        830        840 
VRESVLPEDA ILPLMKFLEV ELCYMNTNLV QENFSSLLTL LWTHTLTVLV EAAASQRSSS 

       850        860        870        880        890        900 
LASNRLKIAL QNLEICFHAE GCGLPPKALH TATFQALQRD LELQAASSRE LIRKYFCSRI 

       910        920        930        940        950        960 
QQQAETTSEE LGAVTVKASY RASEQKLRVE LLSASSLLPL DSNGSSDPFV QLTLEPRHEF 

       970        980        990       1000       1010       1020 
PELAARETQK HKKDLHPLFD ETFEFLVPAE PCRKAGACLL LTVLDYDTLG ADDLEGEAFL 

      1030       1040       1050       1060       1070       1080 
PLREVPGLSG SEEPGEVPQT RLPLTYPAPN GDPILQLLEG RKGDREAQVF VRLRRHRAKQ 

      1090 
ASQHALRPAP 

« Hide

Isoform 2 [UniParc].

Checksum: 0B16EF1B686C51CE
Show »

FASTA36341,642
Isoform 3 [UniParc].

Checksum: 69183E35C9BB1AAF
Show »

FASTA1,142128,819

References

« Hide 'large scale' references
[1]"Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3)."
Feldmann J., Callebaut I., Raposo G., Certain S., Bacq D., Dumont C., Lambert N., Ouachee-Chardin M., Chedville G., Tamary H., Minard-Colin V., Vilmer E., Blanche S., Le Deist F., Fischer A., de Saint Basile G.
Cell 115:461-473(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN FHL3.
Tissue: Blood.
[2]"Characterization of long cDNA clones from human adult spleen."
Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.
DNA Res. 7:357-366(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Spleen.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Synovium.
[4]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pancreas.
[6]"Munc13-4 is an effector of rab27a and controls secretion of lysosomes in hematopoietic cells."
Neeft M., Wieffer M., de Jong A.S., Negroiu G., Metz C.H., van Loon A., Griffith J., Krijgsveld J., Wulffraat N., Koch H., Heck A.J.R., Brose N., Kleijmeer M., van der Sluijs P.
Mol. Biol. Cell 16:731-741(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB27A, TISSUE SPECIFICITY, DOMAIN, MUTAGENESIS OF 608-VAL--ALA-611.
[7]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4."
Menager M.M., Menasche G., Romao M., Knapnougel P., Ho C.-H., Garfa M., Raposo G., Feldmann J., Fischer A., de Saint Basile G.
Nat. Immunol. 8:257-267(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB27A, DOMAIN.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

UNC13Dbase

UNC13D mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS11730.1. [Q70J99-1]
RefSeqNP_954712.1. NM_199242.2. [Q70J99-1]
UniGeneHs.41045.

3D structure databases

ProteinModelPortalQ70J99.
SMRQ70J99. Positions 116-282, 588-883, 909-1046.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128383. 6 interactions.
STRING9606.ENSP00000207549.

PTM databases

PhosphoSiteQ70J99.

Polymorphism databases

DMDM51316668.

Proteomic databases

MaxQBQ70J99.
PaxDbQ70J99.
PeptideAtlasQ70J99.
PRIDEQ70J99.

Protocols and materials databases

DNASU201294.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000207549; ENSP00000207549; ENSG00000092929. [Q70J99-1]
ENST00000412096; ENSP00000388093; ENSG00000092929. [Q70J99-3]
GeneID201294.
KEGGhsa:201294.
UCSCuc002jpp.3. human. [Q70J99-1]

Organism-specific databases

CTD201294.
GeneCardsGC17M073823.
GeneReviewsUNC13D.
HGNCHGNC:23147. UNC13D.
MIM608897. gene.
608898. phenotype.
neXtProtNX_Q70J99.
Orphanet540. Familial hemophagocytic lymphohistiocytosis.
PharmGKBPA134919958.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG290002.
HOGENOMHOG000060231.
HOVERGENHBG104909.
InParanoidQ70J99.
OMAPYCLLGI.
OrthoDBEOG7XPZ4S.
PhylomeDBQ70J99.
TreeFamTF315526.

Gene expression databases

ArrayExpressQ70J99.
BgeeQ70J99.
CleanExHS_UNC13D.
GenevestigatorQ70J99.

Family and domain databases

Gene3D2.60.40.150. 2 hits.
InterProIPR000008. C2_dom.
IPR014770. Munc13_1.
IPR014772. Munc13_dom-2.
IPR019558. Munc13_subgr_dom-2.
[Graphical view]
PfamPF00168. C2. 2 hits.
PF10540. Membr_traf_MHD. 1 hit.
[Graphical view]
SMARTSM00239. C2. 2 hits.
[Graphical view]
SUPFAMSSF49562. SSF49562. 4 hits.
PROSITEPS50004. C2. 2 hits.
PS51258. MHD1. 1 hit.
PS51259. MHD2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiUNC13D.
GenomeRNAi201294.
NextBio90129.
PROQ70J99.
SOURCESearch...

Entry information

Entry nameUN13D_HUMAN
AccessionPrimary (citable) accession number: Q70J99
Secondary accession number(s): B4DWG9, Q9H7K5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM