ID DCSTP_HUMAN Reviewed; 470 AA. AC Q9H295; B7ZVW2; E7ESG0; Q2M2D5; DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 08-NOV-2023, entry version 152. DE RecName: Full=Dendritic cell-specific transmembrane protein; DE Short=DC-STAMP; DE Short=hDC-STAMP; DE AltName: Full=Dendrocyte-expressed seven transmembrane protein; DE AltName: Full=IL-four-induced protein; DE Short=FIND; DE AltName: Full=Transmembrane 7 superfamily member 4; GN Name=DCSTAMP; Synonyms=TM7SF4; 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] {ECO:0000305, ECO:0000312|EMBL:AAG39167.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TOPOLOGY, RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION. RC TISSUE=Dendritic cell {ECO:0000312|EMBL:AAG39167.1}; RX PubMed=11169400; RX DOI=10.1002/1521-4141(200012)30:12<3585::aid-immu3585>3.0.co;2-y; RA Hartgers F.C., Vissers J.L.M., Looman M.W.G., van Zoelen C., Huffin C., RA Figdor C.G., Adema G.J.; RT "DC-STAMP, a novel multimembrane-spanning molecule preferentially expressed RT by dendritic cells."; RL Eur. J. Immunol. 30:3585-3590(2000). RN [2] {ECO:0000305, ECO:0000312|EMBL:AAL02152.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION. RC TISSUE=Macrophage {ECO:0000269|PubMed:11345586}, and Monocyte; RX PubMed=11345586; DOI=10.1007/s002510100306; RA Staege H., Brauchlin A., Schoedon G., Schaffner A.; RT "Two novel genes FIND and LIND differentially expressed in deactivated and RT Listeria-infected human macrophages."; RL Immunogenetics 53:105-113(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [4] {ECO:0000312|EMBL:AAH69349.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [5] RP SUBCELLULAR LOCATION. RX PubMed=15601667; DOI=10.1189/jlb.0804441; RA Eleveld-Trancikova D., Triantis V., Moulin V., Looman M.W., Wijers M., RA Fransen J.A., Lemckert A.A., Havenga M.J., Figdor C.G., Janssen R.A., RA Adema G.J.; RT "The dendritic cell-derived protein DC-STAMP is highly conserved and RT localizes to the endoplasmic reticulum."; RL J. Leukoc. Biol. 77:337-343(2005). RN [6] RP INTERACTION WITH CREB3. RX PubMed=20546900; DOI=10.1016/j.molimm.2010.04.019; RA Eleveld-Trancikova D., Sanecka A., van Hout-Kuijer M.A., Looman M.W., RA Hendriks I.A., Jansen B.J., Adema G.J.; RT "DC-STAMP interacts with ER-resident transcription factor LUMAN which RT becomes activated during DC maturation."; RL Mol. Immunol. 47:1963-1973(2010). CC -!- FUNCTION: Probable cell surface receptor that plays several roles in CC cellular fusion, cell differentiation, bone and immune homeostasis. CC Plays a role in TNFSF11-mediated osteoclastogenesis. Cooperates with CC OCSTAMP in modulating cell-cell fusion in both osteoclasts and foreign CC body giant cells (FBGCs). Participates in osteoclast bone resorption. CC Involved in inducing the expression of tartrate-resistant acid CC phosphatase in osteoclast precursors. Plays a role in haematopoietic CC stem cell differentiation of bone marrow cells toward the myeloid CC lineage. Inhibits the development of neutrophilic granulocytes. Plays CC also a role in the regulation of dendritic cell (DC) antigen CC presentation activity by controlling phagocytic activity. Involved in CC the maintenance of immune self-tolerance and avoidance of autoimmune CC reactions. CC -!- SUBUNIT: Monomer. Homodimer. Isoform 1 interacts (via the C-terminus CC cytoplasmic tail) with OS9 isoform 1 (via the C-terminus tail); the CC interaction induces DCSTAMP redistribution to the endoplasmic CC reticulum-Golgi intermediate compartment. Isoform 1 interacts (via the CC C-terminus cytoplasmic tail) with OS9 isoform 2 (via the C-terminus CC tail) (By similarity). Interacts with CREB3. {ECO:0000250, CC ECO:0000269|PubMed:20546900}. CC -!- INTERACTION: CC Q9H295; O43889-2: CREB3; NbExp=6; IntAct=EBI-6095316, EBI-625022; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane CC protein {ECO:0000250}. Endoplasmic reticulum membrane; Multi-pass CC membrane protein. Endoplasmic reticulum-Golgi intermediate compartment CC membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. CC Endosome {ECO:0000250}. Note=Localizes to the cell surface in CC osteoclasts and undifferentiated monocytes. Intracellular internalized CC DCSTAMP is detected in a fraction of RANKL-induced osteoclast CC precursor. Colocalizes with OS9 in the endoplasmic reticulum (ER) of CC immature dendritic cell (DC). Translocates from the endoplasmic CC reticulum to the intermediate/Golgi compartment upon maturation of DC CC in a OS9-dependent manner. Colocalizes with LAMP1 in endosomes (By CC similarity). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9H295-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H295-2; Sequence=VSP_044787, VSP_044788; CC -!- TISSUE SPECIFICITY: Preferentially expressed by dendritic cells (DCs). CC Detected in both immature and mature DCs. Highly expressed in lymph CC nodes, lung, kidney and liver. Expressed at lower levels in pancreas, CC bone marrow, spleen, leukocytes, in freshly isolated peripheral blood CC mononuclear cells (PBMC) and B-cells. Not expressed in freshly isolated CC monocytes. {ECO:0000269|PubMed:11169400, ECO:0000269|PubMed:11345586}. CC -!- DEVELOPMENTAL STAGE: Constitutively expressed in dendritic cells from CC day 3-8 in culture. {ECO:0000269|PubMed:11169400}. CC -!- INDUCTION: Expression is down-regulated by dexamethasone and up- CC regulated by IL4/interleukin-4 in macrophages. Down-regulated in CD40L- CC activated dendritic cells. {ECO:0000269|PubMed:11169400, CC ECO:0000269|PubMed:11345586}. CC -!- DOMAIN: Several domains are necessary for interacting with OS9. The CC region in the cytoplasmic tail that is necessary for interaction with CC OS9, is also required for its transport (By similarity). {ECO:0000250}. CC -!- PTM: Glycosylated. {ECO:0000250}. 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; AF305068; AAG39167.1; -; mRNA. DR EMBL; AF277290; AAL02152.1; -; mRNA. DR EMBL; AP003471; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC069349; AAH69349.1; -; mRNA. DR EMBL; BC112018; AAI12019.1; -; mRNA. DR EMBL; BC112020; AAI12021.1; -; mRNA. DR EMBL; BC171732; AAI71732.1; -; mRNA. DR CCDS; CCDS59111.1; -. [Q9H295-2] DR CCDS; CCDS6301.1; -. [Q9H295-1] DR RefSeq; NP_001244246.1; NM_001257317.1. [Q9H295-2] DR RefSeq; NP_110415.1; NM_030788.3. [Q9H295-1] DR RefSeq; XP_011515623.1; XM_011517321.1. DR RefSeq; XP_011515626.1; XM_011517324.1. DR RefSeq; XP_016869367.1; XM_017013878.1. DR RefSeq; XP_016869369.1; XM_017013880.1. DR AlphaFoldDB; Q9H295; -. DR BioGRID; 123504; 1. DR IntAct; Q9H295; 1. DR STRING; 9606.ENSP00000297581; -. DR TCDB; 1.N.1.1.1; the osteoclast fusion complex (ofc) family. DR iPTMnet; Q9H295; -. DR PhosphoSitePlus; Q9H295; -. DR BioMuta; DCSTAMP; -. DR DMDM; 71153342; -. DR PaxDb; 9606-ENSP00000297581; -. DR PeptideAtlas; Q9H295; -. DR ProteomicsDB; 17984; -. DR ProteomicsDB; 80513; -. [Q9H295-1] DR Antibodypedia; 42882; 84 antibodies from 17 providers. DR DNASU; 81501; -. DR Ensembl; ENST00000297581.2; ENSP00000297581.2; ENSG00000164935.6. [Q9H295-1] DR Ensembl; ENST00000517991.5; ENSP00000428869.1; ENSG00000164935.6. [Q9H295-2] DR Ensembl; ENST00000622554.1; ENSP00000480546.1; ENSG00000164935.6. [Q9H295-2] DR GeneID; 81501; -. DR KEGG; hsa:81501; -. DR MANE-Select; ENST00000297581.2; ENSP00000297581.2; NM_030788.4; NP_110415.1. DR UCSC; uc003ylx.3; human. [Q9H295-1] DR AGR; HGNC:18549; -. DR CTD; 81501; -. DR DisGeNET; 81501; -. DR GeneCards; DCSTAMP; -. DR HGNC; HGNC:18549; DCSTAMP. DR HPA; ENSG00000164935; Tissue enhanced (epididymis, lung). DR MIM; 605933; gene. DR neXtProt; NX_Q9H295; -. DR OpenTargets; ENSG00000164935; -. DR PharmGKB; PA134938623; -. DR VEuPathDB; HostDB:ENSG00000164935; -. DR eggNOG; ENOG502QWDQ; Eukaryota. DR GeneTree; ENSGT00940000153269; -. DR HOGENOM; CLU_046145_0_0_1; -. DR InParanoid; Q9H295; -. DR OMA; FKHLRCF; -. DR OrthoDB; 5354738at2759; -. DR PhylomeDB; Q9H295; -. DR TreeFam; TF318254; -. DR PathwayCommons; Q9H295; -. DR Reactome; R-HSA-8874211; CREB3 factors activate genes. DR SignaLink; Q9H295; -. DR BioGRID-ORCS; 81501; 7 hits in 1141 CRISPR screens. DR GenomeRNAi; 81501; -. DR Pharos; Q9H295; Tbio. DR PRO; PR:Q9H295; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9H295; Protein. DR Bgee; ENSG00000164935; Expressed in stromal cell of endometrium and 103 other tissues. DR Genevisible; Q9H295; HS. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell. DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0071353; P:cellular response to interleukin-4; IDA:UniProtKB. DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; ISS:UniProtKB. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB. DR GO; GO:0061025; P:membrane fusion; ISS:UniProtKB. DR GO; GO:0043011; P:myeloid dendritic cell differentiation; ISS:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB. DR GO; GO:0030316; P:osteoclast differentiation; ISS:UniProtKB. DR GO; GO:0072675; P:osteoclast fusion; ISS:UniProtKB. DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB. DR GO; GO:0034241; P:positive regulation of macrophage fusion; ISS:UniProtKB. DR GO; GO:0045657; P:positive regulation of monocyte differentiation; ISS:UniProtKB. DR InterPro; IPR012858; DC_STAMP-like. DR PANTHER; PTHR21041; DENDRITIC CELL-SPECIFIC TRANSMEMBRANE PROTEIN; 1. DR PANTHER; PTHR21041:SF2; DENDRITIC CELL-SPECIFIC TRANSMEMBRANE PROTEIN; 1. DR Pfam; PF07782; DC_STAMP; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Differentiation; KW Endoplasmic reticulum; Endosome; Immunity; Membrane; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1..470 FT /note="Dendritic cell-specific transmembrane protein" FT /id="PRO_0000072584" FT TOPO_DOM 1..34 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 35..55 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 56..57 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 58..78 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 79..97 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 98..118 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 119..209 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 210..230 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 231..292 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 293..313 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 314..376 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 377..397 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 398..470 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:11169400" FT VAR_SEQ 277..283 FT /note="YVIIPTF -> FISGFQS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_044787" FT VAR_SEQ 284..470 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_044788" FT VARIANT 349 FT /note="D -> G (in dbSNP:rs3802204)" FT /id="VAR_051438" FT CONFLICT 200 FT /note="M -> R (in Ref. 4; AAI71732)" FT /evidence="ECO:0000305" SQ SEQUENCE 470 AA; 53393 MW; EA2B858FD2C7560C CRC64; MGIWTSGTDI FLSLWEIYVS PRSPGWMDFI QHLGVCCLVA LISVGLLSVA ACWFLPSIIA AAASWIITCV LLCCSKHARC FILLVFLSCG LREGRNALIA AGTGIVILGH VENIFHNFKG LLDGMTCNLR AKSFSIHFPL LKKYIEAIQW IYGLATPLSV FDDLVSWNQT LAVSLFSPSH VLEAQLNDSK GEVLSVLYQM ATTTEVLSSL GQKLLAFAGL SLVLLGTGLF MKRFLGPCGW KYENIYITRQ FVQFDERERH QQRPCVLPLN KEERRKYVII PTFWPTPKER KNLGLFFLPI LIHLCIWVLF AAVDYLLYRL IFSVSKQFQS LPGFEVHLKL HGEKQGTQDI IHDSSFNISV FEPNCIPKPK FLLSETWVPL SVILLILVML GLLSSILMQL KILVSASFYP SVERKRIQYL HAKLLKKRSK QPLGEVKRRL SLYLTKIHFW LPVLKMIRKK QMDMASADKS //