DCST1_HUMAN
ID DCST1_HUMAN Reviewed; 706 AA.
AC Q5T197; B4DXA0; E9PHV3; Q5T198; Q6P1W6; Q71S70; Q96M70;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=E3 ubiquitin-protein ligase DCST1 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:27782195};
DE AltName: Full=DC-STAMP domain-containing protein 1;
DE AltName: Full=RING-type E3 ubiquitin transferase {ECO:0000305};
GN Name=DCST1;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP LEU-512.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT LEU-512.
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 620-706.
RA Karkkainen I., Ortiz R.M., Huovila A.-P.J.;
RT "The characterization of human ADAM15 gene structure and promoter region.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH STAT2, SUBCELLULAR
RP LOCATION, INDUCTION, AND DOMAIN.
RX PubMed=27782195; DOI=10.1038/srep36179;
RA Nair S., Bist P., Dikshit N., Krishnan M.N.;
RT "Global functional profiling of human ubiquitome identifies E3 ubiquitin
RT ligase DCST1 as a novel negative regulator of Type-I interferon
RT signaling.";
RL Sci. Rep. 6:36179-36179(2016).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which mediates 'Lys-48'-linked
CC ubiquitination of STAT2 and induces its proteosomal degradation thereby
CC negatively regulating type-I-interferon signaling.
CC {ECO:0000269|PubMed:27782195}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:27782195};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:27782195}.
CC -!- SUBUNIT: Interacts with STAT2; the interaction results in STAT2 'Lys-
CC 48'-linked ubiquitination leading to its proteasomal degradation.
CC {ECO:0000269|PubMed:27782195}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27782195};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5T197-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5T197-2; Sequence=VSP_023406, VSP_023407;
CC Name=3;
CC IsoId=Q5T197-3; Sequence=VSP_045619;
CC -!- INDUCTION: Induced by IFNB1. {ECO:0000269|PubMed:27782195}.
CC -!- DOMAIN: The RING-type zinc finger domain is responsible for E3
CC ubiquitin ligase activity. {ECO:0000269|PubMed:27782195}.
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DR EMBL; AK057347; BAB71440.1; -; mRNA.
DR EMBL; AK301876; BAG63312.1; -; mRNA.
DR EMBL; AL451085; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC064844; AAH64844.1; -; mRNA.
DR EMBL; AF314227; AAS46286.1; -; Genomic_DNA.
DR CCDS; CCDS1083.1; -. [Q5T197-1]
DR CCDS; CCDS44235.1; -. [Q5T197-3]
DR RefSeq; NP_001137159.1; NM_001143687.2. [Q5T197-3]
DR RefSeq; NP_689707.2; NM_152494.3. [Q5T197-1]
DR AlphaFoldDB; Q5T197; -.
DR BioGRID; 127192; 19.
DR IntAct; Q5T197; 2.
DR STRING; 9606.ENSP00000295542; -.
DR GlyGen; Q5T197; 5 sites.
DR iPTMnet; Q5T197; -.
DR PhosphoSitePlus; Q5T197; -.
DR BioMuta; DCST1; -.
DR DMDM; 74756229; -.
DR EPD; Q5T197; -.
DR MassIVE; Q5T197; -.
DR PaxDb; Q5T197; -.
DR PeptideAtlas; Q5T197; -.
DR PRIDE; Q5T197; -.
DR ProteomicsDB; 20607; -.
DR ProteomicsDB; 64248; -. [Q5T197-1]
DR ProteomicsDB; 64249; -. [Q5T197-2]
DR Antibodypedia; 20409; 86 antibodies from 20 providers.
DR DNASU; 149095; -.
DR Ensembl; ENST00000295542.6; ENSP00000295542.2; ENSG00000163357.11. [Q5T197-1]
DR Ensembl; ENST00000368419.2; ENSP00000357404.2; ENSG00000163357.11. [Q5T197-2]
DR Ensembl; ENST00000423025.6; ENSP00000387369.2; ENSG00000163357.11. [Q5T197-3]
DR GeneID; 149095; -.
DR KEGG; hsa:149095; -.
DR MANE-Select; ENST00000295542.6; ENSP00000295542.2; NM_152494.4; NP_689707.2.
DR UCSC; uc001fgn.3; human. [Q5T197-1]
DR CTD; 149095; -.
DR DisGeNET; 149095; -.
DR GeneCards; DCST1; -.
DR HGNC; HGNC:26539; DCST1.
DR HPA; ENSG00000163357; Group enriched (retina, skin, testis).
DR MIM; 619860; gene.
DR neXtProt; NX_Q5T197; -.
DR OpenTargets; ENSG00000163357; -.
DR PharmGKB; PA142672005; -.
DR VEuPathDB; HostDB:ENSG00000163357; -.
DR eggNOG; KOG3726; Eukaryota.
DR GeneTree; ENSGT00940000153269; -.
DR HOGENOM; CLU_015030_1_1_1; -.
DR InParanoid; Q5T197; -.
DR OMA; MAKPFTN; -.
DR PhylomeDB; Q5T197; -.
DR TreeFam; TF318254; -.
DR PathwayCommons; Q5T197; -.
DR SignaLink; Q5T197; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 149095; 9 hits in 1071 CRISPR screens.
DR GenomeRNAi; 149095; -.
DR Pharos; Q5T197; Tbio.
DR PRO; PR:Q5T197; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5T197; protein.
DR Bgee; ENSG00000163357; Expressed in skin of abdomen and 84 other tissues.
DR ExpressionAtlas; Q5T197; baseline and differential.
DR Genevisible; Q5T197; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR InterPro; IPR012858; DC_STAMP-like.
DR InterPro; IPR001841; Znf_RING.
DR Pfam; PF07782; DC_STAMP; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Immunity;
KW Innate immunity; Membrane; Metal-binding; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..706
FT /note="E3 ubiquitin-protein ligase DCST1"
FT /id="PRO_0000278824"
FT TOPO_DOM 1..48
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..69
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 70..79
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..372
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 394..463
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 464..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..553
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 554..574
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 575..706
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 646..685
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 525
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 63..87
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045619"
FT VAR_SEQ 624..664
FT /note="RHPLADILHRGCPLLRRWLCRRCVVCQAPETPESYVCRTLD -> VFTEPQF
FT LPLKNGKTGEICKACSLEISLEWWSGVGLRCQRA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023406"
FT VAR_SEQ 665..706
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023407"
FT VARIANT 158
FT /note="T -> I (in dbSNP:rs9427170)"
FT /id="VAR_056859"
FT VARIANT 512
FT /note="M -> L (in dbSNP:rs11264300)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_030868"
FT CONFLICT 467
FT /note="L -> P (in Ref. 1; BAB71440)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 706 AA; 80712 MW; FAE1ADED291F846C CRC64;
MDIKHHQNGT RGQRRKQPHT TVQRLLTWGL PVSCSWFLWR QPGEFPVTAL LLGAGAGGLL
AIGLFQLLVN PMNIYEEQKI MFLYSLVGLG AMGWGTSPHI RCASLLLVPK MLGKEGRLFV
LGYALAAIYV GPVANLRHNL NNVIASLGCT VELQINNTRA AWRISTAPLR AMFKDLLSSK
ELLRAETRNI SATFEDLDAQ VNSETGYTPE DTMDSGETAQ GREARQAPAS RLHLSTQKMY
ELKTKLRCSY VVNQAILSCR RWFDRKHEQC MKHIWVPLLT HLLCLPMKFK FFCGIAKVME
VWCRNRIPVE GNFGQTYDSL NQSIRGLDGE FSANIDFKEE KQAGVLGLNT SWERVSTEVR
DYVYRQEARL EWALGLLHVL LSCTFLLVLH ASFSYMDSYN HDIRFDNIYI STYFCQIDDR
RKKLGKRTLL PLRKAEEKTV IFPCKPTIQA SEMSNVVREL LETLPILLLL VVLCGLDWAL
YSIFDTIRHH SFLQYSFRSS HKLEVKVGGD SMLARLLRKT IGALNTSSET VMESNNMPCL
PQPVGLDARA YWRAAVPIGL LVCLCLLQAF GYRLRRVIAA FYFPKREKKR ILFLYNDLLK
KRAAFTKLRR AAILRRERQQ KAPRHPLADI LHRGCPLLRR WLCRRCVVCQ APETPESYVC
RTLDCEAVYC WSCWDDMRQR CPVCTPREEL SSSAFSDSND DTAYAG
