CD1C_HUMAN
ID CD1C_HUMAN Reviewed; 333 AA.
AC P29017; Q5TDJ7; Q6IAS4; Q9UMM0; Q9UN96;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=T-cell surface glycoprotein CD1c;
DE AltName: CD_antigen=CD1c;
DE Flags: Precursor;
GN Name=CD1C;
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 [GENOMIC DNA].
RX PubMed=2447586; DOI=10.1073/pnas.84.24.9189;
RA Martin L.H., Calabi F., Lefebvre F.-A., Bilsland C.A.G., Milstein C.;
RT "Structure and expression of the human thymocyte antigens CD1a, CD1b, and
RT CD1c.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:9189-9193(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-300.
RX PubMed=2701945;
RA Aruffo A., Seed B.;
RT "Expression of cDNA clones encoding the thymocyte antigens CD1a, b, c
RT demonstrates a hierarchy of exclusion in fibroblasts.";
RL J. Immunol. 143:1723-1730(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 19-109.
RX PubMed=10488738; DOI=10.1034/j.1399-0039.1999.540202.x;
RA Han M., Hannick L.I., DiBrino M., Robinson M.A.;
RT "Polymorphism of human CD1 genes.";
RL Tissue Antigens 54:122-127(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 204-296.
RX PubMed=3097645; DOI=10.1073/pnas.83.23.9154;
RA Martin L.H., Calabi F., Milstein C.;
RT "Isolation of CD1 genes: a family of major histocompatibility complex-
RT related differentiation antigens.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:9154-9158(1986).
RN [8]
RP FUNCTION, INTERNALIZATION SIGNAL, AND SUBCELLULAR LOCATION.
RX PubMed=10899914; DOI=10.1084/jem.192.2.281;
RA Briken V., Jackman R.M., Watts G.F.M., Rogers R.A., Porcelli S.A.;
RT "Human CD1b and CD1c isoforms survey different intracellular compartments
RT for the presentation of microbial lipid antigens.";
RL J. Exp. Med. 192:281-288(2000).
RN [9]
RP FUNCTION.
RX PubMed=10786796; DOI=10.1038/35009119;
RA Moody D.B., Ulrichs T., Muehlecker W., Young D.C., Gurcha S.S., Grant E.,
RA Rosat J.-P., Brenner M.B., Costello C.E., Besra G.S., Porcelli S.A.;
RT "CD1c-mediated T-cell recognition of isoprenoid glycolipids in
RT Mycobacterium tuberculosis infection.";
RL Nature 404:884-888(2000).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10890914; DOI=10.1073/pnas.150236797;
RA Sugita M., van Der Wel N., Rogers R.A., Peters P.J., Brenner M.B.;
RT "CD1c molecules broadly survey the endocytic system.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8445-8450(2000).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-38 AND ASN-75.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 19-201 IN COMPLEX WITH
RP MANNOSYL-BETA1-PHOSPHOMYCOKETIDE, FUNCTION, SUBUNIT, DISULFIDE BOND, AND
RP GLYCOSYLATION AT ASN-38.
RX PubMed=21167756; DOI=10.1016/j.immuni.2010.11.026;
RA Scharf L., Li N.S., Hawk A.J., Garzon D., Zhang T., Fox L.M., Kazen A.R.,
RA Shah S., Haddadian E.J., Gumperz J.E., Saghatelian A., Faraldo-Gomez J.D.,
RA Meredith S.C., Piccirilli J.A., Adams E.J.;
RT "The 2.5 a structure of CD1c in complex with a mycobacterial lipid reveals
RT an open groove ideally suited for diverse antigen presentation.";
RL Immunity 33:853-862(2010).
CC -!- FUNCTION: Antigen-presenting protein that binds self and non-self lipid
CC and glycolipid antigens and presents them to T-cell receptors on
CC natural killer T-cells. {ECO:0000269|PubMed:10786796,
CC ECO:0000269|PubMed:10890914, ECO:0000269|PubMed:10899914,
CC ECO:0000269|PubMed:21167756}.
CC -!- SUBUNIT: Heterodimer with B2M (beta-2-microglobulin).
CC {ECO:0000269|PubMed:21167756}.
CC -!- INTERACTION:
CC P29017; Q9UBB4: ATXN10; NbExp=3; IntAct=EBI-2836704, EBI-702390;
CC P29017; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2836704, EBI-1055254;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10890914,
CC ECO:0000269|PubMed:10899914}; Single-pass type I membrane protein
CC {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:10890914,
CC ECO:0000269|PubMed:3097645}; Single-pass type I membrane protein.
CC Lysosome {ECO:0000269|PubMed:10890914}. Note=Subject to intracellular
CC trafficking between the cell membrane and endosomes.
CC {ECO:0000269|PubMed:10890914, ECO:0000269|PubMed:3097645}.
CC -!- TISSUE SPECIFICITY: Expressed on cortical thymocytes, on certain T-cell
CC leukemias, and in various other tissues.
CC -!- MISCELLANEOUS: During protein synthesis and maturation, CD1 family
CC members bind endogenous lipids that are replaced by lipid or glycolipid
CC antigens when the proteins are internalized and pass through endosomes
CC or lysosomes, before trafficking back to the cell surface.
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DR EMBL; M22178; AAA51942.1; -; Genomic_DNA.
DR EMBL; M22174; AAA51942.1; JOINED; Genomic_DNA.
DR EMBL; M22175; AAA51942.1; JOINED; Genomic_DNA.
DR EMBL; M22176; AAA51942.1; JOINED; Genomic_DNA.
DR EMBL; M22177; AAA51942.1; JOINED; Genomic_DNA.
DR EMBL; M28827; AAA51941.1; -; mRNA.
DR EMBL; CR457080; CAG33361.1; -; mRNA.
DR EMBL; AL121986; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC126465; AAI26466.1; -; mRNA.
DR EMBL; BC126467; AAI26468.1; -; mRNA.
DR EMBL; AF142667; AAD37580.1; -; Genomic_DNA.
DR EMBL; M14667; AAA51938.1; -; Genomic_DNA.
DR CCDS; CCDS1175.1; -.
DR PIR; C45801; HLHUCC.
DR RefSeq; NP_001756.2; NM_001765.2.
DR PDB; 3OV6; X-ray; 2.50 A; A=19-201.
DR PDB; 4ONO; X-ray; 2.70 A; A=24-201.
DR PDB; 5C9J; X-ray; 2.40 A; A=24-203.
DR PDB; 6C09; X-ray; 2.95 A; A=19-297.
DR PDB; 6C15; X-ray; 3.21 A; A=19-297.
DR PDBsum; 3OV6; -.
DR PDBsum; 4ONO; -.
DR PDBsum; 5C9J; -.
DR PDBsum; 6C09; -.
DR PDBsum; 6C15; -.
DR AlphaFoldDB; P29017; -.
DR SMR; P29017; -.
DR IntAct; P29017; 4.
DR STRING; 9606.ENSP00000357152; -.
DR GlyGen; P29017; 5 sites.
DR iPTMnet; P29017; -.
DR PhosphoSitePlus; P29017; -.
DR SwissPalm; P29017; -.
DR BioMuta; CD1C; -.
DR DMDM; 143811371; -.
DR jPOST; P29017; -.
DR MassIVE; P29017; -.
DR MaxQB; P29017; -.
DR PaxDb; P29017; -.
DR PeptideAtlas; P29017; -.
DR PRIDE; P29017; -.
DR ProteomicsDB; 54513; -.
DR Antibodypedia; 20454; 737 antibodies from 34 providers.
DR DNASU; 911; -.
DR Ensembl; ENST00000368170.8; ENSP00000357152.3; ENSG00000158481.13.
DR GeneID; 911; -.
DR KEGG; hsa:911; -.
DR MANE-Select; ENST00000368170.8; ENSP00000357152.3; NM_001765.3; NP_001756.2.
DR UCSC; uc001fru.4; human.
DR CTD; 911; -.
DR DisGeNET; 911; -.
DR GeneCards; CD1C; -.
DR HGNC; HGNC:1636; CD1C.
DR HPA; ENSG00000158481; Tissue enriched (lymphoid).
DR MIM; 188340; gene.
DR neXtProt; NX_P29017; -.
DR OpenTargets; ENSG00000158481; -.
DR PharmGKB; PA26195; -.
DR VEuPathDB; HostDB:ENSG00000158481; -.
DR eggNOG; ENOG502SJH6; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_047501_9_2_1; -.
DR InParanoid; P29017; -.
DR OMA; FVNQSWA; -.
DR OrthoDB; 827472at2759; -.
DR PhylomeDB; P29017; -.
DR TreeFam; TF336723; -.
DR PathwayCommons; P29017; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; P29017; -.
DR BioGRID-ORCS; 911; 8 hits in 1063 CRISPR screens.
DR ChiTaRS; CD1C; human.
DR EvolutionaryTrace; P29017; -.
DR GenomeRNAi; 911; -.
DR Pharos; P29017; Tbio.
DR PRO; PR:P29017; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P29017; protein.
DR Bgee; ENSG00000158481; Expressed in thymus and 139 other tissues.
DR ExpressionAtlas; P29017; baseline and differential.
DR Genevisible; P29017; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0030883; F:endogenous lipid antigen binding; IDA:UniProtKB.
DR GO; GO:0030884; F:exogenous lipid antigen binding; IDA:UniProtKB.
DR GO; GO:0051861; F:glycolipid binding; IDA:UniProtKB.
DR GO; GO:0071723; F:lipopeptide binding; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0048006; P:antigen processing and presentation, endogenous lipid antigen via MHC class Ib; IBA:GO_Central.
DR GO; GO:0048007; P:antigen processing and presentation, exogenous lipid antigen via MHC class Ib; IBA:GO_Central.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IBA:GO_Central.
DR GO; GO:0002286; P:T cell activation involved in immune response; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.500.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR011161; MHC_I-like_Ag-recog.
DR InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
DR InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR Pfam; PF07654; C1-set; 1.
DR Pfam; PF16497; MHC_I_3; 1.
DR SMART; SM00407; IGc1; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF54452; SSF54452; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; Endosome;
KW Glycoprotein; Immunity; Immunoglobulin domain; Lipid-binding; Lysosome;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..333
FT /note="T-cell surface glycoprotein CD1c"
FT /id="PRO_0000014580"
FT TOPO_DOM 18..302
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..333
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 206..296
FT /note="Ig-like"
FT MOTIF 329..332
FT /note="Internalization signal"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:21167756"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 120..185
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:21167756"
FT DISULFID 225..280
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VARIANT 70
FT /note="N -> T (in dbSNP:rs3138100)"
FT /id="VAR_031564"
FT VARIANT 300
FT /note="F -> S (in dbSNP:rs3138105)"
FT /evidence="ECO:0000269|PubMed:2701945"
FT /id="VAR_031565"
FT CONFLICT 290
FT /note="Q -> R (in Ref. 3; CAG33361)"
FT /evidence="ECO:0000305"
FT CONFLICT 327..333
FT /note="CSYQDIL -> W (in Ref. 1; AAA51942)"
FT /evidence="ECO:0000305"
FT STRAND 25..38
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 41..50
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 53..59
FT /evidence="ECO:0007829|PDB:5C9J"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:5C9J"
FT TURN 70..75
FT /evidence="ECO:0007829|PDB:5C9J"
FT HELIX 78..103
FT /evidence="ECO:0007829|PDB:5C9J"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 111..123
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:6C09"
FT STRAND 129..136
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:6C09"
FT HELIX 157..168
FT /evidence="ECO:0007829|PDB:5C9J"
FT HELIX 171..182
FT /evidence="ECO:0007829|PDB:5C9J"
FT HELIX 184..200
FT /evidence="ECO:0007829|PDB:5C9J"
FT STRAND 207..214
FT /evidence="ECO:0007829|PDB:6C09"
FT STRAND 221..233
FT /evidence="ECO:0007829|PDB:6C09"
FT STRAND 235..241
FT /evidence="ECO:0007829|PDB:6C09"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:6C09"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:6C09"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:3OV6"
FT STRAND 278..284
FT /evidence="ECO:0007829|PDB:6C09"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:6C09"
FT STRAND 292..295
FT /evidence="ECO:0007829|PDB:6C09"
SQ SEQUENCE 333 AA; 37654 MW; 8E4E057097E3E440 CRC64;
MLFLQFLLLA LLLPGGDNAD ASQEHVSFHV IQIFSFVNQS WARGQGSGWL DELQTHGWDS
ESGTIIFLHN WSKGNFSNEE LSDLELLFRF YLFGLTREIQ DHASQDYSKY PFEVQVKAGC
ELHSGKSPEG FFQVAFNGLD LLSFQNTTWV PSPGCGSLAQ SVCHLLNHQY EGVTETVYNL
IRSTCPRFLL GLLDAGKMYV HRQVRPEAWL SSRPSLGSGQ LLLVCHASGF YPKPVWVTWM
RNEQEQLGTK HGDILPNADG TWYLQVILEV ASEEPAGLSC RVRHSSLGGQ DIILYWGHHF
SMNWIALVVI VPLVILIVLV LWFKKHCSYQ DIL
