P15813 (CD1D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Antigen-presenting glycoprotein CD1d

Alternative name(s):
R3G1
CD_antigen=CD1d

Gene names

Name:

CD1D

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	335 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells. Ref.11
Subunit structure	Heterodimer with B2M (beta-2-microglobulin). Interacts with MHC II. Ref.9
Subcellular location	Cell membrane; Single-pass type I membrane protein. Endosome membrane. Lysosome membrane. Note: Subject to intracellular trafficking between the cell membrane, endosomes and lysosomes. Ref.8 Ref.9 Ref.11
Tissue specificity	Expressed on cortical thymocytes, on certain T-cell leukemias, and in various other tissues.
Miscellaneous	During protein synthesis and maturation, CD1 family members bind endogenous lipids that are replaced by lipid or glycolipid antigens when the proteins are internalized and pass through endosomes, before trafficking back to the cell surface By similarity.
Sequence similarities	Contains 1 Ig-like (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Host-virus interaction Immunity Innate immunity
Cellular component	Cell membrane Endosome Lysosome Membrane
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell selection Traceable author statement PubMed 14500461. Source: UniProtKB antigen processing and presentation, endogenous lipid antigen via MHC class Ib Inferred from direct assay PubMed 10523605. Source: UniProtKB detection of bacterium Traceable author statement PubMed 14500461. Source: UniProtKB heterotypic cell-cell adhesion Traceable author statement PubMed 19124746. Source: BHF-UCL innate immune response Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of T cell proliferation Inferred from direct assay PubMed 19124746. Source: BHF-UCL positive regulation of innate immune response Traceable author statement PubMed 14500461. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cell surface Inferred from direct assay PubMed 19124746. Source: BHF-UCL cytoplasm Inferred from direct assay PubMed 19124746. Source: BHF-UCL endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement PubMed 11315191. Source: UniProtKB lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	beta-2-microglobulin binding Traceable author statement PubMed 14500461. Source: UniProtKB eukaryotic cell surface binding Inferred from direct assay PubMed 19124746. Source: BHF-UCL exogenous lipid antigen binding Inferred from direct assay PubMed 10523605. Source: UniProtKB receptor activity Inferred by curator PubMed 11315191. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

By similarity

Chain

20 – 335

316

Antigen-presenting glycoprotein CD1d

PRO_0000014581

Regions

Topological domain

20 – 301

282

Extracellular Potential

Transmembrane

302 – 322

21

Helical; Potential

Topological domain

323 – 335

13

Cytoplasmic Potential

Domain

185 – 292

108

Ig-like

Motif

331 – 334

4

Internalization signal

Sites

Binding site

98

1

Glycolipid

Binding site

169

1

Glycolipid

Binding site

172

1

Glycolipid

Amino acid modifications

Glycosylation

38

1

N-linked (GlcNAc...) Ref.14

Glycosylation

60

1

N-linked (GlcNAc...) Ref.12 Ref.14

Glycosylation

126

1

N-linked (GlcNAc...) Potential

Glycosylation

181

1

N-linked (GlcNAc...) Potential

Disulfide bond

120 ↔ 184

Ref.13

Disulfide bond

224 ↔ 279

Ref.13

Natural variations

Natural variant

64

1

T → S. Ref.6

VAR_010211

Experimental info

Mutagenesis

331

1

Y → A: Strongly reduced internalization. Ref.8

Mutagenesis

334

1

V → A: Strongly reduced internalization. Ref.8

Secondary structure

1

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335

Helix Strand Turn

Details...

Beta strand

28 – 38

11

Beta strand

41 – 50

10

Beta strand

53 – 58

6

Beta strand

63 – 67

5

Turn

70 – 75

6

Helix

78 – 105

28

Beta strand

112 – 122

11

Beta strand

124 – 126

3

Beta strand

128 – 136

9

Beta strand

139 – 145

7

Beta strand

148 – 151

4

Helix

158 – 166

9

Helix

170 – 181

12

Helix

183 – 194

12

Helix

196 – 199

4

Beta strand

206 – 211

6

Beta strand

216 – 232

17

Beta strand

235 – 240

6

Beta strand

241 – 243

3

Beta strand

248 – 250

3

Turn

257 – 259

3

Beta strand

261 – 272

12

Beta strand

278 – 282

5

Turn

284 – 287

4

Beta strand

291 – 294

4

Sequences

	Sequence		Length	Mass (Da)
	P15813 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: EA041C1C45A5777F	FASTA	335	37,717
	10 20 30 40 50 60 MGCLLFLLLW ALLQAWGSAE VPQRLFPLRC LQISSFANSS WTRTDGLAWL GELQTHSWSN 70 80 90 100 110 120 DSDTVRSLKP WSQGTFSDQQ WETLQHIFRV YRSSFTRDVK EFAKMLRLSY PLELQVSAGC 130 140 150 160 170 180 EVHPGNASNN FFHVAFQGKD ILSFQGTSWE PTQEAPLWVN LAIQVLNQDK WTRETVQWLL 190 200 210 220 230 240 NGTCPQFVSG LLESGKSELK KQVKPKAWLS RGPSPGPGRL LLVCHVSGFY PKPVWVKWMR 250 260 270 280 290 300 GEQEQQGTQP GDILPNADET WYLRATLDVV AGEAAGLSCR VKHSSLEGQD IVLYWGGSYT 310 320 330 SMGLIALAVL ACLLFLLIVG FTSRFKRQTS YQGVL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two classes of CD1 genes." Calabi F., Jarvis J.M., Martin L., Milstein C. Eur. J. Immunol. 19:285-292(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Isolation and characterization of a cDNA and gene coding for a fourth CD1 molecule." Balk S.P., Bleicher P.A., Terhorst C. Proc. Natl. Acad. Sci. U.S.A. 86:252-256(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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]. Tissue: Pancreas.
[6]	"Polymorphism of human CD1 genes." Han M., Hannick L.I., DiBrino M., Robinson M.A. Tissue Antigens 54:122-127(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 19-109, VARIANT SER-64.
[7]	"Isolation of CD1 genes: a family of major histocompatibility complex-related differentiation antigens." Martin L.H., Calabi F., Milstein C. Proc. Natl. Acad. Sci. U.S.A. 83:9154-9158(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 203-295.
[8]	"A critical tyrosine residue in the cytoplasmic tail is important for CD1d internalization but not for its basolateral sorting in MDCK cells." Rodionov D.G., Nordeng T.W., Pedersen K., Balk S.P., Bakke O. J. Immunol. 162:1488-1495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-331 AND VAL-334.
[9]	"Regulation of intracellular trafficking of human CD1d by association with MHC class II molecules." Kang S.-J., Cresswell P. EMBO J. 21:1650-1660(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH B2M AND MHC II.
[10]	"CD1d ligands: the good, the bad, and the ugly." Brutkiewicz R.R. J. Immunol. 177:769-775(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[11]	"Distinct endosomal trafficking requirements for presentation of autoantigens and exogenous lipids by human CD1d molecules." Chen X., Wang X., Keaton J.M., Reddington F., Illarionov P.A., Besra G.S., Gumperz J.E. J. Immunol. 178:6181-6190(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-60, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"The crystal structure of human CD1d with and without alpha-galactosylceramide." Koch M., Stronge V.S., Shepherd D., Gadola S.D., Mathew B., Ritter G., Fersht A.R., Besra G.S., Schmidt R.R., Jones E.Y., Cerundolo V. Nat. Immunol. 6:819-826(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 19-299 IN COMPLEX WITH B2M AND GALACTOSYLCERAMIDE, DISULFIDE BONDS.
[14]	"CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor." Borg N.A., Wun K.S., Kjer-Nielsen L., Wilce M.C.J., Pellicci D.G., Koh R., Besra G.S., Bharadwaj M., Godfrey D.I., McCluskey J., Rossjohn J. Nature 448:44-49(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 24-295 IN COMPLEX WITH B2M AND T-CELL RECEPTOR, GLYCOSYLATION AT ASN-38 AND ASN-60.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L38820 , L38815, L38817, L38816, L38818, L38819 Genomic DNA. Translation: AAA59672.1.
X14974 Genomic DNA. Translation: CAA33099.1.
J04142 mRNA. Translation: AAA59673.1.
AL138899 Genomic DNA. Translation: CAH73515.1.
CH471121 Genomic DNA. Translation: EAW52847.1.
CH471121 Genomic DNA. Translation: EAW52848.1.
CH471121 Genomic DNA. Translation: EAW52849.1.
BC027926 mRNA. Translation: AAH27926.1.
AF142668 Genomic DNA. Translation: AAD37581.1.
M14664 Genomic DNA. Translation: AAA51935.1.

IPI

IPI00013435.

PIR

HLHUR3. S07715.

RefSeq

NP_001757.1. NM_001766.3.

UniGene

Hs.1799.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZT4	X-ray	3.00	A/C	19-299	[»]
2PO6	X-ray	3.20	A/E	24-295	[»]
3HUJ	X-ray	2.50	A/C	21-295	[»]
3SDX	X-ray	3.12	A/C	24-295	[»]
3TZV	X-ray	3.06	C	21-295	[»]
3U0P	X-ray	2.80	A/C/E	21-295	[»]
3VWJ	X-ray	3.09	A	21-295	[»]
3VWK	X-ray	2.94	A	21-295	[»]
4EN3	X-ray	2.57	C	21-295	[»]

ProteinModelPortal

P15813.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000357153.

PTM databases

PhosphoSite

P15813.

Polymorphism databases

DMDM

115964.

Proteomic databases

PaxDb

P15813.

PRIDE

P15813.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368171; ENSP00000357153; ENSG00000158473.

GeneID

912.

KEGG

hsa:912.

UCSC

uc001frr.3. human.

Organism-specific databases

CTD

912.

GeneCards

GC01P158149.

HGNC

HGNC:1637. CD1D.

HPA

CAB016107.

MIM

188410. gene.

neXtProt

NX_P15813.

PharmGKB

PA26196.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG26626.

HOGENOM

HOG000111666.

HOVERGEN

HBG004453.

InParanoid

P15813.

KO

K06448.

OMA

LNDTCPQ.

OrthoDB

EOG40ZQZZ.

PhylomeDB

P15813.

Gene expression databases

Bgee

P15813.

CleanEx

HS_CD1D.

Genevestigator

P15813.

GermOnline

ENSG00000158473. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.
3.30.500.10. 1 hit.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003597. Ig_C1-set.
IPR011161. MHC_I-like_Ag-recog.
IPR011162. MHC_I/II-like_Ag-recog.
[Graphical view]

Pfam

PF07654. C1-set. 1 hit.
[Graphical view]

SMART

SM00407. IGc1. 1 hit.
[Graphical view]

SUPFAM

SSF54452. MHC_I/II-like_Ag-recog. 1 hit.

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1649053.

EvolutionaryTrace

P15813.

GenomeRNAi

912.

NextBio

3762.

SOURCE

Search...

Entry information

Entry name

CD1D_HUMAN

Accession

Primary (citable) accession number: P15813
Secondary accession number(s): D3DVD5 , Q5W0J3, Q9UMM3, Q9Y5M4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	May 1, 2013
This is version 136 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.