P08571 (CD14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Monocyte differentiation antigen CD14

Alternative name(s):
Myeloid cell-specific leucine-rich glycoprotein
CD_antigen=CD14

Cleaved into the following 2 chains:

1. Monocyte differentiation antigen CD14, urinary form
2. Monocyte differentiation antigen CD14, membrane-bound form

Gene names

Name:

CD14

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	375 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	In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the MD-2/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Up-regulates cell surface molecules, including adhesion molecules. Ref.15
Subunit structure	Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, MD-2 and TLR4.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor.
Tissue specificity	Expressed strongly on the surface of monocytes and weakly on the surface of granulocytes; also expressed by most tissue macrophages.
Post-translational modification	N- and O- glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan.
Sequence similarities	Contains 11 LRR (leucine-rich) repeats.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Leucine-rich repeat Repeat Signal
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB kinase/NF-kappaB cascade Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome apoptotic process Traceable author statement PubMed 9548256. Source: ProtInc cellular response to lipopolysaccharide Inferred from direct assay PubMed 12594207. Source: MGI cellular response to lipoteichoic acid Inferred from direct assay PubMed 12594207. Source: MGI inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome phagocytosis Traceable author statement PubMed 9548256. Source: ProtInc positive regulation of cytokine secretion Inferred from electronic annotation. Source: Compara positive regulation of endocytosis Inferred from electronic annotation. Source: Compara positive regulation of tumor necrosis factor production Inferred from direct assay PubMed 12594207. Source: MGI response to heat Inferred from electronic annotation. Source: Compara toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from electronic annotation. Source: Compara endosome membrane Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara membrane raft Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	lipopolysaccharide binding Inferred from direct assay PubMed 12594207. Source: MGI lipoteichoic acid binding Inferred from direct assay PubMed 12594207. Source: MGI opsonin receptor activity Traceable author statement PubMed 2402637. Source: BHF-UCL peptidoglycan receptor activity Traceable author statement PubMed 8798531. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19
	Chain	20 – 367	348	Monocyte differentiation antigen CD14, urinary form		PRO_0000020884
	Chain	20 – 345	326	Monocyte differentiation antigen CD14, membrane-bound form		PRO_0000020885
	Propeptide	346 – 375	30	Removed in mature form Potential		PRO_0000020886
Regions
	Repeat	54 – 82	29	LRR 1
	Repeat	83 – 118	36	LRR 2
	Repeat	119 – 144	26	LRR 3
	Repeat	145 – 172	28	LRR 4
	Repeat	173 – 196	24	LRR 5
	Repeat	197 – 224	28	LRR 6
	Repeat	225 – 251	27	LRR 7
	Repeat	252 – 278	27	LRR 8
	Repeat	279 – 299	21	LRR 9
	Repeat	300 – 321	22	LRR 10
	Repeat	322 – 349	28	LRR 11
	Region	42 – 89	48	Ligand-binding pocket rim
Amino acid modifications
	Lipidation	345	1	GPI-anchor amidated asparagine Potential
	Glycosylation	37	1	N-linked (GlcNAc...) Potential
	Glycosylation	151	1	N-linked (GlcNAc...) Ref.12
	Glycosylation	282	1	N-linked (GlcNAc...) Ref.12
	Glycosylation	323	1	N-linked (GlcNAc...) Ref.13
	Glycosylation	336	1	O-linked (GalNAc...) Ref.14
	Disulfide bond	25 ↔ 36		Ref.15
	Disulfide bond	34 ↔ 51		Ref.15
	Disulfide bond	187 ↔ 217		Ref.15
	Disulfide bond	241 ↔ 272		Ref.15
Natural variations
	Natural variant	204	1	N → D. Corresponds to variant rs2228049 [ dbSNP | Ensembl ].		VAR_024302
	Natural variant	341	1	E → K. Corresponds to variant rs11556179 [ dbSNP | Ensembl ].		VAR_050771
Experimental info
	Sequence conflict	187	1	C → Y in CAA29999. Ref.2
	Sequence conflict	303	1	D → E in AAC83816. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P08571 [UniParc]. Last modified March 27, 2002. Version 2. Checksum: 1746CDB41F394F8D	FASTA	375	40,076
	10 20 30 40 50 60 MERASCLLLL LLPLVHVSAT TPEPCELDDE DFRCVCNFSE PQPDWSEAFQ CVSAVEVEIH 70 80 90 100 110 120 AGGLNLEPFL KRVDADADPR QYADTVKALR VRRLTVGAAQ VPAQLLVGAL RVLAYSRLKE 130 140 150 160 170 180 LTLEDLKITG TMPPLPLEAT GLALSSLRLR NVSWATGRSW LAELQQWLKP GLKVLSIAQA 190 200 210 220 230 240 HSPAFSCEQV RAFPALTSLD LSDNPGLGER GLMAALCPHK FPAIQNLALR NTGMETPTGV 250 260 270 280 290 300 CAALAAAGVQ PHSLDLSHNS LRATVNPSAP RCMWSSALNS LNLSFAGLEQ VPKGLPAKLR 310 320 330 340 350 360 VLDLSCNRLN RAPQPDELPE VDNLTLDGNP FLVPGTALPH EGSMNSGVVP ACARSTLSVG 370 VSGTLVLLQG ARGFA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage." Haziot A., Chen S., Ferrero E., Low M.G., Silber R., Goyert S.M. J. Immunol. 141:547-552(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Nucleotide sequence of the gene encoding the monocyte differentiation antigen, CD14." Ferrero E., Goyert S.M. Nucleic Acids Res. 16:4173-4173(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lymphocyte.
[3]	"Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein) primary structure deduced from cDNA clones." Setoguchi M., Nasu N., Yoshida S., Higuchi Y., Akizuki S., Yamamoto S. Biochim. Biophys. Acta 1008:213-222(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Macrophage.
[4]	"Monocyte antigen CD14 is a phospholipid anchored membrane protein." Simmons D.L., Tan S., Tenen D.G., Nicholson-Weller A., Seed B. Blood 73:284-289(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Cloning and sequencing of human CD14 gene." Long J.Y., Xue Y.N., Sun L., Wang H.X. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 25:377-378(1998) Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Promyelocytic leukemia.
[6]	"Natural selection in the TLR-related genes in the course of primate evolution." Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A. Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	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].
[9]	"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: Brain.
[10]	"Expression and secretion of CD14 in glial neoplasms of the brain." Deininger M.H., Meyermann R., Schluesener H.J. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-125. Tissue: Glioblastoma.
[11]	"Structural relationship between the soluble and membrane-bound forms of human monocyte surface glycoprotein CD14." Bazil V., Baudys M., Hilgert I., Stefanova I., Low M.G., Zbrozek J., Horejsi V. Mol. Immunol. 26:657-662(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 362-367.
[12]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-151 AND ASN-282, MASS SPECTROMETRY. Tissue: Plasma.
[13]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-323, MASS SPECTROMETRY. Tissue: Liver.
[14]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-336, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[15]	"The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket." Kelley S.L., Lukk T., Nair S.K., Tapping R.I. J. Immunol. 190:1304-1311(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 26-335, DISULFIDE BONDS, FUNCTION.
+	Additional computationally mapped references.

Web resources

Wikipedia

CD14 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X06882 Genomic DNA. Translation: CAA29999.1.
X13334 mRNA. Translation: CAA31711.1.
M86511 mRNA. Translation: AAA51930.1.
AF097942 mRNA. Translation: AAC83816.1.
AB446505 mRNA. Translation: BAG55282.1.
BT007331 mRNA. Translation: AAP35995.1.
CH471062 Genomic DNA. Translation: EAW62037.1.
BC010507 mRNA. Translation: AAH10507.1.
AY044269 mRNA. Translation: AAL02401.1.

IPI

IPI00029260.

PIR

TDHUM4. A27637.

RefSeq

NP_000582.1. NM_000591.3.
NP_001035110.1. NM_001040021.2.
NP_001167575.1. NM_001174104.1.
NP_001167576.1. NM_001174105.1.

UniGene

Hs.163867.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4GLP	X-ray	4.00	A	26-335	[»]

ProteinModelPortal

P08571.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1030N.

IntAct

P08571. 6 interactions.

STRING

9606.ENSP00000304236.

PTM databases

PhosphoSite

P08571.

Polymorphism databases

DMDM

20141203.

Proteomic databases

PaxDb

P08571.

PeptideAtlas

P08571.

PRIDE

P08571.

Protocols and materials databases

DNASU

929.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000302014; ENSP00000304236; ENSG00000170458.
ENST00000401743; ENSP00000385519; ENSG00000170458.

GeneID

929.

KEGG

hsa:929.

UCSC

uc003lgi.2. human.

Organism-specific databases

CTD

929.

GeneCards

GC05M139991.

HGNC

HGNC:1628. CD14.

HPA

HPA001887.
HPA002127.

MIM

158120. gene.

neXtProt

NX_P08571.

PharmGKB

PA26188.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG86091.

HOGENOM

HOG000237268.

HOVERGEN

HBG005269.

InParanoid

P08571.

KO

K04391.

OMA

LCPHKFP.

OrthoDB

EOG4868CS.

PhylomeDB

P08571.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P08571.

Bgee

P08571.

CleanEx

HS_CD14.

Genevestigator

P08571.

GermOnline

ENSG00000170458. Homo sapiens.

Family and domain databases

InterPro

IPR001611. Leu-rich_rpt.
IPR016337. Monocyte_diff_Ag_CD14.
[Graphical view]

Pfam

PF00560. LRR_1. 1 hit.
[Graphical view]

PIRSF

PIRSF002017. CD14. 1 hit.

PROSITE

PS51450. LRR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

929.

NextBio

3850.

PMAP-CutDB

P08571.

SOURCE

Search...

Entry information

Entry name

CD14_HUMAN

Accession

Primary (citable) accession number: P08571
Secondary accession number(s): Q53XT5 , Q96FR6, Q96L99, Q9UNS3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	March 27, 2002
Last modified:	May 1, 2013
This is version 145 of the entry and version 2 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.