P34810 (CD68_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Macrosialin

Alternative name(s):
Gp110
CD_antigen=CD68

Gene names

Name:

CD68

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	354 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	Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular sites. Rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane may allow macrophages to crawl over selectin-bearing substrates or other cells.
Subcellular location	Isoform Short: Cell membrane; Single-pass type I membrane protein. Isoform Long: Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein.
Tissue specificity	Highly expressed by blood monocytes and tissue macrophages. Also expressed in lymphocytes, fibroblasts and endothelial cells. Expressed in many tumor cell lines which could allow them to attach to selectins on vascular endothelium, facilitating their dissemination to secondary sites. Ref.11
Post-translational modification	N- and O-glycosylated.
Sequence similarities	Belongs to the LAMP family.
Caution	CD68 is a commonly used marker for macrophages. However, a number of studies (Ref.8, Ref.9 and Ref.11) have shown that CD68 antibodies react with other hematopoietic and non-hematopoietic cell types, suggesting that CD68 may not be a macrophage-specific antigen.

Ontologies

Keywords
Cellular component	Cell membrane Endosome Lysosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to organic substance Inferred from electronic annotation. Source: Compara
Cellular_component	endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Traceable author statement Ref.1. Source: ProtInc lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P34810-1)

Also known as: CD68.1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P34810-2)

Also known as: CD68.2;

The sequence of this isoform differs from the canonical sequence as follows:
     17-43: Missing.
     83-112: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 354	333	Macrosialin		PRO_0000017102
Regions
	Topological domain	22 – 319	298	Extracellular Potential
	Transmembrane	320 – 344	25	Helical; Potential
	Topological domain	345 – 354	10	Cytoplasmic Potential
	Repeat	70 – 99	30	1
	Repeat	100 – 129	30	2
	Region	23 – 140	118	Mucin-like
	Region	70 – 129	60	2 X 30 AA tandem repeats
	Compositional bias	140 – 152	13	Pro-rich (hinge)
Amino acid modifications
	Glycosylation	88	1	N-linked (GlcNAc...) Potential
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	118	1	N-linked (GlcNAc...) Potential
	Glycosylation	126	1	N-linked (GlcNAc...) Potential
	Glycosylation	164	1	N-linked (GlcNAc...) Potential
	Glycosylation	199	1	N-linked (GlcNAc...) Ref.12
	Glycosylation	246	1	N-linked (GlcNAc...) Potential
	Glycosylation	261	1	N-linked (GlcNAc...) Ref.10 Ref.12
	Glycosylation	279	1	N-linked (GlcNAc...) Ref.12
	Disulfide bond	169 ↔ 207		By similarity
	Disulfide bond	277 ↔ 314		By similarity
Natural variations
	Alternative sequence	17 – 43	27	Missing in isoform Short.		VSP_003041
	Alternative sequence	83 – 112	30	Missing in isoform Short.		VSP_003042
	Natural variant	254	1	Q → K. Ref.1 Corresponds to variant rs25679 [ dbSNP | Ensembl ].		VAR_016144
	Natural variant	329	1	I → T. Corresponds to variant rs35452170 [ dbSNP | Ensembl ].		VAR_049725
	Natural variant	340	1	A → T. Corresponds to variant rs17607 [ dbSNP | Ensembl ].		VAR_016145
	Natural variant	350	1	A → T. Corresponds to variant rs9901675 [ dbSNP | Ensembl ].		VAR_049726
Experimental info
	Sequence conflict	95	1	S → G in BAD96234. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long (CD68.1) [UniParc]. Last modified May 15, 2007. Version 2. Checksum: 69E68D69EDE8EFB0	FASTA	354	37,408
	10 20 30 40 50 60 MRLAVLFSGA LLGLLAAQGT GNDCPHKKSA TLLPSFTVTP TVTESTGTTS HRTTKSHKTT 70 80 90 100 110 120 THRTTTTGTT SHGPTTATHN PTTTSHGNVT VHPTSNSTAT SQGPSTATHS PATTSHGNAT 130 140 150 160 170 180 VHPTSNSTAT SPGFTSSAHP EPPPPSPSPS PTSKETIGDY TWTNGSQPCV HLQAQIQIRV 190 200 210 220 230 240 MYTTQGGGEA WGISVLNPNK TKVQGSCEGA HPHLLLSFPY GHLSFGFMQD LQQKVVYLSY 250 260 270 280 290 300 MAVEYNVSFP HAAQWTFSAQ NASLRDLQAP LGQSFSCSNS SIILSPAVHL DLLSLRLQAA 310 320 330 340 350 QLPHTGVFGQ SFSCPSDRSI LLPLIIGLIL LGLLALVLIA FCIIRRRPSA YQAL
	Isoform Short (CD68.2) [UniParc]. Checksum: B0A78BF5F01BC0B0	FASTA	297	31,738
	10 20 30 40 50 60 MRLAVLFSGA LLGLLAESTG TTSHRTTKSH KTTTHRTTTT GTTSHGPTTA THNPTTTSHG 70 80 90 100 110 120 NATVHPTSNS TATSPGFTSS AHPEPPPPSP SPSPTSKETI GDYTWTNGSQ PCVHLQAQIQ 130 140 150 160 170 180 IRVMYTTQGG GEAWGISVLN PNKTKVQGSC EGAHPHLLLS FPYGHLSFGF MQDLQQKVVY 190 200 210 220 230 240 LSYMAVEYNV SFPHAAQWTF SAQNASLRDL QAPLGQSFSC SNSSIILSPA VHLDLLSLRL 250 260 270 280 290 QAAQLPHTGV FGQSFSCPSD RSILLPLIIG LILLGLLALV LIAFCIIRRR PSAYQAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins." Holness C.L., Simmons D.L. Blood 81:1607-1613(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), VARIANT LYS-254.
[2]	"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 (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Umbilical cord blood.
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Adipose tissue.
[5]	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].
[6]	"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] (ISOFORM LONG). Tissue: Skin.
[7]	"The linked human elongation initiation factor 4A1 (EIF4A1) and CD68 genes map to chromosome 17p13." Jones E., Quinn C.M., See C.G., Montgomery D.S., Ford M.J., Koelble K., Gordon S., Greaves D.R. Genomics 53:248-250(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[8]	"Macrophage specificity of three anti-CD68 monoclonal antibodies (KP1, EBM11, and PGM1) widely used for immunohistochemistry and flow cytometry." Kunisch E., Fuhrmann R., Roth A., Winter R., Lungershausen W., Kinne R.W. Ann. Rheum. Dis. 63:774-784(2004) [PubMed] [Europe PMC] [Abstract] Cited for: USE AS A MACROPHAGE MARKER.
[9]	"CD68 is not a macrophage-specific antigen." Beranek J.T. Ann. Rheum. Dis. 64:342-343(2005) [PubMed] [Europe PMC] [Abstract] Cited for: USE AS A MACROPHAGE MARKER.
[10]	"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach." Lewandrowski U., Moebius J., Walter U., Sickmann A. Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-261, MASS SPECTROMETRY. Tissue: Platelet.
[11]	"Expression of CD68 in non-myeloid cell types." Gottfried E., Kunz-Schughart L.A., Weber A., Rehli M., Peuker A., Muller A., Kastenberger M., Brockhoff G., Andreesen R., Kreutz M. Scand. J. Immunol. 67:453-463(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"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-199; ASN-261 AND ASN-279, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S57235 mRNA. Translation: AAB25811.1. BT009923 mRNA. Translation: AAP88925.1. AK290238 mRNA. Translation: BAF82927.1. AK222492 mRNA. Translation: BAD96212.1. AK222514 mRNA. Translation: BAD96234.1. CH471108 Genomic DNA. Translation: EAW90165.1. BC015557 mRNA. Translation: AAH15557.1. AF060540 Genomic DNA. Translation: AAC70006.1.
IPI	IPI00002252. IPI00217167.
PIR	A48931.
RefSeq	NP_001035148.1. NM_001040059.1. NP_001242.2. NM_001251.2.
UniGene	Hs.647419.
3D structure databases
ProteinModelPortal	P34810.
SMR	P34810. Positions 156-316.
ModBase	Search...
Protein-protein interaction databases
IntAct	P34810. 2 interactions.
MINT	MINT-4824093.
STRING	9606.ENSP00000250092.
PTM databases
PhosphoSite	P34810.
Polymorphism databases
DMDM	147744552.
Proteomic databases
PaxDb	P34810.
PRIDE	P34810.
Protocols and materials databases
DNASU	968.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000250092; ENSP00000250092; ENSG00000129226.
GeneID	968.
KEGG	hsa:968.
UCSC	uc002ghv.3. human.
Organism-specific databases
CTD	968.
GeneCards	GC17P007482.
HGNC	HGNC:1693. CD68.
HPA	CAB000051. CAB000066. HPA048982.
MIM	153634. gene.
neXtProt	NX_P34810.
PharmGKB	PA26232.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG244352.
HOGENOM	HOG000070034.
HOVERGEN	HBG005287.
InParanoid	P34810.
KO	K06501.
OMA	GNDCPHK.
OrthoDB	EOG4RFKTR.
PhylomeDB	P34810.
Gene expression databases
ArrayExpress	P34810.
Bgee	P34810.
CleanEx	HS_CD68.
Genevestigator	P34810.
Family and domain databases
InterPro	IPR018134. LAMP_CS. IPR002000. Lysosome-assoc_membr_glycop. [Graphical view]
PANTHER	PTHR11506. PTHR11506. 1 hit.
Pfam	PF01299. Lamp. 1 hit. [Graphical view]
PRINTS	PR00336. LYSASSOCTDMP.
PROSITE	PS00311. LAMP_2. 1 hit. PS51407. LAMP_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CD68. human.
GenomeRNAi	968.
NextBio	4050.
SOURCE	Search...

Entry information

Entry name

CD68_HUMAN

Accession

Primary (citable) accession number: P34810
Secondary accession number(s): Q53HR6, Q53XI3, Q96BI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	May 15, 2007
Last modified:	May 1, 2013
This is version 120 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.