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CD68_MOUSE
ID   CD68_MOUSE              Reviewed;         326 AA.
AC   P31996; O54688; O70321; Q3S4A9; Q5F2A8; Q9DD15;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   03-AUG-2022, entry version 152.
DE   RecName: Full=Macrosialin;
DE   AltName: CD_antigen=CD68;
DE   Flags: Precursor;
GN   Name=Cd68;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC   STRAIN=BALB/cJ; TISSUE=Macrophage;
RX   PubMed=8486654; DOI=10.1016/s0021-9258(18)98400-0;
RA   Holness C.L., da Silva R.P., Fawcett J., Gordon S., Simmons D.L.;
RT   "Macrosialin, a mouse macrophage-restricted glycoprotein, is a member of
RT   the lamp/lgp family.";
RL   J. Biol. Chem. 268:9661-9666(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/SvJ;
RX   PubMed=9653646; DOI=10.1006/geno.1998.5327;
RA   Jiang Z., Shih D.M., Xia Y.R., Lusis A.J., de Beer F.C.,
RA   de Villiers W.J.S., van der Westhuyzen D.R., de Beer M.C.;
RT   "Structure, organization, and chromosomal mapping of the gene encoding
RT   macrosialin, a macrophage-restricted protein.";
RL   Genomics 50:199-205(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/Sv;
RX   PubMed=9806844; DOI=10.1006/geno.1998.5546;
RA   Greaves D.R., Quinn C.M., Seldin M.F., Gordon S.;
RT   "Functional comparison of the murine macrosialin and human CD68 promoters
RT   in macrophage and nonmacrophage cell lines.";
RL   Genomics 54:165-168(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9479000; DOI=10.1074/jbc.273.9.5389;
RA   Li A.C., Guidez F.R.B., Collier J.G., Glass C.K.;
RT   "The macrosialin promoter directs high levels of transcriptional activity
RT   in macrophages dependent on combinatorial interactions between PU.1 and c-
RT   Jun.";
RL   J. Biol. Chem. 273:5389-5399(1998).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129;
RX   PubMed=10524236; DOI=10.1016/s0378-1119(99)00301-7;
RA   Miyashita A., Shimizu N., Endo N., Hanyuu T., Ishii N., Ito K., Itoh Y.,
RA   Shirai M., Nakajima T., Odani S., Kuwano R.;
RT   "Five different genes, Eif4a1, Cd68, Supl15h, Sox15 and Fxr2h, are
RT   clustered in a 40 kb region of mouse chromosome 11.";
RL   Gene 237:53-60(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Dendritic cell, and Kidney;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
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   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 33-203 (ISOFORMS LONG/SHORT).
RC   STRAIN=129/Sv; TISSUE=Brain;
RX   PubMed=16521125; DOI=10.1002/jnr.20798;
RA   Denny C.A., Kasperzyk J.L., Gorham K.N., Bronson R.T., Seyfried T.N.;
RT   "Influence of caloric restriction on motor behavior, longevity, and brain
RT   lipid composition in Sandhoff disease mice.";
RL   J. Neurosci. Res. 83:1028-1038(2006).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Could play a role in phagocytic activities of tissue
CC       macrophages, both in intracellular lysosomal metabolism and
CC       extracellular cell-cell and cell-pathogen interactions. Binds to
CC       tissue- and organ-specific lectins or selectins, allowing homing of
CC       macrophage subsets to particular sites. Rapid recirculation of CD68
CC       from endosomes and lysosomes to the plasma membrane may allow
CC       macrophages to crawl over selectin-bearing substrates or other cells.
CC   -!- SUBCELLULAR LOCATION: [Isoform Long]: Endosome membrane; Single-pass
CC       type I membrane protein. Lysosome membrane; Single-pass type I membrane
CC       protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform Short]: Cell membrane; Single-pass type
CC       I membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long;
CC         IsoId=P31996-1; Sequence=Displayed;
CC       Name=Short;
CC         IsoId=P31996-2; Sequence=VSP_003043;
CC   -!- TISSUE SPECIFICITY: Expressed in tissue macrophages and to a lesser
CC       extent in dendritic cells.
CC   -!- PTM: N- and O-glycosylated.
CC   -!- SIMILARITY: Belongs to the LAMP family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00740}.
CC   -!- CAUTION: CD68 is a commonly used marker for macrophages. However, a
CC       number of studies in human have shown that CD68 antibodies react with
CC       other hematopoietic and non-hematopoietic cell types, suggesting that
CC       CD68 may not be a macrophage-specific antigen. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA23738.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; X68273; CAA48334.1; -; mRNA.
DR   EMBL; AF022651; AAC40151.1; -; Genomic_DNA.
DR   EMBL; AF045554; AAC15685.1; -; Genomic_DNA.
DR   EMBL; AF039399; AAC40056.1; -; Genomic_DNA.
DR   EMBL; AB009287; BAA23738.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AK002264; BAB21975.1; -; mRNA.
DR   EMBL; AK170443; BAE41801.1; -; mRNA.
DR   EMBL; AL603707; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC021637; AAH21637.1; -; mRNA.
DR   EMBL; DQ167574; ABA02181.1; -; mRNA.
DR   CCDS; CCDS70216.1; -. [P31996-1]
DR   PIR; A46676; A46676.
DR   RefSeq; NP_001277987.1; NM_001291058.1. [P31996-1]
DR   AlphaFoldDB; P31996; -.
DR   SMR; P31996; -.
DR   BioGRID; 198607; 1.
DR   STRING; 10090.ENSMUSP00000104294; -.
DR   GlyGen; P31996; 9 sites.
DR   iPTMnet; P31996; -.
DR   PhosphoSitePlus; P31996; -.
DR   SwissPalm; P31996; -.
DR   MaxQB; P31996; -.
DR   PaxDb; P31996; -.
DR   PeptideAtlas; P31996; -.
DR   PRIDE; P31996; -.
DR   ProteomicsDB; 283750; -. [P31996-1]
DR   ProteomicsDB; 283751; -. [P31996-2]
DR   ABCD; P31996; 2 sequenced antibodies.
DR   DNASU; 12514; -.
DR   Ensembl; ENSMUST00000018918; ENSMUSP00000018918; ENSMUSG00000018774. [P31996-1]
DR   GeneID; 12514; -.
DR   KEGG; mmu:12514; -.
DR   UCSC; uc007jqy.2; mouse. [P31996-1]
DR   CTD; 968; -.
DR   MGI; MGI:88342; Cd68.
DR   VEuPathDB; HostDB:ENSMUSG00000018774; -.
DR   eggNOG; KOG4818; Eukaryota.
DR   GeneTree; ENSGT00940000164775; -.
DR   HOGENOM; CLU_071610_0_0_1; -.
DR   InParanoid; P31996; -.
DR   OrthoDB; 1321296at2759; -.
DR   PhylomeDB; P31996; -.
DR   TreeFam; TF316339; -.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   BioGRID-ORCS; 12514; 5 hits in 74 CRISPR screens.
DR   PRO; PR:P31996; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P31996; protein.
DR   Bgee; ENSMUSG00000018774; Expressed in stroma of bone marrow and 176 other tissues.
DR   ExpressionAtlas; P31996; baseline and differential.
DR   Genevisible; P31996; MM.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0031902; C:late endosome membrane; IBA:GO_Central.
DR   GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR   GO; GO:0005764; C:lysosome; IDA:ARUK-UCL.
DR   GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR   GO; GO:0007568; P:aging; IEP:ARUK-UCL.
DR   GO; GO:0035425; P:autocrine signaling; ISO:MGI.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:ARUK-UCL.
DR   GO; GO:0031669; P:cellular response to nutrient levels; IDA:ARUK-UCL.
DR   GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR   GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; IDA:ARUK-UCL.
DR   GO; GO:0072594; P:establishment of protein localization to organelle; IBA:GO_Central.
DR   GO; GO:0002437; P:inflammatory response to antigenic stimulus; IDA:ARUK-UCL.
DR   GO; GO:0002605; P:negative regulation of dendritic cell antigen processing and presentation; IMP:ARUK-UCL.
DR   InterPro; IPR018134; LAMP_CS.
DR   InterPro; IPR002000; Lysosome-assoc_membr_glycop.
DR   PANTHER; PTHR11506; PTHR11506; 1.
DR   Pfam; PF01299; Lamp; 1.
DR   PRINTS; PR00336; LYSASSOCTDMP.
DR   PROSITE; PS00311; LAMP_2; 1.
DR   PROSITE; PS51407; LAMP_3; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Disulfide bond; Endosome;
KW   Glycoprotein; Lysosome; Membrane; Reference proteome; Repeat; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..326
FT                   /note="Macrosialin"
FT                   /id="PRO_0000017103"
FT   TOPO_DOM        21..291
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        292..316
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   TOPO_DOM        317..326
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   REPEAT          44..49
FT                   /note="1-1"
FT   REPEAT          50..64
FT                   /note="2-1"
FT   REPEAT          65..72
FT                   /note="1-2"
FT   REPEAT          73..88
FT                   /note="2-2"
FT   REGION          21..109
FT                   /note="Mucin-like"
FT   REGION          38..129
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        38..107
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        108..122
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        60
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        84
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        97
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        169
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        218
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        233
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        251
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        139..177
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   DISULFID        249..286
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   VAR_SEQ         319..326
FT                   /note="Missing (in isoform Short)"
FT                   /evidence="ECO:0000303|PubMed:8486654"
FT                   /id="VSP_003043"
FT   CONFLICT        117
FT                   /note="P -> T (in Ref. 3; AAC15685)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        129
FT                   /note="N -> K (in Ref. 6; BAB21975)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        137
FT                   /note="Q -> H (in Ref. 3; AAC15685)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        205
FT                   /note="P -> T (in Ref. 6; BAB21975)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   326 AA;  34818 MW;  AB7203A9A7EA47BA CRC64;
     MRLPVCLILL GPLIAQGTEE DCPHKKAVTL LPSFTMTPTA TESTASPTTS HRPTTTSHGN
     VTVHTSSGPT TVTHNPATTT SHGNATISHA TVSPTTNGTA TSPRSSTVGP HPGPPPPSPS
     PRSKGALGNY TWANGSQPCV QLQAQIQIRI LYPIQGGRKA WGISVLNPNK TKVQGGCDGT
     HPHLSLSFPY GQLTFGFKQD LHQSPSTVYL DYMAVEYNVS FPQAAQWTFM AQNSSLRELQ
     APLGQSFCCG NASIVLSPAV HLDLLSLRLQ AAQLPDKGHF GPCFSCNRDQ SLLLPLIIGL
     VLLGLLTLVL IAFCITRRRQ STYQPL
 
 
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