DOCK8_MOUSE
ID DOCK8_MOUSE Reviewed; 2100 AA.
AC Q8C147; Q6KAM7; Q6PIS0; Q7TMQ5; Q8CAP6; Q8K105; Q9DBQ2;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 4.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Dedicator of cytokinesis protein 8;
GN Name=Dock8;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1581-2100 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Lung, Skin, and Thymus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 967-2100 (ISOFORM 1).
RC STRAIN=C57BL/6J, FVB/N, and FVB/N-3; 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 992-2100 (ISOFORM 1).
RC STRAIN=ICR; TISSUE=Embryonic tail;
RX PubMed=15449545; DOI=10.1093/dnares/11.2.127;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of FLJ genes: the
RT complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified
RT by screening of terminal sequences of cDNA clones randomly sampled from
RT size-fractionated libraries.";
RL DNA Res. 11:127-135(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-905 AND SER-1244, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and 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).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND POLYMORPHISM.
RX PubMed=25713392; DOI=10.1073/pnas.1501554112;
RA Krishnaswamy J.K., Singh A., Gowthaman U., Wu R., Gorrepati P.,
RA Sales Nascimento M., Gallman A., Liu D., Rhebergen A.M., Calabro S., Xu L.,
RA Ranney P., Srivastava A., Ranson M., Gorham J.D., McCaw Z.,
RA Kleeberger S.R., Heinz L.X., Mueller A.C., Bennett K.L., Superti-Furga G.,
RA Henao-Mejia J., Sutterwala F.S., Williams A., Flavell R.A.,
RA Eisenbarth S.C.;
RT "Coincidental loss of DOCK8 function in NLRP10-deficient and C3H/HeJ mice
RT results in defective dendritic cell migration.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:3056-3061(2015).
RN [8]
RP FUNCTION, INTERACTION WITH LRCH1, TISSUE SPECIFICITY, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND MUTAGENESIS OF SER-1827.
RX PubMed=28028151; DOI=10.1084/jem.20160068;
RA Xu X., Han L., Zhao G., Xue S., Gao Y., Xiao J., Zhang S., Chen P.,
RA Wu Z.Y., Ding J., Hu R., Wei B., Wang H.;
RT "LRCH1 interferes with DOCK8-Cdc42-induced T cell migration and ameliorates
RT experimental autoimmune encephalomyelitis.";
RL J. Exp. Med. 214:209-226(2017).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 1787-2067 IN COMPLEX WITH HUMAN
RP CDC42, FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=22461490; DOI=10.1182/blood-2012-01-407098;
RA Harada Y., Tanaka Y., Terasawa M., Pieczyk M., Habiro K., Katakai T.,
RA Hanawa-Suetsugu K., Kukimoto-Niino M., Nishizaki T., Shirouzu M., Duan X.,
RA Uruno T., Nishikimi A., Sanematsu F., Yokoyama S., Stein J.V., Kinashi T.,
RA Fukui Y.;
RT "DOCK8 is a Cdc42 activator critical for interstitial dendritic cell
RT migration during immune responses.";
RL Blood 119:4451-4461(2012).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) which specifically
CC activates small GTPase CDC42 by exchanging bound GDP for free GTP
CC (PubMed:28028151, PubMed:22461490). During immune responses, required
CC for interstitial dendritic cell (DC) migration by locally activating
CC CDC42 at the leading edge membrane of DC (PubMed:22461490,
CC PubMed:25713392). Required for CD4(+) T-cell migration in response to
CC chemokine stimulation by promoting CDC42 activation at T cell leading
CC edge membrane (PubMed:28028151). Is involved in NK cell cytotoxicity
CC controlling polarization of microtubule-organizing center (MTOC), and
CC possibly regulating CCDC88B-mediated lytic granule transport to MTOC
CC during cell killing (By similarity). {ECO:0000250|UniProtKB:Q8NF50,
CC ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:25713392,
CC ECO:0000269|PubMed:28028151}.
CC -!- SUBUNIT: Interacts (via DOCKER domain) with GTPase CDC42; the
CC interaction activates CDC42 by exchanging GDP for GTP
CC (PubMed:22461490). The unphosphorylated form interacts (via DOCKER
CC domain) with LRCH1 (via LRR repeats); the interaction prevents the
CC association between DOCK8 and CDC42 (PubMed:28028151). Interacts with
CC CCDC88B (By similarity). {ECO:0000250|UniProtKB:Q8NF50,
CC ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:28028151}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8NF50}. Cell
CC membrane {ECO:0000269|PubMed:22461490}; Peripheral membrane protein
CC {ECO:0000305|PubMed:22461490}; Cytoplasmic side {ECO:0000305}. Cell
CC projection, lamellipodium membrane {ECO:0000305|PubMed:22461490};
CC Peripheral membrane protein {ECO:0000305|PubMed:22461490}; Cytoplasmic
CC side {ECO:0000305}. Note=Enriched and co-localizes with GTPase CDC42 at
CC the immunological synapse formed during T cell/antigen presenting cell
CC cognate interaction. Translocates from the cytoplasm to the plasma
CC membrane in response to chemokine CXCL12/SDF-1-alpha stimulation.
CC {ECO:0000250|UniProtKB:Q8NF50}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C147-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C147-2; Sequence=VSP_027374, VSP_027375, VSP_027376;
CC -!- TISSUE SPECIFICITY: Expressed in T cells (PubMed:28028151). Expressed
CC in bone marrow-derived dendritic cells (PubMed:25713392).
CC {ECO:0000269|PubMed:25713392, ECO:0000269|PubMed:28028151}.
CC -!- DOMAIN: The DOCKER domain is necessary and sufficient for the GEF
CC activity. {ECO:0000269|PubMed:22461490}.
CC -!- PTM: In response to chemokine CXCL12/SDF-1-alpha stimulation,
CC phosphorylated by PRKCA/PKC-alpha which promotes DOCK8 dissociation
CC from LRCH1. {ECO:0000250|UniProtKB:Q8NF50}.
CC -!- POLYMORPHISM: Strain C3H/HeJ mice harbor a point mutation in Dock8
CC which results in impaired dendritic cell migration. The mutation is not
CC observed in strains CBA/J, C3H/HeOuJ or C3HeB/FeJ.
CC {ECO:0000269|PubMed:25713392}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile (PubMed:22461490).
CC The number of CD4(+) and CD8(+) T-cells are reduced by 50 percent in
CC the spleen and peripheral lymph nodes (PubMed:22461490). The number of
CC marginal zone B cells in the spleen are also reduced (PubMed:22461490).
CC In response to an immune challenge, impaired migration of epidermal
CC dendritic cells to the draining lymph nodes resulting in a failure to
CC prime CD4(+) T-cells characterized by a lack of CD4(+) T-cell
CC proliferation in lymph nodes and a lack of antigen-specific IgG
CC antibody production (PubMed:25713392, PubMed:22461490).
CC {ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:25713392}.
CC -!- SIMILARITY: Belongs to the DOCK family. {ECO:0000255|PROSITE-
CC ProRule:PRU00983}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH30316.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB23587.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC26219.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAD21430.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AC139711; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132319; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK004816; BAB23587.1; ALT_INIT; mRNA.
DR EMBL; AK028968; BAC26219.2; ALT_INIT; mRNA.
DR EMBL; AK038285; BAC29959.1; -; mRNA.
DR EMBL; BC029018; AAH29018.2; -; mRNA.
DR EMBL; BC030316; AAH30316.2; ALT_INIT; mRNA.
DR EMBL; BC043470; AAH43470.1; -; mRNA.
DR EMBL; BC055295; AAH55295.1; -; mRNA.
DR EMBL; AK131180; BAD21430.1; ALT_INIT; mRNA.
DR CCDS; CCDS37943.1; -. [Q8C147-1]
DR RefSeq; NP_083061.2; NM_028785.3. [Q8C147-1]
DR PDB; 3VHL; X-ray; 2.08 A; A=1787-2067.
DR PDB; 7CLX; X-ray; 1.50 A; A=556-740.
DR PDB; 7CLY; X-ray; 1.43 A; A=556-740.
DR PDBsum; 3VHL; -.
DR PDBsum; 7CLX; -.
DR PDBsum; 7CLY; -.
DR AlphaFoldDB; Q8C147; -.
DR SMR; Q8C147; -.
DR BioGRID; 217953; 7.
DR CORUM; Q8C147; -.
DR IntAct; Q8C147; 5.
DR STRING; 10090.ENSMUSP00000025831; -.
DR iPTMnet; Q8C147; -.
DR PhosphoSitePlus; Q8C147; -.
DR SwissPalm; Q8C147; -.
DR EPD; Q8C147; -.
DR jPOST; Q8C147; -.
DR MaxQB; Q8C147; -.
DR PaxDb; Q8C147; -.
DR PeptideAtlas; Q8C147; -.
DR PRIDE; Q8C147; -.
DR ProteomicsDB; 279760; -. [Q8C147-1]
DR ProteomicsDB; 279761; -. [Q8C147-2]
DR Antibodypedia; 758; 311 antibodies from 27 providers.
DR Ensembl; ENSMUST00000025831; ENSMUSP00000025831; ENSMUSG00000052085. [Q8C147-1]
DR GeneID; 76088; -.
DR KEGG; mmu:76088; -.
DR UCSC; uc008hba.1; mouse. [Q8C147-1]
DR UCSC; uc008hbc.1; mouse. [Q8C147-2]
DR CTD; 81704; -.
DR MGI; MGI:1921396; Dock8.
DR VEuPathDB; HostDB:ENSMUSG00000052085; -.
DR eggNOG; KOG1997; Eukaryota.
DR GeneTree; ENSGT00940000155876; -.
DR HOGENOM; CLU_000624_0_0_1; -.
DR InParanoid; Q8C147; -.
DR OMA; VIAGQTX; -.
DR OrthoDB; 20156at2759; -.
DR PhylomeDB; Q8C147; -.
DR TreeFam; TF313629; -.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 76088; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Dock8; mouse.
DR PRO; PR:Q8C147; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8C147; protein.
DR Bgee; ENSMUSG00000052085; Expressed in granulocyte and 167 other tissues.
DR Genevisible; Q8C147; MM.
DR GO; GO:0031252; C:cell leading edge; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031256; C:leading edge membrane; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:MGI.
DR GO; GO:1990869; P:cellular response to chemokine; ISO:MGI.
DR GO; GO:0036336; P:dendritic cell migration; IMP:UniProtKB.
DR GO; GO:0001771; P:immunological synapse formation; IMP:MGI.
DR GO; GO:0061485; P:memory T cell proliferation; ISO:MGI.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IMP:MGI.
DR GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:MGI.
DR GO; GO:2000406; P:positive regulation of T cell migration; IMP:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR CDD; cd08696; C2_Dock-C; 1.
DR Gene3D; 1.20.58.740; -; 1.
DR Gene3D; 1.25.40.410; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR IDEAL; IID50262; -.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR037808; C2_Dock-C.
DR InterPro; IPR027007; C2_DOCK-type_domain.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR026791; DOCK.
DR InterPro; IPR021816; DOCK_C/D_N.
DR InterPro; IPR043161; DOCK_C_lobe_A.
DR InterPro; IPR043162; DOCK_C_lobe_C.
DR InterPro; IPR027357; DOCKER_dom.
DR PANTHER; PTHR23317; PTHR23317; 1.
DR Pfam; PF06920; DHR-2; 1.
DR Pfam; PF14429; DOCK-C2; 1.
DR Pfam; PF11878; DUF3398; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS51650; C2_DOCK; 1.
DR PROSITE; PS51651; DOCKER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..2100
FT /note="Dedicator of cytokinesis protein 8"
FT /id="PRO_0000189998"
FT DOMAIN 561..730
FT /note="C2 DOCK-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00983"
FT DOMAIN 1633..2067
FT /note="DOCKER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00984"
FT REGION 424..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NF50"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NF50"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NF50"
FT MOD_RES 905
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 937
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NF50"
FT MOD_RES 1146
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NF50"
FT MOD_RES 1244
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2088
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NF50"
FT VAR_SEQ 1..366
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027374"
FT VAR_SEQ 1042..1044
FT /note="ESE -> VAV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027375"
FT VAR_SEQ 1045..2100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027376"
FT MUTAGEN 1827
FT /note="S->P: In an experimental autoimmune
FT encephalomyelitis (EAE) disease model, 50 percent of
FT animals have no EAE symptoms. In the remaining animals, EAE
FT is less severe with a reduction in the demyelination of the
FT spinal cord and in the number of CD4(+) T-cells
FT infiltrating the central nervous system. In addition,
FT CD4(+) T-cell proliferation and apoptosis are increased.
FT Reduced CD4(+) T-cell transmigration towards chemokine
FT CXCL12 and CCL5."
FT /evidence="ECO:0000269|PubMed:28028151"
FT CONFLICT 1608
FT /note="L -> M (in Ref. 2; BAC26219)"
FT /evidence="ECO:0000305"
FT CONFLICT 1616
FT /note="E -> K (in Ref. 3; AAH43470)"
FT /evidence="ECO:0000305"
FT STRAND 559..571
FT /evidence="ECO:0007829|PDB:7CLY"
FT HELIX 578..580
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 584..594
FT /evidence="ECO:0007829|PDB:7CLY"
FT HELIX 595..597
FT /evidence="ECO:0007829|PDB:7CLY"
FT TURN 607..609
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 611..613
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 615..617
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 632..635
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 645..652
FT /evidence="ECO:0007829|PDB:7CLY"
FT HELIX 658..660
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 665..676
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 683..687
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 690..692
FT /evidence="ECO:0007829|PDB:7CLY"
FT HELIX 698..700
FT /evidence="ECO:0007829|PDB:7CLY"
FT HELIX 716..719
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 723..734
FT /evidence="ECO:0007829|PDB:7CLY"
FT STRAND 1794..1802
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1803..1808
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 1812..1820
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1823..1838
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1840..1842
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 1843..1846
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1854..1856
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 1861..1871
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1875..1878
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 1891..1900
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 1904..1906
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1910..1912
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 1914..1927
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 1929..1943
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1945..1965
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1971..1982
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 1985..1987
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 1990..1997
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 2005..2035
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 2038..2040
FT /evidence="ECO:0007829|PDB:3VHL"
FT HELIX 2041..2062
FT /evidence="ECO:0007829|PDB:3VHL"
SQ SEQUENCE 2100 AA; 238978 MW; E867E04339CC6009 CRC64;
MATLPSAERR AFALKINRYS SSEIRKQFTL PPNLGQYHRH SISTSGFPSL QLPQLYEPVE
PVDFEGLVMT HLNSLDAELA QELGDLTDDD LHVAFTPKEC RTLQHSLPEE GVELDPHVRD
CVQTYIREWL IVNRKNQGSS EFCSFKKTGS RRDFQKTLQK QTFESETLEC SEPDTQTGPR
HPLNVLCDVS GKGPLTSCDF DLRSLQPDER LENLLQLVSA EDFEKEKEEA RKTNRPAELF
ALYPPVDEED AVEIRPVPEC PKEHLGNRIL VKVLTLKFEI EIEPLFASIA LYDVKERKKI
SENFHCDLNS DQFKGFLRAH TPSIDPSSQA RSAVFSVTYP SSDIYLVVKI EKVLQQGEIA
DCAEPYMIIK ESDGGKSKEK VEKLKLQAES FCQRLGKYRM PFAWAPISLA SFFNISTLER
ESTDVEPGVG RNSVGEKRSL SQSRRPSERT LSLEENGVGS NFKATTLATN IFFKQEGDRL
SDEDLFKFLA DYKRSSSLQR RVKSIPGSLR LEISPAPDVM NCCLTPEMLP VKPFPENRTR
PHKEILEFPI REVYVPHTVY RNLLYVYPQR LNFASKLASA RNITIKIQFM CGEDPSNAMP
VIFGKSSGPE FLQEVYTAIT YHNKSPDFYE EVKIKLPAKL TVNHHLLFTF YHISCQQKQG
ASGESLLGYS WLPILLNERL QTGSYCLPVA LEKLPPNYSI HSAEKVPLQN PPIKWAEGHK
GVFNIEVQAV SSVHTQDNHL EKFFTLCHSL ESQVSFPIRV LDQKITESTL EHELKLSIIC
LNSSRLEPLV LFLHLVLDKL FQLSVQPMVI AGQTANFSQF AFESVVAIAN SLHNSKDLRK
DQHGRNCLLA SYVHYVFRLP ELHRDTSKSG GPTTVVPDPR YHTYGRTSAA AVSSKLMQAR
VMSSSNPDLT GSHCAADEEV KNIMSSKIAD RNCSRMSYYC SGNSDAPGST AAPRPVSKKH
FHEELALQMV VSTGVVRETV FKYAWFFFEL LVKSMAQYVH NLDKRDSFRR TRFSDRFKDD
ITTIVNVVTS EIAALLVKPQ KESEQAEKIN ISLAFFLYDL LSIMDRGFVF NLIKHYCSQL
SAKLNILPTL ISMRLEFLRI LCSHEHYLNL NLLFMNTDTA PASPCPSISS QNSSSCSSFQ
DQKIASMFDL TPEYRQQHFL TGLLFTELAV ALDAEGDGIS RVQRKAVSAI HSLLCSHDLD
PRCRKPEVKV KIAALYLPLV GIILDALPQL YDFTDARSGR SRASGSYEEQ DVANGINQNV
ALAIAGNHFN LKTSGAMLSS LPYKQYNMLN ADTTRHLMIC FLWIMKNADQ SLIRKWIADL
PSMQLNRILD LLFICVSCFE YKGKQSSDKV SNQVLQKSRD VKAKLEEALL RGEGARGEMM
RRRIPGTDRF PGINENLRWR KEQTQWRQAN EKLDKTKAEL DQEALISGNL ATEANLIILD
MQENIIQASS ALDCKDSLLG GVLRVLVNSL SCDQSTTYLT HCFATLRALI AKFGDLLFEE
EMEQCADLCQ RVLHHCSSSM DVTRSQACAT LYLLMRFSFG ATSNFARVKM QVTMALASLV
GKAPDFNEEH LRRSLRTILA YSEEDTAMQT TPFPMQVEEL LCNLNSILYD TVKMREFQED
PEMLMDLMYR IAKSYQASPD LRLTWLQNMA EKHTKKKCFT EAAMCLVHAA ALVAEYLSML
EDHSYLPVGS VSFQNISSNV LEESAVSDDT LSPDEDGVCS GRYFTESGLV GLLEQAAELF
STGGLYETVN EVYKLVIPIL EAHRDFRKLT STHDKLQKAF DNIINKDHKR MFGTYFRVGF
YGSRFGDLDE QEFVYKEPAI TKLPEISHRL EGFYGQCFGA EFVEVIKDST PVDKTKLDPN
KAYIQITFVE PYFDEYEMKD RVTYFEKNFN LRRFMYTTPF TLEGRPRGEL HEQHRRNTVL
TTMHAFPYIK TRIRVSQKEE FVLTPIEVAI EDMKKKTLQL AVATHQEPPD AKMLQMVLQG
SVGATVNQGP LEVAQVFLAE IPADPKLYRH HNKLRLCFKE FIMRCGEAVE KNRRLITAEQ
REYQQELKKN YNKLRDSLRP MIERKIPELY KPIFRVDSQK RDSFHRSSFR KCETQLSQGS
