MILL2_MOUSE
ID MILL2_MOUSE Reviewed; 355 AA.
AC Q8HWE5; Q8HWE6;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=MHC class I-like protein MILL2 {ECO:0000305};
DE AltName: Full=MHC class I-like located near the leukocyte receptor complex 2 {ECO:0000303|PubMed:12370446};
DE Flags: Precursor;
GN Name=Mill2 {ECO:0000303|PubMed:12370446};
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 {ECO:0000312|Proteomes:UP000000589};
RN [1] {ECO:0000312|EMBL:BAC21671.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:BAC21671.1};
RX PubMed=12370446; DOI=10.1073/pnas.212375299;
RA Kasahara M., Watanabe Y., Sumasu M., Nagata T.;
RT "A family of MHC class I-like genes located in the vicinity of the mouse
RT leukocyte receptor complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13687-13692(2002).
RN [2] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
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 [3] {ECO:0000312|EMBL:AAI44887.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI44887.1};
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] {ECO:0000305}
RP SUBUNIT, INTERACTION WITH B2M, SUBCELLULAR LOCATION, GLYCOSYLATION, AND
RP GPI-ANCHOR AT ASP-330.
RX PubMed=16920948; DOI=10.4049/jimmunol.177.5.3108;
RA Kajikawa M., Baba T., Tomaru U., Watanabe Y., Koganei S.,
RA Tsuji-Kawahara S., Matsumoto N., Yamamoto K., Miyazawa M., Maenaka K.,
RA Ishizu A., Kasahara M.;
RT "MHC class I-like MILL molecules are beta2-microglobulin-associated, GPI-
RT anchored glycoproteins that do not require TAP for cell surface
RT expression.";
RL J. Immunol. 177:3108-3115(2006).
RN [5] {ECO:0007744|PDB:6A97}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 30-320 IN COMPLEX WITH B2M,
RP FUNCTION, SUBUNIT, DISULFIDE BONDS, AND MUTAGENESIS OF 116-LYS--LYS-120;
RP ARG-109; ARG-216; ARG-238; ARG-244; 273-LYS--ARG-276; ARG-291 AND ARG-295.
RX PubMed=30337538; DOI=10.1038/s41467-018-06797-8;
RA Kajikawa M., Ose T., Fukunaga Y., Okabe Y., Matsumoto N., Yonezawa K.,
RA Shimizu N., Kollnberger S., Kasahara M., Maenaka K.;
RT "Structure of MHC class I-like MILL2 reveals heparan-sulfate binding and
RT interdomain flexibility.";
RL Nat. Commun. 9:4330-4330(2018).
CC -!- FUNCTION: Binds to heparan sulfate proteoglycans on the surface of
CC fibroblast (NIH-3T3) cells. {ECO:0000269|PubMed:30337538}.
CC -!- SUBUNIT: Heterodimer with B2M (beta-2-microglobulin).
CC {ECO:0000269|PubMed:16920948, ECO:0000269|PubMed:30337538}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16920948};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:16920948}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long {ECO:0000303|PubMed:12370446};
CC IsoId=Q8HWE5-1; Sequence=Displayed;
CC Name=2; Synonyms=Short {ECO:0000303|PubMed:12370446};
CC IsoId=Q8HWE5-2; Sequence=VSP_060927;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in neonatal and adult
CC tissues. {ECO:0000269|PubMed:12370446}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16920948}.
CC -!- SIMILARITY: Belongs to the MHC class I family.
CC {ECO:0000255|RuleBase:RU004439}.
CC -!- CAUTION: Lacks key residues involved in peptide docking and also does
CC not require TAP (transporter involved in antigen processing) for cell
CC surface expression, suggesting that this is a non-classical MHC class I
CC protein which does not play a role in antigen presentation.
CC {ECO:0000305|PubMed:12370446, ECO:0000305|PubMed:16920948,
CC ECO:0000305|PubMed:30337538}.
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DR EMBL; AB086266; BAC21670.1; -; mRNA.
DR EMBL; AB086267; BAC21671.1; -; mRNA.
DR EMBL; AC153651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137748; AAI37749.1; -; mRNA.
DR EMBL; BC144886; AAI44887.1; -; mRNA.
DR CCDS; CCDS20879.1; -. [Q8HWE5-2]
DR CCDS; CCDS20880.1; -. [Q8HWE5-1]
DR RefSeq; NP_715641.1; NM_153760.2. [Q8HWE5-2]
DR RefSeq; NP_715642.2; NM_153761.3. [Q8HWE5-1]
DR RefSeq; XP_006539995.1; XM_006539932.3. [Q8HWE5-1]
DR RefSeq; XP_006539996.1; XM_006539933.3. [Q8HWE5-2]
DR RefSeq; XP_017177723.1; XM_017322234.1. [Q8HWE5-1]
DR PDB; 6A97; X-ray; 2.15 A; A/C=30-320.
DR PDBsum; 6A97; -.
DR AlphaFoldDB; Q8HWE5; -.
DR SMR; Q8HWE5; -.
DR STRING; 10090.ENSMUSP00000072223; -.
DR GlyGen; Q8HWE5; 3 sites.
DR PhosphoSitePlus; Q8HWE5; -.
DR MaxQB; Q8HWE5; -.
DR PaxDb; Q8HWE5; -.
DR ProteomicsDB; 330471; -.
DR ProteomicsDB; 331214; -.
DR DNASU; 243864; -.
DR Ensembl; ENSMUST00000072386; ENSMUSP00000072223; ENSMUSG00000040987. [Q8HWE5-1]
DR Ensembl; ENSMUST00000072415; ENSMUSP00000072246; ENSMUSG00000040987. [Q8HWE5-2]
DR Ensembl; ENSMUST00000227379; ENSMUSP00000154222; ENSMUSG00000040987. [Q8HWE5-2]
DR Ensembl; ENSMUST00000228493; ENSMUSP00000154268; ENSMUSG00000040987. [Q8HWE5-1]
DR GeneID; 243864; -.
DR KEGG; mmu:243864; -.
DR UCSC; uc009fjt.1; mouse. [Q8HWE5-1]
DR UCSC; uc009fju.1; mouse.
DR CTD; 243864; -.
DR MGI; MGI:2179989; Mill2.
DR VEuPathDB; HostDB:ENSMUSG00000040987; -.
DR eggNOG; ENOG502RU00; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_047501_4_0_1; -.
DR InParanoid; Q8HWE5; -.
DR OMA; DTINATC; -.
DR OrthoDB; 912212at2759; -.
DR PhylomeDB; Q8HWE5; -.
DR TreeFam; TF339076; -.
DR BioGRID-ORCS; 243864; 0 hits in 72 CRISPR screens.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8HWE5; protein.
DR Bgee; ENSMUSG00000040987; Expressed in urinary bladder and 49 other tissues.
DR ExpressionAtlas; Q8HWE5; baseline and differential.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0046703; F:natural killer cell lectin-like receptor binding; ISO:MGI.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.500.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR011161; MHC_I-like_Ag-recog.
DR InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
DR InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR InterPro; IPR001039; MHC_I_a_a1/a2.
DR Pfam; PF07654; C1-set; 1.
DR Pfam; PF00129; MHC_I; 1.
DR PRINTS; PR01638; MHCCLASSI.
DR SMART; SM00407; IGc1; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF54452; SSF54452; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Reference proteome;
KW Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..330
FT /note="MHC class I-like protein MILL2"
FT /evidence="ECO:0000305|PubMed:16920948"
FT /id="PRO_5015099155"
FT PROPEP 331..355
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:16920948"
FT /id="PRO_0000452207"
FT DOMAIN 231..321
FT /note="Ig-like C1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 46..137
FT /note="Alpha-1"
FT /evidence="ECO:0000255"
FT REGION 138..229
FT /note="Alpha-2"
FT /evidence="ECO:0000255"
FT REGION 230..323
FT /note="Alpha-3"
FT /evidence="ECO:0000255"
FT REGION 324..329
FT /note="Connecting peptide"
FT /evidence="ECO:0000255"
FT LIPID 330
FT /note="GPI-anchor amidated aspartate"
FT /evidence="ECO:0000305|PubMed:16920948"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 96..107
FT /evidence="ECO:0000269|PubMed:30337538,
FT ECO:0007744|PDB:6A97"
FT DISULFID 147..210
FT /evidence="ECO:0000269|PubMed:30337538,
FT ECO:0007744|PDB:6A97"
FT DISULFID 249..306
FT /evidence="ECO:0000269|PubMed:30337538,
FT ECO:0007744|PDB:6A97"
FT VAR_SEQ 35..49
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_060927"
FT MUTAGEN 109
FT /note="R->A: No effect on binding to NIH-3T3 fibroblast
FT cells; when associated with A-216."
FT /evidence="ECO:0000269|PubMed:30337538"
FT MUTAGEN 116..120
FT /note="KVEEK->AVEEA: No effect on binding to NIH-3T3
FT fibroblast cells."
FT /evidence="ECO:0000269|PubMed:30337538"
FT MUTAGEN 216
FT /note="R->A: No effect on binding to NIH-3T3 fibroblast
FT cells; when associated with A-109."
FT /evidence="ECO:0000269|PubMed:30337538"
FT MUTAGEN 238
FT /note="R->A: Fails to bind to heparan sulfate or to NIH-3T3
FT fibroblast cells; when associated with A-244 and A-295."
FT /evidence="ECO:0000269|PubMed:30337538"
FT MUTAGEN 244
FT /note="R->A: Fails to bind to heparan sulfate or to NIH-3T3
FT fibroblast cells; when associated with A-238 and A-295."
FT /evidence="ECO:0000269|PubMed:30337538"
FT MUTAGEN 273..276
FT /note="KTFR->ATFA: Fails to bind to NIH-3T3 fibroblast
FT cells; when associated with A-291."
FT /evidence="ECO:0000269|PubMed:30337538"
FT MUTAGEN 291
FT /note="R->A: Fails to bind to NIH-3T3 fibroblast cells;
FT when associated with 273-A--A-276."
FT /evidence="ECO:0000269|PubMed:30337538"
FT MUTAGEN 295
FT /note="R->A: Fails to bind to heparan sulfate or to NIH-3T3
FT fibroblast cells; when associated with A-238 and A-244."
FT /evidence="ECO:0000269|PubMed:30337538"
FT STRAND 51..61
FT /evidence="ECO:0007829|PDB:6A97"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 70..76
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:6A97"
FT HELIX 103..124
FT /evidence="ECO:0007829|PDB:6A97"
FT HELIX 126..132
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 141..149
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 155..163
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 166..172
FT /evidence="ECO:0007829|PDB:6A97"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:6A97"
FT HELIX 186..195
FT /evidence="ECO:0007829|PDB:6A97"
FT HELIX 199..207
FT /evidence="ECO:0007829|PDB:6A97"
FT HELIX 209..221
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 232..238
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 245..257
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 259..265
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 268..275
FT /evidence="ECO:0007829|PDB:6A97"
FT TURN 277..279
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 288..296
FT /evidence="ECO:0007829|PDB:6A97"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 304..310
FT /evidence="ECO:0007829|PDB:6A97"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:6A97"
SQ SEQUENCE 355 AA; 39224 MW; B52D0EEA0871C2C5 CRC64;
MKASSGKPRE FRPAVLLLIL GLLLRDSRGS SIQGFLADVE VHGSSRLTRT HTLRYNVRAH
SLEGSEKTQL LVLIYVDEEL FLKYNGDSRE TEPLGCWIKG HGGNETCARE TNNLLKVEEK
LRGMMAEVIN QKSQEEGLHT LQATLGCELL SNGSTRGFWH LGYDGQNFLT FDQKTLTWTV
DGPSTQQNKM FWKTHAPRAD LVKTFLDDIC PAHLQRYLAS LRNGLQDTGP PMVTVTCRNY
PVGRVTLTCR AFNLYTREAT LVWLQDGKPV QQKTFRSETI LPSGDGTYQA RVSIRVLPGQ
EPQFSCNLRH GNHSIMQTAV SGHAAEDSQD VASSATASAG SALPVVLAVA LARAN
