HMHB1_HUMAN
ID HMHB1_HUMAN Reviewed; 41 AA.
AC O97980; Q9MY25;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Minor histocompatibility protein HB-1;
DE Contains:
DE RecName: Full=Minor histocompatibility antigen HB-1;
DE Short=mHag HB-1;
GN Name=HMHB1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 9-18, TISSUE SPECIFICITY,
RP FUNCTION, AND VARIANT TYR-16.
RX PubMed=9892612; DOI=10.1084/jem.189.2.301;
RA Dolstra H., Fredrix H., Maas F., Coulie P.G., Brasseur F., Mensink E.,
RA Adema G.J., de Witte T.M., Figdor C.G., van de Wiel-van Kemenade E.;
RT "A human minor histocompatibility antigen specific for B cell acute
RT lymphoblastic leukemia.";
RL J. Exp. Med. 189:301-308(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36.
RA Balas A., Aviles M.J., Vicario J.L.;
RT "Genomic identification of the HB-1 gene.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8992968;
RA Dolstra H., Fredrix H., Preijers F., Goulmy E., Figdor C.G., de Witte T.M.,
RA van de Wiel-van Kemenade E.;
RT "Recognition of a B cell leukemia-associated minor histocompatibility
RT antigen by CTL.";
RL J. Immunol. 158:560-565(1997).
RN [5]
RP INTERACTION WITH HLA-B44, AND MUTAGENESIS OF GLU-9; GLU-10; LYS-11; ARG-12;
RP GLY-13; SER-14; LEU-15; HIS-16; VAL-17 AND TRP-18.
RX PubMed=12355426;
RX DOI=10.1002/1521-4141(2002010)32:10<2748::aid-immu2748>3.0.co;2-t;
RA Dolstra H., de Rijke B., Fredrix H., Balas A., Maas F., Scherpen F.,
RA Aviles M.J., Vicario J.L., Beekman N.J., Ossendorp F., de Witte T.M.,
RA van de Wiel-van Kemenade E.;
RT "Bi-directional allelic recognition of the human minor histocompatibility
RT antigen HB-1 by cytotoxic T lymphocytes.";
RL Eur. J. Immunol. 32:2748-2758(2002).
RN [6]
RP FUNCTION.
RX PubMed=15102363; DOI=10.1016/j.it.2003.12.002;
RA Spierings E., Wieles B., Goulmy E.;
RT "Minor histocompatibility antigens -- big in tumour therapy.";
RL Trends Immunol. 25:56-60(2004).
CC -!- FUNCTION: Precursor of the histocomplatibility antigen HB-1. More
CC generally, minor histocomplatibility antigens (mHags) refer to
CC immunogenic peptide which, when complexed with MHC, can generate an
CC immune response after recognition by specific T-cells. The peptides are
CC derived from polymorphic intracellular proteins, which are cleaved by
CC normal pathways of antigen processing. The binding of these peptides to
CC MHC class I or class II molecules and its expression on the cell
CC surface can stimulate T-cell responses and thereby trigger graft
CC rejection or graft-versus-host disease (GVHD) after hematopoietic stem
CC cell transplantation from HLA-identical sibling donor. GVHD is a
CC frequent complication after bone marrow transplantation (BMT), due to
CC mismatch of minor histocomplatibility antigen in HLA-matched sibling
CC marrow transplants. HB-1 is presented on the cell surface by MHC class
CC I HLA-B44. This complex specifically elicits donor-cytotoxic T
CC lymphocyte (CTL) reactivity in B-cell acute lymphoblastic leukemia (B-
CC ALL) after treatment by HLA-identical allogenic bone marrow
CC transplantation (BMT). It induces cell recognition and lysis by CTL.
CC However, HB-1 restricted expression in B-ALL cells and not in normal
CC tissues may allow a specific CTL reactivity against B-ALL without the
CC risk of evoking graft-versus-host disease.
CC {ECO:0000269|PubMed:15102363, ECO:0000269|PubMed:8992968,
CC ECO:0000269|PubMed:9892612}.
CC -!- SUBUNIT: HB-1 forms a complex with MHC class I HLA-B44.
CC -!- TISSUE SPECIFICITY: Expressed in acute lymphoblastic leukemia B-cells
CC and Epstein-Barr virus-transformed B-cells.
CC {ECO:0000269|PubMed:8992968, ECO:0000269|PubMed:9892612}.
CC -!- CAUTION: This sequence containing mHag HB-1 may not represent the full-
CC length protein, because functional domains are absent in this short
CC gene product. {ECO:0000305|PubMed:15102363}.
CC -!- CAUTION: PubMed:9892612 postulated that the initiator methionine is
CC coded by a non-canonical CTG leucine codon. {ECO:0000305}.
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DR EMBL; AF103884; AAC78642.1; -; mRNA.
DR EMBL; BC104412; AAI04413.1; -; mRNA.
DR EMBL; BC104413; AAI04414.1; -; mRNA.
DR EMBL; AF233094; AAF81110.1; -; Genomic_DNA.
DR CCDS; CCDS43376.1; -.
DR RefSeq; NP_067005.1; NM_021182.1.
DR AlphaFoldDB; O97980; -.
DR STRING; 9606.ENSP00000289448; -.
DR iPTMnet; O97980; -.
DR PhosphoSitePlus; O97980; -.
DR BioMuta; HMHB1; -.
DR PaxDb; O97980; -.
DR PRIDE; O97980; -.
DR DNASU; 57824; -.
DR Ensembl; ENST00000289448.4; ENSP00000289448.3; ENSG00000158497.6.
DR GeneID; 57824; -.
DR KEGG; hsa:57824; -.
DR MANE-Select; ENST00000289448.4; ENSP00000289448.3; NM_021182.3; NP_067005.1.
DR UCSC; uc003lnj.5; human.
DR CTD; 57824; -.
DR DisGeNET; 57824; -.
DR GeneCards; HMHB1; -.
DR HGNC; HGNC:29677; HMHB1.
DR HPA; ENSG00000158497; Tissue enhanced (lymphoid tissue, testis).
DR MIM; 609961; gene.
DR neXtProt; NX_O97980; -.
DR OpenTargets; ENSG00000158497; -.
DR PharmGKB; PA147357973; -.
DR eggNOG; ENOG502R1ZM; Eukaryota.
DR GeneTree; ENSGT00390000009781; -.
DR HOGENOM; CLU_218939_0_0_1; -.
DR InParanoid; O97980; -.
DR OrthoDB; 1881096at2759; -.
DR PhylomeDB; O97980; -.
DR TreeFam; TF341229; -.
DR PathwayCommons; O97980; -.
DR SignaLink; O97980; -.
DR BioGRID-ORCS; 57824; 23 hits in 917 CRISPR screens.
DR GenomeRNAi; 57824; -.
DR Pharos; O97980; Tbio.
DR PRO; PR:O97980; -.
DR Proteomes; UP000005640; Chromosome 5.
DR Bgee; ENSG00000158497; Expressed in pancreatic ductal cell and 72 other tissues.
DR ExpressionAtlas; O97980; baseline and differential.
DR Genevisible; O97980; HS.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW Adaptive immunity; Direct protein sequencing; Immunity; Reference proteome.
FT CHAIN 1..41
FT /note="Minor histocompatibility protein HB-1"
FT /id="PRO_0000330317"
FT PEPTIDE 9..18
FT /note="Minor histocompatibility antigen HB-1"
FT /id="PRO_0000330318"
FT REGION 9..17
FT /note="Loss of recognition by cytotoxic T lymphocyte (CTL)"
FT VARIANT 16
FT /note="H -> Y (in allele HB-1Y; loss of CTL recognition for
FT epitope HB-1. No influence on HLA-B/HLA-B44 binding, nor on
FT the processing by the proteasome; dbSNP:rs161557)"
FT /evidence="ECO:0000269|PubMed:9892612"
FT /id="VAR_042698"
FT MUTAGEN 9
FT /note="E->A: Decreased CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 10
FT /note="E->A: Decreased CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 11
FT /note="K->A: Complete loss of CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 12
FT /note="R->A: Complete loss of CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 13
FT /note="G->A: Complete loss of CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 14
FT /note="S->A: Complete loss of CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 15
FT /note="L->A: Complete loss of CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 16
FT /note="H->A: Complete loss of CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 16
FT /note="H->R: CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 17
FT /note="V->A: Decreased CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
FT MUTAGEN 18
FT /note="W->A: Complete loss of CTL recognition."
FT /evidence="ECO:0000269|PubMed:12355426"
SQ SEQUENCE 41 AA; 4965 MW; CF81D8EB0AE6F206 CRC64;
MEEQPECREE KRGSLHVWKS ELVEVEDDVY LRHSSSLTYR L
