ID   HMSDV_HUMAN             Reviewed;          53 AA.
AC   P0C7T4;
DT   22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2008, sequence version 1.
DT   03-AUG-2022, entry version 69.
DE   RecName: Full=Minor histocompatibility protein HMSD variant form;
DE            Short=HSMD-v;
DE   Contains:
DE     RecName: Full=Minor histocompatibility antigen ACC-6;
DE              Short=mHA ACC-6;
GN   Name=HMSD; Synonyms=C18orf53;
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], FUNCTION, SUBUNIT, TISSUE SPECIFICITY, AND
RP   POLYMORPHISM.
RX   PubMed=17409267; DOI=10.1182/blood-2007-02-075911;
RA   Kawase T., Akatsuka Y., Torikai H., Morishima S., Oka A., Tsujimura A.,
RA   Miyazaki M., Tsujimura K., Miyamura K., Ogawa S., Inoko H., Morishima Y.,
RA   Kodera Y., Kuzushima K., Takahashi T.;
RT   "Alternative splicing due to an intronic SNP in HMSD generates a novel
RT   minor histocompatibility antigen.";
RL   Blood 110:1055-1063(2007).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16177791; DOI=10.1038/nature03983;
RA   Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA   Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA   Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA   Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA   Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA   Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA   Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA   Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 18.";
RL   Nature 437:551-555(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: This allelic splice variant of HMSD is the precursor of the
CC       histocompatibility antigen ACC-6. More generally, minor
CC       histocompatibility antigens (mHags) refer to immunogenic peptide which,
CC       when complexed with MHC, can generate an immune response after
CC       recognition by specific T-cells. The peptides are derived from
CC       polymorphic intracellular proteins, which are cleaved by normal
CC       pathways of antigen processing. The binding of these peptides to MHC
CC       class I or class II molecules and its expression on the cell surface
CC       can stimulate T-cell responses and thereby trigger graft rejection or
CC       graft-versus-host disease (GVHD) after hematopoietic stem cell
CC       transplantation from HLA-identical sibling donor. GVHD is a frequent
CC       complication after bone marrow transplantation (BMT), due to mismatch
CC       of minor histocompatibility antigen in HLA-matched sibling marrow
CC       transplants. However, associated with GVHD, a favorable graft-versus-
CC       leukemia (GVL) can be induced by donor-recipient disparities in mHags.
CC       ACC-6 is presented to the cell surface by MHC HLA-B*4403. This complex
CC       specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity
CC       against hematologic malignancies after treatment by HLA-identical
CC       allogenic BMT. It induces cell recognition and lysis by CTL.
CC       Immunogenicity of most autosomal mHags results from single-nucleotide
CC       polymorphisms that cause amino-acid substitutions within epitopes,
CC       leading to the differential recognition of peptides between donor and
CC       recipient. {ECO:0000269|PubMed:17409267}.
CC   -!- SUBUNIT: ACC-6 forms a complex with MHC HLA-B*4403.
CC       {ECO:0000269|PubMed:17409267}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=2; Synonyms=HMSD-v;
CC         IsoId=P0C7T4-1; Sequence=Displayed;
CC       Name=1; Synonyms=HMSD;
CC         IsoId=A8MTL9-1; Sequence=External;
CC   -!- TISSUE SPECIFICITY: Highly expressed in dendritic cells and primary
CC       leukemia cells, especially those of myeloid lineage. ACC-6 expression
CC       is limited to cells of the hematopoietic lineage.
CC       {ECO:0000269|PubMed:17409267}.
CC   -!- POLYMORPHISM: Minor histocompatibility antigen ACC-6 (mHA ACC-6) is
CC       encoded by HMSD-v which is an allelic variant of HMSD. HMSD-v results
CC       from an intronic single-nucleotide polymorphism located at position 5
CC       of HMSD intron 2 leading to a G to A substitution. This variation in
CC       intron 2 induces skipping of exon 2 and frameshift, resulting in
CC       expression of ACC-6.
CC   -!- MISCELLANEOUS: [Isoform 2]: This alternative splicing event arises as a
CC       consequence of an intronic polymorphism.
CC   -!- CAUTION: Translation of HMSD-v form generating mHA ACC-6 is in a frame
CC       different from that resulting in HMSD non variant form expression.
CC       Thus, the HMSD non variant form sequence does not contain the mHA ACC-6
CC       peptide. {ECO:0000305}.
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DR   EMBL; AC009802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471096; EAW63164.1; -; Genomic_DNA.
DR   AlphaFoldDB; P0C7T4; -.
DR   SMR; P0C7T4; -.
DR   BioMuta; HMSD; -.
DR   MassIVE; P0C7T4; -.
DR   MaxQB; P0C7T4; -.
DR   PeptideAtlas; P0C7T4; -.
DR   PRIDE; P0C7T4; -.
DR   Ensembl; ENST00000526932.1; ENSP00000431632.1; ENSG00000221887.6. [P0C7T4-1]
DR   UCSC; uc060pwo.1; human. [P0C7T4-1]
DR   GeneCards; HMSD; -.
DR   HGNC; HGNC:23037; HMSD.
DR   HPA; ENSG00000221887; Tissue enhanced (brain).
DR   MIM; 612086; gene.
DR   neXtProt; NX_P0C7T4; -.
DR   OpenTargets; ENSG00000221887; -.
DR   VEuPathDB; HostDB:ENSG00000221887; -.
DR   GeneTree; ENSGT00940000154519; -.
DR   HOGENOM; CLU_3067960_0_0_1; -.
DR   SignaLink; P0C7T4; -.
DR   ChiTaRS; HMSD; human.
DR   Pharos; P0C7T4; Tbio.
DR   Proteomes; UP000005640; Chromosome 18.
DR   Bgee; ENSG00000221887; Expressed in C1 segment of cervical spinal cord and 94 other tissues.
DR   ExpressionAtlas; P0C7T4; baseline and differential.
DR   GO; GO:0002253; P:activation of immune response; IMP:UniProtKB.
DR   GO; GO:0019835; P:cytolysis; IMP:UniProtKB.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma production; IMP:UniProtKB.
PE   1: Evidence at protein level;
KW   Alternative splicing; Reference proteome.
FT   CHAIN           1..53
FT                   /note="Minor histocompatibility protein HMSD variant form"
FT                   /id="PRO_0000343869"
FT   PEPTIDE         1..11
FT                   /note="Minor histocompatibility antigen ACC-6"
FT                   /id="PRO_0000343870"
SQ   SEQUENCE   53 AA;  6023 MW;  3B10E476A2B5AF53 CRC64;
     MEIFIEVFSH FLLQLTELTL NMCLELPTGS LEKSLMISSQ VLQIPVANST KQR