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Identification
HMDB Protein ID HMDBP10953
Secondary Accession Numbers
  • 17266
Name Minor histocompatibility protein HA-1
Synonyms
  1. Minor histocompatibility antigen HA-1
  2. mHag HA-1
Gene Name HMHA1
Protein Type Unknown
Biological Properties
General Function Involved in intracellular signaling pathway
Specific Function Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA- identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor- cytotoxic T lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular
Process
biological regulation
regulation of biological process
regulation of cellular process
signal transduction
intracellular signaling pathway
signaling
signaling pathway
Cellular Location Not Available
Gene Properties
Chromosome Location Chromosome:1
Locus 19p13.3
SNPs HMHA1
Gene Sequence
>3411 bp
ATGTTCTCCAGGAAGAAACGAGAGCTCATGAAAACCCCTTCCATCTCGAAAAAGAACCGC
GCGGGAAGCCCCAGCCCGCAGCCCTCGGGGGAGCTGCCCAGGAAGGATGGGGCTGACGCG
GTGTTCCCCGGACCAAGCCTGGAGCCGCCCGCTGGGTCCTCCGGCGTCAAGGCCACAGGG
ACCCTCAAGCGGCCCACCAGCCTGAGCCGCCACGCCAGCGCGGCTGGCTTCCCCCTGTCG
GGTGCTGCCTCCTGGACACTGGGCCGGAGCCACCGGAGCCCACTGACAGCCGCCAGCCCG
GGCGAGCTGCCCACCGAGGGTGCCGGCCCGGACGTCGTCGAGGACATCTCCCATCTGCTG
GCGGACGTGGCCCGCTTCGCTGAGGGCCTTGAGAAACTTAAGGAGTGTGTGTTGCGTGAC
GACCTCCTTGAGGCCCGCCGCCCGCGGGCCCACGAGTGCCTGGGTGAGGCTCTGCGTGTC
ATGCATCAGATCATCTCCAAGTACCCGCTGCTGAACACCGTGGAGACGCTCACCGCAGCC
GGCACCCTCATTGCCAAGGTCAAAGCCTTCCATTATGAGAGCAACAATGATCTGGAGAAA
CAGGAGTTCGAGAAGGCCCTGGAGACGATTGCTGTGGCCTTCAGTAGCACAGTGTCCGAG
TTCCTCATGGGTGAAGTGGACAGCAGCACCCTCCTAGCAGTGCCTCCTGGGGACTCGAGC
CAGTCCATGGAAAGCCTGTATGGACCGGGCAGTGAGGGCACGCCTCCCAGCCTGGAAGAC
TGTGACGCCGGCTGCCTGCCCGCCGAGGAGGTGGACGTGCTGCTACAGCGCTGTGAGGGG
GGCGTGGATGCCGCACTGCTGTATGCCAAGAACATGGCCAAGTACATGAAGGACCTCATC
AGCTACCTGGAGAAGCGGACGACGCTGGAGATGGAGTTTGCCAAGGGCCTGCAGAAGATC
GCTCACAACTGCAGACAGAGCGTCATGCAGGAGCCCCACATGCCGCTCCTGTCCATCTAC
TCGCTGGCCCTGGAGCAGGACCTGGAGTTCGGCCACAGCATGGTGCAGGCGGTGGGCACC
TTGCAGACCCAGACCTTCATGCAGCCCCTGACCCTGCGGCGGCTTGAACACGAGAAGCGC
AGGAAGGAGATCAAGGAGGCCTGGCACCGTGCCCAGAGGAAGCTGCAAGAGGCGGAGTCC
AACCTGCGCAAGGCCAAGCAGGGTTACGTGCAGCGCTGCGAGGACCACGACAAGGCTCGC
TTCCTCGTGGCCAAGGCGGAGGAGGAGCAGGCTGGCAGCGCGCCGGGAGCAGGCAGCACG
GCCACCAAGACCCTGGACAAGCGGCGGCGGCTGGAGGAGGAGGCCAAGAACAAGGCGGAG
GAAGCTATGGCCACCTACCGCACCTGCGTGGCCGACGCGAAGACGCAGAAGCAGGAGCTG
GAGGATACCAAGGTGACGGCGCTGCGGCAGATCCAGGAGGTCATCCGGCAGAGCGACCAA
ACCATCAAGTCGGCCACGATCTCCTACTACCAGATGATGCATATGCAGACGGCGCCGCTG
CCCGTGCACTTCCAGATGCTGTGTGAGAGCAGCAAGCTGTATGACCCAGGCCAGCAGTAC
GCCTCCCACGTGCGCCAGCTGCAGCGGGACCAGGAGCCCGATGTGCACTACGACTTTGAG
CCCCACGTCTCCGCCAACGCCTGGTCCCCCGTCATGCGTGCCCGGAAGAGCAGCTTCAAC
GTGAGTGATGTGGCGCGGCCGGAGGCTGCCGGGAGCCCCCCAGAAGAAGGCGGGTGCACT
GAGGGCACACCTGCCAAGGACCACAGGGCCGGGCGAGGACACCAGGTTCACAAGTCATGG
CCGCTCTCGATCTCAGACTCGGACAGTGGGCTGGACCCCGGCCCTGGCGCAGGGGACTTT
AAGAAGTTCGAGCGGACGTCATCCAGTGGTACCATGTCGTCCACGGAGGAGCTGGTGGAC
CCAGACGGTGGAGCCGGGGCTTCAGCCTTTGAGCAGGCTGACCTCAACGGCATGACCCCC
GAGCTGCCGGTGGCCGTGCCCAGTGGACCGTTCCGCCACGAGGGGCTGTCCAAGGCGGCC
CGTACTCACCGGCTCCGGAAGCTCCGCACGCCCGCCAAGTGCCGCGAGTGCAACAGCTAC
GTCTACTTCCAGGGTGCTGAGTGTGAAGAGTGCTGCCTGGCCTGCCACAAGAAATGTCTG
GAGACGCTGGCCATACAGTGCGGGCACAAGAAGCTGCAAGGCCGCCTGCAGCTGTTCGGC
CAGGACTTCAGCCACGCGGCCCGCAGCGCCCCCGACGGCGTGCCCTTCATCGTCAAGAAG
TGCGTCTGCGAGATCGAGCGGCGGGCGCTGCGCACCAAGGGCATCTACCGGGTCAATGGG
GTAAAGACACGCGTGGAGAAGCTGTGCCAGGCCTTCGAGAACGGCAAGGAGCTGGTCGAG
CTGTCGCAGGCCTCGCCCCACGACATCAGCAACGTCCTCAAGCTCTACCTGCGTCAGCTT
CCCGAGCCGCTCATCTCCTTCCGCCTCTACCACGAGCTCGTAGGGCTGGCCAAGGACAGC
CTGAAGGCAGAGGCCGAGGCCAAGGCGGCGTCCCGGGGCCGGCAGGACGGCTCGGAGAGC
GAGGCAGTGGCGGTGGCCCTGGCAGGTCGGCTGCGGGAGCTCCTGCGGGACCTGCCGCCT
GAGAACCGGGCCTCGCTGCAGTACCTGCTGCGTCACCTACGCAGGATCGTGGAGGTGGAG
CAGGACAACAAGATGACCCCCGGGAACCTGGGCATCGTGTTCGGGCCCACGCTGCTTCGG
CCACGGCCCACCGAGGCCACCGTGTCCCTCTCCTCCCTGGTGGATTATCCCCATCAGGCC
CGCGTCATCGAGACTCTCATCGTCCACTACGGCCTGGTCTTCGAGGAGGAGCCGGAGGAG
ACCCCCGGGGGCCAGGACGAGTCATCCAACCAGCGAGCTGAGGTAGTCGTCCAGGTGCCG
TACCTGGAGGCGGGCGAGGCGGTGGTCTACCCGCTGCAGGAGGCGGCGGCGGACGGGTGC
AGAGAATCCCGAGTTGTGTCCAACGATTCGGACTCGGACCTAGAGGAGGCCTCCGAGCTG
CTGTCCTCATCGGAGGCCAGTGCCCTGGGCCACCTCAGCTTCCTGGAGCAGCAGCAGAGC
GAGGCCAGCCTAGAGGTGGCTTCTGGCAGCCACAGCGGCAGTGAGGAGCAGCTGGAGGCC
ACAGCCCGGGAGGACGGGGACGGGGACGAGGACGGCCCGGCCCAGCAGCTCTCAGGATTC
AACACCAACCAGTCCAACAACGTGCTGCAGGCCCCACTGCCCCCCATGAGGCTCCGTGGC
GGGCGGATGACACTGGGCTCCTGCAGGGAAAGGCAGCCGGAATTCGTGTGA
Protein Properties
Number of Residues 1136
Molecular Weight 124613.1
Theoretical pI 6.0
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Minor histocompatibility protein HA-1
MFSRKKRELMKTPSISKKNRAGSPSPQPSGELPRKDGADAVFPGPSLEPPAGSSGVKATG
TLKRPTSLSRHASAAGFPLSGAASWTLGRSHRSPLTAASPGELPTEGAGPDVVEDISHLL
ADVARFAEGLEKLKECVLRDDLLEARRPRAHECLGEALRVMHQIISKYPLLNTVETLTAA
GTLIAKVKAFHYESNNDLEKQEFEKALETIAVAFSSTVSEFLMGEVDSSTLLAVPPGDSS
QSMESLYGPGSEGTPPSLEDCDAGCLPAEEVDVLLQRCEGGVDAALLYAKNMAKYMKDLI
SYLEKRTTLEMEFAKGLQKIAHNCRQSVMQEPHMPLLSIYSLALEQDLEFGHSMVQAVGT
LQTQTFMQPLTLRRLEHEKRRKEIKEAWHRAQRKLQEAESNLRKAKQGYVQRCEDHDKAR
FLVAKAEEEQAGSAPGAGSTATKTLDKRRRLEEEAKNKAEEAMATYRTCVADAKTQKQEL
EDTKVTALRQIQEVIRQSDQTIKSATISYYQMMHMQTAPLPVHFQMLCESSKLYDPGQQY
ASHVRQLQRDQEPDVHYDFEPHVSANAWSPVMRARKSSFNVSDVARPEAAGSPPEEGGCT
EGTPAKDHRAGRGHQVHKSWPLSISDSDSGLDPGPGAGDFKKFERTSSSGTMSSTEELVD
PDGGAGASAFEQADLNGMTPELPVAVPSGPFRHEGLSKAARTHRLRKLRTPAKCRECNSY
VYFQGAECEECCLACHKKCLETLAIQCGHKKLQGRLQLFGQDFSHAARSAPDGVPFIVKK
CVCEIERRALRTKGIYRVNGVKTRVEKLCQAFENGKELVELSQASPHDISNVLKLYLRQL
PEPLISFRLYHELVGLAKDSLKAEAEAKAASRGRQDGSESEAVAVALAGRLRELLRDLPP
ENRASLQYLLRHLRRIVEVEQDNKMTPGNLGIVFGPTLLRPRPTEATVSLSSLVDYPHQA
RVIETLIVHYGLVFEEEPEETPGGQDESSNQRAEVVVQVPYLEAGEAVVYPLQEAAADGC
RESRVVSNDSDSDLEEASELLSSSEASALGHLSFLEQQQSEASLEVASGSHSGSEEQLEA
TAREDGDGDEDGPAQQLSGFNTNQSNNVLQAPLPPMRLRGGRMTLGSCRERQPEFV
GenBank ID Protein 47834348
UniProtKB/Swiss-Prot ID Q92619
UniProtKB/Swiss-Prot Entry Name HMHA1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_012292.2
GeneCard ID HMHA1
GenAtlas ID HMHA1
HGNC ID HGNC:17102
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [PubMed:16964243 ]
  5. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [PubMed:18220336 ]
  6. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [PubMed:15057824 ]
  7. Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N: Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res. 1996 Oct 31;3(5):321-9, 341-54. [PubMed:9039502 ]
  8. Carrascal M, Ovelleiro D, Casas V, Gay M, Abian J: Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment. J Proteome Res. 2008 Dec;7(12):5167-76. [PubMed:19367720 ]
  9. Kaminski WE, Piehler A, Schmitz G: Genomic organization of the human cholesterol-responsive ABC transporter ABCA7: tandem linkage with the minor histocompatibility antigen HA-1 gene. Biochem Biophys Res Commun. 2000 Nov 30;278(3):782-9. [PubMed:11095984 ]
  10. Arostegui JI, Gallardo D, Rodriguez-Luaces M, Querol S, Madrigal JA, Garcia-Lopez J, Granena A: Genomic typing of minor histocompatibility antigen HA-1 by reference strand mediated conformation analysis (RSCA). Tissue Antigens. 2000 Jul;56(1):69-76. [PubMed:10958358 ]
  11. Graziano C, Giorgi M, Malentacchi C, Mattiuz PL, Porfirio B: Sequence diversity within the HA-1 gene as detected by melting temperature assay without oligonucleotide probes. BMC Med Genet. 2005 Oct 4;6:36. [PubMed:16202172 ]
  12. den Haan JM, Meadows LM, Wang W, Pool J, Blokland E, Bishop TL, Reinhardus C, Shabanowitz J, Offringa R, Hunt DF, Engelhard VH, Goulmy E: The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism. Science. 1998 Feb 13;279(5353):1054-7. [PubMed:9461441 ]
  13. Marijt WA, Veenhof WF, Goulmy E, Willemze R, van Rood JJ, Falkenburg JH: Minor histocompatibility antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T-cell clones inhibit human hematopoietic progenitor cell growth by a mechanism that is dependent on direct cell-cell contact. Blood. 1993 Dec 15;82(12):3778-85. [PubMed:8260714 ]
  14. Goulmy E, Schipper R, Pool J, Blokland E, Falkenburg JH, Vossen J, Gratwohl A, Vogelsang GB, van Houwelingen HC, van Rood JJ: Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation. N Engl J Med. 1996 Feb 1;334(5):281-5. [PubMed:8532022 ]
  15. van Lochem E, van der Keur M, Mommaas AM, de Gast GC, Goulmy E: Functional expression of minor histocompatibility antigens on human peripheral blood dendritic cells and epidermal Langerhans cells. Transpl Immunol. 1996 Jun;4(2):151-7. [PubMed:8843592 ]
  16. Rufer N, Wolpert E, Helg C, Tiercy JM, Gratwohl A, Chapuis B, Jeannet M, Goulmy E, Roosnek E: HA-1 and the SMCY-derived peptide FIDSYICQV (H-Y) are immunodominant minor histocompatibility antigens after bone marrow transplantation. Transplantation. 1998 Oct 15;66(7):910-6. [PubMed:9798702 ]
  17. Fujii N, Hiraki A, Ikeda K, Ohmura Y, Nozaki I, Shinagawa K, Ishimaru F, Kiura K, Shimizu N, Tanimoto M, Harada M: Expression of minor histocompatibility antigen, HA-1, in solid tumor cells. Transplantation. 2002 Apr 15;73(7):1137-41. [PubMed:11965046 ]
  18. Marijt WA, Heemskerk MH, Kloosterboer FM, Goulmy E, Kester MG, van der Hoorn MA, van Luxemburg-Heys SA, Hoogeboom M, Mutis T, Drijfhout JW, van Rood JJ, Willemze R, Falkenburg JH: Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2742-7. Epub 2003 Feb 24. [PubMed:12601144 ]
  19. Tseng LH, Lin MT, Martin PJ, Pei J, Smith AG, Hansen JA: Definition of the gene encoding the minor histocompatibility antigen HA-1 and typing for HA-1 from genomic DNA. Tissue Antigens. 1998 Oct;52(4):305-11. [PubMed:9820595 ]
  20. Di Terlizzi S, Zino E, Mazzi B, Magnani C, Tresoldi C, Perna SK, Bregni M, Rossini S, Ciceri F, Bordignon C, Bonini C, Fleischhauer K: Therapeutic and diagnostic applications of minor histocompatibility antigen HA-1 and HA-2 disparities in allogeneic hematopoietic stem cell transplantation: a survey of different populations. Biol Blood Marrow Transplant. 2006 Jan;12(1):95-101. [PubMed:16399573 ]