LOCUS       NM_002215               2904 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens inter-alpha-trypsin inhibitor heavy chain 1 (ITIH1),
            transcript variant 1, mRNA.
ACCESSION   NM_002215
VERSION     NM_002215.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2904)
  AUTHORS   Qian,X., Bao,Z.M., Yao,D. and Shi,Y.
  TITLE     Lysine demethylase 5C epigenetically reduces transcription of ITIH1
            that results in augmented progression of liver hepatocellular
            carcinoma
  JOURNAL   Kaohsiung J Med Sci 38 (5), 437-446 (2022)
   PUBMED   35080113
  REMARK    GeneRIF: Lysine demethylase 5C epigenetically reduces transcription
            of ITIH1 that results in augmented progression of liver
            hepatocellular carcinoma.
REFERENCE   2  (bases 1 to 2904)
  AUTHORS   Chang,Q.H., Mao,T., Tao,Y., Dong,T., Tang,X.X., Ge,G.H. and Xu,Z.J.
  TITLE     Pan-cancer analysis identifies ITIH1 as a novel prognostic
            indicator for hepatocellular carcinoma
  JOURNAL   Aging (Albany NY) 13 (8), 11096-11119 (2021)
   PUBMED   33744857
  REMARK    GeneRIF: Pan-cancer analysis identifies ITIH1 as a novel prognostic
            indicator for hepatocellular carcinoma.
REFERENCE   3  (bases 1 to 2904)
  AUTHORS   Scavenius,C., Poulsen,E.C., Thogersen,I.B., Roebuck,M.,
            Frostick,S., Bou-Gharios,G., Yamamoto,K., Deleuran,B. and
            Enghild,J.J.
  TITLE     Matrix-degrading protease ADAMTS-5 cleaves inter-alpha-inhibitor
            and releases active heavy chain 2 in synovial fluids from arthritic
            patients
  JOURNAL   J Biol Chem 294 (42), 15495-15504 (2019)
   PUBMED   31484722
  REMARK    GeneRIF: Both IalphaI and the HC-hyaluronan complex are substrates
            for the extracellular matrix proteases ADAMTS-5 and matrix
            metalloprotease (MMP) -3, -7, and -13.
REFERENCE   4  (bases 1 to 2904)
  AUTHORS   Naba,A., Pearce,O.M.T., Del Rosario,A., Ma,D., Ding,H., Rajeeve,V.,
            Cutillas,P.R., Balkwill,F.R. and Hynes,R.O.
  TITLE     Characterization of the Extracellular Matrix of Normal and Diseased
            Tissues Using Proteomics
  JOURNAL   J Proteome Res 16 (8), 3083-3091 (2017)
   PUBMED   28675934
REFERENCE   5  (bases 1 to 2904)
  AUTHORS   Diarra-Mehrpour,M., Sarafan,N., Bourguignon,J., Bonnet,F., Bost,F.
            and Martin,J.P.
  TITLE     Human inter-alpha-trypsin inhibitor heavy chain H3 gene. Genomic
            organization, promoter analysis, and gene linkage
  JOURNAL   J Biol Chem 273 (41), 26809-26819 (1998)
   PUBMED   9756925
  REMARK    Erratum:[J Biol Chem 1998 Nov 13;273(46):30842]
REFERENCE   6  (bases 1 to 2904)
  AUTHORS   Bost,F., Bourguignon,J., Martin,J.P., Sesboue,R., Thiberville,L.
            and Diarra-Mehrpour,M.
  TITLE     Isolation and characterization of the human inter-alpha-trypsin
            inhibitor heavy-chain H1 gene
  JOURNAL   Eur J Biochem 218 (2), 283-291 (1993)
   PUBMED   7505744
REFERENCE   7  (bases 1 to 2904)
  AUTHORS   Malki,N., Balduyck,M., Maes,P., Capon,C., Mizon,C., Han,K.K.,
            Tartar,A., Fournet,B. and Mizon,J.
  TITLE     The heavy chains of human plasma inter-alpha-trypsin inhibitor:
            their isolation, their identification by electrophoresis and
            partial sequencing. Differential reactivity with concanavalin A
  JOURNAL   Biol Chem Hoppe Seyler 373 (10), 1009-1018 (1992)
   PUBMED   1384548
REFERENCE   8  (bases 1 to 2904)
  AUTHORS   Salier,J.P., Simon,D., Rouet,P., Raguenez,G., Muscatelli,F.,
            Gebhard,W., Guenet,J.L. and Mattei,M.G.
  TITLE     Homologous chromosomal locations of the four genes for
            inter-alpha-inhibitor and pre-alpha-inhibitor family in human and
            mouse: assignment of the ancestral gene for the lipocalin
            superfamily
  JOURNAL   Genomics 14 (1), 83-88 (1992)
   PUBMED   1385302
REFERENCE   9  (bases 1 to 2904)
  AUTHORS   Diarra-Mehrpour,M., Bourguignon,J., Bost,F., Sesboue,R.,
            Muschio,F., Sarafan,N. and Martin,J.P.
  TITLE     Human inter-alpha-trypsin inhibitor: full-length cDNA sequence of
            the heavy chain H1
  JOURNAL   Biochim Biophys Acta 1132 (1), 114-118 (1992)
   PUBMED   1380832
REFERENCE   10 (bases 1 to 2904)
  AUTHORS   Salier,J.P., Diarra-Mehrpour,M., Sesboue,R., Bourguignon,J.,
            Benarous,R., Ohkubo,I., Kurachi,S., Kurachi,K. and Martin,J.P.
  TITLE     Isolation and characterization of cDNAs encoding the heavy chain of
            human inter-alpha-trypsin inhibitor (I alpha TI): unambiguous
            evidence for multipolypeptide chain structure of I alpha TI
  JOURNAL   Proc Natl Acad Sci U S A 84 (23), 8272-8276 (1987)
   PUBMED   2446322
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC069464.1 and AA897466.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_002215.3.
            
            Summary: This gene encodes a member of the inter-alpha-trypsin
            inhibitor family of proteins. Alternative splicing results in
            multiple transcript variants, at least one of which encodes a
            preproprotein that is proteolytically processed to generate the
            heavy chain of the inter-alpha-trypsin inhibitor complex, which is
            secreted by hepatocytes into the blood. The heavy chain also
            interacts with hyaluronan, and this interaction may play a role in
            ovulation and fertilization, and has been implicated in multiple
            inflammatory diseases. This gene is present in a gene cluster on
            chromosome 3. [provided by RefSeq, Nov 2015].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (a).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: X63652.1, SRR5189664.80686.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145122, SAMEA2155590
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000273283.7/ ENSP00000273283.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2801              BC069464.1         8-2808
            2802-2904           AA897466.1         9-111               c
FEATURES             Location/Qualifiers
     source          1..2904
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p21.1"
     gene            1..2904
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /note="inter-alpha-trypsin inhibitor heavy chain 1"
                     /db_xref="GeneID:3697"
                     /db_xref="HGNC:HGNC:6166"
                     /db_xref="MIM:147270"
     exon            1..134
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     CDS             18..2753
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /note="isoform a preproprotein is encoded by transcript
                     variant 1; inter-alpha (globulin) inhibitor, H1
                     polypeptide; inter-alpha-trypsin inhibitor heavy chain H1;
                     serum-derived hyaluronan-associated protein;
                     inter-alpha-trypsin inhibitor complex component III; ITI
                     heavy chain H1; inter-alpha-inhibitor heavy chain 1"
                     /codon_start=1
                     /product="inter-alpha-trypsin inhibitor heavy chain H1
                     isoform a preproprotein"
                     /protein_id="NP_002206.2"
                     /db_xref="CCDS:CCDS2864.1"
                     /db_xref="GeneID:3697"
                     /db_xref="HGNC:HGNC:6166"
                     /db_xref="MIM:147270"
                     /translation="MDGAMGPRGLLLCMYLVSLLILQAMPALGSATGRSKSSEKRQAV
                     DTAVDGVFIRSLKVNCKVTSRFAHYVVTSQVVNTANEAREVAFDLEIPKTAFISDFAV
                     TADGNAFIGDIKDKVTAWKQYRKAAISGENAGLVRASGRTMEQFTIHLTVNPQSKVTF
                     QLTYEEVLKRNHMQYEIVIKVKPKQLVHHFEIDVDIFEPQGISKLDAQASFLPKELAA
                     QTIKKSFSGKKGHVLFRPTVSQQQSCPTCSTSLLNGHFKVTYDVSRDKICDLLVANNH
                     FAHFFAPQNLTNMNKNVVFVIDISGSMRGQKVKQTKEALLKILGDMQPGDYFDLVLFG
                     TRVQSWKGSLVQASEANLQAAQDFVRGFSLDEATNLNGGLLRGIEILNQVQESLPELS
                     NHASILIMLTDGDPTEGVTDRSQILKNVRNAIRGRFPLYNLGFGHNVDFNFLEVMSME
                     NNGRAQRIYEDHDATQQLQGFYSQVAKPLLVDVDLQYPQDAVLALTQNHHKQYYEGSE
                     IVVAGRIADNKQSSFKADVQAHGEGQEFSITCLVDEEEMKKLLRERGHMLENHVERLW
                     AYLTIQELLAKRMKVDREERANLSSQALQMSLDYGFVTPLTSMSIRGMADQDGLKPTI
                     DKPSEDSPPLEMLGPRRTFVLSALQPSPTHSSSNTQRLPDRVTGVDTDPHFIIHVPQK
                     EDTLCFNINEEPGVILSLVQDPNTGFSVNGQLIGNKARSPGQHDGTYFGRLGIANPAT
                     DFQLEVTPQNITLNPGFGGPVFSWRDQAVLRQDGVVVTINKKRNLVVSVDDGGTFEVV
                     LHRVWKGSSVHQDFLGFYVLDSHRMSARTHGLLGQFFHPIGFEVSDIHPGSDPTKPDA
                     TMVVRNRRLTVTRGLQKDYSKDPWHGAEVSCWFIHNNGAGLIDGAYTDYIVPDIF"
     exon            135..155
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            156..322
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            323..427
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            428..590
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            591..704
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            705..830
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            831..947
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            948..1116
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1117..1242
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1243..1424
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1425..1610
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1611..1750
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1751..1905
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1906..1920
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1921..1941
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1942..2022
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2023..2136
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2137..2338
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2339..2511
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2512..2623
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2624..2904
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2884..2889
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /note="hexamer: ATTAAA"
     polyA_site      2904
                     /gene="ITIH1"
                     /gene_synonym="H1P; IATIH; IGHEP1; ITI-HC1; ITIH; SHAP"
                     /note="major polyA site"
ORIGIN      
        1 agcaggagcc ttagagcatg gacggtgcca tggggcctcg ggggctgctg ttgtgcatgt
       61 acctggtatc tctcctcatc ctgcaggcca tgcctgccct gggctcggct acaggcaggt
      121 ccaagagcag cgagaagcga caggctgtgg acaccgctgt cgatggcgtg ttcatccgga
      181 gtttgaaagt caactgcaaa gtcacctctc gcttcgccca ctatgttgtc accagccaag
      241 tggtcaacac tgccaatgaa gccagggaag tggccttcga cctggaaatc cccaagacag
      301 cattcatcag tgactttgcc gttacagcag atggaaacgc atttatcgga gacataaagg
      361 acaaggtgac tgcatggaag cagtaccgga aagcagctat ctcaggagag aatgccggcc
      421 ttgtcagggc ctcggggaga actatggagc aattcaccat ccacctcacc gtcaatcccc
      481 agagcaaggt cacgtttcag ctgacttatg aggaagtgct gaagagaaac catatgcagt
      541 atgaaattgt catcaaagtc aagcccaagc agctggtgca tcattttgag attgatgtgg
      601 acatcttcga gccccagggg atcagcaagc tggatgccca ggcctctttc ctgccgaagg
      661 aactggcagc ccaaactatc aagaagtcct tctcaggaaa aaagggtcat gtgctgttcc
      721 gtcccaccgt gagccagcag cagtcctgcc ccacatgctc tacatcctta ctgaacgggc
      781 acttcaaggt gacctacgat gtcagtcgag acaagatctg cgacctcctg gtggccaata
      841 accactttgc ccacttcttt gccccccaaa acctgacaaa catgaacaag aacgtggttt
      901 ttgtgattga catcagtggc tccatgagag gccagaaagt gaagcagacc aaggaggcac
      961 tccttaaaat tctgggggac atgcagccag gggactactt tgacctggtt ctttttggga
     1021 ctcgagtaca atcgtggaag ggctcgctgg tgcaagcatc tgaggccaac ctacaagcag
     1081 ctcaagactt tgtgcggggc ttttccctgg atgaggccac aaacctgaat ggaggtttgc
     1141 tccggggaat tgagatcttg aaccaagttc aggaaagcct cccagaactc agcaaccatg
     1201 cctcaatact catcatgttg acagatggcg atcccacaga gggggtgacg gaccgttccc
     1261 aaatcctcaa gaacgtccgc aacgccatcc ggggcaggtt cccgctctac aacctgggtt
     1321 tcggccacaa tgtggacttt aactttctgg aggtcatgtc catggagaac aacggacggg
     1381 cccagagaat ctacgaggac catgatgcca cccagcagct gcagggtttc tacagccagg
     1441 tagccaaacc cctgctggtg gatgtggatt tgcagtaccc ccaggatgct gtcttggccc
     1501 tgacccagaa ccaccataaa cagtactacg aaggctcaga gattgtggtg gccgggcgca
     1561 ttgctgacaa caaacagagc agcttcaagg ctgatgtgca ggcccatggg gagggacaag
     1621 aattcagtat aacctgccta gtggatgagg aggagatgaa gaaactgctc cgagagcgtg
     1681 gccacatgct ggagaaccac gtcgagcgcc tctgggccta cctcaccatc caggagctgc
     1741 tggccaagcg gatgaaggtg gacagggagg agagggccaa cctgtcatcc caggccctgc
     1801 agatgtcgct ggactatggg tttgtgaccc cactgacctc catgagcatc aggggcatgg
     1861 cggaccagga cggcctgaag cccaccatcg acaagccctc agaggattct ccgcctttgg
     1921 agatgctggg acccagaagg acgttcgtgc tgtcagcctt gcagccttct cctactcatt
     1981 ccagctccaa tacccagcgg ctgccagacc gagtgaccgg cgtggacaca gaccctcact
     2041 tcatcatcca cgtgccccag aaagaggaca ccctgtgctt caacatcaat gaggagcctg
     2101 gtgttatcct gagcctggta caggacccca acacaggctt ctcagtgaat ggacagctca
     2161 ttggcaacaa ggccaggagc cctgggcagc atgacggcac gtacttcggg cggctgggaa
     2221 tcgcaaaccc tgccacggac tttcagttgg aagtgactcc tcagaacatt acgctgaacc
     2281 ccggctttgg tgggcctgtg ttttcctgga gggaccaagc tgtgctgcgg caggacgggg
     2341 tggtggtgac catcaacaag aagaggaacc tggtggtgtc tgtggacgac ggtggcacct
     2401 ttgaggttgt tttgcaccga gtgtggaagg ggagctcggt ccaccaggac ttcctgggct
     2461 tctatgtgct ggacagtcat cggatgtcag cccggacgca cgggctgctg gggcaatttt
     2521 tccaccccat cggttttgaa gtgtctgaca tccacccagg ctctgacccc acaaagccag
     2581 atgccacgat ggtggtgagg aaccgccggc tcacggtcac caggggtttg caaaaagact
     2641 acagcaagga cccgtggcat ggggccgagg tgtcctgctg gttcattcac aacaatgggg
     2701 ctggactcat cgatggtgcc tacactgatt atatcgtccc cgacatcttc tgagccctct
     2761 ggccagcacg cctgtcctcc cccggggcca aggcagagga ggaggacgac atcctgacct
     2821 gctgctgagg ctgtacctcc ttgactaagc tggttccttg tgtcaaagca cctcatgcct
     2881 tccattaaag agaggccgtg tcca
//
