LOCUS       NM_002217               2797 bp    mRNA    linear   PRI 08-APR-2024
DEFINITION  Homo sapiens inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3),
            transcript variant 4, mRNA.
ACCESSION   NM_002217
VERSION     NM_002217.4
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 2797)
  AUTHORS   Takeuchi,H., Tomita,H., Taki,Y., Kikuchi,Y., Ono Tanaka,C., Yu,Z.,
            Matsudaira,I., Nouchi,R., Imanishi,T. and Kawashima,R.
  TITLE     A psychiatric disorder risk polymorphism of ITIH3 is associated
            with multiple neuroimaging phenotypes in young healthy adults
  JOURNAL   Psychiatry Clin Neurosci 76 (6), 271-273 (2022)
   PUBMED   35261121
  REMARK    GeneRIF: A psychiatric disorder risk polymorphism of ITIH3 is
            associated with multiple neuroimaging phenotypes in young healthy
            adults.
REFERENCE   2  (bases 1 to 2797)
  AUTHORS   Li,Y., Ma,C., Li,S., Wang,J., Li,W., Yang,Y., Li,X., Liu,J.,
            Yang,J., Liu,Y., Li,K., Li,J., Huang,D., Chen,R., Lv,L., Xiao,X.,
            Li,M. and Luo,X.J.
  TITLE     Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia
            Risk By Regulating CTCF Binding and SFMBT1 Expression
  JOURNAL   Adv Sci (Weinh) 9 (6), e2104786 (2022)
   PUBMED   34978167
  REMARK    GeneRIF: Regulatory Variant rs2535629 in ITIH3 Intron Confers
            Schizophrenia Risk By Regulating CTCF Binding and SFMBT1
            Expression.
REFERENCE   3  (bases 1 to 2797)
  AUTHORS   Li,K., Li,Y., Wang,J., Huo,Y., Huang,D., Li,S., Liu,J., Li,X.,
            Liu,R., Chen,X., Yao,Y.G., Chen,C., Xiao,X., Li,M. and Luo,X.J.
  TITLE     A functional missense variant in ITIH3 affects protein expression
            and neurodevelopment and confers schizophrenia risk in the Han
            Chinese population
  JOURNAL   J Genet Genomics 47 (5), 233-248 (2020)
   PUBMED   32712163
  REMARK    GeneRIF: A functional missense variant in ITIH3 affects protein
            expression and neurodevelopment and confers schizophrenia risk in
            the Han Chinese population.
REFERENCE   4  (bases 1 to 2797)
  AUTHORS   Xie,X., Meng,H., Wu,H., Hou,F., Chen,Y., Zhou,Y., Xue,Q., Zhang,J.,
            Gong,J., Li,L. and Song,R.
  TITLE     Integrative analyses indicate an association between ITIH3
            polymorphisms with autism spectrum disorder
  JOURNAL   Sci Rep 10 (1), 5223 (2020)
   PUBMED   32251353
  REMARK    GeneRIF: Integrative analyses indicate an association between ITIH3
            polymorphisms with autism spectrum disorder.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2797)
  AUTHORS   Miyake,Y., Tanaka,K. and Arakawa,M.
  TITLE     ITIH3 and ITIH4 polymorphisms and depressive symptoms during
            pregnancy in Japan: the Kyushu Okinawa Maternal and Child Health
            Study
  JOURNAL   J Neural Transm (Vienna) 125 (10), 1503-1509 (2018)
   PUBMED   29992445
  REMARK    GeneRIF: ITIH3 SNPs rs2535629 and rs736408 were studied in pregnant
            depressed Japanese women. Neither was related to depressive
            symptoms during pregnancy.The GCCT haplotype of rs2535629,
            rs736408, rs3821831, and rs2239547 was significantly positively
            associated with depressive symptoms during pregnancy.
REFERENCE   6  (bases 1 to 2797)
  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   7  (bases 1 to 2797)
  AUTHORS   Enghild,J.J., Salvesen,G., Hefta,S.A., Thogersen,I.B.,
            Rutherfurd,S. and Pizzo,S.V.
  TITLE     Chondroitin 4-sulfate covalently cross-links the chains of the
            human blood protein pre-alpha-inhibitor
  JOURNAL   J Biol Chem 266 (2), 747-751 (1991)
   PUBMED   1898736
REFERENCE   8  (bases 1 to 2797)
  AUTHORS   Enghild,J.J., Thogersen,I.B., Pizzo,S.V. and Salvesen,G.
  TITLE     Analysis of inter-alpha-trypsin inhibitor and a novel trypsin
            inhibitor, pre-alpha-trypsin inhibitor, from human plasma.
            Polypeptide chain stoichiometry and assembly by glycan
  JOURNAL   J Biol Chem 264 (27), 15975-15981 (1989)
   PUBMED   2476436
REFERENCE   9  (bases 1 to 2797)
  AUTHORS   Diarra-Mehrpour,M., Bourguignon,J., Sesboue,R., Mattei,M.G.,
            Passage,E., Salier,J.P. and Martin,J.P.
  TITLE     Human plasma inter-alpha-trypsin inhibitor is encoded by four genes
            on three chromosomes
  JOURNAL   Eur J Biochem 179 (1), 147-154 (1989)
   PUBMED   2465147
REFERENCE   10 (bases 1 to 2797)
  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 AC006254.10.
            
            On Feb 1, 2021 this sequence version replaced NM_002217.3.
            
            Summary: This gene encodes the heavy chain subunit of the
            pre-alpha-trypsin inhibitor complex. This complex may stabilize the
            extracellular matrix through its ability to bind hyaluronic acid.
            Polymorphisms of this gene may be associated with increased risk
            for schizophrenia and major depressive disorder. This gene is
            present in an inter-alpha-trypsin inhibitor family gene cluster on
            chromosome 3. [provided by RefSeq, Jul 2015].
            
            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 :: AK222757.1, AK223483.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968540
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000449956.3/ ENSP00000415769.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-101               AC006254.10        35860-35960         c
            102-122             AC006254.10        35133-35153         c
            123-289             AC006254.10        34109-34275         c
            290-394             AC006254.10        33913-34017         c
            395-557             AC006254.10        33489-33651         c
            558-671             AC006254.10        32826-32939         c
            672-797             AC006254.10        31665-31790         c
            798-914             AC006254.10        31268-31384         c
            915-1083            AC006254.10        30835-31003         c
            1084-1209           AC006254.10        30093-30218         c
            1210-1391           AC006254.10        29610-29791         c
            1392-1577           AC006254.10        28237-28422         c
            1578-1717           AC006254.10        27950-28089         c
            1718-1872           AC006254.10        26747-26901         c
            1873-1881           AC006254.10        26022-26030         c
            1882-1914           AC006254.10        24916-24948         c
            1915-1950           AC006254.10        24618-24653         c
            1951-2064           AC006254.10        24350-24463         c
            2065-2269           AC006254.10        23651-23855         c
            2270-2439           AC006254.10        22840-23009         c
            2440-2551           AC006254.10        22535-22646         c
            2552-2797           AC006254.10        21959-22204         c
FEATURES             Location/Qualifiers
     source          1..2797
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p21.1"
     gene            1..2797
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /note="inter-alpha-trypsin inhibitor heavy chain 3"
                     /db_xref="GeneID:3699"
                     /db_xref="HGNC:HGNC:6168"
                     /db_xref="MIM:146650"
     exon            1..101
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     CDS             9..2681
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /note="isoform 4 preproprotein is encoded by transcript
                     variant 4; pre-alpha (globulin) inhibitor, H3 polypeptide;
                     inter-alpha (globulin) inhibitor, H3 polypeptide;
                     inter-alpha-trypsin inhibitor heavy chain H3; ITI heavy
                     chain H3; inter-alpha (globulin) inhibitor H3;
                     inter-alpha-inhibitor heavy chain 3; serum-derived
                     hyaluronan-associated protein"
                     /codon_start=1
                     /product="inter-alpha-trypsin inhibitor heavy chain H3
                     isoform 4 preproprotein"
                     /protein_id="NP_002208.3"
                     /db_xref="CCDS:CCDS46845.1"
                     /db_xref="GeneID:3699"
                     /db_xref="HGNC:HGNC:6168"
                     /db_xref="MIM:146650"
                     /translation="MAFAWWPCLILALLSSLAASGFPRSPFRLLGKRSLPEGVANGIE
                     VYSTKINSKVTSRFAHNVVTMRAVNRADTAKEVSFDVELPKTAFITNFTLTIDGVTYP
                     GNVKEKEVAKKQYEKAVSQGKTAGLVKASGRKLEKFTVSVNVAAGSKVTFELTYEELL
                     KRHKGKYEMYLKVQPKQLVKHFEIEVDIFEPQGISMLDAEASFITNDLLGSALTKSFS
                     GKKGHVSFKPSLDQQRSCPTCTDSLLNGDFTITYDVNRESPGNVQIVNGYFVHFFAPQ
                     GLPVVPKNVAFVIDISGSMAGRKLEQTKEALLRILEDMQEEDYLNFILFSGDVSTWKE
                     HLVQATPENLQEARTFVKSMEDKGMTNINDGLLRGISMLNKAREEHRIPERSTSIVIM
                     LTDGDANVGESRPEKIQENVRNAIGGKFPLYNLGFGNNLNYNFLENMALENHGFARRI
                     YEDSDADLQLQGFYEEVANPLLTGVEMEYPENAILDLTQNTYQHFYDGSEIVVAGRLV
                     DEDMNSFKADVKGHGATNDLTFTEEVDMKEMEKALQERDYIFGNYIERLWAYLTIEQL
                     LEKRKNAHGEEKENLTARALDLSLKYHFVTPLTSMVVTKPEDNEDERAIADKPGEDAE
                     ATPVSPAMSYLTSYQPPQNPYYYVDGDPHFIIQIPEKDDALCFNIDEAPGTVLRLIQD
                     AVTGLTVNGQITGDKRGSPDSKTRKTYFGKLGIANAQMDFQVEVTTEKITLWNRAVPS
                     TFSWLDTVTVTQDGLSMMINRKNMVVSFGDGVTFVVVLHQVWKKHPVHRDFLGFYVVD
                     SHRMSAQTHGLLGQFFQPFDFKVSDIRPGSDPTKPDATLVVKNHQLIVTRGSQKDYRK
                     DASIGTKVVCWFVHNNGEGLIDGVHTDYIVPNLF"
     exon            102..122
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            123..289
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            290..394
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            395..557
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            558..671
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            672..797
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            798..914
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            915..1083
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1084..1209
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1210..1391
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1392..1577
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1578..1717
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1718..1872
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1873..1881
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1882..1914
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1915..1950
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            1951..2064
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2065..2269
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2270..2439
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2440..2551
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     exon            2552..2797
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2775..2780
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /note="hexamer: AATAAA"
     polyA_site      2797
                     /gene="ITIH3"
                     /gene_synonym="H3P; ITI-HC3; SHAP"
                     /note="major polyA site"
ORIGIN      
        1 attcagcgat ggcatttgca tggtggccct gtctcatctt ggctctgctc tccagcttgg
       61 cagcctctgg cttcccgaga agcccctttc ggctgcttgg gaaacggagc ctcccggaag
      121 gggtggccaa tggcatcgag gtctacagta ccaaaatcaa ctccaaggtg acctcccgtt
      181 ttgctcacaa tgttgtcacc atgagagccg tcaaccgtgc agacacggcc aaggaggttt
      241 cctttgatgt ggagctgccc aagacggcct tcatcaccaa cttcaccttg accatcgacg
      301 gtgttaccta ccctgggaat gtcaaggaga aggaagttgc caagaagcag tatgaaaagg
      361 ctgtgtccca gggcaagacg gccggcttgg tcaaggcctc tgggaggaag ttggagaagt
      421 tcacagtctc ggtcaacgtg gctgcaggca gcaaagtcac cttcgagcta acctacgagg
      481 agctgctgaa gaggcacaag ggcaagtacg agatgtacct caaggtccag cctaagcaac
      541 tggtcaaaca ctttgagatc gaggtagaca tcttcgagcc tcagggaatc agcatgctgg
      601 atgctgaggc ctctttcatc accaacgacc tcctgggaag cgccctcacc aagtccttct
      661 cagggaaaaa gggccatgtg tccttcaagc ccagcttaga ccaacagcgt tcatgcccaa
      721 cctgtacaga ctccctcctc aatggagatt tcactatcac ctatgacgtg aacagagaat
      781 ctcctggcaa cgtgcagata gtcaatggct acttcgtgca cttctttgca cctcaaggcc
      841 ttccagtggt gcctaagaac gtggcctttg tgattgacat cagcggctcc atggctggtc
      901 ggaaattaga gcagacaaag gaggcccttc tcagaatcct ggaagatatg caagaggaag
      961 actatctgaa tttcatcctg ttcagtggag atgtgtccac atggaaagag cacttagtcc
     1021 aggccacgcc cgagaacctc caggaggcca ggacgtttgt gaagagcatg gaggataaag
     1081 gaatgaccaa catcaatgac gggctgctga ggggcatcag tatgctgaac aaggcccgag
     1141 aggagcacag aatcccagag aggagcacct ccattgtcat catgctgact gatggggatg
     1201 ccaatgttgg tgagagcaga cccgaaaaaa tccaagagaa tgtgcggaat gccatcgggg
     1261 gcaagttccc cttgtataac ctgggctttg gcaacaatct gaattataac ttcctggaga
     1321 acatggccct ggagaaccat gggtttgccc ggcgcattta tgaggactct gatgccgatt
     1381 tgcagttgca gggcttctat gaggaggtgg ccaacccact gctgacgggt gtggagatgg
     1441 agtaccccga gaacgctatc ctggacctca cccagaacac ttaccagcac ttctacgatg
     1501 gctctgagat cgtggtggcc gggcgcctgg tggacgagga catgaacagc tttaaggcag
     1561 atgtgaaggg ccatggggcc accaacgacc tgaccttcac agaggaggtg gacatgaagg
     1621 agatggagaa ggccctgcag gagcgggact acatcttcgg gaattacatt gagcggctct
     1681 gggcctacct caccattgag cagctgctgg agaagcgcaa gaacgcccat ggcgaggaga
     1741 aggagaacct cacggcccgg gccctggacc tgtccctcaa gtatcacttt gtgactccac
     1801 tgacctcaat ggtggtgacc aagcctgagg acaacgagga tgagagggcc attgccgaca
     1861 agcctgggga agatgcagaa gccacaccgg tgagccccgc catgtcctac ctgaccagct
     1921 accagcctcc tcaaaacccc tactactatg tggacgggga tccccacttc atcatccaaa
     1981 ttccggagaa agacgatgcc ctctgcttca acatcgatga agccccaggc acagtgctgc
     2041 gccttattca ggatgcagtc acaggcctca cagttaatgg gcagatcact ggcgacaaga
     2101 gaggcagccc tgactccaag accagaaaga cttactttgg aaaactgggc atcgccaatg
     2161 ctcagatgga cttccaggtg gaggtgacaa cggagaagat caccctgtgg aacagggccg
     2221 tgccgagcac tttcagctgg ctggacacag tcacagtcac gcaggatggg ctgtccatga
     2281 tgatcaacag gaagaacatg gtggtctcct ttggagatgg ggttaccttc gtggtcgtcc
     2341 tacaccaggt gtggaagaaa catcctgtcc accgtgactt tctaggcttc tacgtggtgg
     2401 acagtcaccg gatgtcagca cagacgcatg ggctgctggg gcaattcttc caaccctttg
     2461 actttaaagt gtctgacatc cggccaggct ctgaccccac aaagccagat gccacattgg
     2521 tggtgaagaa ccatcagctg attgtcacca ggggctccca gaaagactac agaaaggatg
     2581 ccagcatcgg cacgaaggtt gtctgctggt tcgtccacaa caacggagaa gggctgattg
     2641 atggtgtcca cactgactac attgtcccca acctgttttg agtagacaca ccagctcctg
     2701 ttgggatgga tggcccggat tttatggcat ctggaacatg ggcacagaga ggggcctgtg
     2761 ggaggggctg ggaaaataaa gtccaaggtc gagacca
//
