LOCUS       NP_002209                930 aa            linear   PRI 02-AUG-2024
DEFINITION  inter-alpha-trypsin inhibitor heavy chain H4 isoform 1 precursor
            [Homo sapiens].
ACCESSION   NP_002209
VERSION     NP_002209.2
DBSOURCE    REFSEQ: accession NM_002218.5
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  (residues 1 to 930)
  AUTHORS   Ravindran,A., Holappa,L., Niskanen,H., Skovorodkin,I., Kaisto,S.,
            Beter,M., Kiema,M., Selvarajan,I., Nurminen,V., Aavik,E.,
            Aherrahrou,R., Pasonen-Seppanen,S., Fortino,V., Laakkonen,J.P.,
            Yla-Herttuala,S., Vainio,S., Ord,T. and Kaikkonen,M.U.
  TITLE     Translatome profiling reveals Itih4 as a novel smooth muscle
            cell-specific gene in atherosclerosis
  JOURNAL   Cardiovasc Res 120 (8), 869-882 (2024)
   PUBMED   38289873
  REMARK    GeneRIF: Translatome profiling reveals Itih4 as a novel smooth
            muscle cell-specific gene in atherosclerosis.
REFERENCE   2  (residues 1 to 930)
  AUTHORS   Sun,Z., Zhang,Y., Zhou,H., Li,J., Zhou,Y. and Wang,L.
  TITLE     Serum interalpha-trypsin inhibitor heavy chain H4 may be an
            anti-inflammatory marker reflecting disease risk, activity and
            treatment outcome of ankylosing spondylitis
  JOURNAL   Scand J Clin Lab Invest 83 (8), 540-547 (2023)
   PUBMED   38156824
  REMARK    GeneRIF: Serum interalpha-trypsin inhibitor heavy chain H4 may be
            an anti-inflammatory marker reflecting disease risk, activity and
            treatment outcome of ankylosing spondylitis.
REFERENCE   3  (residues 1 to 930)
  AUTHORS   Du,J., Lin,Y., Liang,H., Li,J., Wang,F., Jiang,C. and Shao,B.
  TITLE     Hyperglycosylated N-Linked Site 339 of gp120 Appears to Be Unique
            and May Contribute to CRF01_AE Transmission Among Men Who Have Sex
            with Men in China and Thailand
  JOURNAL   AIDS Res Hum Retroviruses 39 (9), 505-510 (2023)
   PUBMED   37335061
  REMARK    GeneRIF: Hyperglycosylated N-Linked Site 339 of gp120 Appears to Be
            Unique and May Contribute to CRF01_AE Transmission Among Men Who
            Have Sex with Men in China and Thailand.
REFERENCE   4  (residues 1 to 930)
  AUTHORS   Park,H.B., Choi,B.C. and Baek,K.H.
  TITLE     PGK1 modulates balance between pro- and anti-inflammatory cytokines
            by interacting with ITI-H4
  JOURNAL   Biomed Pharmacother 161, 114437 (2023)
   PUBMED   36841032
  REMARK    GeneRIF: PGK1 modulates balance between pro- and anti-inflammatory
            cytokines by interacting with ITI-H4.
REFERENCE   5  (residues 1 to 930)
  AUTHORS   Huo,Y., Lai,Y., Feng,Q., Wang,Q. and Li,J.
  TITLE     Serum ITIH4 in coronary heart disease: a potential
            anti-inflammatory biomarker related to stenosis degree and risk of
            major adverse cardiovascular events
  JOURNAL   Biomark Med 16 (18), 1279-1288 (2022)
   PUBMED   36891881
  REMARK    GeneRIF: Serum ITIH4 in coronary heart disease: a potential
            anti-inflammatory biomarker related to stenosis degree and risk of
            major adverse cardiovascular events.
REFERENCE   6  (residues 1 to 930)
  AUTHORS   Saguchi,K., Tobe,T., Hashimoto,K., Nagasaki,Y., Oda,E., Nakano,Y.,
            Miura,N.H. and Tomita,M.
  TITLE     Isolation and characterization of the human inter-alpha-trypsin
            inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1)
  JOURNAL   J Biochem 119 (5), 898-905 (1996)
   PUBMED   8797089
REFERENCE   7  (residues 1 to 930)
  AUTHORS   Choi-Miura,N.H., Sano,Y., Oda,E., Nakano,Y., Tobe,T.,
            Yanagishita,T., Taniyama,M., Katagiri,T. and Tomita,M.
  TITLE     Purification and characterization of a novel glycoprotein which has
            significant homology to heavy chains of inter-alpha-trypsin
            inhibitor family from human plasma
  JOURNAL   J Biochem 117 (2), 400-407 (1995)
   PUBMED   7541790
REFERENCE   8  (residues 1 to 930)
  AUTHORS   Nishimura,H., Kakizaki,I., Muta,T., Sasaki,N., Pu,P.X.,
            Yamashita,T. and Nagasawa,S.
  TITLE     cDNA and deduced amino acid sequence of human PK-120, a plasma
            kallikrein-sensitive glycoprotein
  JOURNAL   FEBS Lett 357 (2), 207-211 (1995)
   PUBMED   7805892
REFERENCE   9  (residues 1 to 930)
  AUTHORS   Saguchi,K., Tobe,T., Hashimoto,K., Sano,Y., Nakano,Y., Miura,N.H.
            and Tomita,M.
  TITLE     Cloning and characterization of cDNA for inter-alpha-trypsin
            inhibitor family heavy chain-related protein (IHRP), a novel human
            plasma glycoprotein
  JOURNAL   J Biochem 117 (1), 14-18 (1995)
   PUBMED   7775381
REFERENCE   10 (residues 1 to 930)
  AUTHORS   Tobe,T., Saguchi,K., Hashimoto,K., Miura,N.H., Tomita,M., Li,F.,
            Wang,Y., Minoshima,S. and Shimizu,N.
  TITLE     Mapping of human inter-alpha-trypsin inhibitor family heavy
            chain-related protein gene (ITIHL1) to human chromosome 3p21-->p14
  JOURNAL   Cytogenet Cell Genet 71 (3), 296-298 (1995)
   PUBMED   7587397
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC136392.1, BC136393.1,
            AW291001.1 and AC006254.10.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 9, 2003 this sequence version replaced NP_002209.1.
            
            Summary: The protein encoded by this gene is secreted into the
            blood, where it is cleaved by plasma kallikrein into two smaller
            forms. Expression of this gene has been detected only in liver, and
            it seems to be upregulated during surgical trauma. This gene is
            part of a cluster of similar genes on chromosome 3. Two transcript
            variants encoding different isoforms have been found for this gene.
            [provided by RefSeq, Oct 2009].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: D38595.1, BC136393.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2155590 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000266041.9/ ENSP00000266041.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..930
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p21.1"
     Protein         1..930
                     /product="inter-alpha-trypsin inhibitor heavy chain H4
                     isoform 1 precursor"
                     /note="plasma kallikrein-sensitive glycoprotein 120;
                     inter-alpha-trypsin inhibitor, heavy chain-like, 1;
                     inter-alpha (globulin) inhibitor H4 (plasma
                     Kallikrein-sensitive glycoprotein); ITI heavy chain H4;
                     inter-alpha-inhibitor heavy chain 4; inter-alpha-trypsin
                     inhibitor family heavy chain-related protein;
                     inter-alpha-trypsin inhibitor heavy chain family member 4"
                     /calculated_mol_wt=100301
     sig_peptide     1..28
                     /inference="COORDINATES: ab initio prediction:SignalP:6.0"
                     /calculated_mol_wt=3075
     Region          21..148
                     /region_name="VIT"
                     /note="Vault protein Inter-alpha-Trypsin domain;
                     smart00609"
                     /db_xref="CDD:197803"
     mat_peptide     29..930
                     /product="inter-alpha-trypsin inhibitor heavy chain H4
                     isoform 1"
                     /calculated_mol_wt=100301
     Site            81
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952,
                     ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:24884609;
                     propagated from UniProtKB/Swiss-Prot (Q14624.4)"
     Site            207
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:12754519,
                     ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
                     ECO:0000269|PubMed:24884609; propagated from
                     UniProtKB/Swiss-Prot (Q14624.4)"
     Region          271..452
                     /region_name="vWA_interalpha_trypsin_inhibitor"
                     /note="vWA_interalpha trypsin inhibitor (ITI): ITI is a
                     glycoprotein composed of three polypeptides- two heavy
                     chains and one light chain (bikunin). Bikunin confers the
                     protease-inhibitor function while the heavy chains are
                     involved in rendering stability to...; cd01461"
                     /db_xref="CDD:238738"
     Site            274
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine, atypical.
                     /evidence=ECO:0000269|PubMed:24884609; propagated from
                     UniProtKB/Swiss-Prot (Q14624.4)"
     Site            order(280,282,284,350,385)
                     /site_type="other"
                     /note="metal ion-dependent adhesion site (MIDAS)"
                     /db_xref="CDD:238738"
     Site            517
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:14760718,
                     ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
                     ECO:0000269|PubMed:24884609; propagated from
                     UniProtKB/Swiss-Prot (Q14624.4)"
     Site            577
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952,
                     ECO:0000269|PubMed:24884609; propagated from
                     UniProtKB/Swiss-Prot (Q14624.4)"
     Region          595..618
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14624.4)"
     Region          658..688
                     /region_name="Proline-rich (PRR) potential bioactive
                     peptide"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14624.4)"
     Site            688..689
                     /site_type="cleavage"
                     /note="Cleavage, by kallikrein; propagated from
                     UniProtKB/Swiss-Prot (Q14624.4)"
     Region          719..725
                     /region_name="O-glycosylated at three sites"
                     /note="propagated from UniProtKB/Swiss-Prot (Q14624.4)"
     Site            719
                     /site_type="glycosylation"
                     /note="O-linked (GalNAc...) threonine.
                     /evidence=ECO:0000250|UniProtKB:Q3T052; propagated from
                     UniProtKB/Swiss-Prot (Q14624.4)"
     Site            720
                     /site_type="glycosylation"
                     /note="O-linked (GalNAc...) threonine.
                     /evidence=ECO:0000269|PubMed:22171320; propagated from
                     UniProtKB/Swiss-Prot (Q14624.4)"
     Site            722
                     /site_type="glycosylation"
                     /note="O-linked (GalNAc...) threonine.
                     /evidence=ECO:0000250|UniProtKB:Q3T052; propagated from
                     UniProtKB/Swiss-Prot (Q14624.4)"
     Region          764..928
                     /region_name="ITI_HC_C"
                     /note="Inter-alpha-trypsin inhibitor heavy chain
                     C-terminus; cl46397"
                     /db_xref="CDD:480737"
     CDS             1..930
                     /gene="ITIH4"
                     /gene_synonym="GP120; H4P; IHRP; ITI-HC4; ITIHL1; PK-120;
                     PK120"
                     /coded_by="NM_002218.5:31..2823"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS2865.1"
                     /db_xref="GeneID:3700"
                     /db_xref="HGNC:HGNC:6169"
                     /db_xref="MIM:600564"
ORIGIN      
        1 mkpprpvrtc skvlvllsll aihqtttaek ngidiysltv dsrvssrfah tvvtsrvvnr
       61 antvqeatfq melpkkafit nfsmiidgmt ypgiikekae aqaqysaava kgksaglvka
      121 tgrnmeqfqv svsvapnaki tfelvyeell krrlgvyell lkvrpqqlvk hlqmdihife
      181 pqgisflete stfmtnqlvd alttwqnktk ahirfkptls qqqkspeqqe tvldgnliir
      241 ydvdraisgg siqiengyfv hyfapegltt mpknvvfvid ksgsmsgrki qqtrealiki
      301 lddlsprdqf nlivfsteat qwrpslvpas aenvnkarsf aagiqalggt nindamlmav
      361 qlldssnqee rlpegsvsli illtdgdptv getnprsiqn nvreavsgry slfclgfgfd
      421 vsyaflekla ldngglarri hedsdsalql qdfyqevanp lltavtfeyp snaveevtqn
      481 nfrllfkgse mvvagklqdr gpdvltatvs gklptqnitf qtessvaeqe aefqspkyif
      541 hnfmerlway ltiqqlleqt vsasdadqqa lrnqalnlsl aysfvtplts mvvtkpddqe
      601 qsqvaekpme gesrnrnvhs gstffkyylq gakipkpeas fsprrgwnrq agaagsrmnf
      661 rpgvlssrql glpgppdvpd haayhpfrrl ailpasappa tsnpdpavsr vmnmkieett
      721 mttqtpapiq apsailplpg qsverlcvdp rhrqgpvnll sdpeqgvevt gqyerekagf
      781 swievtfknp lvwvhaspeh vvvtrnrrss aykwketlfs vmpglkmtmd ktgllllsdp
      841 dkvtigllfw dgrgeglrll lrdtdrfssh vggtlgqfyq evlwgspaas ddgrrtlrvq
      901 gndhsatrer rldyqegppg veiscwsvel
//
