ID ITIH4_HUMAN Reviewed; 930 AA.
AC Q14624; B7Z545; E9PGN5; Q15135; Q9P190; Q9UQ54;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 4.
DT 24-JAN-2024, entry version 196.
DE RecName: Full=Inter-alpha-trypsin inhibitor heavy chain H4;
DE Short=ITI heavy chain H4;
DE Short=ITI-HC4;
DE Short=Inter-alpha-inhibitor heavy chain 4;
DE AltName: Full=Inter-alpha-trypsin inhibitor family heavy chain-related protein;
DE Short=IHRP;
DE AltName: Full=Plasma kallikrein sensitive glycoprotein 120;
DE Short=Gp120;
DE Short=PK-120;
DE Contains:
DE RecName: Full=70 kDa inter-alpha-trypsin inhibitor heavy chain H4;
DE Contains:
DE RecName: Full=35 kDa inter-alpha-trypsin inhibitor heavy chain H4;
DE Flags: Precursor;
GN Name=ITIH4; Synonyms=IHRP, ITIHL1, PK120; ORFNames=PRO1851;
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] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=7805892; DOI=10.1016/0014-5793(94)01364-7;
RA Nishimura H., Kakizaki I., Muta T., Sasaki N., Pu P.X., Yamashita T.,
RA Nagasawa S.;
RT "cDNA and deduced amino acid sequence of human PK-120, a plasma kallikrein-
RT sensitive glycoprotein.";
RL FEBS Lett. 357:207-211(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE,
RP IDENTIFICATION, TISSUE SPECIFICITY, AND VARIANT ASN-85.
RC TISSUE=Liver;
RX PubMed=7775381; DOI=10.1093/oxfordjournals.jbchem.a124701;
RA Saguchi K., Tobe T., Hashimoto K., Sano Y., Nakano Y., Miura N.-H.,
RA Tomita M.;
RT "Cloning and characterization of cDNA for inter-alpha-trypsin inhibitor
RT family heavy chain-related protein (IHRP), a novel human plasma
RT glycoprotein.";
RL J. Biochem. 117:14-18(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=8797089; DOI=10.1093/oxfordjournals.jbchem.a021327;
RA Saguchi K., Tobe T., Hashimoto K., Nagasaki Y., Oda E., Nakano Y.,
RA Miura N.H., Tomita M.;
RT "Isolation and characterization of the human inter-alpha-trypsin inhibitor
RT family heavy chain-related protein (IHRP) gene (ITIHL1).";
RL J. Biochem. 119:898-905(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND INTERACTION WITH DNAJC1.
RX PubMed=16271702; DOI=10.1016/j.bbrc.2005.10.101;
RA Kroczynska B., King-Simmons L., Alloza L., Alava M.A., Elguindi E.C.,
RA Blond S.Y.;
RT "BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-trypsin inhibitor
RT heavy chain 4.";
RL Biochem. Biophys. Res. Commun. 338:1467-1477(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 271-930 (ISOFORM 2).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F.;
RT "Functional prediction of the coding sequences of 79 new genes deduced by
RT analysis of cDNA clones from human fetal liver.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP PROTEIN SEQUENCE OF 29-44; 99-119; 140-151; 163-170; 194-208; 211-243;
RP 274-281; 290-329; 429-487; 497-567; 608-626 AND 816-831, PROTEOLYTIC
RP PROCESSING, AND GLYCOSYLATION.
RC TISSUE=Plasma;
RX PubMed=7541790; DOI=10.1093/jb/117.2.400;
RA Choi-Miura N.-H., Sano Y., Oda E., Nakano Y., Tobe T., Yanagishita T.,
RA Taniyama M., Katagiri T., Tomita M.;
RT "Purification and characterization of a novel glycoprotein which has
RT significant homology to heavy chains of inter-alpha-trypsin inhibitor
RT family from human plasma.";
RL J. Biochem. 117:400-407(1995).
RN [9]
RP PARTIAL PROTEIN SEQUENCE, AND PROTEOLYTIC PROCESSING.
RX PubMed=7947966; DOI=10.1016/0167-4838(94)90122-8;
RA Pu X.P., Iwamoto A., Nishimura H., Nagasawa S.;
RT "Purification and characterization of a novel substrate for plasma
RT kallikrein (PK-120) in human plasma.";
RL Biochim. Biophys. Acta 1208:338-343(1994).
RN [10]
RP IDENTIFICATION, AND INDUCTION.
RX PubMed=10486281; DOI=10.1006/bbrc.1999.1349;
RA Pineiro M., Alava M.A., Gonzalez-Ramon N., Osada J., Lasierra P.,
RA Larrad L., Pineiro A., Lampreave F.;
RT "ITIH4 serum concentration increases during acute-phase processes in human
RT patients and is up-regulated by interleukin-6 in hepatocarcinoma HepG2
RT cells.";
RL Biochem. Biophys. Res. Commun. 263:224-229(1999).
RN [11]
RP GLYCOSYLATION AT ASN-207.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-517.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81; ASN-207; ASN-517 AND
RP ASN-577.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [14]
RP FUNCTION, AND INDUCTION.
RX PubMed=19263524; DOI=10.1016/j.cca.2009.01.009;
RA Kashyap R.S., Nayak A.R., Deshpande P.S., Kabra D., Purohit H.J.,
RA Taori G.M., Daginawala H.F.;
RT "Inter-alpha-trypsin inhibitor heavy chain 4 is a novel marker of acute
RT ischemic stroke.";
RL Clin. Chim. Acta 402:160-163(2009).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81; ASN-207 AND ASN-517.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [16]
RP POSSIBLE ROLE OF ACTIVE PEPTIDE AS A BIOMARKER FOR BREAST CANCER.
RX PubMed=21137033; DOI=10.1002/prca.201000035;
RA van den Broek I., Sparidans R.W., van Winden A.W., Gast M.C.,
RA van Dulken E.J., Schellens J.H., Beijnen J.H.;
RT "The absolute quantification of eight inter-alpha-trypsin inhibitor heavy
RT chain 4 (ITIH4)-derived peptides in serum from breast cancer patients.";
RL Proteomics Clin. Appl. 4:931-939(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP GLYCOSYLATION AT THR-720, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [19]
RP GLYCOSYLATION AT ASN-81; ASN-207; ASN-274; ASN-517 AND ASN-577, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=24884609; DOI=10.1021/pr500394z;
RA Chandler K.B., Brnakova Z., Sanda M., Wang S., Stalnaker S.H., Bridger R.,
RA Zhao P., Wells L., Edwards N.J., Goldman R.;
RT "Site-specific glycan microheterogeneity of inter-alpha-trypsin inhibitor
RT heavy chain H4.";
RL J. Proteome Res. 13:3314-3329(2014).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP VARIANT ASN-86.
RX PubMed=12147176; DOI=10.1186/1471-2350-3-6;
RA Tozaki T., Choi-Miura N.-H., Taniyama M., Kurosawa M., Tomita M.;
RT "SNP analysis of the inter-alpha-trypsin inhibitor family heavy chain-
RT related protein (IHRP) gene by a fluorescence-adapted SSCP method.";
RL BMC Med. Genet. 3:6-6(2002).
CC -!- FUNCTION: Type II acute-phase protein (APP) involved in inflammatory
CC responses to trauma. May also play a role in liver development or
CC regeneration. {ECO:0000269|PubMed:19263524}.
CC -!- SUBUNIT: Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain);
CC this interaction protects ITIH4 against cleavage by kallikrein in
CC vitro. {ECO:0000269|PubMed:16271702}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q14624-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14624-2; Sequence=VSP_002761, VSP_002762;
CC Name=3;
CC IsoId=Q14624-3; Sequence=VSP_002761;
CC Name=4;
CC IsoId=Q14624-4; Sequence=VSP_002761, VSP_044764, VSP_044765;
CC -!- TISSUE SPECIFICITY: Liver specific. {ECO:0000269|PubMed:7775381,
CC ECO:0000269|PubMed:7805892}.
CC -!- INDUCTION: Levels increase from 1.4 to 3-fold in acute-phase processes
CC such as in acute ischemia stroke (AIS), unstable angina and programmed
CC surgery. In hepatocytes, induced by IL6 but not by other cytokines such
CC as IL1B. {ECO:0000269|PubMed:10486281, ECO:0000269|PubMed:19263524}.
CC -!- PTM: Cleaved by plasma kallikrein to yield 100 kDa and 35 kDa
CC fragments, and the resulting 100 kDa fragment is further converted to a
CC 70 kDa fragment.
CC -!- PTM: N- and O-glycosylated. In urine, O-linked glycosylation on
CC threonine residues in the region from Thr-719 to Thr-725 consists of
CC core 1 or possibly core 8 glycans. Mainly Hex(HexNAc)(2), but also some
CC Hex(3)(HexNAc)(3). N-glycosylated but not O-glycosylated in plasma.
CC {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718,
CC ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:7541790}.
CC -!- MISCELLANEOUS: Possible biomarker for acute ischemic stroke
CC (PubMed:19263524). Peptides derived from the proline-rich potentially
CC active peptide (PRO_0000016542) may be biomarkers for a variety of
CC disease states including breast cancer (PubMed:21137033).
CC {ECO:0000305|PubMed:19263524, ECO:0000305|PubMed:21137033}.
CC -!- SIMILARITY: Belongs to the ITIH family. {ECO:0000305}.
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DR EMBL; D38535; BAA07536.1; -; mRNA.
DR EMBL; D38595; BAA07602.1; -; mRNA.
DR EMBL; U43163; AAD05198.1; -; Genomic_DNA.
DR EMBL; U42015; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U42016; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U43155; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U43156; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U43157; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U43158; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U43159; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U43160; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U43161; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; U43162; AAD05198.1; JOINED; Genomic_DNA.
DR EMBL; AK298412; BAH12781.1; -; mRNA.
DR EMBL; AC006254; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC099667; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF119856; AAF69610.1; -; mRNA.
DR CCDS; CCDS2865.1; -. [Q14624-1]
DR CCDS; CCDS54596.1; -. [Q14624-3]
DR PIR; JX0368; JX0368.
DR RefSeq; NP_001159921.1; NM_001166449.1. [Q14624-3]
DR RefSeq; NP_002209.2; NM_002218.4. [Q14624-1]
DR AlphaFoldDB; Q14624; -.
DR SMR; Q14624; -.
DR BioGRID; 109906; 28.
DR IntAct; Q14624; 3.
DR STRING; 9606.ENSP00000266041; -.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR CarbonylDB; Q14624; -.
DR GlyConnect; 711; 67 N-Linked glycans (5 sites), 10 O-Linked glycans (3 sites).
DR GlyCosmos; Q14624; 14 sites, 127 glycans.
DR GlyGen; Q14624; 14 sites, 120 N-linked glycans (5 sites), 14 O-linked glycans (9 sites).
DR iPTMnet; Q14624; -.
DR PhosphoSitePlus; Q14624; -.
DR SwissPalm; Q14624; -.
DR BioMuta; ITIH4; -.
DR DMDM; 229463048; -.
DR EPD; Q14624; -.
DR jPOST; Q14624; -.
DR MassIVE; Q14624; -.
DR PaxDb; 9606-ENSP00000266041; -.
DR PeptideAtlas; Q14624; -.
DR ProteomicsDB; 20355; -.
DR ProteomicsDB; 60074; -. [Q14624-1]
DR ProteomicsDB; 60075; -. [Q14624-2]
DR Antibodypedia; 862; 471 antibodies from 36 providers.
DR DNASU; 3700; -.
DR Ensembl; ENST00000266041.9; ENSP00000266041.4; ENSG00000055955.17. [Q14624-1]
DR Ensembl; ENST00000406595.5; ENSP00000384425.1; ENSG00000055955.17. [Q14624-3]
DR GeneID; 3700; -.
DR KEGG; hsa:3700; -.
DR MANE-Select; ENST00000266041.9; ENSP00000266041.4; NM_002218.5; NP_002209.2.
DR UCSC; uc003dfz.4; human. [Q14624-1]
DR AGR; HGNC:6169; -.
DR CTD; 3700; -.
DR DisGeNET; 3700; -.
DR GeneCards; ITIH4; -.
DR HGNC; HGNC:6169; ITIH4.
DR HPA; ENSG00000055955; Tissue enriched (liver).
DR MIM; 600564; gene.
DR neXtProt; NX_Q14624; -.
DR OpenTargets; ENSG00000055955; -.
DR PharmGKB; PA29967; -.
DR VEuPathDB; HostDB:ENSG00000055955; -.
DR eggNOG; ENOG502QPS2; Eukaryota.
DR GeneTree; ENSGT00940000161039; -.
DR HOGENOM; CLU_008101_0_0_1; -.
DR InParanoid; Q14624; -.
DR OMA; EFIYWIN; -.
DR OrthoDB; 608326at2759; -.
DR PhylomeDB; Q14624; -.
DR TreeFam; TF328982; -.
DR PathwayCommons; Q14624; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR SignaLink; Q14624; -.
DR BioGRID-ORCS; 3700; 19 hits in 1151 CRISPR screens.
DR ChiTaRS; ITIH4; human.
DR GeneWiki; ITIH4; -.
DR GenomeRNAi; 3700; -.
DR Pharos; Q14624; Tbio.
DR PRO; PR:Q14624; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q14624; Protein.
DR Bgee; ENSG00000055955; Expressed in right lobe of liver and 106 other cell types or tissues.
DR ExpressionAtlas; Q14624; baseline and differential.
DR Genevisible; Q14624; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0031089; C:platelet dense granule lumen; TAS:Reactome.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0006953; P:acute-phase response; IEP:UniProtKB.
DR GO; GO:0030212; P:hyaluronan metabolic process; IEA:InterPro.
DR GO; GO:0034097; P:response to cytokine; IEP:UniProtKB.
DR CDD; cd01461; vWA_interalpha_trypsin_inhibitor; 1.
DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1.
DR InterPro; IPR010600; ITI_HC_C.
DR InterPro; IPR013694; VIT.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR PANTHER; PTHR10338; INTER-ALPHA-TRYPSIN INHIBITOR HEAVY CHAIN FAMILY MEMBER; 1.
DR PANTHER; PTHR10338:SF119; INTER-ALPHA-TRYPSIN INHIBITOR HEAVY CHAIN H4; 1.
DR Pfam; PF06668; ITI_HC_C; 1.
DR Pfam; PF08487; VIT; 1.
DR Pfam; PF00092; VWA; 1.
DR SMART; SM00609; VIT; 1.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; vWA-like; 1.
DR PROSITE; PS51468; VIT; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW Acute phase; Alternative splicing; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Protease inhibitor; Reference proteome;
KW Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:7541790"
FT CHAIN 29..661
FT /note="70 kDa inter-alpha-trypsin inhibitor heavy chain H4"
FT /id="PRO_0000016541"
FT PROPEP 662..688
FT /note="Potentially active peptide"
FT /id="PRO_0000016542"
FT CHAIN 689..930
FT /note="35 kDa inter-alpha-trypsin inhibitor heavy chain H4"
FT /id="PRO_0000016543"
FT DOMAIN 29..148
FT /note="VIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00801"
FT DOMAIN 272..432
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT REGION 595..618
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 658..688
FT /note="Proline-rich (PRR) potential bioactive peptide"
FT REGION 719..725
FT /note="O-glycosylated at three sites"
FT COMPBIAS 600..614
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 688..689
FT /note="Cleavage; by kallikrein"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:24884609"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:24884609"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine; atypical"
FT /evidence="ECO:0000269|PubMed:24884609"
FT CARBOHYD 517
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:24884609"
FT CARBOHYD 577
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:24884609"
FT CARBOHYD 719
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q3T052"
FT CARBOHYD 720
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 722
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q3T052"
FT DISULFID 747..925
FT /evidence="ECO:0000305"
FT VAR_SEQ 621..650
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:16271702, ECO:0000303|Ref.7"
FT /id="VSP_002761"
FT VAR_SEQ 727..765
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16271702"
FT /id="VSP_044764"
FT VAR_SEQ 727
FT /note="A -> ACPSCSRSRAPAVPA (in isoform 2)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_002762"
FT VAR_SEQ 851..866
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16271702"
FT /id="VSP_044765"
FT VARIANT 85
FT /note="I -> N (in dbSNP:rs13072536)"
FT /evidence="ECO:0000269|PubMed:7775381"
FT /id="VAR_027869"
FT VARIANT 86
FT /note="I -> N"
FT /evidence="ECO:0000269|PubMed:12147176"
FT /id="VAR_013836"
FT VARIANT 669
FT /note="Q -> L (in dbSNP:rs2276814)"
FT /id="VAR_027870"
FT VARIANT 698
FT /note="P -> T (in dbSNP:rs4687657)"
FT /id="VAR_027871"
FT VARIANT 714
FT /note="M -> I (in dbSNP:rs2256734)"
FT /id="VAR_027872"
FT VARIANT 791
FT /note="L -> P (in dbSNP:rs2535621)"
FT /id="VAR_027873"
FT CONFLICT 85
FT /note="I -> K (in Ref. 3; AAD05198)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="S -> N (in Ref. 2; BAA07602)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="N -> F (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 221
FT /note="Q -> E (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="R -> V (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="W -> Y (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 370
FT /note="E -> G (in Ref. 6; BAH12781)"
FT /evidence="ECO:0000305"
FT CONFLICT 816..817
FT /note="ET -> QR (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 905
FT /note="S -> F (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 927
FT /note="S -> T (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 930 AA; 103357 MW; 847A9A5CB886C5A4 CRC64;
MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR
ANTVQEATFQ MELPKKAFIT NFSMIIDGMT YPGIIKEKAE AQAQYSAAVA KGKSAGLVKA
TGRNMEQFQV SVSVAPNAKI TFELVYEELL KRRLGVYELL LKVRPQQLVK HLQMDIHIFE
PQGISFLETE STFMTNQLVD ALTTWQNKTK AHIRFKPTLS QQQKSPEQQE TVLDGNLIIR
YDVDRAISGG SIQIENGYFV HYFAPEGLTT MPKNVVFVID KSGSMSGRKI QQTREALIKI
LDDLSPRDQF NLIVFSTEAT QWRPSLVPAS AENVNKARSF AAGIQALGGT NINDAMLMAV
QLLDSSNQEE RLPEGSVSLI ILLTDGDPTV GETNPRSIQN NVREAVSGRY SLFCLGFGFD
VSYAFLEKLA LDNGGLARRI HEDSDSALQL QDFYQEVANP LLTAVTFEYP SNAVEEVTQN
NFRLLFKGSE MVVAGKLQDR GPDVLTATVS GKLPTQNITF QTESSVAEQE AEFQSPKYIF
HNFMERLWAY LTIQQLLEQT VSASDADQQA LRNQALNLSL AYSFVTPLTS MVVTKPDDQE
QSQVAEKPME GESRNRNVHS GSTFFKYYLQ GAKIPKPEAS FSPRRGWNRQ AGAAGSRMNF
RPGVLSSRQL GLPGPPDVPD HAAYHPFRRL AILPASAPPA TSNPDPAVSR VMNMKIEETT
MTTQTPAPIQ APSAILPLPG QSVERLCVDP RHRQGPVNLL SDPEQGVEVT GQYEREKAGF
SWIEVTFKNP LVWVHASPEH VVVTRNRRSS AYKWKETLFS VMPGLKMTMD KTGLLLLSDP
DKVTIGLLFW DGRGEGLRLL LRDTDRFSSH VGGTLGQFYQ EVLWGSPAAS DDGRRTLRVQ
GNDHSATRER RLDYQEGPPG VEISCWSVEL
//
