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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR Genevisible; Q14624; HS. 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 //