ITIH4_MOUSE
ID ITIH4_MOUSE Reviewed; 942 AA.
AC A6X935; O54882; Q505P8; Q8C7G9; Q8C7K5; Q91W60; Q9DBK8;
DT 09-JAN-2013, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 2.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Inter alpha-trypsin inhibitor, heavy chain 4;
DE Short=ITI heavy chain H4;
DE Short=ITI-HC4;
DE Short=Inter-alpha-inhibitor heavy chain 4;
DE Flags: Precursor;
GN Name=Itih4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP POSSIBLE FUNCTION.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=9602042; DOI=10.1016/s0167-4781(98)00049-9;
RA Cai T., Yu P., Monga S.P.S., Mishra B., Mishra L.;
RT "Identification of mouse itih-4 encoding a glycoprotein with two EF-hand
RT motifs from early embryonic liver.";
RL Biochim. Biophys. Acta 1398:32-37(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH DNJAC1.
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 [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81; ASN-517; ASN-577 AND
RP ASN-874.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81; ASN-517; ASN-577 AND
RP ASN-874.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=17330941; DOI=10.1021/pr0604559;
RA Bernhard O.K., Kapp E.A., Simpson R.J.;
RT "Enhanced analysis of the mouse plasma proteome using cysteine-containing
RT tryptic glycopeptides.";
RL J. Proteome Res. 6:987-995(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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.
CC -!- SUBUNIT: Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain).
CC {ECO:0000269|PubMed:16271702}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A6X935-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A6X935-2; Sequence=VSP_044763;
CC -!- TISSUE SPECIFICITY: Highly expressed in liver. Weak expression in lung
CC and heart. {ECO:0000269|PubMed:9602042}.
CC -!- DEVELOPMENTAL STAGE: During mid-embryonic gestation, expressed
CC abundantly in liver, less in heart and brain. Highest expression at day
CC 14.5. {ECO:0000269|PubMed:9602042}.
CC -!- PTM: May be O-glycosylated (By similarity). N-glycosylated.
CC {ECO:0000250, ECO:0000269|PubMed:16944957,
CC ECO:0000269|PubMed:17330941}.
CC -!- SIMILARITY: Belongs to the ITIH family. {ECO:0000305}.
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DR EMBL; AF023919; AAC25786.1; -; mRNA.
DR EMBL; AK004893; BAB23649.1; -; mRNA.
DR EMBL; AK050016; BAC34032.1; -; mRNA.
DR EMBL; AK050270; BAC34155.1; -; mRNA.
DR EMBL; CT025528; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466573; EDL24772.1; -; Genomic_DNA.
DR EMBL; BC016500; AAH16500.1; -; mRNA.
DR EMBL; BC092258; AAH92258.1; -; mRNA.
DR EMBL; BC094457; AAH94457.1; -; mRNA.
DR CCDS; CCDS26901.1; -. [A6X935-1]
DR RefSeq; NP_001152771.1; NM_001159299.2.
DR RefSeq; NP_001276561.1; NM_001289632.1.
DR RefSeq; NP_001276562.1; NM_001289633.1.
DR RefSeq; NP_061216.2; NM_018746.4. [A6X935-1]
DR AlphaFoldDB; A6X935; -.
DR SMR; A6X935; -.
DR BioGRID; 200839; 2.
DR IntAct; A6X935; 1.
DR STRING; 10090.ENSMUSP00000006703; -.
DR GlyConnect; 786; 1 N-Linked glycan (1 site).
DR GlyGen; A6X935; 5 sites, 2 N-linked glycans (1 site).
DR iPTMnet; A6X935; -.
DR PhosphoSitePlus; A6X935; -.
DR CPTAC; non-CPTAC-3554; -.
DR jPOST; A6X935; -.
DR MaxQB; A6X935; -.
DR PaxDb; A6X935; -.
DR PeptideAtlas; A6X935; -.
DR PRIDE; A6X935; -.
DR ProteomicsDB; 269108; -. [A6X935-1]
DR ProteomicsDB; 269109; -. [A6X935-2]
DR Antibodypedia; 862; 429 antibodies from 36 providers.
DR DNASU; 16427; -.
DR Ensembl; ENSMUST00000120269; ENSMUSP00000112798; ENSMUSG00000021922. [A6X935-1]
DR GeneID; 16427; -.
DR KEGG; mmu:16427; -.
DR UCSC; uc007svv.3; mouse. [A6X935-1]
DR UCSC; uc007svx.3; mouse. [A6X935-2]
DR CTD; 3700; -.
DR MGI; MGI:109536; Itih4.
DR VEuPathDB; HostDB:ENSMUSG00000021922; -.
DR eggNOG; ENOG502QPS2; Eukaryota.
DR GeneTree; ENSGT00940000161039; -.
DR InParanoid; A6X935; -.
DR OMA; FFKGSEM; -.
DR OrthoDB; 955432at2759; -.
DR PhylomeDB; A6X935; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR BioGRID-ORCS; 16427; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Itih4; mouse.
DR PRO; PR:A6X935; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; A6X935; protein.
DR Bgee; ENSMUSG00000021922; Expressed in left lobe of liver and 37 other tissues.
DR ExpressionAtlas; A6X935; baseline and differential.
DR Genevisible; A6X935; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0030212; P:hyaluronan metabolic process; IEA:InterPro.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR010600; ITI_HC_C.
DR InterPro; IPR013694; VIT.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
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; SSF53300; 1.
DR PROSITE; PS51468; VIT; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW Acute phase; Alternative splicing; Coiled coil; Disulfide bond;
KW Glycoprotein; Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000250"
FT CHAIN 29..942
FT /note="Inter alpha-trypsin inhibitor, heavy chain 4"
FT /id="PRO_0000420864"
FT DOMAIN 29..148
FT /note="VIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00801"
FT DOMAIN 274..457
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT REGION 658..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 726..745
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 552..586
FT /evidence="ECO:0000255"
FT COMPBIAS 662..691
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957,
FT ECO:0000269|PubMed:17330941"
FT CARBOHYD 517
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957,
FT ECO:0000269|PubMed:17330941"
FT CARBOHYD 577
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957,
FT ECO:0000269|PubMed:17330941"
FT CARBOHYD 732
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q3T052"
FT CARBOHYD 874
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957,
FT ECO:0000269|PubMed:17330941"
FT DISULFID 761..937
FT /evidence="ECO:0000250"
FT VAR_SEQ 741..779
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_044763"
FT CONFLICT 491
FT /note="Missing (in Ref. 2; BAC34032)"
FT /evidence="ECO:0000305"
FT CONFLICT 517
FT /note="N -> H (in Ref. 2; BAC34032)"
FT /evidence="ECO:0000305"
FT CONFLICT 650
FT /note="L -> R (in Ref. 1; AAC25786 and 5; AAH92258/
FT AAH94457/AAH16500)"
FT /evidence="ECO:0000305"
FT CONFLICT 713
FT /note="Missing (in Ref. 2; BAB23649 and 5; AAH16500/
FT AAH92258)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 942 AA; 104659 MW; 5D613FFBAB52A608 CRC64;
MKSPAPAHMW NLVLFLPSLL AVLPTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR
ADAVQEATFQ VELPRKAFIT NFSMIIDGVT YPGVVKEKAE AQKQYSAAVG RGESAGIVKT
TGRQTEKFEV SVNVAPGSKI TFELIYQELL QRRLGMYELL LKVRPQQLVK HLQMDIYIFE
PQGISILETE STFMTPELAN ALTTSQNKTK AHIRFKPTLS QQQKSQSEQD TVLNGDFIVR
YDVNRSDSGG SIQIEEGYFV HHFAPENLPT MSKNVIFVID KSGSMSGKKI QQTREALVKI
LKDLSPQDQF NLIEFSGEAN QWKQSLVQAT EENLNKAVNY ASRIRAHGGT NINNAVLLAV
ELLDRSNQAE LLPSKSVSLI ILLTDGDPTV GETNPTIIQN NVREAINGQY SLFCLGFGFD
VNYPFLEKMA LDNGGLARRI YEDSDSALQL QDFYHEVANP LLSSVAFEYP SDAVEEVTRY
KFQHHFKGSE MVVAGKLQDQ GPDVLLAKVS GQMHMQNITF QTEASVAQQE KEFKSPKYIF
HNFMERLWAL LTIQQQLEQR ISASGAELEA LEAQVLNLSL KYNFVTPLTH MVVTKPEGQE
QFQVAEKPVE VGDGMQRLPL AAQAHPFRPP VRGSKLMTVL KGSRSQIPRL GDAVRASRQY
IPPGFPGPPG PPGFPAPPGP PGFPAPPGPP LASGSDFSLQ PSYERMLSLP SVAAQYPADP
HLVVTEKSKE STIPEESPNP DHPQVPTITL PLPGSSVDQL CVDILHSEKP MKLFVDPSQG
LEVTGKYENT GFSWLEVTIQ KPHLQVHATP ERLVVTRGRK NTEYKWKKTL FSVLPGLKMT
MNMMGLLQLS GPDKVTIGLL SLDDPQRGLM LLLNDTQHFS NNVKGELGQF YRDIVWEPPV
EPDNTKRTVK VQGVDYLATR ELKLSYQEGF PGAEISCWTV EI
