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Protein

Inter alpha-trypsin inhibitor, heavy chain 4

Gene

Itih4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Acute phase

Enzyme and pathway databases

ReactomeiR-MMU-114608. Platelet degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Inter alpha-trypsin inhibitor, heavy chain 4
Short name:
ITI heavy chain H4
Short name:
ITI-HC4
Short name:
Inter-alpha-inhibitor heavy chain 4
Gene namesi
Name:Itih4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:109536. Itih4.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: MGI
  • cytoplasm Source: MGI
  • extracellular exosome Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828By similarityAdd
BLAST
Chaini29 – 942914Inter alpha-trypsin inhibitor, heavy chain 4PRO_0000420864Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi81 – 811N-linked (GlcNAc...)2 Publications
Glycosylationi517 – 5171N-linked (GlcNAc...)2 Publications
Glycosylationi577 – 5771N-linked (GlcNAc...)2 Publications
Glycosylationi732 – 7321O-linked (GalNAc...)By similarity
Disulfide bondi761 ↔ 937By similarity
Glycosylationi874 – 8741N-linked (GlcNAc...)2 Publications

Post-translational modificationi

May be O-glycosylated (By similarity). N-glycosylated.By similarity2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiA6X935.
MaxQBiA6X935.
PaxDbiA6X935.
PeptideAtlasiA6X935.
PRIDEiA6X935.

PTM databases

iPTMnetiA6X935.

Expressioni

Tissue specificityi

Highly expressed in liver. Weak expression in lung and heart.1 Publication

Developmental stagei

During mid-embryonic gestation, expressed abundantly in liver, less in heart and brain. Highest expression at day 14.5.1 Publication

Gene expression databases

BgeeiA6X935.
ExpressionAtlasiA6X935. baseline and differential.
GenevisibleiA6X935. MM.

Interactioni

Subunit structurei

Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain).1 Publication

Protein-protein interaction databases

IntActiA6X935. 4 interactions.
MINTiMINT-1858652.
STRINGi10090.ENSMUSP00000006703.

Structurei

3D structure databases

ProteinModelPortaliA6X935.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 148120VITPROSITE-ProRule annotationAdd
BLAST
Domaini274 – 457184VWFAPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili552 – 58635Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi662 – 75392Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the ITIH family.Curated
Contains 1 VIT domain.PROSITE-ProRule annotation
Contains 1 VWFA domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiENOG410IEJB. Eukaryota.
COG2304. LUCA.
GeneTreeiENSGT00550000074468.
HOGENOMiHOG000000680.
HOVERGENiHBG057734.
InParanoidiA6X935.
OMAiKGSEMVV.
OrthoDBiEOG7CRTP5.
PhylomeDBiA6X935.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR010600. ITI_HC_C.
IPR013694. VIT.
IPR002035. VWF_A.
[Graphical view]
PfamiPF06668. ITI_HC_C. 1 hit.
PF08487. VIT. 1 hit.
PF00092. VWA. 1 hit.
[Graphical view]
SMARTiSM00609. VIT. 1 hit.
SM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiPS51468. VIT. 1 hit.
PS50234. VWFA. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: A6X935-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKSPAPAHMW NLVLFLPSLL AVLPTTTAEK NGIDIYSLTV DSRVSSRFAH
60 70 80 90 100
TVVTSRVVNR ADAVQEATFQ VELPRKAFIT NFSMIIDGVT YPGVVKEKAE
110 120 130 140 150
AQKQYSAAVG RGESAGIVKT TGRQTEKFEV SVNVAPGSKI TFELIYQELL
160 170 180 190 200
QRRLGMYELL LKVRPQQLVK HLQMDIYIFE PQGISILETE STFMTPELAN
210 220 230 240 250
ALTTSQNKTK AHIRFKPTLS QQQKSQSEQD TVLNGDFIVR YDVNRSDSGG
260 270 280 290 300
SIQIEEGYFV HHFAPENLPT MSKNVIFVID KSGSMSGKKI QQTREALVKI
310 320 330 340 350
LKDLSPQDQF NLIEFSGEAN QWKQSLVQAT EENLNKAVNY ASRIRAHGGT
360 370 380 390 400
NINNAVLLAV ELLDRSNQAE LLPSKSVSLI ILLTDGDPTV GETNPTIIQN
410 420 430 440 450
NVREAINGQY SLFCLGFGFD VNYPFLEKMA LDNGGLARRI YEDSDSALQL
460 470 480 490 500
QDFYHEVANP LLSSVAFEYP SDAVEEVTRY KFQHHFKGSE MVVAGKLQDQ
510 520 530 540 550
GPDVLLAKVS GQMHMQNITF QTEASVAQQE KEFKSPKYIF HNFMERLWAL
560 570 580 590 600
LTIQQQLEQR ISASGAELEA LEAQVLNLSL KYNFVTPLTH MVVTKPEGQE
610 620 630 640 650
QFQVAEKPVE VGDGMQRLPL AAQAHPFRPP VRGSKLMTVL KGSRSQIPRL
660 670 680 690 700
GDAVRASRQY IPPGFPGPPG PPGFPAPPGP PGFPAPPGPP LASGSDFSLQ
710 720 730 740 750
PSYERMLSLP SVAAQYPADP HLVVTEKSKE STIPEESPNP DHPQVPTITL
760 770 780 790 800
PLPGSSVDQL CVDILHSEKP MKLFVDPSQG LEVTGKYENT GFSWLEVTIQ
810 820 830 840 850
KPHLQVHATP ERLVVTRGRK NTEYKWKKTL FSVLPGLKMT MNMMGLLQLS
860 870 880 890 900
GPDKVTIGLL SLDDPQRGLM LLLNDTQHFS NNVKGELGQF YRDIVWEPPV
910 920 930 940
EPDNTKRTVK VQGVDYLATR ELKLSYQEGF PGAEISCWTV EI
Length:942
Mass (Da):104,659
Last modified:January 9, 2013 - v2
Checksum:i5D613FFBAB52A608
GO
Isoform 2 (identifier: A6X935-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     741-779: Missing.

Show »
Length:903
Mass (Da):100,395
Checksum:iE897BFE3CAEEF508
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti491 – 4911Missing in BAC34032 (PubMed:16141072).Curated
Sequence conflicti517 – 5171N → H in BAC34032 (PubMed:16141072).Curated
Sequence conflicti650 – 6501L → R in AAC25786 (PubMed:9602042).Curated
Sequence conflicti650 – 6501L → R in AAH92258 (PubMed:15489334).Curated
Sequence conflicti650 – 6501L → R in AAH94457 (PubMed:15489334).Curated
Sequence conflicti650 – 6501L → R in AAH16500 (PubMed:15489334).Curated
Sequence conflicti713 – 7131Missing in BAB23649 (PubMed:16141072).Curated
Sequence conflicti713 – 7131Missing in AAH16500 (PubMed:15489334).Curated
Sequence conflicti713 – 7131Missing in AAH92258 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei741 – 77939Missing in isoform 2. 1 PublicationVSP_044763Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF023919 mRNA. Translation: AAC25786.1.
AK004893 mRNA. Translation: BAB23649.1.
AK050016 mRNA. Translation: BAC34032.1.
AK050270 mRNA. Translation: BAC34155.1.
CT025528 Genomic DNA. Translation: CAO78004.1.
CT025528 Genomic DNA. Translation: CAO78005.1.
CH466573 Genomic DNA. Translation: EDL24772.1.
BC016500 mRNA. Translation: AAH16500.1.
BC092258 mRNA. Translation: AAH92258.1.
BC094457 mRNA. Translation: AAH94457.1.
CCDSiCCDS26901.1. [A6X935-1]
RefSeqiNP_001152771.1. NM_001159299.2.
NP_001276561.1. NM_001289632.1.
NP_001276562.1. NM_001289633.1.
NP_061216.2. NM_018746.4. [A6X935-1]
UniGeneiMm.34819.

Genome annotation databases

EnsembliENSMUST00000006703; ENSMUSP00000006703; ENSMUSG00000021922. [A6X935-1]
GeneIDi16427.
KEGGimmu:16427.
UCSCiuc007svv.3. mouse. [A6X935-1]
uc007svx.3. mouse. [A6X935-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF023919 mRNA. Translation: AAC25786.1.
AK004893 mRNA. Translation: BAB23649.1.
AK050016 mRNA. Translation: BAC34032.1.
AK050270 mRNA. Translation: BAC34155.1.
CT025528 Genomic DNA. Translation: CAO78004.1.
CT025528 Genomic DNA. Translation: CAO78005.1.
CH466573 Genomic DNA. Translation: EDL24772.1.
BC016500 mRNA. Translation: AAH16500.1.
BC092258 mRNA. Translation: AAH92258.1.
BC094457 mRNA. Translation: AAH94457.1.
CCDSiCCDS26901.1. [A6X935-1]
RefSeqiNP_001152771.1. NM_001159299.2.
NP_001276561.1. NM_001289632.1.
NP_001276562.1. NM_001289633.1.
NP_061216.2. NM_018746.4. [A6X935-1]
UniGeneiMm.34819.

3D structure databases

ProteinModelPortaliA6X935.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiA6X935. 4 interactions.
MINTiMINT-1858652.
STRINGi10090.ENSMUSP00000006703.

PTM databases

iPTMnetiA6X935.

Proteomic databases

EPDiA6X935.
MaxQBiA6X935.
PaxDbiA6X935.
PeptideAtlasiA6X935.
PRIDEiA6X935.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006703; ENSMUSP00000006703; ENSMUSG00000021922. [A6X935-1]
GeneIDi16427.
KEGGimmu:16427.
UCSCiuc007svv.3. mouse. [A6X935-1]
uc007svx.3. mouse. [A6X935-2]

Organism-specific databases

CTDi3700.
MGIiMGI:109536. Itih4.

Phylogenomic databases

eggNOGiENOG410IEJB. Eukaryota.
COG2304. LUCA.
GeneTreeiENSGT00550000074468.
HOGENOMiHOG000000680.
HOVERGENiHBG057734.
InParanoidiA6X935.
OMAiKGSEMVV.
OrthoDBiEOG7CRTP5.
PhylomeDBiA6X935.

Enzyme and pathway databases

ReactomeiR-MMU-114608. Platelet degranulation.

Miscellaneous databases

PROiA6X935.
SOURCEiSearch...

Gene expression databases

BgeeiA6X935.
ExpressionAtlasiA6X935. baseline and differential.
GenevisibleiA6X935. MM.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR010600. ITI_HC_C.
IPR013694. VIT.
IPR002035. VWF_A.
[Graphical view]
PfamiPF06668. ITI_HC_C. 1 hit.
PF08487. VIT. 1 hit.
PF00092. VWA. 1 hit.
[Graphical view]
SMARTiSM00609. VIT. 1 hit.
SM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiPS51468. VIT. 1 hit.
PS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of mouse itih-4 encoding a glycoprotein with two EF-hand motifs from early embryonic liver."
    Cai T., Yu P., Monga S.P.S., Mishra B., Mishra L.
    Biochim. Biophys. Acta 1398:32-37(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, POSSIBLE FUNCTION.
    Strain: BALB/cJ.
    Tissue: Liver.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Liver.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Liver.
  6. "BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-trypsin inhibitor heavy chain 4."
    Kroczynska B., King-Simmons L., Alloza L., Alava M.A., Elguindi E.C., Blond S.Y.
    Biochem. Biophys. Res. Commun. 338:1467-1477(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DNJAC1.
  7. "Proteome-wide characterization of N-glycosylation events by diagonal chromatography."
    Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.
    J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81; ASN-517; ASN-577 AND ASN-874.
    Strain: C57BL/6J.
    Tissue: Plasma.
  8. "Enhanced analysis of the mouse plasma proteome using cysteine-containing tryptic glycopeptides."
    Bernhard O.K., Kapp E.A., Simpson R.J.
    J. Proteome Res. 6:987-995(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81; ASN-517; ASN-577 AND ASN-874.
    Strain: C57BL/6J.
    Tissue: Plasma.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiITIH4_MOUSE
AccessioniPrimary (citable) accession number: A6X935
Secondary accession number(s): O54882
, Q505P8, Q8C7G9, Q8C7K5, Q91W60, Q9DBK8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 9, 2013
Last sequence update: January 9, 2013
Last modified: July 6, 2016
This is version 68 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.