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Protein

Inter-alpha-trypsin inhibitor heavy chain H4

Gene

ITIH4

Organism
Homo sapiens (Human)
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.1 Publication

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: ProtInc
  • serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

GO - Biological processi

  • acute-phase response Source: UniProtKB
  • hyaluronan metabolic process Source: InterPro
  • platelet degranulation Source: Reactome
  • response to cytokine Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Acute phase

Enzyme and pathway databases

BioCyciZFISH:ENSG00000055955-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Inter-alpha-trypsin inhibitor heavy chain H4
Short name:
ITI heavy chain H4
Short name:
ITI-HC4
Short name:
Inter-alpha-inhibitor heavy chain 4
Alternative name(s):
Inter-alpha-trypsin inhibitor family heavy chain-related protein
Short name:
IHRP
Plasma kallikrein sensitive glycoprotein 120
Short name:
Gp120
Short name:
PK-120
Cleaved into the following 2 chains:
Gene namesi
Name:ITIH4
Synonyms:IHRP, ITIHL1, PK120
ORF Names:PRO1851
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6169. ITIH4.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • plasma membrane Source: Ensembl
  • platelet dense granule lumen Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3700.
MalaCardsiITIH4.
OpenTargetsiENSG00000055955.
PharmGKBiPA29967.

Polymorphism and mutation databases

BioMutaiITIH4.
DMDMi229463048.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 281 PublicationAdd BLAST28
ChainiPRO_000001654129 – 66170 kDa inter-alpha-trypsin inhibitor heavy chain H4Add BLAST633
PropeptideiPRO_0000016542662 – 688Potentially active peptideAdd BLAST27
ChainiPRO_0000016543689 – 93035 kDa inter-alpha-trypsin inhibitor heavy chain H4Add BLAST242

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi81N-linked (GlcNAc...)3 Publications1
Glycosylationi207N-linked (GlcNAc...)4 Publications1
Glycosylationi274N-linked (GlcNAc...); atypical1 Publication1
Glycosylationi517N-linked (GlcNAc...)4 Publications1
Glycosylationi577N-linked (GlcNAc...)2 Publications1
Glycosylationi719O-linked (GalNAc...)By similarity1
Glycosylationi720O-linked (GalNAc...)1 Publication1
Glycosylationi722O-linked (GalNAc...)By similarity1
Disulfide bondi747 ↔ 925Curated

Post-translational modificationi

Cleaved by plasma kallikrein to yield 100 kDa and 35 kDa fragments, and the resulting 100 kDa fragment is further converted to a 70 kDa fragment.
N- and O-glycosylated. In urine, O-linked glycosylation on threonine residues in the region from Thr-719 to Thr-725 consists of core 1 or possibly core 8 glycans. Mainly Hex(HexNAc)2, but also some Hex3(HexNAc)3. N-glycosylated but not O-glycosylated in plasma.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei688 – 689Cleavage; by kallikrein2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ14624.
PeptideAtlasiQ14624.
PRIDEiQ14624.

PTM databases

iPTMnetiQ14624.
PhosphoSitePlusiQ14624.

Expressioni

Tissue specificityi

Liver specific.2 Publications

Inductioni

Levels increase from 1.4 to 3-fold in acute-phase processes such as in acute ischemia stroke (AIS), unstable angina and programmed surgery. In hepatocytes, induced by IL6 but not by other cytokines such as IL1B.2 Publications

Gene expression databases

BgeeiENSG00000055955.
CleanExiHS_ITIH4.
ExpressionAtlasiQ14624. baseline and differential.
GenevisibleiQ14624. HS.

Organism-specific databases

HPAiCAB072872.
HPA001835.
HPA003948.

Interactioni

Subunit structurei

Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain); this interaction protects ITIH4 against cleavage by kallikrein in vitro.1 Publication

Protein-protein interaction databases

BioGridi109906. 4 interactors.
IntActiQ14624. 2 interactors.
STRINGi9606.ENSP00000266041.

Structurei

3D structure databases

ProteinModelPortaliQ14624.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 148VITPROSITE-ProRule annotationAdd BLAST120
Domaini272 – 432VWFAPROSITE-ProRule annotationAdd BLAST161

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni658 – 688Proline-rich (PRR) potential bioactive peptideAdd BLAST31
Regioni719 – 725O-glycosylated at three sites7

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IEJB. Eukaryota.
COG2304. LUCA.
GeneTreeiENSGT00550000074468.
HOGENOMiHOG000000680.
HOVERGENiHBG057734.
InParanoidiQ14624.
PhylomeDBiQ14624.
TreeFamiTF328982.

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 (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14624-1) [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
MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH
60 70 80 90 100
TVVTSRVVNR ANTVQEATFQ MELPKKAFIT NFSMIIDGMT YPGIIKEKAE
110 120 130 140 150
AQAQYSAAVA KGKSAGLVKA TGRNMEQFQV SVSVAPNAKI TFELVYEELL
160 170 180 190 200
KRRLGVYELL LKVRPQQLVK HLQMDIHIFE PQGISFLETE STFMTNQLVD
210 220 230 240 250
ALTTWQNKTK AHIRFKPTLS QQQKSPEQQE TVLDGNLIIR YDVDRAISGG
260 270 280 290 300
SIQIENGYFV HYFAPEGLTT MPKNVVFVID KSGSMSGRKI QQTREALIKI
310 320 330 340 350
LDDLSPRDQF NLIVFSTEAT QWRPSLVPAS AENVNKARSF AAGIQALGGT
360 370 380 390 400
NINDAMLMAV QLLDSSNQEE RLPEGSVSLI ILLTDGDPTV GETNPRSIQN
410 420 430 440 450
NVREAVSGRY SLFCLGFGFD VSYAFLEKLA LDNGGLARRI HEDSDSALQL
460 470 480 490 500
QDFYQEVANP LLTAVTFEYP SNAVEEVTQN NFRLLFKGSE MVVAGKLQDR
510 520 530 540 550
GPDVLTATVS GKLPTQNITF QTESSVAEQE AEFQSPKYIF HNFMERLWAY
560 570 580 590 600
LTIQQLLEQT VSASDADQQA LRNQALNLSL AYSFVTPLTS MVVTKPDDQE
610 620 630 640 650
QSQVAEKPME GESRNRNVHS GSTFFKYYLQ GAKIPKPEAS FSPRRGWNRQ
660 670 680 690 700
AGAAGSRMNF RPGVLSSRQL GLPGPPDVPD HAAYHPFRRL AILPASAPPA
710 720 730 740 750
TSNPDPAVSR VMNMKIEETT MTTQTPAPIQ APSAILPLPG QSVERLCVDP
760 770 780 790 800
RHRQGPVNLL SDPEQGVEVT GQYEREKAGF SWIEVTFKNP LVWVHASPEH
810 820 830 840 850
VVVTRNRRSS AYKWKETLFS VMPGLKMTMD KTGLLLLSDP DKVTIGLLFW
860 870 880 890 900
DGRGEGLRLL LRDTDRFSSH VGGTLGQFYQ EVLWGSPAAS DDGRRTLRVQ
910 920 930
GNDHSATRER RLDYQEGPPG VEISCWSVEL
Length:930
Mass (Da):103,357
Last modified:May 5, 2009 - v4
Checksum:i847A9A5CB886C5A4
GO
Isoform 2 (identifier: Q14624-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     621-650: Missing.
     727-727: A → ACPSCSRSRAPAVPA

Note: No experimental confirmation available.
Show »
Length:914
Mass (Da):101,241
Checksum:i79F2D903E65026CD
GO
Isoform 3 (identifier: Q14624-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     621-650: Missing.

Note: No experimental confirmation available.
Show »
Length:900
Mass (Da):99,857
Checksum:iB18BE8E1C3BF634C
GO
Isoform 4 (identifier: Q14624-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     621-650: Missing.
     727-765: Missing.
     851-866: Missing.

Note: No experimental confirmation available.
Show »
Length:845
Mass (Da):93,852
Checksum:i60436CD8050B7D46
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti85I → K in AAD05198 (PubMed:8797089).Curated1
Sequence conflicti114S → N in BAA07602 (PubMed:7775381).Curated1
Sequence conflicti207N → F AA sequence (PubMed:7541790).Curated1
Sequence conflicti221Q → E AA sequence (PubMed:7541790).Curated1
Sequence conflicti307R → V AA sequence (PubMed:7541790).Curated1
Sequence conflicti322W → Y AA sequence (PubMed:7541790).Curated1
Sequence conflicti370E → G in BAH12781 (PubMed:16641997).Curated1
Sequence conflicti816 – 817ET → QR AA sequence (PubMed:7541790).Curated2
Sequence conflicti905S → F no nucleotide entry (PubMed:8797089).Curated1
Sequence conflicti927S → T no nucleotide entry (PubMed:8797089).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02786985I → N.1 PublicationCorresponds to variant rs13072536dbSNPEnsembl.1
Natural variantiVAR_01383686I → N.1 Publication1
Natural variantiVAR_027870669Q → L.Corresponds to variant rs2276814dbSNPEnsembl.1
Natural variantiVAR_027871698P → T.Corresponds to variant rs4687657dbSNPEnsembl.1
Natural variantiVAR_027872714M → I.Corresponds to variant rs2256734dbSNPEnsembl.1
Natural variantiVAR_027873791L → P.Corresponds to variant rs2535621dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002761621 – 650Missing in isoform 2, isoform 3 and isoform 4. 3 PublicationsAdd BLAST30
Alternative sequenceiVSP_044764727 – 765Missing in isoform 4. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_002762727A → ACPSCSRSRAPAVPA in isoform 2. 1 Publication1
Alternative sequenceiVSP_044765851 – 866Missing in isoform 4. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38535 mRNA. Translation: BAA07536.1.
D38595 mRNA. Translation: BAA07602.1.
U43163
, U42015, U42016, U43155, U43156, U43157, U43158, U43159, U43160, U43161, U43162 Genomic DNA. Translation: AAD05198.1.
AK298412 mRNA. Translation: BAH12781.1.
AC006254 Genomic DNA. No translation available.
AC099667 Genomic DNA. No translation available.
AF119856 mRNA. Translation: AAF69610.1.
CCDSiCCDS2865.1. [Q14624-1]
CCDS54596.1. [Q14624-3]
PIRiJX0368.
RefSeqiNP_001159921.1. NM_001166449.1. [Q14624-3]
NP_002209.2. NM_002218.4. [Q14624-1]
UniGeneiHs.709406.

Genome annotation databases

EnsembliENST00000266041; ENSP00000266041; ENSG00000055955. [Q14624-1]
ENST00000406595; ENSP00000384425; ENSG00000055955. [Q14624-3]
GeneIDi3700.
KEGGihsa:3700.
UCSCiuc003dfz.4. human. [Q14624-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38535 mRNA. Translation: BAA07536.1.
D38595 mRNA. Translation: BAA07602.1.
U43163
, U42015, U42016, U43155, U43156, U43157, U43158, U43159, U43160, U43161, U43162 Genomic DNA. Translation: AAD05198.1.
AK298412 mRNA. Translation: BAH12781.1.
AC006254 Genomic DNA. No translation available.
AC099667 Genomic DNA. No translation available.
AF119856 mRNA. Translation: AAF69610.1.
CCDSiCCDS2865.1. [Q14624-1]
CCDS54596.1. [Q14624-3]
PIRiJX0368.
RefSeqiNP_001159921.1. NM_001166449.1. [Q14624-3]
NP_002209.2. NM_002218.4. [Q14624-1]
UniGeneiHs.709406.

3D structure databases

ProteinModelPortaliQ14624.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109906. 4 interactors.
IntActiQ14624. 2 interactors.
STRINGi9606.ENSP00000266041.

PTM databases

iPTMnetiQ14624.
PhosphoSitePlusiQ14624.

Polymorphism and mutation databases

BioMutaiITIH4.
DMDMi229463048.

Proteomic databases

PaxDbiQ14624.
PeptideAtlasiQ14624.
PRIDEiQ14624.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000266041; ENSP00000266041; ENSG00000055955. [Q14624-1]
ENST00000406595; ENSP00000384425; ENSG00000055955. [Q14624-3]
GeneIDi3700.
KEGGihsa:3700.
UCSCiuc003dfz.4. human. [Q14624-1]

Organism-specific databases

CTDi3700.
DisGeNETi3700.
GeneCardsiITIH4.
HGNCiHGNC:6169. ITIH4.
HPAiCAB072872.
HPA001835.
HPA003948.
MalaCardsiITIH4.
MIMi600564. gene.
neXtProtiNX_Q14624.
OpenTargetsiENSG00000055955.
PharmGKBiPA29967.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEJB. Eukaryota.
COG2304. LUCA.
GeneTreeiENSGT00550000074468.
HOGENOMiHOG000000680.
HOVERGENiHBG057734.
InParanoidiQ14624.
PhylomeDBiQ14624.
TreeFamiTF328982.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000055955-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.

Miscellaneous databases

ChiTaRSiITIH4. human.
GeneWikiiITIH4.
GenomeRNAii3700.
PROiQ14624.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000055955.
CleanExiHS_ITIH4.
ExpressionAtlasiQ14624. baseline and differential.
GenevisibleiQ14624. HS.

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...

Entry informationi

Entry nameiITIH4_HUMAN
AccessioniPrimary (citable) accession number: Q14624
Secondary accession number(s): B7Z545
, E9PGN5, Q15135, Q9P190, Q9UQ54
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 5, 2009
Last modified: November 2, 2016
This is version 155 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Possible biomarker for acute ischemic stroke (PubMed:19263524). Peptides derived from the proline-rich potentially active peptide (PRO_0000016542) may be biomarkers for a variety of disease states including breast cancer (PubMed:21137033).2 Publications

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.