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Protein

Inter-alpha-trypsin inhibitor heavy chain H1

Gene

ITIH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.
Contains a potential peptide which could stimulate a broad spectrum of phagocytotic cells.

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000055957-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Inter-alpha-trypsin inhibitor heavy chain H1
Short name:
ITI heavy chain H1
Short name:
ITI-HC1
Short name:
Inter-alpha-inhibitor heavy chain 1
Alternative name(s):
Inter-alpha-trypsin inhibitor complex component III
Serum-derived hyaluronan-associated protein
Short name:
SHAP
Gene namesi
Name:ITIH1
Synonyms:IGHEP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6166. ITIH1.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3697.
OpenTargetsiENSG00000055957.
PharmGKBiPA29964.

Polymorphism and mutation databases

BioMutaiITIH1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
PropeptideiPRO_000001650628 – 341 Publication7
ChainiPRO_000001650735 – 672Inter-alpha-trypsin inhibitor heavy chain H1Add BLAST638
PropeptideiPRO_0000016508673 – 911Add BLAST239

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi60S-linked (Hex...)1 Publication1
Modified residuei129PhosphoserineCombined sources1
Disulfide bondi244 ↔ 2471 Publication
Disulfide bondi268 ↔ 5401 Publication
GlycosylationiCAR_000138285N-linked (GlcNAc...) (complex)4 Publications1
Modified residuei402PhosphothreonineCombined sources1
Modified residuei407PhosphothreonineCombined sources1
GlycosylationiCAR_000139588N-linked (GlcNAc...) (complex)3 Publications1
GlycosylationiCAR_000213653O-linked (GalNAc...)1 Publication1
Modified residuei672Aspartate 1-(chondroitin 4-sulfate)-ester1
Glycosylationi750N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

Heavy chains are linked to bikunin via chondroitin 4-sulfate esterified to the alpha-carboxyl of the C-terminal aspartate after propeptide cleavage.
The S-linked glycan is composed of two 6-carbon sugars, possibly Glc or Gal.6 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Proteoglycan

Proteomic databases

PaxDbiP19827.
PeptideAtlasiP19827.
PRIDEiP19827.

PTM databases

iPTMnetiP19827.
PhosphoSitePlusiP19827.
UniCarbKBiP19827.

Expressioni

Gene expression databases

BgeeiENSG00000055957.
CleanExiHS_ITIH1.
ExpressionAtlasiP19827. baseline and differential.
GenevisibleiP19827. HS.

Organism-specific databases

HPAiHPA041639.
HPA042049.

Interactioni

Subunit structurei

I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (H1, H2 or H3) and one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of H1, H2 and bikunin, inter-alpha-like inhibitor (I-alpha-LI) of H2 and bikunin, and pre-alpha-inhibitor (P-alpha-I) of H3 and bikunin.

Protein-protein interaction databases

BioGridi109903. 5 interactors.
IntActiP19827. 4 interactors.
STRINGi9606.ENSP00000273283.

Structurei

3D structure databases

ProteinModelPortaliP19827.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini37 – 166VITPROSITE-ProRule annotationAdd BLAST130
Domaini290 – 450VWFAPROSITE-ProRule annotationAdd BLAST161

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni387 – 911Hyaluronan-bindingAdd BLAST525

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi181 – 184Phagocytosis uptake signalSequence analysis4

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.
InParanoidiP19827.
KOiK19014.
OMAiMSMENNG.
OrthoDBiEOG091G01HF.
PhylomeDBiP19827.
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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P19827-1) [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
MDGAMGPRGL LLCMYLVSLL ILQAMPALGS ATGRSKSSEK RQAVDTAVDG
60 70 80 90 100
VFIRSLKVNC KVTSRFAHYV VTSQVVNTAN EAREVAFDLE IPKTAFISDF
110 120 130 140 150
AVTADGNAFI GDIKDKVTAW KQYRKAAISG ENAGLVRASG RTMEQFTIHL
160 170 180 190 200
TVNPQSKVTF QLTYEEVLKR NHMQYEIVIK VKPKQLVHHF EIDVDIFEPQ
210 220 230 240 250
GISKLDAQAS FLPKELAAQT IKKSFSGKKG HVLFRPTVSQ QQSCPTCSTS
260 270 280 290 300
LLNGHFKVTY DVSRDKICDL LVANNHFAHF FAPQNLTNMN KNVVFVIDIS
310 320 330 340 350
GSMRGQKVKQ TKEALLKILG DMQPGDYFDL VLFGTRVQSW KGSLVQASEA
360 370 380 390 400
NLQAAQDFVR GFSLDEATNL NGGLLRGIEI LNQVQESLPE LSNHASILIM
410 420 430 440 450
LTDGDPTEGV TDRSQILKNV RNAIRGRFPL YNLGFGHNVD FNFLEVMSME
460 470 480 490 500
NNGRAQRIYE DHDATQQLQG FYSQVAKPLL VDVDLQYPQD AVLALTQNHH
510 520 530 540 550
KQYYEGSEIV VAGRIADNKQ SSFKADVQAH GEGQEFSITC LVDEEEMKKL
560 570 580 590 600
LRERGHMLEN HVERLWAYLT IQELLAKRMK VDREERANLS SQALQMSLDY
610 620 630 640 650
GFVTPLTSMS IRGMADQDGL KPTIDKPSED SPPLEMLGPR RTFVLSALQP
660 670 680 690 700
SPTHSSSNTQ RLPDRVTGVD TDPHFIIHVP QKEDTLCFNI NEEPGVILSL
710 720 730 740 750
VQDPNTGFSV NGQLIGNKAR SPGQHDGTYF GRLGIANPAT DFQLEVTPQN
760 770 780 790 800
ITLNPGFGGP VFSWRDQAVL RQDGVVVTIN KKRNLVVSVD DGGTFEVVLH
810 820 830 840 850
RVWKGSSVHQ DFLGFYVLDS HRMSARTHGL LGQFFHPIGF EVSDIHPGSD
860 870 880 890 900
PTKPDATMVV RNRRLTVTRG LQKDYSKDPW HGAEVSCWFI HNNGAGLIDG
910
AYTDYIVPDI F
Length:911
Mass (Da):101,389
Last modified:July 15, 1998 - v3
Checksum:i8FE715FF223FC917
GO
Isoform 2 (identifier: P19827-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-142: Missing.

Note: No experimental confirmation available.
Show »
Length:769
Mass (Da):86,192
Checksum:i9447D42CB083BC9F
GO
Isoform 3 (identifier: P19827-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-288: Missing.

Note: No experimental confirmation available.
Show »
Length:623
Mass (Da):69,495
Checksum:iEBB1BB3250D74DA7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51V → T AA sequence (PubMed:2476436).Curated1
Sequence conflicti54R → A AA sequence (PubMed:2476436).Curated1
Sequence conflicti266K → E in CAA45188 (PubMed:1380832).Curated1
Sequence conflicti539T → A in BAH12794 (PubMed:14702039).Curated1
Sequence conflicti798V → A in BAH12794 (PubMed:14702039).Curated1

Mass spectrometryi

Molecular mass is 76258 Da from positions 28 - 672. Determined by MALDI. 1 Publication

Polymorphismi

There are 3 common alleles; ITIH1*1 with Glu-585/Gln-595, ITIH1*2 with Val-585/Arg-595 and ITIH1*3 with Glu-585/Arg-595.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011873263S → T.1 PublicationCorresponds to variant rs1042777dbSNPEnsembl.1
Natural variantiVAR_004019585E → V in allele ITIH1*2. 3 PublicationsCorresponds to variant rs678dbSNPEnsembl.1
Natural variantiVAR_004020595Q → R in allele ITIH1*2 and allele ITIH1*3. 3 PublicationsCorresponds to variant rs1042779dbSNPEnsembl.1
Natural variantiVAR_011874695G → C.Corresponds to variant rs1042904dbSNPEnsembl.1
Natural variantiVAR_011875844D → E.Corresponds to variant rs1042849dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0454191 – 288Missing in isoform 3. 1 PublicationAdd BLAST288
Alternative sequenceiVSP_0454201 – 142Missing in isoform 2. 1 PublicationAdd BLAST142

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63652 mRNA. Translation: CAA45188.1.
X69532
, X69533, X69534, X69535, X69536, X69537, X69538, X69539, X69540, X69541, X69542, X69543, X69544, X69545, X69546, X69547 Genomic DNA. Translation: CAA49279.1.
AK292750 mRNA. Translation: BAF85439.1.
AK298455 mRNA. Translation: BAH12794.1.
AK303156 mRNA. Translation: BAH13906.1.
AK314198 mRNA. Translation: BAG36876.1.
AC006254 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW65259.1.
BC069464 mRNA. Translation: AAH69464.1.
X16260 mRNA. Translation: CAA34346.1.
M18192 mRNA. Translation: AAA60557.1.
X75318 Genomic DNA. Translation: CAA53067.1.
CCDSiCCDS2864.1. [P19827-1]
CCDS54595.1. [P19827-3]
PIRiS39527. A39967.
RefSeqiNP_001159906.1. NM_001166434.2. [P19827-2]
NP_001159907.1. NM_001166435.2. [P19827-3]
NP_002206.2. NM_002215.3. [P19827-1]
UniGeneiHs.420257.
Hs.76716.

Genome annotation databases

EnsembliENST00000273283; ENSP00000273283; ENSG00000055957. [P19827-1]
ENST00000537050; ENSP00000443847; ENSG00000055957. [P19827-3]
GeneIDi3697.
KEGGihsa:3697.
UCSCiuc003dfs.4. human. [P19827-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63652 mRNA. Translation: CAA45188.1.
X69532
, X69533, X69534, X69535, X69536, X69537, X69538, X69539, X69540, X69541, X69542, X69543, X69544, X69545, X69546, X69547 Genomic DNA. Translation: CAA49279.1.
AK292750 mRNA. Translation: BAF85439.1.
AK298455 mRNA. Translation: BAH12794.1.
AK303156 mRNA. Translation: BAH13906.1.
AK314198 mRNA. Translation: BAG36876.1.
AC006254 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW65259.1.
BC069464 mRNA. Translation: AAH69464.1.
X16260 mRNA. Translation: CAA34346.1.
M18192 mRNA. Translation: AAA60557.1.
X75318 Genomic DNA. Translation: CAA53067.1.
CCDSiCCDS2864.1. [P19827-1]
CCDS54595.1. [P19827-3]
PIRiS39527. A39967.
RefSeqiNP_001159906.1. NM_001166434.2. [P19827-2]
NP_001159907.1. NM_001166435.2. [P19827-3]
NP_002206.2. NM_002215.3. [P19827-1]
UniGeneiHs.420257.
Hs.76716.

3D structure databases

ProteinModelPortaliP19827.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109903. 5 interactors.
IntActiP19827. 4 interactors.
STRINGi9606.ENSP00000273283.

PTM databases

iPTMnetiP19827.
PhosphoSitePlusiP19827.
UniCarbKBiP19827.

Polymorphism and mutation databases

BioMutaiITIH1.

Proteomic databases

PaxDbiP19827.
PeptideAtlasiP19827.
PRIDEiP19827.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273283; ENSP00000273283; ENSG00000055957. [P19827-1]
ENST00000537050; ENSP00000443847; ENSG00000055957. [P19827-3]
GeneIDi3697.
KEGGihsa:3697.
UCSCiuc003dfs.4. human. [P19827-1]

Organism-specific databases

CTDi3697.
DisGeNETi3697.
GeneCardsiITIH1.
HGNCiHGNC:6166. ITIH1.
HPAiHPA041639.
HPA042049.
MIMi147270. gene.
neXtProtiNX_P19827.
OpenTargetsiENSG00000055957.
PharmGKBiPA29964.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEJB. Eukaryota.
COG2304. LUCA.
GeneTreeiENSGT00550000074468.
HOGENOMiHOG000000680.
HOVERGENiHBG057734.
InParanoidiP19827.
KOiK19014.
OMAiMSMENNG.
OrthoDBiEOG091G01HF.
PhylomeDBiP19827.
TreeFamiTF328982.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000055957-MONOMER.

Miscellaneous databases

GeneWikiiITIH1.
GenomeRNAii3697.
PROiP19827.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000055957.
CleanExiHS_ITIH1.
ExpressionAtlasiP19827. baseline and differential.
GenevisibleiP19827. 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 nameiITIH1_HUMAN
AccessioniPrimary (citable) accession number: P19827
Secondary accession number(s): A8K9N5
, B2RAH9, B7Z558, B7Z8C0, F5H165, F5H7Y8, P78455, Q01746, Q562G1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: July 15, 1998
Last modified: November 2, 2016
This is version 170 of the entry and version 3 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

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.