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UniProtKB - P19823 (ITIH2_HUMAN)

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Protein

Inter-alpha-trypsin inhibitor heavy chain H2

Gene

ITIH2

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.

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: ProtInc
  • serine-type endopeptidase inhibitor activity Source: UniProtKB-KW
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

ReactomeiR-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-HSA-8957275. Post-translational protein phosphorylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Inter-alpha-trypsin inhibitor heavy chain H2
Short name:
ITI heavy chain H2
Short name:
ITI-HC2
Short name:
Inter-alpha-inhibitor heavy chain 2
Alternative name(s):
Inter-alpha-trypsin inhibitor complex component II
Serum-derived hyaluronan-associated protein
Short name:
SHAP
Gene namesi
Name:ITIH2
Synonyms:IGHEP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:6167. ITIH2.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • endoplasmic reticulum lumen Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3698.
OpenTargetsiENSG00000151655.
PharmGKBiPA29965.

Polymorphism and mutation databases

BioMutaiITIH2.
DMDMi229462889.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
PropeptideiPRO_000001651719 – 54Add BLAST36
ChainiPRO_000001651855 – 702Inter-alpha-trypsin inhibitor heavy chain H2Add BLAST648
PropeptideiPRO_0000016519703 – 946Add BLAST244

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei60Phosphoserine; by FAM20CCombined sources1 Publication1
Glycosylationi96N-linked (GlcNAc...) asparagine1 Publication1
GlycosylationiCAR_000140118N-linked (GlcNAc...) (complex) asparagine5 Publications1
Disulfide bondi261 ↔ 2641 Publication
Modified residuei2824-carboxyglutamate1 Publication1
Modified residuei2834-carboxyglutamate1 Publication1
Glycosylationi445N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei466Phosphoserine; by FAM20C1 Publication1
Disulfide bondi650 ↔ 6511 Publication
GlycosylationiCAR_000214666O-linked (GalNAc...) threonine; partial2 Publications1
GlycosylationiCAR_000215673O-linked (GalNAc...) serine2 Publications1
GlycosylationiCAR_000216675O-linked (GalNAc...) threonine2 Publications1
GlycosylationiCAR_000217691O-linked (GalNAc...) threonine3 Publications1
Modified residuei702Aspartate 1-(chondroitin 4-sulfate)-ester1
Modified residuei886Phosphoserine; by FAM20C1 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.By similarity
N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.7 Publications
Phosphorylated by FAM20C in the extracellular medium.1 Publication

Keywords - PTMi

Disulfide bond, Gamma-carboxyglutamic acid, Glycoprotein, Phosphoprotein, Proteoglycan

Proteomic databases

MaxQBiP19823.
PaxDbiP19823.
PeptideAtlasiP19823.
PRIDEiP19823.

PTM databases

iPTMnetiP19823.
PhosphoSitePlusiP19823.
UniCarbKBiP19823.

Expressioni

Tissue specificityi

Plasma.

Gene expression databases

BgeeiENSG00000151655.
CleanExiHS_ITIH2.
ExpressionAtlasiP19823. baseline and differential.
GenevisibleiP19823. HS.

Organism-specific databases

HPAiHPA059150.

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

BioGridi109904. 15 interactors.
IntActiP19823. 3 interactors.
MINTiMINT-1415907.
STRINGi9606.ENSP00000351190.

Structurei

3D structure databases

ProteinModelPortaliP19823.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 185VITPROSITE-ProRule annotationAdd BLAST130
Domaini308 – 468VWFAPROSITE-ProRule annotationAdd BLAST161

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni665 – 679O-glycosylated at three sitesAdd BLAST15

Sequence similaritiesi

Belongs to the ITIH family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IEJB. Eukaryota.
COG2304. LUCA.
GeneTreeiENSGT00550000074468.
HOVERGENiHBG057734.
InParanoidiP19823.
KOiK19015.
OMAiGLIGQFM.
OrthoDBiEOG091G01HF.
PhylomeDBiP19823.
TreeFamiTF328982.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiView protein in InterPro
IPR010600. ITI_HC_C.
IPR013694. VIT.
IPR002035. VWF_A.
PfamiView protein in Pfam
PF06668. ITI_HC_C. 1 hit.
PF08487. VIT. 1 hit.
PF00092. VWA. 1 hit.
SMARTiView protein in SMART
SM00609. VIT. 1 hit.
SM00327. VWA. 1 hit.
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiView protein in PROSITE
PS51468. VIT. 1 hit.
PS50234. VWFA. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P19823-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRLTCFFIC FFLSEVSGFE IPINGLSEFV DYEDLVELAP GKFQLVAENR 
        60         70         80         90        100
RYQRSLPGES EEMMEEVDQV TLYSYKVQST ITSRMATTMI QSKVVNNSPQ 
       110        120        130        140        150
PQNVVFDVQI PKGAFISNFS MTVDGKTFRS SIKEKTVGRA LYAQARAKGK 
       160        170        180        190        200
TAGLVRSSAL DMENFRTEVN VLPGAKVQFE LHYQEVKWRK LGSYEHRIYL 
       210        220        230        240        250
QPGRLAKHLE VDVWVIEPQG LRFLHVPDTF EGHFDGVPVI SKGQQKAHVS 
       260        270        280        290        300
FKPTVAQQRI CPNCRETAVD GELVVLYDVK REEKAGELEV FNGYFVHFFA 
       310        320        330        340        350
PDNLDPIPKN ILFVIDVSGS MWGVKMKQTV EAMKTILDDL RAEDHFSVID 
       360        370        380        390        400
FNQNIRTWRN DLISATKTQV ADAKRYIEKI QPSGGTNINE ALLRAIFILN 
       410        420        430        440        450
EANNLGLLDP NSVSLIILVS DGDPTVGELK LSKIQKNVKE NIQDNISLFS 
       460        470        480        490        500
LGMGFDVDYD FLKRLSNENH GIAQRIYGNQ DTSSQLKKFY NQVSTPLLRN 
       510        520        530        540        550
VQFNYPHTSV TDVTQNNFHN YFGGSEIVVA GKFDPAKLDQ IESVITATSA 
       560        570        580        590        600
NTQLVLETLA QMDDLQDFLS KDKHADPDFT RKLWAYLTIN QLLAERSLAP 
       610        620        630        640        650
TAAAKRRITR SILQMSLDHH IVTPLTSLVI ENEAGDERML ADAPPQDPSC 
       660        670        680        690        700
CSGALYYGSK VVPDSTPSWA NPSPTPVISM LAQGSQVLES TPPPHVMRVE 
       710        720        730        740        750
NDPHFIIYLP KSQKNICFNI DSEPGKILNL VSDPESGIVV NGQLVGAKKP 
       760        770        780        790        800
NNGKLSTYFG KLGFYFQSED IKIEISTETI TLSHGSSTFS LSWSDTAQVT 
       810        820        830        840        850
NQRVQISVKK EKVVTITLDK EMSFSVLLHR VWKKHPVNVD FLGIYIPPTN 
       860        870        880        890        900
KFSPKAHGLI GQFMQEPKIH IFNERPGKDP EKPEASMEVK GQKLIITRGL 
       910        920        930        940 
QKDYRTDLVF GTDVTCWFVH NSGKGFIDGH YKDYFVPQLY SFLKRP
Length:946
Mass (Da):106,463
Last modified:May 5, 2009 - v2
Checksum:iBA626B146DDC2A5F
GO

Sequence cautioni

The sequence CAA30160 differs from that shown. Reason: Frameshift at positions 363 and 373.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti374K → L AA sequence (PubMed:2476436).Curated1
Sequence conflicti705F → S in AAA60558 (PubMed:2446322).Curated1
Sequence conflicti705F → S in AAA59195 (PubMed:2462430).Curated1
Sequence conflicti729N → D in AAA60558 (PubMed:2446322).Curated1
Sequence conflicti729N → D in AAA59195 (PubMed:2462430).Curated1
Sequence conflicti731V → A in AAA60558 (PubMed:2446322).Curated1
Sequence conflicti731V → A in AAA59195 (PubMed:2462430).Curated1

Mass spectrometryi

Molecular mass is 76508 Da from positions 55 - 702. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055248263N → S1 PublicationCorresponds to variant dbSNP:rs7075296Ensembl.1
Natural variantiVAR_055249569L → V. Corresponds to variant dbSNP:rs7084817Ensembl.1
Natural variantiVAR_055250674P → A1 PublicationCorresponds to variant dbSNP:rs3740217Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X07173 mRNA. Translation: CAA30160.1. Frameshift.
AL158044 Genomic DNA. No translation available.
M18193 mRNA. Translation: AAA60558.1.
M33033 mRNA. Translation: AAA59195.1.
CCDSiCCDS31141.1.
PIRiS00346. IYHU2.
RefSeqiNP_002207.2. NM_002216.2.
UniGeneiHs.75285.

Genome annotation databases

EnsembliENST00000358415; ENSP00000351190; ENSG00000151655.
GeneIDi3698.
KEGGihsa:3698.
UCSCiuc001ijs.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.

Entry informationi

Entry nameiITIH2_HUMAN
AccessioniPrimary (citable) accession number: P19823
Secondary accession number(s): Q14659, Q15484, Q5T986
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: May 5, 2009
Last modified: July 5, 2017
This is version 167 of the entry and version 2 of the sequence. See 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 10
    Human chromosome 10: 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