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Protein

Inter-alpha-trypsin inhibitor heavy chain H3

Gene

ITIH3

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

ReactomeiR-HSA-114608. Platelet degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Inter-alpha-trypsin inhibitor heavy chain H3
Short name:
ITI heavy chain H3
Short name:
ITI-HC3
Short name:
Inter-alpha-inhibitor heavy chain 3
Alternative name(s):
Serum-derived hyaluronan-associated protein
Short name:
SHAP
Gene namesi
Name:ITIH3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6168. ITIH3.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • platelet dense granule lumen Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29966.

Polymorphism and mutation databases

BioMutaiITIH3.
DMDMi166203665.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Propeptidei21 – 3414PRO_0000016529Add
BLAST
Chaini35 – 651617Inter-alpha-trypsin inhibitor heavy chain H3PRO_0000016530Add
BLAST
Propeptidei652 – 890239PRO_0000016531Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi91 – 911N-linked (GlcNAc...)1 Publication
Glycosylationi580 – 5801N-linked (GlcNAc...)1 Publication
Modified residuei651 – 6511Aspartate 1-(chondroitin 4-sulfate)-ester

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.

Keywords - PTMi

Glycoprotein, Proteoglycan

Proteomic databases

MaxQBiQ06033.
PaxDbiQ06033.
PeptideAtlasiQ06033.
PRIDEiQ06033.

PTM databases

iPTMnetiQ06033.
PhosphoSiteiQ06033.

Expressioni

Gene expression databases

BgeeiENSG00000162267.
CleanExiHS_ITIH3.
ExpressionAtlasiQ06033. baseline and differential.
GenevisibleiQ06033. HS.

Organism-specific databases

HPAiHPA017373.

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

BioGridi109905. 6 interactions.
IntActiQ06033. 4 interactions.
STRINGi9606.ENSP00000415769.

Structurei

3D structure databases

ProteinModelPortaliQ06033.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 158130VITPROSITE-ProRule annotationAdd
BLAST
Domaini284 – 467184VWFAPROSITE-ProRule annotationAdd
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

Signal

Phylogenomic databases

eggNOGiENOG410IEJB. Eukaryota.
COG2304. LUCA.
GeneTreeiENSGT00550000074468.
HOGENOMiHOG000000680.
HOVERGENiHBG057734.
InParanoidiQ06033.
OMAiFVVVLHQ.
OrthoDBiEOG091G01HF.
PhylomeDBiQ06033.
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 (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: Q06033-1) [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
MAFAWWPCLI LALLSSLAAS GFPRSPFRLL GKRSLPEGVA NGIEVYSTKI
60 70 80 90 100
NSKVTSRFAH NVVTMRAVNR ADTAKEVSFD VELPKTAFIT NFTLTIDGVT
110 120 130 140 150
YPGNVKEKEV AKKQYEKAVS QGKTAGLVKA SGRKLEKFTV SVNVAAGSKV
160 170 180 190 200
TFELTYEELL KRHKGKYEMY LKVQPKQLVK HFEIEVDIFE PQGISMLDAE
210 220 230 240 250
ASFITNDLLG SALTKSFSGK KGHVSFKPSL DQQRSCPTCT DSLLNGDFTI
260 270 280 290 300
TYDVNRESPG NVQIVNGYFV HFFAPQGLPV VPKNVAFVID ISGSMAGRKL
310 320 330 340 350
EQTKEALLRI LEDMQEEDYL NFILFSGDVS TWKEHLVQAT PENLQEARTF
360 370 380 390 400
VKSMEDKGMT NINDGLLRGI SMLNKAREEH RIPERSTSIV IMLTDGDANV
410 420 430 440 450
GESRPEKIQE NVRNAIGGKF PLYNLGFGNN LNYNFLENMA LENHGFARRI
460 470 480 490 500
YEDSDADLQL QGFYEEVANP LLTGVEMEYP ENAILDLTQN TYQHFYDGSE
510 520 530 540 550
IVVAGRLVDE DMNSFKADVK GHGATNDLTF TEEVDMKEME KALQERDYIF
560 570 580 590 600
GNYIERLWAY LTIEQLLEKR KNAHGEEKEN LTARALDLSL KYHFVTPLTS
610 620 630 640 650
MVVTKPEDNE DERAIADKPG EDAEATPVSP AMSYLTSYQP PQNPYYYVDG
660 670 680 690 700
DPHFIIQIPE KDDALCFNID EAPGTVLRLI QDAVTGLTVN GQITGDKRGS
710 720 730 740 750
PDSKTRKTYF GKLGIANAQM DFQVEVTTEK ITLWNRAVPS TFSWLDTVTV
760 770 780 790 800
TQDGLSMMIN RKNMVVSFGD GVTFVVVLHQ VWKKHPVHRD FLGFYVVDSH
810 820 830 840 850
RMSAQTHGLL GQFFQPFDFK VSDIRPGSDP TKPDATLVVK NHQLIVTRGS
860 870 880 890
QKDYRKDASI GTKVVCWFVH NNGEGLIDGV HTDYIVPNLF
Length:890
Mass (Da):99,849
Last modified:December 4, 2007 - v2
Checksum:i03B2B768784CB440
GO
Isoform 2 (identifier: Q06033-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MAFAWWPCLILALLSSLAASG → MVALSHLGSALQLGSLC

Show »
Length:886
Mass (Da):99,328
Checksum:i0B717C8073BE7EF6
GO

Sequence cautioni

The sequence CAA32821 differs from that shown. Reason: Frameshift at positions 732, 736 and 739. Curated
The sequence CAA47439 differs from that shown. Reason: Frameshift at positions 21, 732, 736 and 739. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti113 – 1131K → N in BAD97203 (Ref. 3) Curated
Sequence conflicti113 – 1131K → N in BAD96477 (Ref. 3) Curated
Sequence conflicti348 – 3481R → K in CAA32821 (PubMed:2465147).Curated
Sequence conflicti361 – 3611N → G in CAA32821 (PubMed:2465147).Curated
Sequence conflicti515 – 5151F → L in CAC79611 (PubMed:9756925).Curated
Sequence conflicti667 – 6671F → L in BAD97203 (Ref. 3) Curated
Sequence conflicti667 – 6671F → L in BAD96477 (Ref. 3) Curated
Sequence conflicti716 – 7161A → R in CAA47439 (PubMed:7681778).Curated
Sequence conflicti716 – 7161A → R in CAA32821 (PubMed:2465147).Curated
Sequence conflicti851 – 8511Q → H in CAA32821 (PubMed:2465147).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti315 – 3151Q → K.1 Publication
Corresponds to variant rs3617 [ dbSNP | Ensembl ].
VAR_049647
Natural varianti340 – 3401T → M.
Corresponds to variant rs35271262 [ dbSNP | Ensembl ].
VAR_049648
Natural varianti640 – 6401P → L.
Corresponds to variant rs60805548 [ dbSNP | Ensembl ].
VAR_061275
Natural varianti751 – 7511T → A.
Corresponds to variant rs9883888 [ dbSNP | Ensembl ].
VAR_049649
Natural varianti825 – 8251R → Q.
Corresponds to variant rs2710330 [ dbSNP | Ensembl ].
VAR_049650
Natural varianti858 – 8581A → V.
Corresponds to variant rs2710329 [ dbSNP | Ensembl ].
VAR_049651

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2121MAFAW…LAASG → MVALSHLGSALQLGSLC in isoform 2. 2 PublicationsVSP_029842Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67055 mRNA. Translation: CAA47439.1. Frameshift.
X99854 Genomic DNA. Translation: CAC79611.1.
AK222757 mRNA. Translation: BAD96477.1.
AK223483 mRNA. Translation: BAD97203.1.
AC006254 Genomic DNA. No translation available.
BC107604 mRNA. Translation: AAI07605.1.
BC107605 mRNA. Translation: AAI07606.1.
BC107814 mRNA. Translation: AAI07815.1.
X14690 mRNA. Translation: CAA32821.1. Frameshift.
CCDSiCCDS46845.1. [Q06033-1]
PIRiS30350.
RefSeqiNP_002208.3. NM_002217.3. [Q06033-1]
UniGeneiHs.76716.

Genome annotation databases

EnsembliENST00000449956; ENSP00000415769; ENSG00000162267. [Q06033-1]
GeneIDi3699.
KEGGihsa:3699.
UCSCiuc003dfv.3. human. [Q06033-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67055 mRNA. Translation: CAA47439.1. Frameshift.
X99854 Genomic DNA. Translation: CAC79611.1.
AK222757 mRNA. Translation: BAD96477.1.
AK223483 mRNA. Translation: BAD97203.1.
AC006254 Genomic DNA. No translation available.
BC107604 mRNA. Translation: AAI07605.1.
BC107605 mRNA. Translation: AAI07606.1.
BC107814 mRNA. Translation: AAI07815.1.
X14690 mRNA. Translation: CAA32821.1. Frameshift.
CCDSiCCDS46845.1. [Q06033-1]
PIRiS30350.
RefSeqiNP_002208.3. NM_002217.3. [Q06033-1]
UniGeneiHs.76716.

3D structure databases

ProteinModelPortaliQ06033.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109905. 6 interactions.
IntActiQ06033. 4 interactions.
STRINGi9606.ENSP00000415769.

PTM databases

iPTMnetiQ06033.
PhosphoSiteiQ06033.

Polymorphism and mutation databases

BioMutaiITIH3.
DMDMi166203665.

Proteomic databases

MaxQBiQ06033.
PaxDbiQ06033.
PeptideAtlasiQ06033.
PRIDEiQ06033.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000449956; ENSP00000415769; ENSG00000162267. [Q06033-1]
GeneIDi3699.
KEGGihsa:3699.
UCSCiuc003dfv.3. human. [Q06033-1]

Organism-specific databases

CTDi3699.
GeneCardsiITIH3.
H-InvDBHIX0024346.
HGNCiHGNC:6168. ITIH3.
HPAiHPA017373.
MIMi146650. gene.
neXtProtiNX_Q06033.
PharmGKBiPA29966.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEJB. Eukaryota.
COG2304. LUCA.
GeneTreeiENSGT00550000074468.
HOGENOMiHOG000000680.
HOVERGENiHBG057734.
InParanoidiQ06033.
OMAiFVVVLHQ.
OrthoDBiEOG091G01HF.
PhylomeDBiQ06033.
TreeFamiTF328982.

Enzyme and pathway databases

ReactomeiR-HSA-114608. Platelet degranulation.

Miscellaneous databases

ChiTaRSiITIH3. human.
GeneWikiiITIH3.
GenomeRNAii3699.
PROiQ06033.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162267.
CleanExiHS_ITIH3.
ExpressionAtlasiQ06033. baseline and differential.
GenevisibleiQ06033. 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 nameiITIH3_HUMAN
AccessioniPrimary (citable) accession number: Q06033
Secondary accession number(s): Q3B7H5
, Q53F06, Q6LAM2, Q99085
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: December 4, 2007
Last modified: September 7, 2016
This is version 132 of the entry and version 2 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.