Inter-alpha-trypsin inhibitor heavy chain H2 precursor

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Reviewed, UniProtKB/Swiss-Prot P19823 (ITIH2_HUMAN)

Last modified June 16, 2009. Version 101. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Inter-alpha-trypsin inhibitor heavy chain H2
      Short name=Inter-alpha-inhibitor heavy chain 2
      Short name=ITI heavy chain H2
Alternative name(s):
    Inter-alpha-trypsin inhibitor complex component II
    Serum-derived hyaluronan-associated protein
      Short name=SHAP

Gene names

Name:	ITIH2
Synonyms:	IGHEP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	946 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	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.
Subunit structure	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.
Subcellular location	Secreted.
Post-translational modification	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.
Sequence similarities	Belongs to the ITIH family. Contains 1 VWFA domain.
Mass spectrometry	Molecular mass is 76508 Da from positions 55 - 702. Determined by MALDI. Ref.12

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Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond Gamma-carboxyglutamic acid Glycoprotein Phosphoprotein Proteoglycan
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	hyaluronan metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB
Molecular function	serine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

Potential

Propeptide

19 – 54

Ref.6 Ref.7 Ref.8 Ref.9

PRO_0000016517

Chain

55 – 702

648

Inter-alpha-trypsin inhibitor heavy chain H2

PRO_0000016518

Propeptide

703 – 946

244

PRO_0000016519

Regions

Domain

308 – 468

161

VWFA

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

282

4-carboxyglutamate

Modified residue

283

4-carboxyglutamate

Modified residue

702

Aspartate 1-(chondroitin 4-sulfate)-ester

Glycosylation

N-linked (GlcNAc...) Ref.15

Glycosylation

118

N-linked (GlcNAc...) (complex) Ref.12 Ref.15 Ref.13 Ref.14

CAR_000140

Glycosylation

445

N-linked (GlcNAc...) Ref.15

Glycosylation

666

O-linked (GalNAc...); partial Ref.12 Ref.13

CAR_000214

Glycosylation

671

N-linked (GlcNAc...)

Glycosylation

673

O-linked (GalNAc...) Ref.12 Ref.13

CAR_000215

Glycosylation

675

O-linked (GalNAc...) Ref.12 Ref.13

CAR_000216

Glycosylation

691

O-linked (GalNAc...) Ref.12 Ref.8 Ref.13

Disulfide bond

Disulfide bond

Natural variations

Natural variant

263

N → S: dbSNP rs7075296.

VAR_055248

Natural variant

569

L → V: dbSNP rs7084817.

VAR_055249

Natural variant

674

P → A: dbSNP rs3740217.

VAR_055250

Experimental info

Sequence conflict

374

K → L AA sequence Ref.6

Sequence conflict

705

F → S in AAA60558. Ref.3

Sequence conflict

705

F → S in AAA59195. Ref.4

Sequence conflict

729

N → D in AAA60558. Ref.3

Sequence conflict

729

N → D in AAA59195. Ref.4

Sequence conflict

731

V → A in AAA60558. Ref.3

Sequence conflict

731

V → A in AAA59195. Ref.4

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Sequences

Sequence

Length

Mass (Da)

Tools

P19823-1 [UniParc].

Last modified May 5, 2009. Version 2.
Checksum: BA626B146DDC2A5F
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FASTA

946

106,463

        10         20         30         40         50         60 
MKRLTCFFIC FFLSEVSGFE IPINGLSEFV DYEDLVELAP GKFQLVAENR RYQRSLPGES 

        70         80         90        100        110        120 
EEMMEEVDQV TLYSYKVQST ITSRMATTMI QSKVVNNSPQ PQNVVFDVQI PKGAFISNFS 

       130        140        150        160        170        180 
MTVDGKTFRS SIKEKTVGRA LYAQARAKGK TAGLVRSSAL DMENFRTEVN VLPGAKVQFE 

       190        200        210        220        230        240 
LHYQEVKWRK LGSYEHRIYL QPGRLAKHLE VDVWVIEPQG LRFLHVPDTF EGHFDGVPVI 

       250        260        270        280        290        300 
SKGQQKAHVS FKPTVAQQRI CPNCRETAVD GELVVLYDVK REEKAGELEV FNGYFVHFFA 

       310        320        330        340        350        360 
PDNLDPIPKN ILFVIDVSGS MWGVKMKQTV EAMKTILDDL RAEDHFSVID FNQNIRTWRN 

       370        380        390        400        410        420 
DLISATKTQV ADAKRYIEKI QPSGGTNINE ALLRAIFILN EANNLGLLDP NSVSLIILVS 

       430        440        450        460        470        480 
DGDPTVGELK LSKIQKNVKE NIQDNISLFS LGMGFDVDYD FLKRLSNENH GIAQRIYGNQ 

       490        500        510        520        530        540 
DTSSQLKKFY NQVSTPLLRN VQFNYPHTSV TDVTQNNFHN YFGGSEIVVA GKFDPAKLDQ 

       550        560        570        580        590        600 
IESVITATSA NTQLVLETLA QMDDLQDFLS KDKHADPDFT RKLWAYLTIN QLLAERSLAP 

       610        620        630        640        650        660 
TAAAKRRITR SILQMSLDHH IVTPLTSLVI ENEAGDERML ADAPPQDPSC CSGALYYGSK 

       670        680        690        700        710        720 
VVPDSTPSWA NPSPTPVISM LAQGSQVLES TPPPHVMRVE NDPHFIIYLP KSQKNICFNI 

       730        740        750        760        770        780 
DSEPGKILNL VSDPESGIVV NGQLVGAKKP NNGKLSTYFG KLGFYFQSED IKIEISTETI 

       790        800        810        820        830        840 
TLSHGSSTFS LSWSDTAQVT NQRVQISVKK EKVVTITLDK EMSFSVLLHR VWKKHPVNVD 

       850        860        870        880        890        900 
FLGIYIPPTN KFSPKAHGLI GQFMQEPKIH IFNERPGKDP EKPEASMEVK GQKLIITRGL 

       910        920        930        940 
QKDYRTDLVF GTDVTCWFVH NSGKGFIDGH YKDYFVPQLY SFLKRP

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complementary DNA and derived amino acid sequence of the precursor of one of the three protein components of the inter-alpha-trypsin inhibitor complex." Gebhard W., Schreitmueller T., Hochstrasser K., Wachter E. FEBS Lett. 229:63-67(1988) [PubMed: 2450046] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT SER-263.
[2]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Isolation and characterization of cDNAs encoding the heavy chain of human inter-alpha-trypsin inhibitor (I alpha TI): unambiguous evidence for multipolypeptide chain structure of I alpha TI." Salier J.-P., Diarra-Mehrpour M., Sesboue R., Bourguignon J., Benarous R., Ohkubo I., Kurachi S., Kurachi K., Martin J.-P. Proc. Natl. Acad. Sci. U.S.A. 84:8272-8276(1987) [PubMed: 2446322] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 384-865.
[4]	"Human inter-alpha-trypsin inhibitor. Isolation and characterization of heavy (H) chain cDNA clones coding for a 383 amino-acid sequence of the H chain." Salier J.-P., Diarra-Mehrpour M., Sesboue R., Bourguignon J., Martin J.-P. Biol. Chem. Hoppe-Seyler 369:15-18(1988) [PubMed: 2462430] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 384-766, VARIANT ALA-674.
[5]	"cDNA cloning of human inter-alpha-trypsin inhibitor discloses three different proteins." Schreitmueller T., Hochstrasser K., Resinger P.W.M., Wachter E., Gebhard W. Biol. Chem. Hoppe-Seyler 368:963-970(1987) [PubMed: 3663330] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[6]	"Analysis of inter-alpha-trypsin inhibitor and a novel trypsin inhibitor, pre-alpha-trypsin inhibitor, from human plasma. Polypeptide chain stoichiometry and assembly by glycan." Enghild J.J., Thoegersen I.B., Pizzo S.V., Salvesen G. J. Biol. Chem. 264:15975-15981(1989) [PubMed: 2476436] [Abstract] Cited for: PROTEIN SEQUENCE OF 55-74; 116-127; 224-246; 295-307 AND 365-385.
[7]	"The heavy chains of human plasma inter-alpha-trypsin inhibitor: their isolation, their identification by electrophoresis and partial sequencing. Differential reactivity with concanavalin A." Malki N., Balduyck M., Maes P., Capon C., Mizon C., Han K.K., Tartar A., Fournet B., Mizon J. Biol. Chem. Hoppe-Seyler 373:1009-1018(1992) [PubMed: 1384548] [Abstract] Cited for: PROTEIN SEQUENCE OF 55-64. Tissue: Plasma.
[8]	"Presence of the protein-glycosaminoglycan-protein covalent cross-link in the inter-alpha-inhibitor-related proteinase inhibitor heavy chain 2/bikunin." Enghild J.J., Salvesen G., Thoegersen I.B., Valnickova Z., Pizzo S.V., Hefta S.A. J. Biol. Chem. 268:8711-8716(1993) [PubMed: 7682553] [Abstract] Cited for: PROTEIN SEQUENCE OF 55-64 AND 681-702, CROSS-LINK STRUCTURE, GLYCOSYLATION AT THR-691.
[9]	"TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor." Wisniewski H.-G., Burgess W.H., Oppenheim J.D., Vilcek J. Biochemistry 33:7423-7429(1994) [PubMed: 7516184] [Abstract] Cited for: PROTEIN SEQUENCE OF 55-64, INTERACTION WITH TNFAIP6.
[10]	"A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the inter alpha-trypsin inhibitor." Huang L., Yoneda M., Kimata K. J. Biol. Chem. 268:26725-26730(1993) [PubMed: 7504674] [Abstract] Cited for: PROTEIN SEQUENCE OF 67-101, HYALURONAN BINDING. Tissue: Serum.
[11]	"Chondroitin sulphate covalently cross-links the three polypeptide chains of inter-alpha-trypsin inhibitor." Morelle W., Capon C., Balduyck M., Sautiere P., Kouach M., Michalski C., Fournet B., Mizon J. Eur. J. Biochem. 221:881-888(1994) [PubMed: 7513643] [Abstract] Cited for: PROTEIN SEQUENCE OF 699-702, COVALENT LINKAGE WITH CHONDROITIN SULFATE. Tissue: Plasma.
[12]	"Glycosylation pattern of human inter-alpha-inhibitor heavy chains." Flahaut C., Capon C., Balduyck M., Ricart G., Sautiere P., Mizon J. Biochem. J. 333:749-756(1998) [PubMed: 9677337] [Abstract] Cited for: GLYCOSYLATION AT ASN-118; THR-666; SER-673; THR-675 AND THR-691, MASS SPECTROMETRY.
[13]	"Posttranslational modifications of human inter-alpha-inhibitor: identification of glycans and disulfide bridges in heavy chains 1 and 2." Olsen E.H.N., Rahbek-Nielsen H., Thoegersen I.B., Roepstorff P., Enghild J.J. Biochemistry 37:408-416(1998) [PubMed: 9425062] [Abstract] Cited for: GLYCOSYLATION AT ASN-118; THR-666; SER-673; THR-675 AND THR-691, DISULFIDE BONDS.
[14]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-118.
[15]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-96; ASN-118 AND ASN-445, MASS SPECTROMETRY. Tissue: Plasma.
[16]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[17]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-118, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	X07173 mRNA. Translation: CAA30160.1. Sequence problems. AL158044 Genomic DNA. Translation: CAI12957.1. M18193 mRNA. Translation: AAA60558.1. M33033 mRNA. Translation: AAA59195.1.
IPI	IPI00305461.
PIR	IYHU2. S00346.
RefSeq	NP_002207.2.
UniGene	Hs.75285
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P19823. 1 interaction.
PTM databases
GlycoSuiteDB	P19823.
PhosphoSite	P19823.
Proteomic databases
PRIDE	P19823.
Genome annotation databases
Ensembl	ENSG00000151655. Homo sapiens. [Contig view]
GeneID	3698.
KEGG	hsa:3698.
Organism-specific databases
GeneCards	GC10P007785.
H-InvDB	HIX0035419.
HGNC	HGNC:6167. ITIH2.
HPA	CAB008644.
MIM	146640. gene.
PharmGKB	PA29965.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P19823.
HOVERGEN	P19823.
Gene expression databases
ArrayExpress	P19823.
Bgee	P19823.
CleanEx	HS_ITIH2.
GermOnline	ENSG00000151655. Homo sapiens.
Family and domain databases
InterPro	IPR010600. ITI_HC_C. IPR013694. VIT. IPR006587. VIT_met. IPR002035. VWF_A. [Graphical view]
Pfam	PF06668. ITI_HC_C. 1 hit. PF08487. VIT. 1 hit. PF00092. VWA. 1 hit. [Graphical view]
SMART	SM00609. VIT. 1 hit. SM00327. VWA. 1 hit. [Graphical view]
PROSITE	PS50234. VWFA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	14495.
SOURCE	Search...

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Entry information

Entry name

ITIH2_HUMAN

Accession

Primary (citable) accession number: P19823
Secondary accession number(s): Q14659, Q15484, Q5T986

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	May 5, 2009
Last modified:	June 16, 2009
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents