P19823 (ITIH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 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

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

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.
Tissue specificity	Plasma. Ref.17
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. Phosphorylation sites are present in the extracelllular medium.
Sequence similarities	Belongs to the ITIH family. Contains 1 VIT domain. Contains 1 VWFA domain.
Mass spectrometry	Molecular mass is 76508 Da from positions 55 - 702. Determined by MALDI. Ref.12
Sequence caution	The sequence CAA30160.1 differs from that shown. Reason: Frameshift at positions 363 and 373.

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	Complete proteome Direct protein sequencing Reference proteome
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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Propeptide	19 – 54	36			PRO_0000016517
	Chain	55 – 702	648	Inter-alpha-trypsin inhibitor heavy chain H2		PRO_0000016518
	Propeptide	703 – 946	244			PRO_0000016519
Regions
	Domain	56 – 185	130	VIT
	Domain	308 – 468	161	VWFA
Amino acid modifications
	Modified residue	60	1	Phosphoserine Ref.17
	Modified residue	282	1	4-carboxyglutamate
	Modified residue	283	1	4-carboxyglutamate
	Modified residue	702	1	Aspartate 1-(chondroitin 4-sulfate)-ester
	Glycosylation	96	1	N-linked (GlcNAc...) Ref.15
	Glycosylation	118	1	N-linked (GlcNAc...) (complex) Ref.12 Ref.13 Ref.14 Ref.15 Ref.16		CAR_000140
	Glycosylation	445	1	N-linked (GlcNAc...) Ref.15
	Glycosylation	666	1	O-linked (GalNAc...); partial Ref.12 Ref.13		CAR_000214
	Glycosylation	673	1	O-linked (GalNAc...) Ref.12 Ref.13		CAR_000215
	Glycosylation	675	1	O-linked (GalNAc...) Ref.12 Ref.13		CAR_000216
	Glycosylation	691	1	O-linked (GalNAc...) Ref.8 Ref.12 Ref.13		CAR_000217
	Disulfide bond	261 ↔ 264		Ref.13
	Disulfide bond	650 ↔ 651		Ref.13
Natural variations
	Natural variant	263	1	N → S. Ref.1 Corresponds to variant rs7075296 [ dbSNP | Ensembl ].		VAR_055248
	Natural variant	569	1	L → V. Corresponds to variant rs7084817 [ dbSNP | Ensembl ].		VAR_055249
	Natural variant	674	1	P → A. Ref.4 Corresponds to variant rs3740217 [ dbSNP | Ensembl ].		VAR_055250
Experimental info
	Sequence conflict	374	1	K → L AA sequence Ref.6
	Sequence conflict	705	1	F → S in AAA60558. Ref.3
	Sequence conflict	705	1	F → S in AAA59195. Ref.4
	Sequence conflict	729	1	N → D in AAA60558. Ref.3
	Sequence conflict	729	1	N → D in AAA59195. Ref.4
	Sequence conflict	731	1	V → A in AAA60558. Ref.3
	Sequence conflict	731	1	V → A in AAA59195. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P19823 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: BA626B146DDC2A5F	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

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. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., 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]	"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.
[17]	"An initial characterization of the serum phosphoproteome." Zhou W., Ross M.M., Tessitore A., Ornstein D., Vanmeter A., Liotta L.A., Petricoin E.F. III J. Proteome Res. 8:5523-5531(2009) [PubMed: 19824718] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, TISSUE SPECIFICITY, MASS SPECTROMETRY. Tissue: Serum.
[18]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X07173 mRNA. Translation: CAA30160.1. Frameshift. 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. NM_002216.2.
UniGene	Hs.75285.
3D structure databases
ProteinModelPortal	P19823.
ModBase	Search...
Protein-protein interaction databases
IntAct	P19823. 1 interaction.
MINT	MINT-1415907.
STRING	P19823.
PTM databases
GlycoSuiteDB	P19823.
PhosphoSite	P19823.
Polymorphism databases
DMDM	229462889.
Proteomic databases
PRIDE	P19823.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000358415; ENSP00000351190; ENSG00000151655.
GeneID	3698.
KEGG	hsa:3698.
Organism-specific databases
CTD	3698.
GeneCards	GC10P007785.
H-InvDB	HIX0035419.
HGNC	HGNC:6167. ITIH2.
HPA	CAB008644.
MIM	146640. gene.
neXtProt	NX_P19823.
PharmGKB	PA29965.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00550000074468.
HOGENOM	HBG713262.
HOVERGEN	HBG057734.
InParanoid	P19823.
OMA	PPQDHSC.
OrthoDB	EOG4TQM8G.
PhylomeDB	P19823.
Gene expression databases
ArrayExpress	P19823.
Bgee	P19823.
CleanEx	HS_ITIH2.
Genevestigator	P19823.
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	PS51468. VIT. 1 hit. PS50234. VWFA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	14495.
SOURCE	Search...

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:	January 25, 2012
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.