Q14624 (ITIH4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inter-alpha-trypsin inhibitor heavy chain H4
Short name=ITI heavy chain H4
Short name=ITI-HC4
Short name=Inter-alpha-inhibitor heavy chain 4

Alternative name(s):
Inter-alpha-trypsin inhibitor family heavy chain-related protein
Short name=IHRP
Plasma kallikrein sensitive glycoprotein 120
Short name=Gp120
Short name=PK-120

Cleaved into the following 2 chains:

1. 70 kDa inter-alpha-trypsin inhibitor heavy chain H4
2. 35 kDa inter-alpha-trypsin inhibitor heavy chain H4

Gene names

Name:	ITIH4
Synonyms:	IHRP, ITIHL1, PK120
ORF Names:	PRO1851

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	930 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	Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration. Ref.14
Subunit structure	Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain); this interaction protects ITIH4 against cleavage by kallikrein in vitro. Ref.5
Subcellular location	Secreted.
Tissue specificity	Liver specific. Ref.1 Ref.2
Induction	Levels increase from 1.4 to 3-fold in acute-phase processes such as in acute ischemia stroke (AIS), unstable angina and programmed surgery. In hepatocytes, induced by IL6 but not by other cytokines such as IL1B. Ref.10 Ref.14
Post-translational modification	Cleaved by plasma kallikrein to yield 100 kDa and 35 kDa fragments, and the resulting 100 kDa fragment is further converted to a 70 kDa fragment. N- and O-glycosylated. In urine, O-linked glycosylation on threonine residues in the region from Thr-719 to Thr-725 consists of core 1 or possibly core 8 glycans. Mainly Hex(HexNAc)2, but also some Hex3(HexNAc)3. N-glycosylated but not O-glycosylated in plasma. Ref.8 Ref.11 Ref.18
Miscellaneous	Possible biomarker for acute ischemic stroke (Ref.14). Peptides derived from the proline-rich potentially active peptide (PRO_0000016542) may be biomarkers for a variety of disease states including breast cancer (Ref.16).
Sequence similarities	Belongs to the ITIH family. Contains 1 VIT domain. Contains 1 VWFA domain.

Ontologies

Keywords
Biological process	Acute phase
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	acute-phase response Inferred from expression pattern Ref.14. Source: UniProtKB hyaluronan metabolic process Inferred from electronic annotation. Source: InterPro response to cytokine stimulus Inferred from expression pattern Ref.10. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular region Non-traceable author statement PubMed 14718574. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	endopeptidase inhibitor activity Traceable author statement PubMed 9756925. Source: ProtInc serine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q14624-1)

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.

Isoform 2 (identifier: Q14624-2)

The sequence of this isoform differs from the canonical sequence as follows:
     621-650: Missing.
     727-727: A → ACPSCSRSRAPAVPA

Note: No experimental confirmation available.

Isoform 3 (identifier: Q14624-3)

The sequence of this isoform differs from the canonical sequence as follows:
     621-650: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q14624-4)

The sequence of this isoform differs from the canonical sequence as follows:
     621-650: Missing.
     727-765: Missing.
     851-866: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Ref.8
	Chain	29 – 661	633	70 kDa inter-alpha-trypsin inhibitor heavy chain H4		PRO_0000016541
	Propeptide	662 – 688	27	Potentially active peptide		PRO_0000016542
	Chain	689 – 930	242	35 kDa inter-alpha-trypsin inhibitor heavy chain H4		PRO_0000016543
Regions
	Domain	29 – 148	120	VIT
	Domain	272 – 432	161	VWFA
	Region	658 – 688	31	Proline-rich (PRR) potential bioactive peptide
	Region	719 – 725	7	O-glycosylated at three sites
Sites
	Site	688 – 689	2	Cleavage; by kallikrein
Amino acid modifications
	Glycosylation	81	1	N-linked (GlcNAc...) Ref.13 Ref.15
	Glycosylation	207	1	N-linked (GlcNAc...) Ref.11 Ref.13 Ref.15
	Glycosylation	517	1	N-linked (GlcNAc...) Ref.12 Ref.13 Ref.15
	Glycosylation	577	1	N-linked (GlcNAc...) Ref.13
	Glycosylation	720	1	O-linked (GlcNAc...) Ref.18
	Disulfide bond	747 ↔ 925		Probable
Natural variations
	Alternative sequence	621 – 650	30	Missing in isoform 2, isoform 3 and isoform 4.		VSP_002761
	Alternative sequence	727 – 765	39	Missing in isoform 4.		VSP_044764
	Alternative sequence	727	1	A → ACPSCSRSRAPAVPA in isoform 2.		VSP_002762
	Alternative sequence	851 – 866	16	Missing in isoform 4.		VSP_044765
	Natural variant	85	1	I → N. Ref.2 Corresponds to variant rs13072536 [ dbSNP | Ensembl ].		VAR_027869
	Natural variant	86	1	I → N. Ref.19		VAR_013836
	Natural variant	669	1	Q → L. Corresponds to variant rs2276814 [ dbSNP | Ensembl ].		VAR_027870
	Natural variant	698	1	P → T. Corresponds to variant rs4687657 [ dbSNP | Ensembl ].		VAR_027871
	Natural variant	714	1	M → I. Corresponds to variant rs2256734 [ dbSNP | Ensembl ].		VAR_027872
	Natural variant	791	1	L → P. Corresponds to variant rs2535621 [ dbSNP | Ensembl ].		VAR_027873
Experimental info
	Sequence conflict	85	1	I → K in AAD05198. Ref.3
	Sequence conflict	114	1	S → N in BAA07602. Ref.2
	Sequence conflict	207	1	N → F AA sequence Ref.8
	Sequence conflict	221	1	Q → E AA sequence Ref.8
	Sequence conflict	307	1	R → V AA sequence Ref.8
	Sequence conflict	322	1	W → Y AA sequence Ref.8
	Sequence conflict	370	1	E → G in BAH12781. Ref.6
	Sequence conflict	816 – 817	2	ET → QR AA sequence Ref.8
	Sequence conflict	905	1	S → F no nucleotide entry Ref.3
	Sequence conflict	927	1	S → T no nucleotide entry Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 4. Checksum: 847A9A5CB886C5A4	FASTA	930	103,357
	10 20 30 40 50 60 MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR 70 80 90 100 110 120 ANTVQEATFQ MELPKKAFIT NFSMIIDGMT YPGIIKEKAE AQAQYSAAVA KGKSAGLVKA 130 140 150 160 170 180 TGRNMEQFQV SVSVAPNAKI TFELVYEELL KRRLGVYELL LKVRPQQLVK HLQMDIHIFE 190 200 210 220 230 240 PQGISFLETE STFMTNQLVD ALTTWQNKTK AHIRFKPTLS QQQKSPEQQE TVLDGNLIIR 250 260 270 280 290 300 YDVDRAISGG SIQIENGYFV HYFAPEGLTT MPKNVVFVID KSGSMSGRKI QQTREALIKI 310 320 330 340 350 360 LDDLSPRDQF NLIVFSTEAT QWRPSLVPAS AENVNKARSF AAGIQALGGT NINDAMLMAV 370 380 390 400 410 420 QLLDSSNQEE RLPEGSVSLI ILLTDGDPTV GETNPRSIQN NVREAVSGRY SLFCLGFGFD 430 440 450 460 470 480 VSYAFLEKLA LDNGGLARRI HEDSDSALQL QDFYQEVANP LLTAVTFEYP SNAVEEVTQN 490 500 510 520 530 540 NFRLLFKGSE MVVAGKLQDR GPDVLTATVS GKLPTQNITF QTESSVAEQE AEFQSPKYIF 550 560 570 580 590 600 HNFMERLWAY LTIQQLLEQT VSASDADQQA LRNQALNLSL AYSFVTPLTS MVVTKPDDQE 610 620 630 640 650 660 QSQVAEKPME GESRNRNVHS GSTFFKYYLQ GAKIPKPEAS FSPRRGWNRQ AGAAGSRMNF 670 680 690 700 710 720 RPGVLSSRQL GLPGPPDVPD HAAYHPFRRL AILPASAPPA TSNPDPAVSR VMNMKIEETT 730 740 750 760 770 780 MTTQTPAPIQ APSAILPLPG QSVERLCVDP RHRQGPVNLL SDPEQGVEVT GQYEREKAGF 790 800 810 820 830 840 SWIEVTFKNP LVWVHASPEH VVVTRNRRSS AYKWKETLFS VMPGLKMTMD KTGLLLLSDP 850 860 870 880 890 900 DKVTIGLLFW DGRGEGLRLL LRDTDRFSSH VGGTLGQFYQ EVLWGSPAAS DDGRRTLRVQ 910 920 930 GNDHSATRER RLDYQEGPPG VEISCWSVEL
	Isoform 2 [UniParc]. Checksum: 79F2D903E65026CD	FASTA	914	101,241
	10 20 30 40 50 60 MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR 70 80 90 100 110 120 ANTVQEATFQ MELPKKAFIT NFSMIIDGMT YPGIIKEKAE AQAQYSAAVA KGKSAGLVKA 130 140 150 160 170 180 TGRNMEQFQV SVSVAPNAKI TFELVYEELL KRRLGVYELL LKVRPQQLVK HLQMDIHIFE 190 200 210 220 230 240 PQGISFLETE STFMTNQLVD ALTTWQNKTK AHIRFKPTLS QQQKSPEQQE TVLDGNLIIR 250 260 270 280 290 300 YDVDRAISGG SIQIENGYFV HYFAPEGLTT MPKNVVFVID KSGSMSGRKI QQTREALIKI 310 320 330 340 350 360 LDDLSPRDQF NLIVFSTEAT QWRPSLVPAS AENVNKARSF AAGIQALGGT NINDAMLMAV 370 380 390 400 410 420 QLLDSSNQEE RLPEGSVSLI ILLTDGDPTV GETNPRSIQN NVREAVSGRY SLFCLGFGFD 430 440 450 460 470 480 VSYAFLEKLA LDNGGLARRI HEDSDSALQL QDFYQEVANP LLTAVTFEYP SNAVEEVTQN 490 500 510 520 530 540 NFRLLFKGSE MVVAGKLQDR GPDVLTATVS GKLPTQNITF QTESSVAEQE AEFQSPKYIF 550 560 570 580 590 600 HNFMERLWAY LTIQQLLEQT VSASDADQQA LRNQALNLSL AYSFVTPLTS MVVTKPDDQE 610 620 630 640 650 660 QSQVAEKPME GESRNRNVHS AGAAGSRMNF RPGVLSSRQL GLPGPPDVPD HAAYHPFRRL 670 680 690 700 710 720 AILPASAPPA TSNPDPAVSR VMNMKIEETT MTTQTPACPS CSRSRAPAVP APIQAPSAIL 730 740 750 760 770 780 PLPGQSVERL CVDPRHRQGP VNLLSDPEQG VEVTGQYERE KAGFSWIEVT FKNPLVWVHA 790 800 810 820 830 840 SPEHVVVTRN RRSSAYKWKE TLFSVMPGLK MTMDKTGLLL LSDPDKVTIG LLFWDGRGEG 850 860 870 880 890 900 LRLLLRDTDR FSSHVGGTLG QFYQEVLWGS PAASDDGRRT LRVQGNDHSA TRERRLDYQE 910 GPPGVEISCW SVEL
	Isoform 3 [UniParc]. Checksum: B18BE8E1C3BF634C	FASTA	900	99,857
	10 20 30 40 50 60 MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR 70 80 90 100 110 120 ANTVQEATFQ MELPKKAFIT NFSMIIDGMT YPGIIKEKAE AQAQYSAAVA KGKSAGLVKA 130 140 150 160 170 180 TGRNMEQFQV SVSVAPNAKI TFELVYEELL KRRLGVYELL LKVRPQQLVK HLQMDIHIFE 190 200 210 220 230 240 PQGISFLETE STFMTNQLVD ALTTWQNKTK AHIRFKPTLS QQQKSPEQQE TVLDGNLIIR 250 260 270 280 290 300 YDVDRAISGG SIQIENGYFV HYFAPEGLTT MPKNVVFVID KSGSMSGRKI QQTREALIKI 310 320 330 340 350 360 LDDLSPRDQF NLIVFSTEAT QWRPSLVPAS AENVNKARSF AAGIQALGGT NINDAMLMAV 370 380 390 400 410 420 QLLDSSNQEE RLPEGSVSLI ILLTDGDPTV GETNPRSIQN NVREAVSGRY SLFCLGFGFD 430 440 450 460 470 480 VSYAFLEKLA LDNGGLARRI HEDSDSALQL QDFYQEVANP LLTAVTFEYP SNAVEEVTQN 490 500 510 520 530 540 NFRLLFKGSE MVVAGKLQDR GPDVLTATVS GKLPTQNITF QTESSVAEQE AEFQSPKYIF 550 560 570 580 590 600 HNFMERLWAY LTIQQLLEQT VSASDADQQA LRNQALNLSL AYSFVTPLTS MVVTKPDDQE 610 620 630 640 650 660 QSQVAEKPME GESRNRNVHS AGAAGSRMNF RPGVLSSRQL GLPGPPDVPD HAAYHPFRRL 670 680 690 700 710 720 AILPASAPPA TSNPDPAVSR VMNMKIEETT MTTQTPAPIQ APSAILPLPG QSVERLCVDP 730 740 750 760 770 780 RHRQGPVNLL SDPEQGVEVT GQYEREKAGF SWIEVTFKNP LVWVHASPEH VVVTRNRRSS 790 800 810 820 830 840 AYKWKETLFS VMPGLKMTMD KTGLLLLSDP DKVTIGLLFW DGRGEGLRLL LRDTDRFSSH 850 860 870 880 890 900 VGGTLGQFYQ EVLWGSPAAS DDGRRTLRVQ GNDHSATRER RLDYQEGPPG VEISCWSVEL
	Isoform 4 [UniParc]. Checksum: 60436CD8050B7D46	FASTA	845	93,852
	10 20 30 40 50 60 MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR 70 80 90 100 110 120 ANTVQEATFQ MELPKKAFIT NFSMIIDGMT YPGIIKEKAE AQAQYSAAVA KGKSAGLVKA 130 140 150 160 170 180 TGRNMEQFQV SVSVAPNAKI TFELVYEELL KRRLGVYELL LKVRPQQLVK HLQMDIHIFE 190 200 210 220 230 240 PQGISFLETE STFMTNQLVD ALTTWQNKTK AHIRFKPTLS QQQKSPEQQE TVLDGNLIIR 250 260 270 280 290 300 YDVDRAISGG SIQIENGYFV HYFAPEGLTT MPKNVVFVID KSGSMSGRKI QQTREALIKI 310 320 330 340 350 360 LDDLSPRDQF NLIVFSTEAT QWRPSLVPAS AENVNKARSF AAGIQALGGT NINDAMLMAV 370 380 390 400 410 420 QLLDSSNQEE RLPEGSVSLI ILLTDGDPTV GETNPRSIQN NVREAVSGRY SLFCLGFGFD 430 440 450 460 470 480 VSYAFLEKLA LDNGGLARRI HEDSDSALQL QDFYQEVANP LLTAVTFEYP SNAVEEVTQN 490 500 510 520 530 540 NFRLLFKGSE MVVAGKLQDR GPDVLTATVS GKLPTQNITF QTESSVAEQE AEFQSPKYIF 550 560 570 580 590 600 HNFMERLWAY LTIQQLLEQT VSASDADQQA LRNQALNLSL AYSFVTPLTS MVVTKPDDQE 610 620 630 640 650 660 QSQVAEKPME GESRNRNVHS AGAAGSRMNF RPGVLSSRQL GLPGPPDVPD HAAYHPFRRL 670 680 690 700 710 720 AILPASAPPA TSNPDPAVSR VMNMKIEETT MTTQTPGVEV TGQYEREKAG FSWIEVTFKN 730 740 750 760 770 780 PLVWVHASPE HVVVTRNRRS SAYKWKETLF SVMPGLKMTM DKTGLLLLSD PDKVTIGLLF 790 800 810 820 830 840 WFSSHVGGTL GQFYQEVLWG SPAASDDGRR TLRVQGNDHS ATRERRLDYQ EGPPGVEISC WSVEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA and deduced amino acid sequence of human PK-120, a plasma kallikrein-sensitive glycoprotein." Nishimura H., Kakizaki I., Muta T., Sasaki N., Pu P.X., Yamashita T., Nagasawa S. FEBS Lett. 357:207-211(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Cloning and characterization of cDNA for inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP), a novel human plasma glycoprotein." Saguchi K., Tobe T., Hashimoto K., Sano Y., Nakano Y., Miura N.-H., Tomita M. J. Biochem. 117:14-18(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, IDENTIFICATION, TISSUE SPECIFICITY, VARIANT ASN-85. Tissue: Liver.
[3]	"Isolation and characterization of the human inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1)." Saguchi K., Tobe T., Hashimoto K., Nagasaki Y., Oda E., Nakano Y., Miura N.H., Tomita M. J. Biochem. 119:898-905(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Liver.
[5]	"BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-trypsin inhibitor heavy chain 4." Kroczynska B., King-Simmons L., Alloza L., Alava M.A., Elguindi E.C., Blond S.Y. Biochem. Biophys. Res. Commun. 338:1467-1477(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), INTERACTION WITH DNAJC1.
[6]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Functional prediction of the coding sequences of 79 new genes deduced by analysis of cDNA clones from human fetal liver." Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 271-930 (ISOFORM 2). Tissue: Fetal liver.
[8]	"Purification and characterization of a novel glycoprotein which has significant homology to heavy chains of inter-alpha-trypsin inhibitor family from human plasma." Choi-Miura N.-H., Sano Y., Oda E., Nakano Y., Tobe T., Yanagishita T., Taniyama M., Katagiri T., Tomita M. J. Biochem. 117:400-407(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-44; 99-119; 140-151; 163-170; 194-208; 211-243; 274-281; 290-329; 429-487; 497-567; 608-626 AND 816-831, PROTEOLYTIC PROCESSING, GLYCOSYLATION. Tissue: Plasma.
[9]	"Purification and characterization of a novel substrate for plasma kallikrein (PK-120) in human plasma." Pu X.P., Iwamoto A., Nishimura H., Nagasawa S. Biochim. Biophys. Acta 1208:338-343(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, PROTEOLYTIC PROCESSING.
[10]	"ITIH4 serum concentration increases during acute-phase processes in human patients and is up-regulated by interleukin-6 in hepatocarcinoma HepG2 cells." Pineiro M., Alava M.A., Gonzalez-Ramon N., Osada J., Lasierra P., Larrad L., Pineiro A., Lampreave F. Biochem. Biophys. Res. Commun. 263:224-229(1999) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, INDUCTION.
[11]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-207.
[12]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-517, MASS SPECTROMETRY. Tissue: Plasma.
[13]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81; ASN-207; ASN-517 AND ASN-577, MASS SPECTROMETRY. Tissue: Plasma.
[14]	"Inter-alpha-trypsin inhibitor heavy chain 4 is a novel marker of acute ischemic stroke." Kashyap R.S., Nayak A.R., Deshpande P.S., Kabra D., Purohit H.J., Taori G.M., Daginawala H.F. Clin. Chim. Acta 402:160-163(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION.
[15]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81; ASN-207 AND ASN-517, MASS SPECTROMETRY. Tissue: Liver.
[16]	"The absolute quantification of eight inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)-derived peptides in serum from breast cancer patients." van den Broek I., Sparidans R.W., van Winden A.W., Gast M.C., van Dulken E.J., Schellens J.H., Beijnen J.H. Proteomics Clin. Appl. 4:931-939(2010) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE ROLE OF ACTIVE PEPTIDE AS A BIOMARKER FOR BREAST CANCER.
[17]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD." Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G. Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-720, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
[19]	"SNP analysis of the inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene by a fluorescence-adapted SSCP method." Tozaki T., Choi-Miura N.-H., Taniyama M., Kurosawa M., Tomita M. BMC Med. Genet. 3:6-6(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASN-86.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D38535 mRNA. Translation: BAA07536.1. D38595 mRNA. Translation: BAA07602.1. U43163 , U42015, U42016, U43155, U43156, U43157, U43158, U43159, U43160, U43161, U43162 Genomic DNA. Translation: AAD05198.1. AK298412 mRNA. Translation: BAH12781.1. AC006254 Genomic DNA. No translation available. AC099667 Genomic DNA. No translation available. AF119856 mRNA. Translation: AAF69610.1.
IPI	IPI00218192. IPI00896413. IPI00896419.
PIR	JX0368.
RefSeq	NP_001159921.1. NM_001166449.1. NP_002209.2. NM_002218.4.
UniGene	Hs.709406.
3D structure databases
ProteinModelPortal	Q14624.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14624. 2 interactions.
STRING	9606.ENSP00000266041.
PTM databases
PhosphoSite	Q14624.
Polymorphism databases
DMDM	229463048.
Proteomic databases
PaxDb	Q14624.
PRIDE	Q14624.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000266041; ENSP00000266041; ENSG00000055955. ENST00000346281; ENSP00000340520; ENSG00000055955. ENST00000406595; ENSP00000384425; ENSG00000055955.
GeneID	3700.
KEGG	hsa:3700.
UCSC	uc003dfz.3. human. uc011bel.2. human.
Organism-specific databases
CTD	3700.
GeneCards	GC03M052846.
HGNC	HGNC:6169. ITIH4.
HPA	CAB016676. HPA001835. HPA003948.
MIM	600564. gene.
neXtProt	NX_Q14624.
PharmGKB	PA29967.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2304.
HOGENOM	HOG000239381.
HOVERGEN	HBG057734.
InParanoid	Q14624.
OrthoDB	EOG4MPHPC.
PhylomeDB	Q14624.
Gene expression databases
ArrayExpress	Q14624.
Bgee	Q14624.
CleanEx	HS_ITIH4.
Genevestigator	Q14624.
GermOnline	ENSG00000055955. Homo sapiens.
Family and domain databases
InterPro	IPR010600. ITI_HC_C. IPR013694. VIT. 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
ChiTaRS	ITIH4. human.
GenomeRNAi	3700.
NextBio	14503.
SOURCE	Search...

Entry information

Entry name

ITIH4_HUMAN

Accession

Primary (citable) accession number: Q14624
Secondary accession number(s): B7Z545 , E9PGN5, Q15135, Q9P190, Q9UQ54

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 123 of the entry and version 4 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.