ITIH4 protein expression summary - The Human Protein Atlas

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ITIH4

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HUMAN PROTEIN ATLAS SUMMARYⁱ General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Proteinⁱ Full gene name according to HGNC.	Inter-alpha-trypsin inhibitor heavy chain family member 4
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	ITIH4 (H4P, IHRP, ITIHL1)
Tissue specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected. Read more	Tissue enriched (liver)
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Group enriched (Early spermatids, Hepatocytes, Late spermatids)
Blood specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed blood cell samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Immune cell enhanced (NK-cell)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Not detected in human brain
Cancer prognostic summary	Gene product is not prognostic
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location. Read more	Intracellular, Secreted (different isoforms)
Extracellular locationⁱ All genes with at least one isoform expected to be secreted to the extracellular environment have been annotated and classified either as secreted to blood or as locally secreted, depending on the predicted final location of the corresponding protein. Proteins expected to be locally secreted have been further classified according to their site of expression. Read more	Secreted to blood
Subcellular summaryⁱ The main location is characterized by presence in all tested cell lines and/or increased intensity compared to other locations. Additional locations are characterized by either a markedly lower staining intensity than the main location, or that it is only observed in a subset of the cell lines.	Located in Vesicles
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration.... show less
Molecular function (UniProt)ⁱ Keywords assigned by UniProt to proteins due to their particular molecular function.	Protease inhibitor, Serine protease inhibitor
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Acute phase
Disease involvementⁱ Disease related keywords assigned by UniProt combined with Cancer-related genes and FDA approved drug targets Read more	Cancer-related genes
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	The protein encoded by this gene is secreted into the blood, where it is cleaved by plasma kallikrein into two smaller forms. Expression of this gene has been detected only in liver, and it seems to be upregulated during surgical trauma. This gene is part of a cluster of similar genes on chromosome 3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]... show less

TISSUE ATLASⁱ Summary of data presented in the Tissue Atlas and representative images of protein expression (left) and mRNA expression (right). The images are clickable and will redirect to more Tissue Atlas data. The Tissue Atlas contains information regarding the expression profiles of protein-coding genes in normal human tissue, both on the mRNA and protein level. The protein expression data is derived from antibody-based protein profiling using immunohistochemistry. Read more

Tissue specificity (RNA)ⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected. Read more	Tissue enriched (liver)
Tissue distribution (RNA)ⁱ The RNA distribution category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: detected in all, detected in many, detected in some, detected in single and not detected. Read more	Detected in some
Protein expressionⁱ A summary of the overall protein expression pattern across the analyzed normal tissues. The summary is based on knowledge-based annotation. "Estimation of protein expression could not be performed. View primary data." is shown for genes analyzed with a knowledge-based approach where available RNA-seq and gene/protein characterization data has been evaluated as not sufficient in combination with immunohistochemistry data to yield a reliable estimation of the protein expression profile. Read more	Plasma positivity.

SINGLE CELL TYPE ATLASⁱ Summary of data presented in the Cell Type Atlas and an interactive image showing mRNA expression in cell type groups e.g. epithelial cells and germ cells. The image is clickable and will redirect to more Cell Type Atlas data. The Cell Type Atlas contains information about single cell type RNA expression based on scRNAseq of human tissues. The data also covers transcriptomics analysis of human blood and cultured cell lines. Read more

Cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Group enriched (Early spermatids, Hepatocytes, Late spermatids)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from all cell lines in the Human Protein Atlas. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Cell line enhanced (HDLM-2, JURKAT, U-266/70)

PATHOLOGY ATLASⁱ Summary of data presented in the Pathology Atlas , with representative images of protein expression in cancer (left) and correlation between mRNA expression and patient survival (right). Images are clickable and redirect to pages with more Pathology Atlas data. The Pathology Atlas contains mRNA and protein expression data from 17 different forms of human cancer, as well as correlation analysis of mRNA expression and patient survival. The protein expression data is derived from antibody-based protein profiling using immunohistochemistry. Read more

Prognostic summary	Gene product is not prognostic
Cancer specificity (RNA)ⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected. Read more	Cancer enriched (liver cancer)
Cancer distribution (RNA)ⁱ Distribution of RNA expression in 17 cancer types is categorized as either detected in single, detected in some, detected in many, detected in all, or not detected. Read more	Detected in single

BRAIN ATLASⁱ Summary of data presented in the Brain Atlas and a representative image of mRNA expression in the human brain. The image is clickable and will redirect to more Brain Atlas data. The Brain Atlas explores the protein expression in the mammalian brain by visualization and integration of data from three mammalian species (human, pig and mouse). Transcriptomics data combined with affinity-based protein in situ localization down to single cell level is available in a brain-centric sub atlas of the Human Protein Atlas. Read more

Human regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Not detected
Pig regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Low region specificity
Mouse regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Not detected

BLOOD ATLASⁱ Summary of data presented in the Blood Atlas and a representative image of mRNA expression in immune cells in the blood. The image is clickable and will redirect to more Blood Atlas data. The Blood Atlas contains single cell type RNA information covering various immune cells in the blood, e.g. B-cells and granulocytes. Analysis of the human secretome (including annotation of the genes predicted to be actively secreted to human blood) and proteins detected in human blood are also presented. Read more

Secretome annotationⁱ All genes with at least one predicted secreted isoform have been annotated and classified with the aim to determine if the corresponding protein(s) are: secreted into blood locally secreted or actually being attached to membrane or retained in intracellular locations like mitochondria, endoplasmatic reticulum (ER), Golgi apparatus or lysosomes. Read more	Secreted to blood
Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Cell type enhanced (NK-cell)
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search. Read more	Yes
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.	Yes

CELL ATLASⁱ Summary of data presented in the Cell Atlas and a representative image of subcellular localization. The Cell Atlas provides RNA expression data derived from RNA sequencing of a large panel of cell lines and protein localization data derived from antibody-based profiling by immunofluorescence confocal microscopy, using a subset of cell lines selected based on RNA expression. Read more

Main locationⁱ Main subcellular location(s) and reliability score(s) for the encoded protein(s) in human cells. The main location(s) may be characterized by presence in all tested cell lines and/or ihigher staining intensity compared to the potential additional location(s). If available, links to overrepresentation analyses in Reactome, a free, open-source, curated and peer reviewed biological pathway database, are provided. An analysis is done for the corresponding gene set of the proteome localizing to the main and additional locations of the protein on this page, respectively. Read more	Localized to the Vesicles
Cell cycle dependencyⁱ Cell-cycle dependance of single-cell varations in RNA and/or protein expression as observed in an additional assay for characterizing single-cell varations. "NA" indicates a lack of such data. Read more	NA

GENE INFORMATIONⁱ Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Gene name	ITIH4 (HGNC Symbol)
Synonyms	H4P, IHRP, ITIHL1
Description	Inter-alpha-trypsin inhibitor heavy chain family member 4 (HGNC Symbol)
Chromosome	3
Cytoband	p21.1
Chromosome location (bp)	52812975 - 52831479
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	4
Protein evidence	Evidence at protein level (all genes)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s). Read more	Cancer-related genes Plasma proteins
Ensembl	ENSG00000055955 (version 92.38)
Entrez gene	3700
UniProt	Q14624 (UniProt - Evidence at protein level)
neXtProt	NX_Q14624
Antibodypedia	ITIH4 antibodies

PROTEIN BROWSERⁱ

ITIH4-201

ITIH4-202

ITIH4-203

ITIH4-212

PROTEIN INFORMATIONⁱ The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database. The ENSP identifier links to the Ensembl website protein summary, while the ENST identifier links to the Ensembl website transcript summary for the selected splice variant. The data in the UniProt column can be expanded to show links to all matching UniProt identifiers for this protein. The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class. The Gene Ontology terms assigned to this protein are listed if expanding the Gene ontology column. The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide (according to a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius) and the number of predicted transmembrane region(s) (according to MDM) are also reported.
Splice variant	UniProt	Protein class	Gene ontology	Length & mass	Signal peptide (predicted)	Transmembrane regions (predicted)
ITIH4-201 ENSP00000266041 ENST00000266041	Q14624 [Direct mapping] Inter-alpha-trypsin inhibitor heavy chain H4 70 kDa inter-alpha-trypsin inhibitor heavy chain H4 35 kDa inter-alpha-trypsin inhibitor heavy chain H4 Show all	MEMSAT3 predicted membrane proteins Predicted secreted proteins Secreted proteins predicted by MDSEC SignalP predicted secreted proteins Phobius predicted secreted proteins SPOCTOPUS predicted secreted proteins Plasma proteins Cancer-related genes Candidate cancer biomarkers Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas) Show all	GO:0002576 [platelet degranulation] GO:0004866 [endopeptidase inhibitor activity] GO:0004867 [serine-type endopeptidase inhibitor activity] GO:0005515 [protein binding] GO:0005576 [extracellular region] GO:0006953 [acute-phase response] GO:0010466 [negative regulation of peptidase activity] GO:0010951 [negative regulation of endopeptidase activity] GO:0030212 [hyaluronan metabolic process] GO:0030414 [peptidase inhibitor activity] GO:0031089 [platelet dense granule lumen] GO:0034097 [response to cytokine] GO:0070062 [extracellular exosome] GO:0072562 [blood microparticle] Show all	930 aa 103.4 kDa	Yes	0
ITIH4-202 ENSP00000384425 ENST00000406595	Q14624 [Direct mapping] Inter-alpha-trypsin inhibitor heavy chain H4 70 kDa inter-alpha-trypsin inhibitor heavy chain H4 35 kDa inter-alpha-trypsin inhibitor heavy chain H4 Show all	MEMSAT3 predicted membrane proteins Predicted secreted proteins Secreted proteins predicted by MDSEC SignalP predicted secreted proteins Phobius predicted secreted proteins SPOCTOPUS predicted secreted proteins Plasma proteins Cancer-related genes Candidate cancer biomarkers Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas) Show all	GO:0002576 [platelet degranulation] GO:0004866 [endopeptidase inhibitor activity] GO:0004867 [serine-type endopeptidase inhibitor activity] GO:0005515 [protein binding] GO:0005576 [extracellular region] GO:0006953 [acute-phase response] GO:0010466 [negative regulation of peptidase activity] GO:0010951 [negative regulation of endopeptidase activity] GO:0030212 [hyaluronan metabolic process] GO:0030414 [peptidase inhibitor activity] GO:0031089 [platelet dense granule lumen] GO:0034097 [response to cytokine] GO:0070062 [extracellular exosome] GO:0072562 [blood microparticle] Show all	900 aa 99.9 kDa	Yes	0
ITIH4-203 ENSP00000395634 ENST00000441637	H7C0L5 [Direct mapping] Inter-alpha-trypsin inhibitor heavy chain H4 Show all	Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Show all	GO:0004867 [serine-type endopeptidase inhibitor activity] GO:0010951 [negative regulation of endopeptidase activity] GO:0030212 [hyaluronan metabolic process] Show all	719 aa 80 kDa	No	0
ITIH4-212 ENSP00000417824 ENST00000485816	B7ZKJ8 [Direct mapping] ITIH4 protein; Inter-alpha-trypsin inhibitor heavy chain H4 Show all	MEMSAT3 predicted membrane proteins Predicted secreted proteins Secreted proteins predicted by MDSEC SignalP predicted secreted proteins Phobius predicted secreted proteins SPOCTOPUS predicted secreted proteins Show all	GO:0004867 [serine-type endopeptidase inhibitor activity] GO:0010951 [negative regulation of endopeptidase activity] GO:0030212 [hyaluronan metabolic process] Show all	935 aa 103.9 kDa	Yes	0

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The Human Protein Atlas project is funded
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