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HTRA4 Gene

protein-coding GIFtS: 42

GC08P037364

HtrA serine peptidase 4
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc , and/or ⁷Ensembl, ⁸miRBase)
About This Section

Aliases & Descriptions
HtrA serine peptidase 4¹ ²
FLJ90724¹ ²
probable serine protease HTRA4²
EC 3.4.21.-³

External Ids:	HGNC: 26909¹	Entrez Gene: 203100²	Ensembl: ENSG00000169495⁷	UniProtKB: P83105³

Export aliases for HTRA4 gene to outside databases

Previous GC identifers: GC08P038951 GC08P038831

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for HTRA4:

This gene encodes a member of the HtrA family of proteases. The encoded protein contains a putative signal peptide, an

insulin growth factor binding domain, a Kazal protease inhibitor domain, a conserved trypsin domain and a PDZ domain.

Based on studies on other related family members, this enzyme may function as a secreted oligomeric chaperone protease

to degrade misfolded secretory proteins. Other human HtrA proteins have been implicated in arthritis, tumor

suppression, unfolded stress response, apoptosis, and aging. (provided by RefSeq)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 60), Regulatory elements and Epigenetics data according to Qiagen and/or SABiosciences)
About This Section

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the HTRA4 gene promoter:
         AhR   Arnt   NRSF form 2   NRSF form 1   IRF-1   MIF-1   Lmo2   Sox9   POU3F2   POU3F2 (N-Oct-5a)
         Other transcription factors

Search SABiosciences Chromatin IP Primers for HTRA4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays for HTRA4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 8p11.22 Ensembl cytogenetic band: 8p11.22 HGNC cytogenetic band: 8p11.23

HTRA4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HTRA4 gene location

GeneLoc gene densities for chromosome 8 GeneLoc Exon Structure

GeneLoc location for GC08P037364: view genomic region (about GC identifiers)

Start:	37,364,830 bp from pter
End:	37,379,022 bp from pter
Size:	14,193 bases
Orientation:	plus strand

1 alternative location:

Chr8+ 38,831,683-38,846,181

RefSeq DNA sequence:

NC_000008.10 NT_167187.1

(According to ¹UniProtKB, neXtProt, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Millipore, Sigma-Aldrich, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, and/or ProSpec,
Biochemical Assays by Millipore, Sigma-Aldrich, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Dec 2010 and Entrez Gene, Antibodies by Millipore, Sigma-Aldrich, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, and/or Epitomics)
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UniProtKB/Swiss-Prot: HTRA4_HUMAN, P83105 (See protein sequence)

Recommended Name: Probable serine protease HTRA4 precursor

Size: 476 amino acids; 50979 Da

Secondary accessions: Q542Z4 Q6PF13

Explore the universe of human proteins at neXtProt for HTRA4: NX_P83105

REFSEQ proteins: NP_710159.1

ENSEMBL proteins:

ENSP00000305919

Human Recombinant Proteins

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1 Gene Ontology (GO) cellular component term (GO ID links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	IEA	--

About this table

HTRA4 for ontologies About GeneDecksing

Antibodies for HTRA4:

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	Uscn ELISAs and CLIAs for HTRA4

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

HTRA4 for domains About GeneDecksing

5/7 InterPro domains/families (see all 7):

IPR002350 Prot_inh_Kazal

IPR001478 PDZ/DHR/GLGF

IPR009003 Ser/Cys_Pept_Trypsin-like

IPR001940 Peptidase_S1C

IPR001254 Peptidase_S1_S6

Graphical View of Domain Structure for InterPro Entry P83105

ProtoNet protein and cluster: P83105

2 Blocks protein families:

IPB001478 PDZ/DHR/GLGF domain

IPB001940 HtrA/DegQ protease family signature

UniProtKB/Swiss-Prot: HTRA4_HUMAN, P83105

Similarity: Belongs to the peptidase S1B family

Similarity: Contains 1 IGFBP N-terminal domain

Similarity: Contains 1 Kazal-like domain

Similarity: Contains 1 PDZ (DHR) domain

(According to UniProtKB, IUBMB,and/or Genatlas, Animal models from MGI Dec 24 2010,
shRNA from OriGene, Sigma-Aldrich, RNAi from Millipore, siRNAs from Sigma-Aldrich, OriGene, Qiagen, Super-pooled esiRNAs from Sigma-Aldrich, microRNA from Sigma-Aldrich, Qiagen, SABiosciences, Clones from Millipore, Sigma-Aldrich, OriGene, GenScript, Sino Biological, Cell Lines from GenScript, Ontologies according to Gene Ontology Consortium 01 Dec 2010 via Entrez Gene.)
About This Section

Inhib. RNA:		Browse for Gene Knock-down Tools from Millipore
		Browse Nano Scale siRNA at Sigma-Aldrich Sigma-Aldrich siRNA Panels and esiRNA and siRNA for HTRA4 Sigma-Aldrich shRNA for HTRA4
		OriGene 29mer shRNA kits in GFP-retroviral vector: HTRA4 OriGene shRNA RFP: HTRA4 OriGene basic RS shRNA: HTRA4 OriGene siRNA: HTRA4
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miRNA:		Browse microRNA Mimics at Sigma-Aldrich Browse microRNA target validation systems at Sigma-Aldrich
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of HTRA4
		Search SABiosciences for Assays for microRNAs that regulate HTRA4

Gene
Editing:

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		OriGene GFP tagged cDNA clones in CMV expression vector: HTRA4 OriGene Myc/DDK tagged cDNA clones in CMV expression vector: HTRA4 OriGene untagged cDNA clones in CMV expression vector: HTRA4 OriGene 3'-UTR clone: HTRA4 Browse MicroRNA Expression Plasmids
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Cell
Lines:

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5 Gene Ontology (GO) molecular function terms (GO ID links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003824	catalytic activity	--	--
GO:0004252	serine-type endopeptidase activity	IEA	--
GO:0005515	protein binding	IEA	--
GO:0005520	insulin-like growth factor binding	IEA	--
GO:0008233	peptidase activity	IEA	--

About this table

HTRA4 for ontologies About GeneDecksing

(Pathways according to Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB, Sets of similar genes according to GeneDecks, PCR Arrays from SABiosciences, Proteins Network according to SABiosciences, Sigma-Aldrich, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Dec 2010 via Entrez Gene).
About This Section

SABiosciences Pathway-Focused PCR Arrays including HTRA4: PAHS-089A PAHS-3401A

Search SABiosciences Gene Network Central^TM Interacting Genes and Proteins Networks for HTRA4

2 Gene Ontology (GO) biological process terms (GO ID links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001558	regulation of cell growth	IEA	--
GO:0006508	proteolysis	IEA	--

About this table

HTRA4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse Small Molecules at Sigma-Aldrich

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(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 228 Homo sapiens; Dec 8 2010) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Millipore,
siRNAs from Sigma-Aldrich, OriGene, Qiagen, Super-pooled esiRNAs from Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene, microRNA from Sigma-Aldrich, Qiagen, SABiosciences,
Tagged/untagged cDNA clones from OriGene, Sigma-Aldrich, GenScript, Primers from OriGene and/or SABiosciences)
About This Section

Inhib. RNA:		Browse for Gene Knock-down Tools from Millipore
		Browse Nano Scale siRNA at Sigma-Aldrich Sigma-Aldrich siRNA Panels and esiRNA and siRNA for HTRA4 Sigma-Aldrich shRNA for HTRA4
		OriGene 29mer shRNA kits in GFP-retroviral vector: HTRA4 OriGene shRNA RFP: HTRA4 OriGene basic RS shRNA: HTRA4 OriGene siRNA: HTRA4
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing of HTRA4

miRNA:		Browse microRNA Mimics at Sigma-Aldrich Browse microRNA target validation systems at Sigma-Aldrich
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of HTRA4
		Search SABiosciences for Assays for microRNAs that regulate HTRA4

Clones:		Browse FLAG tag genes at Sigma-Aldrich
		OriGene GFP tagged cDNA clones in CMV expression vector: HTRA4 OriGene Myc/DDK tagged cDNA clones in CMV expression vector: HTRA4 OriGene untagged cDNA clones in CMV expression vector: HTRA4 OriGene 3'-UTR Clone: HTRA4 Browse OriGene MicroRNA Expression Plasmids
		GenScript Custom cDNA clone Services for HTRA4

Primers:		OriGene genome-wide validated SYBR primer pairs: HTRA4 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay for HTRA4: PPH16906A

REFSEQ mRNAs for HTRA4 gene:

NM_153692.3

Additional cDNA sequence:

AK075205.1 AK300197.1 AY188774.1 BC057765.1 CR590249.1 CR601506.1

3 DOTS entries:

DT.91711356 DT.100749850 DT.100757840

24/30 AceView cDNA sequences (see all 30):

CR601506 AL553302 CR590249 CB991519 CB961875 CB961876 AL576444 AL551062

NM_153692 BU753896 BC057765 AY188774 AL551947 BQ011847 AL545759 AK075205

BX451410 AL551918 BX416892 BX380962 BX358760 AL574735 CB959959 CB997220

highest scoring ESTs for HTRA4:

AK075205 AL551918 AL574735 AL576444 AY188774 BC057765 BF511757 BX358760 AL545720 AL551062

Unigene Cluster for HTRA4:

HtrA serine peptidase 4

Hs.661014 [show with all ESTs]

Unigene Representative Sequence: NM_153692

GeneLoc Exon Structure

1 Ensembl transcript including schematic representation, and UCSC links where relevant:

ENST00000302495(uc003xmj.2)

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 228 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Primers from OriGene and/or SABiosciences )
About This Section

HTRA4 expression in normal and diseased human tissues

¹ / ²

1 probe-set matching HTRA4 gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
1553706_at²	U133Plus2	1	0.73	1.00	--	--	--	--	--	--	--

About this table
Data from Genenote (Publications) and GNF BioGPS
About these images

HTRA4 gene electronic northern expression

About these images

CGAP SAGE TAG: GCACACATTT

SOURCE GeneReport for Unigene cluster: Hs.661014

Primers:		OriGene genome-wide validated SYBR primer pairs: HTRA4 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay for HTRA4: PPH16906A

SABiosciences Expression via Pathway-Focused PCR Arrays including HTRA4: PAHS-089A PAHS-3401A

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Dec 24 2010, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section

Orthologs for HTRA4 gene from 5/6 species (see all 6)

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	HTRA4¹	--	HtrA serine peptidase 4	81.7(n) 72.01(a)	475580 XM_532799.2 XP_532799.2
chimpanzee (Pan troglodytes)	HTRA4¹	--	HtrA serine peptidase 4	99.58(n) 99.37(a)	472743 XM_001135094.1 XP_001135094.1
cow (Bos taurus)	HTRA4¹	--	HtrA serine peptidase 4	78.64(n) 69.12(a)	514946 XM_592866.3 XP_592866.3
rat (Rattus norvegicus)	Htra4¹	--	HtrA serine peptidase 4	74.89(n) 68.18(a)	306564 XM_224963.4 XP_224963.4
mouse (Mus musculus)	Htra4^{1 , 5}	8 (13.70 cM)⁵	HtrA serine peptidase 4^{1, 5}	75.97(n)¹ 68.18(a)¹	330723¹ NM_001081187.1¹ NP_001074656.1¹ AK046614⁵ AV315397⁵ (see all 8)

About this table Species with no ortholog for HTRA4

ENSEMBL Gene Tree for HTRA4 (if available)

(Paralogs according to ¹HomoloGene
and ²Ensembl, Pseudogenes according to ³Pseudogene.org)
About This Section

Paralogs for HTRA4 gene

HTRA2² HTRA1² HTRA3²

HTRA4 for paralogs About GeneDecksing

(SNPs according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Resequencing Primers from Qiagen)
About This Section

SNP ID	Valid	Chr 8 pos	Sequence	Recs	AA Chg	Type	More	Recs	Pop	Total sample
Genomic Data				Transcription Related Data				Allele Frequencies
			--	--	--		--	--
rs4733894^1,2	C,F,	38843393(+)	`AAATGC/TGAAAA`	1	--	int¹		7	EA NA	378
rs4733959^1,2	C,F,A,H,	38835346(+)	`TTCTCG/AGGTGG`	1	--	int¹		12	NA NS EA	638
rs4733960^1,2	C,F,H,	38835456(+)	`TCCCTC/TTTTGG`	1	--	int¹		14	NA NS EA WA	702
rs4733961^1,2	C,F,A,H,	38835666(+)	`ATTAAC/TGTAAG`	2	N	syn¹ ref¹		20	NS EA NA WA	1158
rs4733962^1,2	C,F,A,H,	38840300(+)	`GGCTTC/TGGGAT`	1	--	int¹		11	EA NA NS WA	596
rs4733963^1,2	C,F,H,	38840364(+)	`TTCCTT/CGGCCC`	1	--	int¹		20	NA NS EA WA	1160
rs6474514^1,2	C,F,A,	38835269(+)	`AACACC/TCAAGA`	1	--	int¹		20	NS EA NA WA	1554
rs6474515^1,2	C,F,A,H,	38841052(+)	`aaaaaA/CaaaTA`	1	--	int¹ trp³		5	NA	146
rs6981759^1,2	C,A,	38832841(+)	`aaatcC/Acagct`	1	--	int¹		4	NA EA	164
rs7000059^1,2	C,A,H,	38841495(+)	`TTAGGT/AATTAG`	1	--	int¹		2	NA	74

About this table

HapMap Linkage Disequilibrium images for HTRA4 (up to first 250kb)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for HTRA4: --

QIAGEN SeqTarget long-range PCR primers for resequencing HTRA4

(in which this Gene is Involved, According to OMIM, UniProtKB, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, LSDB, HGMD, GAD, HuGE Navigator, and/or TGDB.)
About This Section

HTRA4 for disorders About GeneDecksing

OMIM: 610700

Export disorders and mutations for HTRA4 gene to outside databases

(Possibly Related Articles in Doctor's Guide)
About This Section

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶UniProtKB/TrEMBL, and/or ⁷Novoseek)
About This Section

6 PubMed articles for HTRA4 gene integrated from 7 sources:
(articles sorted by number of sources associating them with HTRA4)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (2004)
Signal sequence and keyword trap in silico for selection of full- length human cDNAs encoding secretion or membrane proteins from oligo- capped cDNA libraries. (PubMed id 16303743)¹ Otsuki T....Isogai T. (2005)
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)¹ Strausberg R.L....Marra M.A. (2002)
The HtrA family of proteases: implications for protein composition and cell fate. (PubMed id 12408815)¹ Clausen T....Ehrmann M. (2002)
Pattern of expression of HtrA1 during mouse development. (PubMed id 15557215)⁷ De Luca A....Baldi A. (2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 203100	HGNC: 26909	AceView: FLJ90724	Ensembl:ENSG00000169495	euGenes: HUgn203100
ECgene: HTRA4	H-InvDB: HTRA4

(According to HUGE)
About This Section

(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Intellectual Property for HTRA4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from XenneX, Inc.)

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Patent Information for HTRA4 gene:
Search GeneIP for patents involving HTRA4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays by Millipore, Sigma-Aldrich, R&D Systems, Qiagen, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Epitomics, ProSpec, Uscn,
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	QIAGEN Custom miScript Target Protector blocks miRNA-binding site of HTRA4
	SeqTarget long-range PCR primers for resequencing HTRA4
	QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays for HTRA4
	QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing of HTRA4

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HTRA4 Gene

protein-coding GIFtS: 42

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HTRA4 Gene

protein-coding GIFtS: 42

Aliases & Descriptionsfor HTRA4 gene

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