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SPAG4 Gene

protein-coding   GIFtS: 46
GCID: GC20P034203

Sperm Associated Antigen 4

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Sperm Associated Antigen 41 2     SUN42 3
Acrosomal Protein ACR551 2     SUN Domain-Containing Protein 42 3
Cancer/Testis Antigen 1271 2     CT1272
Sad1 And UNC84 Domain Containing 41 2     Sperm Tail Protein2
Outer Dense Fiber-Associated Protein SPAG42 3     Sperm-Associated Antigen 4 Protein2

External Ids:    HGNC: 112141   Entrez Gene: 66762   Ensembl: ENSG000000616567   OMIM: 6030385   UniProtKB: Q9NPE63   

Export aliases for SPAG4 gene to outside databases

Previous GC identifers: GC20P033962 GC20P034872 GC20P034919 GC20P033667 GC20P030981


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for SPAG4 Gene:
The mammalian sperm flagellum contains two cytoskeletal structures associated with the axoneme: the outer dense
fibers surrounding the axoneme in the midpiece and principal piece and the fibrous sheath surrounding the outer
dense fibers in the principal piece of the tail. Defects in these structures are associated with abnormal tail
morphology, reduced sperm motility, and infertility. In the rat, the protein encoded by this gene associates with
an outer dense fiber protein via a leucine zipper motif and localizes to the microtubules of the manchette and
axoneme during sperm tail development. (provided by RefSeq, Jul 2008)

GeneCards Summary for SPAG4 Gene:
SPAG4 (sperm associated antigen 4) is a protein-coding gene. Diseases associated with SPAG4 include infertility, and epididymitis. GO annotations related to this gene include structural molecule activity. An important paralog of this gene is SUN2.

UniProtKB/Swiss-Prot: SPAG4_HUMAN, Q9NPE6
Function: May assist the organization and assembly of outer dense fibers (ODFs), a specific structure of the sperm
tail




(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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000020.11  NT_011362.11  NC_018931.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the SPAG4 gene promoter:
         Pax-5   MEF-2   Brachyury   ATF-2   AP-4   CRE-BP1   HEN1   MEF-2A   aMEF-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): SPAG4 promoter sequence
   Search Chromatin IP Primers for SPAG4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SPAG4


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

Entrez Gene cytogenetic band: 20q11.21   Ensembl cytogenetic band:  20q11.22   HGNC cytogenetic band: 20q11.2

SPAG4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SPAG4 gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20P034203:  view genomic region     (about GC identifiers)

Start:
34,203,809 bp from pter      End:
34,208,971 bp from pter
Size:
5,163 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: SPAG4_HUMAN, Q9NPE6 (See protein sequence)
Recommended Name: Sperm-associated antigen 4 protein  
Size: 437 amino acids; 48165 Da
Subunit: Homodimer. Interacts with ODF1. May associate with microtubules (By similarity)
Caution: Although transmembrane domains are strongly predicted, they may rather represent hydrophobic globular
domains associated with microtubules
Sequence caution: Sequence=AAC32052.1; Type=Erroneous gene model prediction;
Secondary accessions: O43648

Explore the universe of human proteins at neXtProt for SPAG4: NX_Q9NPE6

Explore proteomics data for SPAG4 at MOPED


See SPAG4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_003107.1  
ENSEMBL proteins: 
 ENSP00000363391   ENSP00000396670   ENSP00000399231  

SPAG4 Human Recombinant Protein Products:

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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1 InterPro protein domain:
 IPR012919 Sad1_UNC_C

Graphical View of Domain Structure for InterPro Entry Q9NPE6

ProtoNet protein and cluster: Q9NPE6

1 Blocks protein domain: IPB012919 Sad1/UNC-like

UniProtKB/Swiss-Prot: SPAG4_HUMAN, Q9NPE6
Similarity: Contains 1 SUN domain


SPAG4 for domains           About GeneDecksing


(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

     UniProtKB/Swiss-Prot Summary: SPAG4_HUMAN, Q9NPE6
Function: May assist the organization and assembly of outer dense fibers (ODFs), a specific structure of the sperm
tail

     Genatlas biochemistry entry for SPAG4:
spermatid-specific gene 4 interacting specifically with the 27kDa outer dense fiber protein ODF27 in elongation
spermatid

     Gene Ontology (GO): 1 molecular function term:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005198structural molecule activity TAS9691178
     
SPAG4 for ontologies           About GeneDecksing


Animal Models:
   inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SPAG4
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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot
SPAG4_HUMAN, Q9NPE6: Membrane; Multi-pass membrane protein (Potential). Cytoplasm, cytoskeleton. Cytoplasm,
cytoskeleton, flagellum axoneme (By similarity). Note=In spermatids, it is localized in the transient manchette
and in the axoneme of elongating spermatids and epididymal sperm (By similarity)
Subcellular locations from COMPARTMENTS: 

CompartmentConfidence
cytoskeleton5
plasma membrane3
cytosol1
peroxisome1

Gene Ontology (GO): 4 cellular component terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005737cytoplasm IEA--
GO:0005856cytoskeleton IEA--
GO:0005929cilium IEA--
GO:0016021integral component of membrane IEA--

SPAG4 for ontologies           About GeneDecksing


(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for SPAG4
Interactions:

    GeneGlobe Interaction Network for SPAG4

STRING Interaction Network Preview (showing 5 interactants - click image to see 10)

Selected Interacting proteins for SPAG4 (Q9NPE63 ENSP000003633914) via UniProtKB, MINT, STRING, and/or I2D (see all 10)
InteractantInteraction Details
GeneCardExternal ID(s)
ODF1Q149903, ENSP000002854024I2D: score=2 STRING: ENSP00000285402
TMEM201ENSP000003665934STRING: ENSP00000366593
EBNA1BP2ENSP000002360514STRING: ENSP00000236051
EIF3JENSP000002618684STRING: ENSP00000261868
RRS1ENSP000003223964STRING: ENSP00000322396
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Gene Ontology (GO): 1 biological process term:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0007283spermatogenesis TAS9691178

SPAG4 for ontologies           About GeneDecksing



(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore
   Browse drugs & compounds from Enzo Life Sciences
  Browse compounds at ApexBio 

Browse Tocris compounds for SPAG4

3 Novoseek inferred chemical compound relationships for SPAG4 gene    About this table
Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
pentoxifylline 55.4 2 16524250 (2)
leucine 50.9 5 16211599 (2), 10373309 (1), 11468777 (1)
tyrosine 19 1 10901439 (1)



SPAG4 for compounds           About GeneDecksing



(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for SPAG4 gene: 
NM_003116.1  

Unigene Cluster for SPAG4:

Sperm associated antigen 4
Hs.123159  [show with all ESTs]
Unigene Representative Sequence: AF262992
7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
ENST00000374273(uc002xdb.1 uc010zvi.1) ENST00000463973 ENST00000462896
ENST00000454819 ENST00000468248 ENST00000498203 ENST00000430878
miRNA
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Predesigned siRNA for gene silencing in human, mouse, rat SPAG4
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Additional mRNA sequence: 

AF262992.1 BC143783.1 

4 DOTS entries:

DT.452706  DT.91681448  DT.40117398  DT.100745143 

Selected AceView cDNA sequences (see all 34):

AF262992 NM_003116 AW021925 CB050390 AI623233 BI835507 AI347363 CK904360 
AW513095 CD387254 BF340750 BQ639210 BE207337 BM714003 CF131128 CB050391 
AW630046 BU628759 AW615356 AI635301 AA742708 BF176175 CD683525 BI160392 

GeneLoc Exon Structure

Selected Alternative Splicing Database (ASD) splice patterns (SP) for SPAG4 (see all 6)    About this scheme

ExUns: 1 ^ 2a · 2b · 2c · 2d · 2e ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b · 11c ^ 12 ^ 13
SP1:        -     -     -                             -                 -                                                   
SP2:                                -                 -                 -                                                   
SP3:                                                  -                 -                                                   
SP4:                                                  -                                                                     
SP5:                                                                                                                        


ECgene alternative splicing isoforms for SPAG4

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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SPAG4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: CTGATTTTTG
SPAG4 Expression
About this image

SPAG4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

SPAG4 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.123159
    Custom PCR Arrays for SPAG4
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In Situ
Assay Products:
 

 
Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SPAG4

(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for SPAG4 gene from Selected species (see all 11)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
mouse
(Mus musculus)
Mammalia Spag41 , 5 sperm associated antigen 41, 5 84.56(n)1
82.66(a)1
  2 (77.34 cM)5
2458651  NM_139151.41  NP_631890.31 
 1560651755 
chicken
(Gallus gallus)
Aves --
--
(see all 9)
--
41(a)
39(a)
(see all 9)
many ↔ many
many ↔ many
(see all 9)
Z(34167459-34168773)
2(120829351-120831013)
lizard
(Anolis carolinensis)
Reptilia --
--
37(a)
1 → many
GL343463.1(81656-92789)
fruit fly
(Drosophila melanogaster)
Insecta koi6
klaroid
16(a)
1 → many
2R(2702565-2705704)
worm
(Caenorhabditis elegans)
Secernentea unc-846
Protein UNC-84, isoform a
8(a)
1 → many
X(13584775-13589827) WBGene00006816


ENSEMBL Gene Tree for SPAG4 (if available)
TreeFam Gene Tree for SPAG4 (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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Paralogs for SPAG4 gene
SUN22  SUN12  SUN32  SUN52  
5 SIMAP similar genes for SPAG4 using alignment to 3 protein entries:     SPAG4_HUMAN (see all proteins):
SUN1    UNC84A    SUN2    SUN3    SUN5

SPAG4 for paralogs           About GeneDecksing



(SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Selected SNPs for SPAG4 (see all 217)    About this table    
Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 20 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
rs116999961,2
C,H--34201820(+) AGAATC/AACAAG 1 -- us2k18Minor allele frequency- A:0.07NA EA WA 722
rs1810687001,2
--34201857(+) AAGCTA/GCACTG 1 -- us2k10--------
rs793111411,2
C,F--34202018(+) GGAAAA/CATGGG 1 -- us2k13Minor allele frequency- C:0.06CSA WA NA 240
rs782778151,2
F--34202051(+) CCTGAA/CTGAGC 1 -- us2k13Minor allele frequency- C:0.06CSA WA NA 240
rs1859070801,2
--34202072(+) GATGTC/TTAGGA 1 -- us2k10--------
rs801329071,2
C--34202200(+) ACATGC/TTAGGC 1 -- us2k12Minor allele frequency- T:0.10CSA WA 120
rs1426659321,2
C--34202249(+) CTGTGC/TCCTGA 1 -- us2k10--------
rs1501791431,2
--34202330(+) CATCTC/GTAATC 1 -- us2k10--------
rs1135822531,2
C,F--34202405(+) CAACAC/TAGCGA 1 -- us2k11Minor allele frequency- T:0.50CSA 2
rs1492540101,2
C--34202516(+) CCGGGA/GGATGG 1 -- us2k10--------

HapMap Linkage Disequilibrium report for SPAG4 (34203809 - 34208971 bp)

Structural Variations
     Database of Genomic Variants (DGV) 1 variation for SPAG4:    About this table    
Variant IDTypeSubtypePubMed ID
nsv526188CNV Gain19592680

Site Specific Mutation Identification with PCR Assays
SeqTarget long-range PCR primers for resequencing SPAG4
DNA2.0 Custom Variant and Variant Library Synthesis for SPAG4

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 603038    OMIM disorders: --

2 diseases for SPAG4:    
About MalaCards
infertility    epididymitis


SPAG4 for disorders           About GeneDecksing


Export disorders for SPAG4 gene to outside databases

(in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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PubMed articles for SPAG4 gene, integrated from 10 sources (see all 19):
(articles sorted by number of sources associating them with SPAG4)
    Utopia: connect your pdf to the dynamic
world of online information

  1. A novel testis-specific gene, SPAG4, whose product interacts specifically with outer dense fiber protein ODF27, maps to human chromosome 20q11.2. (PubMed id 9691178)1, 2, 3 Tarnasky H....van der Hoorn F.A. (Cytogenet. Cell Genet. 1998)
  2. Spag4, a novel sperm protein, binds outer dense-fiber protein Odf1 and localizes to microtubules of manchette and axoneme. (PubMed id 10373309)1, 3, 9 Shao X....van der Hoorn F.A. (Dev. Biol. 1999)
  3. Human sperm associated antigen 4 (SPAG4) is a potential cancer marker. (PubMed id 14614621)1, 2, 9 Kennedy C.... O'Bryan M.K. (Cell Tissue Res. 2004)
  4. The DNA sequence and comparative analysis of human chromosome 20. (PubMed id 11780052)1, 2 Deloukas P....Rogers J. (Nature 2001)
  5. Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates cytokinesis, and its expression correlates with the prognosis of renal cell carcinoma. (PubMed id 23602831)1 Shoji K....Nangaku M. (Am. J. Pathol. 2013)
  6. Charting the landscape of tandem BRCT domain-mediated protein interactions. (PubMed id 22990118)1 Woods N.T....Monteiro A.N. (Sci Signal 2012)
  7. 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. (Proc. Natl. Acad. Sci. U.S.A. 2002)
  8. DNA cloning using in vitro site-specific recombination. (PubMed id 11076863)1 Hartley J.L....Brasch M.A. (Genome Res. 2000)
  9. Rat Spag5 associates in somatic cells with endoplasmic reticulum and microtubules but in spermatozoa with outer dense fibers. (PubMed id 16211599)9 Fitzgerald C.J....van der Hoorn F.A. (Mol. Reprod. Dev. 2006)
  10. Cyclic nucleotide phosphodiesterase inhibition increases tyrosine phosphorylation and hyper motility in normal and pathological human spermatozoa. (PubMed id 16524250)9 Yunes R....Acosta A.A. (Biocell 2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 6676 HGNC: 11214 AceView: SPAG4 Ensembl:ENSG00000061656 euGenes: HUgn6676
ECgene: SPAG4 H-InvDB: SPAG4

(According to HUGE)
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  --

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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NameDescription
PharmGKB entry for SPAG4 Pharmacogenomics, SNPs, Pathways

(Patent information from GeneIP,
Licensable technologies from WIS Yeda, Salk, Tufts,
IP news from LifeMap Sciences, Inc.)
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Patent Information for SPAG4 gene:
Search GeneIP for patents involving SPAG4

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



(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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