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A4D126 (ISPD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 56. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Isoprenoid synthase domain-containing protein

EC=2.7.7.-
Alternative name(s):
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein
Gene names
Name:ISPD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length451 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for protein O-linked mannosylation. Probably acts as a nucleotidyltransferase involved in synthesis of a nucleotide sugar. Required for dystroglycan O-mannosylation. Ref.3 Ref.5

Pathway

Protein modification; protein glycosylation.

Tissue specificity

Ubiquitously expressed, with high expression in brain. Ref.3

Involvement in disease

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A7 (MDDGA7) [MIM:614643]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.4 Ref.5

Sequence similarities

Belongs to the IspD family.

Sequence caution

The sequence EAL24288.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: A4D126-1)

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: A4D126-2)

The sequence of this isoform differs from the canonical sequence as follows:
     179-228: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 451451Isoprenoid synthase domain-containing protein
PRO_0000343697

Sites

Site591Transition state stabilizer By similarity
Site661Transition state stabilizer By similarity
Site2051Positions substrate for the nucleophilic attack By similarity
Site2631Positions substrate for the nucleophilic attack By similarity

Natural variations

Alternative sequence179 – 22850Missing in isoform 2.
VSP_044044
Natural variant931Missing in MDDGA7. Ref.3
VAR_069740
Natural variant1221A → P in MDDGA7. Ref.5
VAR_068101
Natural variant1261R → H in MDDGA7. Ref.5
VAR_068102
Natural variant1561D → N in MDDGA7. Ref.4
VAR_069741
Natural variant2131M → R in MDDGA7. Ref.4
VAR_069742
Natural variant2161A → D in MDDGA7. Ref.5
VAR_068103
Natural variant2261Y → H in MDDGA7. Ref.4
VAR_069743
Natural variant2381T → I in MDDGA7. Ref.4
VAR_069744

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 22, 2008. Version 2.
Checksum: 988B9D1CFE98935C

FASTA45149,873
        10         20         30         40         50         60 
MEAGPPGSAR PAEPGPCLSG QRGADHTASA SLQSVAGTEP GRHPQAVAAV LPAGGCGERM 

        70         80         90        100        110        120 
GVPTPKQFCP ILERPLISYT LQALERVCWI KDIVVAVTGE NMEVMKSIIQ KYQHKRISLV 

       130        140        150        160        170        180 
EAGVTRHRSI FNGLKALAED QINSKLSKPE VVIIHDAVRP FVEEGVLLKV VTAAKEHGAA 

       190        200        210        220        230        240 
GAIRPLVSTV VSPSADGCLD YSLERARHRA SEMPQAFLFD VIYEAYQQCS DYDLEFGTEC 

       250        260        270        280        290        300 
LQLALKYCCT KAKLVEGSPD LWKVTYKRDL YAAESIIKER ISQEICVVMD TEEDNKHVGH 

       310        320        330        340        350        360 
LLEEVLKSEL NHVKVTSEAL GHAGRHLQQI ILDQCYNFVC VNVTTSDFQE TQKLLSMLEE 

       370        380        390        400        410        420 
SSLCILYPVV VVSVHFLDFK LVPPSQKMEN LMQIREFAKE VKERNILLYG LLISYPQDDQ 

       430        440        450 
KLQESLRQGA IIIASLIKER NSGLIGQLLI A 

« Hide

Isoform 2 [UniParc].

Checksum: 3FF08B999A88E45F
Show »

FASTA40144,389

References

« Hide 'large scale' references
[1]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome."
Willer T., Lee H., Lommel M., Yoshida-Moriguchi T., de Bernabe D.B., Venzke D., Cirak S., Schachter H., Vajsar J., Voit T., Muntoni F., Loder A.S., Dobyns W.B., Winder T.L., Strahl S., Mathews K.D., Nelson S.F., Moore S.A., Campbell K.P.
Nat. Genet. 44:575-580(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANT MDDGA7 ILE-93 DEL, TISSUE SPECIFICITY.
[4]"Identification of mutations in TMEM5 and ISPD as a cause of severe cobblestone lissencephaly."
Vuillaumier-Barrot S., Bouchet-Seraphin C., Chelbi M., Devisme L., Quentin S., Gazal S., Laquerriere A., Fallet-Bianco C., Loget P., Odent S., Carles D., Bazin A., Aziza J., Clemenson A., Guimiot F., Bonniere M., Monnot S., Bole-Feysot C. expand/collapse author list , Bernard J.P., Loeuillet L., Gonzales M., Socha K., Grandchamp B., Attie-Bitach T., Encha-Razavi F., Seta N.
Am. J. Hum. Genet. 91:1135-1143(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MDDGA7 ASN-156; ARG-213; HIS-226 AND ILE-238.
[5]"Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan."
Roscioli T., Kamsteeg E.J., Buysse K., Maystadt I., van Reeuwijk J., van den Elzen C., van Beusekom E., Riemersma M., Pfundt R., Vissers L.E., Schraders M., Altunoglu U., Buckley M.F., Brunner H.G., Grisart B., Zhou H., Veltman J.A., Gilissen C. expand/collapse author list , Mancini G.M., Delree P., Willemsen M.A., Ramadza D.P., Chitayat D., Bennett C., Sheridan E., Peeters E.A., Tan-Sindhunata G.M., de Die-Smulders C.E., Devriendt K., Kayserili H., El-Hashash O.A., Stemple D.L., Lefeber D.J., Lin Y.Y., van Bokhoven H.
Nat. Genet. 44:581-585(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MDDGA7 PRO-122; HIS-126 AND ASP-216, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC004741 Genomic DNA. No translation available.
AC006035 Genomic DNA. No translation available.
AC073629 Genomic DNA. No translation available.
AC079155 Genomic DNA. No translation available.
CH236948 Genomic DNA. Translation: EAL24288.1. Sequence problems.
CH471073 Genomic DNA. Translation: EAW93668.1.
RefSeqNP_001094887.1. NM_001101417.3. [A4D126-2]
NP_001094896.1. NM_001101426.3. [A4D126-1]
UniGeneHs.636502.

3D structure databases

ProteinModelPortalA4D126.
SMRA4D126. Positions 49-279.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000385478.

PTM databases

PhosphoSiteA4D126.

Proteomic databases

MaxQBA4D126.
PaxDbA4D126.
PRIDEA4D126.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000399310; ENSP00000382249; ENSG00000214960. [A4D126-2]
ENST00000407010; ENSP00000385478; ENSG00000214960. [A4D126-1]
GeneID729920.
KEGGhsa:729920.
UCSCuc010ktx.2. human. [A4D126-1]
uc010kty.2. human. [A4D126-2]

Organism-specific databases

CTD729920.
GeneCardsGC07M016098.
GeneReviewsISPD.
HGNCHGNC:37276. ISPD.
HPAHPA043810.
MIM614631. gene.
614643. phenotype.
neXtProtNX_A4D126.
Orphanet352479. Autosomal recessive limb-girdle muscular dystrophy due to ISPD deficiency.
370980. Congenital muscular dystrophy without intellectual disability.
899. Walker-Warburg syndrome.
PharmGKBPA165618128.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1211.
HOGENOMHOG000113111.
HOVERGENHBG057782.
InParanoidA4D126.
OMACYNFVCV.
OrthoDBEOG7KDFB2.
PhylomeDBA4D126.
TreeFamTF328415.

Enzyme and pathway databases

UniPathwayUPA00378.

Gene expression databases

BgeeA4D126.
GenevestigatorA4D126.

Family and domain databases

Gene3D3.90.550.10. 1 hit.
InterProIPR001228. IspD.
IPR018294. ISPD_synthase_CS.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PfamPF01128. IspD. 1 hit.
[Graphical view]
SUPFAMSSF53448. SSF53448. 1 hit.
PROSITEPS01295. ISPD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi729920.
NextBio131766.
PROA4D126.
SOURCESearch...

Entry information

Entry nameISPD_HUMAN
AccessionPrimary (citable) accession number: A4D126
Secondary accession number(s): A8MU35, H9KVB2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: July 22, 2008
Last modified: July 9, 2014
This is version 56 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM