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Protein

D-ribitol-5-phosphate cytidylyltransferase

Gene

ISPD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytidylyltransferase required for protein O-linked mannosylation (PubMed:26687144, PubMed:27130732, PubMed:27601598, PubMed:22522420, PubMed:22522421). Catalyzes the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate (PubMed:26687144, PubMed:27130732). CDP-ribitol is a substrate of FKTN during the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:26687144, PubMed:27130732). Shows activity toward other pentose phosphate sugars and mediates formation of CDP-ribulose or CDP-ribose using CTP and ribulose-5-phosphate or ribose-5-phosphate, respectively (PubMed:26687144). Not Involved in dolichol production (PubMed:26687144).5 Publications

Catalytic activityi

CTP + D-ribitol 5-phosphate = diphosphate + CDP-ribitol.2 Publications
CTP + D-ribose 5-phosphate = diphosphate + CDP-ribose.2 Publications
CTP + D-ribulose 5-phosphate = diphosphate + CDP-ribulose.1 Publication

Pathwayi: protein glycosylation

This protein is involved in the pathway protein glycosylation, which is part of Protein modification.2 Publications
View all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei59Transition state stabilizerBy similarity1
Sitei66Transition state stabilizerBy similarity1
Sitei205Positions substrate for the nucleophilic attackBy similarity1
Sitei263Positions substrate for the nucleophilic attackBy similarity1

GO - Molecular functioni

  • cytidylyltransferase activity Source: UniProtKB
  • D-ribitol-5-phosphate cytidylyltransferase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • axon guidance Source: Ensembl
  • isoprenoid biosynthetic process Source: InterPro
  • protein O-linked mannosylation Source: UniProtKB

Keywordsi

Molecular functionNucleotidyltransferase, Transferase

Enzyme and pathway databases

UniPathwayiUPA00378.

Names & Taxonomyi

Protein namesi
Recommended name:
D-ribitol-5-phosphate cytidylyltransferaseCurated (EC:2.7.7.402 Publications)
Alternative name(s):
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein
Isoprenoid synthase domain-containing proteinImported
Short name:
hISPD1 Publication
Gene namesi
Name:ISPDImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000214960.9.
HGNCiHGNC:37276. ISPD.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A7 (MDDGA7)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:614643
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06974093Missing in MDDGA7. 1 Publication1
Natural variantiVAR_068101122A → P in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs387907162Ensembl.1
Natural variantiVAR_068102126R → H in MDDGA7; also found in a patient with an atypical phenotype presenting with limb-girdle muscular dystrophy, ocular features and cerebellar involvement. 2 PublicationsCorresponds to variant dbSNP:rs752817129Ensembl.1
Natural variantiVAR_069741156D → N in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs397514547Ensembl.1
Natural variantiVAR_078949205R → H in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs566179705Ensembl.1
Natural variantiVAR_069742213M → R in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs397515408Ensembl.1
Natural variantiVAR_068103216A → D in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs387907160Ensembl.1
Natural variantiVAR_069743226Y → H in MDDGA7. 1 Publication1
Natural variantiVAR_069744238T → I in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs397515409Ensembl.1
Muscular dystrophy-dystroglycanopathy limb-girdle C7 (MDDGC7)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of muscular dystrophy resulting from defective glycosylation of alpha-dystroglycan, and characterized by a limb-girdle phenotype with muscular weakness apparent after ambulation is achieved. MDDGC7 individuals do not show epilepsy, mental retardation, structural eye/brain abnormalities, or white matter changes.
See also OMIM:616052
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07897053A → T in MDDGC7. 1 Publication1
Natural variantiVAR_07195554G → A in MDDGC7; decreased alpha-dystroglycan glycosylation. 1 PublicationCorresponds to variant dbSNP:rs587777797Ensembl.1
Natural variantiVAR_078948149P → L in MDDGC7; atypical form presenting with congenital muscular dystrophy. 1 PublicationCorresponds to variant dbSNP:rs369219851Ensembl.1
Natural variantiVAR_078950215 – 451Missing in MDDGC7; atypical form presenting with congenital muscular dystrophy. 1 PublicationAdd BLAST237
Natural variantiVAR_078951226Y → C in MDDGC7; atypical form with learning difficulties. 1 Publication1
Natural variantiVAR_071956372Missing in MDDGC7; decreased alpha-dystroglycan glycosylation. 3 Publications1
Natural variantiVAR_078952395 – 451Missing in MDDGC7. 1 PublicationAdd BLAST57

Keywords - Diseasei

Congenital muscular dystrophy, Disease mutation, Dystroglycanopathy, Limb-girdle muscular dystrophy, Lissencephaly

Organism-specific databases

DisGeNETi729920.
GeneReviewsiISPD.
MalaCardsiISPD.
MIMi614643. phenotype.
616052. phenotype.
OpenTargetsiENSG00000214960.
Orphaneti352479. Autosomal recessive limb-girdle muscular dystrophy due to ISPD deficiency.
370980. Congenital muscular dystrophy without intellectual disability.
899. Walker-Warburg syndrome.
PharmGKBiPA165618128.

Polymorphism and mutation databases

BioMutaiISPD.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003436971 – 451D-ribitol-5-phosphate cytidylyltransferaseAdd BLAST451

Proteomic databases

EPDiA4D126.
PaxDbiA4D126.
PRIDEiA4D126.

PTM databases

iPTMnetiA4D126.
PhosphoSitePlusiA4D126.

Expressioni

Tissue specificityi

Ubiquitously expressed, with high expression in brain.1 Publication

Gene expression databases

BgeeiENSG00000214960.
ExpressionAtlasiA4D126. baseline and differential.

Organism-specific databases

HPAiHPA043810.
HPA053554.

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

STRINGi9606.ENSP00000385478.

Structurei

Secondary structure

1451
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi45 – 52Combined sources8
Helixi76 – 85Combined sources10
Beta strandi90 – 97Combined sources8
Helixi99 – 101Combined sources3
Helixi102 – 112Combined sources11
Beta strandi116 – 121Combined sources6
Helixi126 – 137Combined sources12
Beta strandi150 – 154Combined sources5
Helixi164 – 177Combined sources14
Beta strandi178 – 185Combined sources8
Beta strandi191 – 193Combined sources3
Beta strandi199 – 202Combined sources4
Helixi205 – 207Combined sources3
Beta strandi209 – 218Combined sources10
Helixi219 – 228Combined sources10
Helixi231 – 236Combined sources6
Helixi240 – 248Combined sources9
Beta strandi253 – 256Combined sources4
Helixi259 – 261Combined sources3
Helixi267 – 280Combined sources14
Beta strandi283 – 289Combined sources7
Helixi293 – 309Combined sources17
Beta strandi314 – 319Combined sources6
Beta strandi337 – 344Combined sources8
Helixi349 – 360Combined sources12
Helixi363 – 366Combined sources4
Beta strandi369 – 377Combined sources9
Beta strandi380 – 382Combined sources3
Helixi385 – 391Combined sources7
Helixi394 – 402Combined sources9
Turni403 – 405Combined sources3
Beta strandi406 – 414Combined sources9
Helixi419 – 439Combined sources21
Helixi442 – 444Combined sources3
Beta strandi448 – 450Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4CVHX-ray2.39A43-451[»]
ProteinModelPortaliA4D126.
SMRiA4D126.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IIH2. Eukaryota.
COG1211. LUCA.
GeneTreeiENSGT00390000006412.
HOGENOMiHOG000113111.
HOVERGENiHBG057782.
InParanoidiA4D126.
KOiK21031.
OMAiCYNFVCV.
OrthoDBiEOG091G0JSI.
PhylomeDBiA4D126.
TreeFamiTF328415.

Family and domain databases

CDDicd02516. CDP-ME_synthetase. 1 hit.
Gene3Di3.90.550.10. 1 hit.
InterProiView protein in InterPro
IPR034683. IspD/TarI.
IPR018294. ISPD_synthase_CS.
IPR029044. Nucleotide-diphossugar_trans.
PfamiView protein in Pfam
PF01128. IspD. 1 hit.
SUPFAMiSSF53448. SSF53448. 1 hit.
PROSITEiView protein in PROSITE
PS01295. ISPD. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: A4D126-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEAGPPGSAR PAEPGPCLSG QRGADHTASA SLQSVAGTEP GRHPQAVAAV
60 70 80 90 100
LPAGGCGERM GVPTPKQFCP ILERPLISYT LQALERVCWI KDIVVAVTGE
110 120 130 140 150
NMEVMKSIIQ KYQHKRISLV EAGVTRHRSI FNGLKALAED QINSKLSKPE
160 170 180 190 200
VVIIHDAVRP FVEEGVLLKV VTAAKEHGAA GAIRPLVSTV VSPSADGCLD
210 220 230 240 250
YSLERARHRA SEMPQAFLFD VIYEAYQQCS DYDLEFGTEC LQLALKYCCT
260 270 280 290 300
KAKLVEGSPD LWKVTYKRDL YAAESIIKER ISQEICVVMD TEEDNKHVGH
310 320 330 340 350
LLEEVLKSEL NHVKVTSEAL GHAGRHLQQI ILDQCYNFVC VNVTTSDFQE
360 370 380 390 400
TQKLLSMLEE SSLCILYPVV VVSVHFLDFK LVPPSQKMEN LMQIREFAKE
410 420 430 440 450
VKERNILLYG LLISYPQDDQ KLQESLRQGA IIIASLIKER NSGLIGQLLI

A
Length:451
Mass (Da):49,873
Last modified:July 22, 2008 - v2
Checksum:i988B9D1CFE98935C
GO
Isoform 2 (identifier: A4D126-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     179-228: Missing.

Note: No experimental confirmation available.
Show »
Length:401
Mass (Da):44,389
Checksum:i3FF08B999A88E45F
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07897053A → T in MDDGC7. 1 Publication1
Natural variantiVAR_07195554G → A in MDDGC7; decreased alpha-dystroglycan glycosylation. 1 PublicationCorresponds to variant dbSNP:rs587777797Ensembl.1
Natural variantiVAR_06974093Missing in MDDGA7. 1 Publication1
Natural variantiVAR_068101122A → P in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs387907162Ensembl.1
Natural variantiVAR_068102126R → H in MDDGA7; also found in a patient with an atypical phenotype presenting with limb-girdle muscular dystrophy, ocular features and cerebellar involvement. 2 PublicationsCorresponds to variant dbSNP:rs752817129Ensembl.1
Natural variantiVAR_078948149P → L in MDDGC7; atypical form presenting with congenital muscular dystrophy. 1 PublicationCorresponds to variant dbSNP:rs369219851Ensembl.1
Natural variantiVAR_069741156D → N in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs397514547Ensembl.1
Natural variantiVAR_078949205R → H in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs566179705Ensembl.1
Natural variantiVAR_069742213M → R in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs397515408Ensembl.1
Natural variantiVAR_078950215 – 451Missing in MDDGC7; atypical form presenting with congenital muscular dystrophy. 1 PublicationAdd BLAST237
Natural variantiVAR_068103216A → D in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs387907160Ensembl.1
Natural variantiVAR_078951226Y → C in MDDGC7; atypical form with learning difficulties. 1 Publication1
Natural variantiVAR_069743226Y → H in MDDGA7. 1 Publication1
Natural variantiVAR_069744238T → I in MDDGA7. 1 PublicationCorresponds to variant dbSNP:rs397515409Ensembl.1
Natural variantiVAR_071956372Missing in MDDGC7; decreased alpha-dystroglycan glycosylation. 3 Publications1
Natural variantiVAR_078952395 – 451Missing in MDDGC7. 1 PublicationAdd BLAST57

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044044179 – 228Missing in isoform 2. CuratedAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_001094887.1. NM_001101417.3. [A4D126-2]
NP_001094896.1. NM_001101426.3. [A4D126-1]
UniGeneiHs.636502.

Genome annotation databases

EnsembliENST00000399310; ENSP00000382249; ENSG00000214960. [A4D126-2]
ENST00000407010; ENSP00000385478; ENSG00000214960. [A4D126-1]
GeneIDi729920.
KEGGihsa:729920.
UCSCiuc010ktx.2. human. [A4D126-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiISPD_HUMAN
AccessioniPrimary (citable) accession number: A4D126
Secondary accession number(s): A8MU35, H9KVB2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: July 22, 2008
Last modified: September 27, 2017
This is version 81 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families