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Protein

ATP-dependent (S)-NAD(P)H-hydrate dehydratase

Gene

CARKD

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

Functioni

Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration.UniRule annotation

Catalytic activityi

ATP + (6S)-6-beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = ADP + phosphate + NADH.UniRule annotation
ATP + (6S)-6-beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = ADP + phosphate + NADPH.

Cofactori

Mg2+UniRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei153 – 1531NAD(P)HX; via amide nitrogenUniRule annotation
Binding sitei275 – 2751NAD(P)HXUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi246 – 2505ATPUniRule annotation
Nucleotide bindingi265 – 27410ATPUniRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. ATP-dependent NAD(P)H-hydrate dehydratase activity Source: UniProtKB-HAMAP

GO - Biological processi

  1. nicotinamide nucleotide metabolic process Source: UniProtKB-HAMAP
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

ATP-binding, NAD, NADP, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000153481-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-dependent (S)-NAD(P)H-hydrate dehydrataseUniRule annotation (EC:4.2.1.93UniRule annotation)
Alternative name(s):
ATP-dependent NAD(P)HX dehydrataseUniRule annotation
Carbohydrate kinase domain-containing proteinUniRule annotation
Gene namesi
Name:CARKDUniRule annotation
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 13

Organism-specific databases

HGNCiHGNC:25576. CARKD.

Subcellular locationi

Mitochondrion UniRule annotation

GO - Cellular componenti

  1. mitochondrion Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA164717652.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 347ATP-dependent (S)-NAD(P)H-hydrate dehydratasePRO_0000337021
Transit peptidei1 – ?MitochondrionUniRule annotation

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei85 – 851PhosphotyrosineBy similarity
Glycosylationi240 – 2401N-linked (GlcNAc...)1 Publication
Glycosylationi297 – 2971N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ8IW45.
PaxDbiQ8IW45.
PRIDEiQ8IW45.

PTM databases

PhosphoSiteiQ8IW45.

Expressioni

Gene expression databases

BgeeiQ8IW45.
CleanExiHS_CARKD.
ExpressionAtlasiQ8IW45. baseline.
GenevestigatoriQ8IW45.

Organism-specific databases

HPAiHPA010551.

Interactioni

Protein-protein interaction databases

BioGridi120857. 14 interactions.
IntActiQ8IW45. 1 interaction.
STRINGi9606.ENSP00000311984.

Structurei

3D structure databases

ProteinModelPortaliQ8IW45.
SMRiQ8IW45. Positions 56-279.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini53 – 344292YjeF C-terminalUniRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni206 – 2127NAD(P)HXUniRule annotation

Sequence similaritiesi

Belongs to the NnrD/CARKD family.UniRule annotation
Contains 1 YjeF C-terminal domain.UniRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0063.
GeneTreeiENSGT00390000000917.
HOGENOMiHOG000163126.
HOVERGENiHBG103700.
InParanoidiQ8IW45.
KOiK17757.
OMAiSHQAVQP.
OrthoDBiEOG76X60M.
PhylomeDBiQ8IW45.
TreeFamiTF300116.

Family and domain databases

Gene3Di3.40.1190.20. 1 hit.
HAMAPiMF_01965. NADHX_dehydratase.
InterProiIPR029056. Ribokinase-like.
IPR000631. YjeF_C.
[Graphical view]
PfamiPF01256. Carb_kinase. 1 hit.
[Graphical view]
SUPFAMiSSF53613. SSF53613. 1 hit.
TIGRFAMsiTIGR00196. yjeF_cterm. 1 hit.
PROSITEiPS51383. YJEF_C_3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IW45-1) [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
MVTRAGAGTA VAGAVVVALL SAALALYGPP LDAVLERAFS LRKAHSIKDM
60 70 80 90 100
ENTLQLVRNI IPPLSSTKHK GQDGRIGVVG GCQEYTGAPY FAAISALKVG
110 120 130 140 150
ADLSHVFCAS AAAPVIKAYS PELIVHPVLD SPNAVHEVEK WLPRLHALVV
160 170 180 190 200
GPGLGRDDAL LRNVQGILEV SKARDIPVVI DADGLWLVAQ QPALIHGYRK
210 220 230 240 250
AVLTPNHVEF SRLYDAVLRG PMDSDDSHGS VLRLSQALGN VTVVQKGERD
260 270 280 290 300
ILSNGQQVLV CSQEGSSRRC GGQGDLLSGS LGVLVHWALL AGPQKTNGSS
310 320 330 340
PLLVAAFGAC SLTRQCNHQA FQKHGRSTTT SDMIAEVGAA FSKLFET
Length:347
Mass (Da):36,576
Last modified:March 1, 2003 - v1
Checksum:i70D42B97D6E8A41B
GO
Isoform 2 (identifier: Q8IW45-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     299-347: SSPLLVAAFG...GAAFSKLFET → GISDLKLTIW...RGGGRLQQAL

Show »
Length:390
Mass (Da):41,360
Checksum:i8A32124EA07160CE
GO
Isoform 3 (identifier: Q8IW45-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-221: Missing.

Show »
Length:126
Mass (Da):13,188
Checksum:i031B1043E9E8AEC9
GO
Isoform 4 (identifier: Q8IW45-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-129: MVTRAGAGTA...SPELIVHPVL → MLPDGPGSSLWGNPGLQTS

Note: No experimental confirmation available.

Show »
Length:237
Mass (Da):25,200
Checksum:i2AED83A9CD769A97
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti206 – 2061N → D in BAA91797 (PubMed:14702039).Curated
Sequence conflicti253 – 2531S → P in BAB14863 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti140 – 1401K → E.
Corresponds to variant rs3742191 [ dbSNP | Ensembl ].
VAR_043564
Natural varianti149 – 1491V → I.
Corresponds to variant rs3742192 [ dbSNP | Ensembl ].
VAR_043565
Natural varianti152 – 1521P → T.
Corresponds to variant rs1044112 [ dbSNP | Ensembl ].
VAR_043566

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 221221Missing in isoform 3. 1 PublicationVSP_033829Add
BLAST
Alternative sequencei1 – 129129MVTRA…VHPVL → MLPDGPGSSLWGNPGLQTS in isoform 4. 1 PublicationVSP_042012Add
BLAST
Alternative sequencei299 – 34749SSPLL…KLFET → GISDLKLTIWGPEIETGVKT RAQGSCGPRTTTPTSPHLLL SPSPQVQPSPGGRVWRLLSH QAVQPPSLPEARSLHHHLRH DRRGGGRLQQAL in isoform 2. 1 PublicationVSP_033830Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK001631 mRNA. Translation: BAA91797.1.
AK024260 mRNA. Translation: BAB14863.1.
AK302117 mRNA. Translation: BAG63496.1.
AL139385 Genomic DNA. Translation: CAI17008.1.
CH471085 Genomic DNA. Translation: EAX09121.1.
CH471085 Genomic DNA. Translation: EAX09125.1.
BC041028 mRNA. Translation: AAH41028.1.
CCDSiCCDS55903.1. [Q8IW45-4]
CCDS9513.1. [Q8IW45-2]
RefSeqiNP_001229810.1. NM_001242881.1. [Q8IW45-1]
NP_001229811.1. NM_001242882.1.
NP_001229812.1. NM_001242883.1. [Q8IW45-4]
NP_060680.2. NM_018210.3. [Q8IW45-2]
UniGeneiHs.408324.

Genome annotation databases

EnsembliENST00000309957; ENSP00000311984; ENSG00000213995. [Q8IW45-2]
ENST00000424185; ENSP00000413191; ENSG00000213995. [Q8IW45-4]
GeneIDi55739.
KEGGihsa:55739.
UCSCiuc001vrb.3. human. [Q8IW45-1]
uc001vrc.3. human. [Q8IW45-2]
uc010tjk.2. human. [Q8IW45-4]
uc021rmn.1. human. [Q8IW45-3]

Polymorphism databases

DMDMi74728128.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK001631 mRNA. Translation: BAA91797.1.
AK024260 mRNA. Translation: BAB14863.1.
AK302117 mRNA. Translation: BAG63496.1.
AL139385 Genomic DNA. Translation: CAI17008.1.
CH471085 Genomic DNA. Translation: EAX09121.1.
CH471085 Genomic DNA. Translation: EAX09125.1.
BC041028 mRNA. Translation: AAH41028.1.
CCDSiCCDS55903.1. [Q8IW45-4]
CCDS9513.1. [Q8IW45-2]
RefSeqiNP_001229810.1. NM_001242881.1. [Q8IW45-1]
NP_001229811.1. NM_001242882.1.
NP_001229812.1. NM_001242883.1. [Q8IW45-4]
NP_060680.2. NM_018210.3. [Q8IW45-2]
UniGeneiHs.408324.

3D structure databases

ProteinModelPortaliQ8IW45.
SMRiQ8IW45. Positions 56-279.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120857. 14 interactions.
IntActiQ8IW45. 1 interaction.
STRINGi9606.ENSP00000311984.

PTM databases

PhosphoSiteiQ8IW45.

Polymorphism databases

DMDMi74728128.

Proteomic databases

MaxQBiQ8IW45.
PaxDbiQ8IW45.
PRIDEiQ8IW45.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309957; ENSP00000311984; ENSG00000213995. [Q8IW45-2]
ENST00000424185; ENSP00000413191; ENSG00000213995. [Q8IW45-4]
GeneIDi55739.
KEGGihsa:55739.
UCSCiuc001vrb.3. human. [Q8IW45-1]
uc001vrc.3. human. [Q8IW45-2]
uc010tjk.2. human. [Q8IW45-4]
uc021rmn.1. human. [Q8IW45-3]

Organism-specific databases

CTDi55739.
GeneCardsiGC13P111267.
H-InvDBHIX0011456.
HIX0011457.
HIX0171873.
HGNCiHGNC:25576. CARKD.
HPAiHPA010551.
MIMi615910. gene.
neXtProtiNX_Q8IW45.
PharmGKBiPA164717652.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0063.
GeneTreeiENSGT00390000000917.
HOGENOMiHOG000163126.
HOVERGENiHBG103700.
InParanoidiQ8IW45.
KOiK17757.
OMAiSHQAVQP.
OrthoDBiEOG76X60M.
PhylomeDBiQ8IW45.
TreeFamiTF300116.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000153481-MONOMER.

Miscellaneous databases

ChiTaRSiCARKD. human.
GeneWikiiCARKD.
GenomeRNAii55739.
NextBioi60690.
PROiQ8IW45.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IW45.
CleanExiHS_CARKD.
ExpressionAtlasiQ8IW45. baseline.
GenevestigatoriQ8IW45.

Family and domain databases

Gene3Di3.40.1190.20. 1 hit.
HAMAPiMF_01965. NADHX_dehydratase.
InterProiIPR029056. Ribokinase-like.
IPR000631. YjeF_C.
[Graphical view]
PfamiPF01256. Carb_kinase. 1 hit.
[Graphical view]
SUPFAMiSSF53613. SSF53613. 1 hit.
TIGRFAMsiTIGR00196. yjeF_cterm. 1 hit.
PROSITEiPS51383. YJEF_C_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
    Tissue: Testis.
  2. "The DNA sequence and analysis of human chromosome 13."
    Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
    Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  5. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-240.
    Tissue: Liver.
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiNNRD_HUMAN
AccessioniPrimary (citable) accession number: Q8IW45
Secondary accession number(s): B4DXT4
, Q5T9X3, Q9H7W1, Q9NVF5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: March 1, 2003
Last modified: March 4, 2015
This is version 89 of the entry and version 1 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.