Q8IW45 (NNRD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-dependent (S)-NAD(P)H-hydrate dehydratase
EC=4.2.1.93

Alternative name(s):
ATP-dependent NAD(P)HX dehydratase
Carbohydrate kinase domain-containing protein

Gene names

Name:

CARKD

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	347 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity. HAMAP-Rule MF_03157
Catalytic activity	ATP + (6S)-6-beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = ADP + phosphate + NADH. HAMAP-Rule MF_03157 ATP + (6S)-6-beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = ADP + phosphate + NADPH.
Cofactor	Magnesium By similarity.
Subcellular location	Mitochondrion By similarity.
Sequence similarities	Belongs to the nnrD/CARKD family. Contains 1 YjeF C-terminal domain.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	ATP-binding NAD NADP Nucleotide-binding
Molecular function	Lyase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nicotinamide nucleotide metabolic process Inferred from electronic annotation. Source: HAMAP
Cellular_component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent NAD(P)H-hydrate dehydratase activity Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IW45-1)

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: Q8IW45-2)

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

Isoform 3 (identifier: Q8IW45-3)

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

Isoform 4 (identifier: Q8IW45-4)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 347		ATP-dependent (S)-NAD(P)H-hydrate dehydratase HAMAP-Rule MF_03157		PRO_0000337021
Regions
	Domain	53 – 344	292	YjeF C-terminal
	Nucleotide binding	246 – 250	5	ATP By similarity
	Nucleotide binding	265 – 274	10	ATP By similarity
	Region	206 – 212	7	NAD(P)HX By similarity
Sites
	Binding site	153	1	NAD(P)HX; via amide nitrogen By similarity
	Binding site	275	1	NAD(P)HX By similarity
Amino acid modifications
	Modified residue	85	1	Phosphotyrosine By similarity
	Glycosylation	240	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	297	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 221	221	Missing in isoform 3.		VSP_033829
	Alternative sequence	1 – 129	129	MVTRA…VHPVL → MLPDGPGSSLWGNPGLQTS in isoform 4.		VSP_042012
	Alternative sequence	299 – 347	49	SSPLL…KLFET → GISDLKLTIWGPEIETGVKT RAQGSCGPRTTTPTSPHLLL SPSPQVQPSPGGRVWRLLSH QAVQPPSLPEARSLHHHLRH DRRGGGRLQQAL in isoform 2.		VSP_033830
	Natural variant	140	1	K → E. Corresponds to variant rs3742191 [ dbSNP | Ensembl ].		VAR_043564
	Natural variant	149	1	V → I. Corresponds to variant rs3742192 [ dbSNP | Ensembl ].		VAR_043565
	Natural variant	152	1	P → T. Corresponds to variant rs1044112 [ dbSNP | Ensembl ].		VAR_043566
Experimental info
	Sequence conflict	206	1	N → D in BAA91797. Ref.1
	Sequence conflict	253	1	S → P in BAB14863. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 70D42B97D6E8A41B	FASTA	347	36,576
	10 20 30 40 50 60 MVTRAGAGTA VAGAVVVALL SAALALYGPP LDAVLERAFS LRKAHSIKDM ENTLQLVRNI 70 80 90 100 110 120 IPPLSSTKHK GQDGRIGVVG GCQEYTGAPY FAAISALKVG ADLSHVFCAS AAAPVIKAYS 130 140 150 160 170 180 PELIVHPVLD SPNAVHEVEK WLPRLHALVV GPGLGRDDAL LRNVQGILEV SKARDIPVVI 190 200 210 220 230 240 DADGLWLVAQ QPALIHGYRK AVLTPNHVEF SRLYDAVLRG PMDSDDSHGS VLRLSQALGN 250 260 270 280 290 300 VTVVQKGERD ILSNGQQVLV CSQEGSSRRC GGQGDLLSGS LGVLVHWALL AGPQKTNGSS 310 320 330 340 PLLVAAFGAC SLTRQCNHQA FQKHGRSTTT SDMIAEVGAA FSKLFET
	Isoform 2 [UniParc]. Checksum: 8A32124EA07160CE	FASTA	390	41,360
	10 20 30 40 50 60 MVTRAGAGTA VAGAVVVALL SAALALYGPP LDAVLERAFS LRKAHSIKDM ENTLQLVRNI 70 80 90 100 110 120 IPPLSSTKHK GQDGRIGVVG GCQEYTGAPY FAAISALKVG ADLSHVFCAS AAAPVIKAYS 130 140 150 160 170 180 PELIVHPVLD SPNAVHEVEK WLPRLHALVV GPGLGRDDAL LRNVQGILEV SKARDIPVVI 190 200 210 220 230 240 DADGLWLVAQ QPALIHGYRK AVLTPNHVEF SRLYDAVLRG PMDSDDSHGS VLRLSQALGN 250 260 270 280 290 300 VTVVQKGERD ILSNGQQVLV CSQEGSSRRC GGQGDLLSGS LGVLVHWALL AGPQKTNGGI 310 320 330 340 350 360 SDLKLTIWGP EIETGVKTRA QGSCGPRTTT PTSPHLLLSP SPQVQPSPGG RVWRLLSHQA 370 380 390 VQPPSLPEAR SLHHHLRHDR RGGGRLQQAL
	Isoform 3 [UniParc]. Checksum: 031B1043E9E8AEC9	FASTA	126	13,188
	10 20 30 40 50 60 MDSDDSHGSV LRLSQALGNV TVVQKGERDI LSNGQQVLVC SQEGSSRRCG GQGDLLSGSL 70 80 90 100 110 120 GVLVHWALLA GPQKTNGSSP LLVAAFGACS LTRQCNHQAF QKHGRSTTTS DMIAEVGAAF SKLFET
	Isoform 4 [UniParc]. Checksum: 2AED83A9CD769A97	FASTA	237	25,200
	10 20 30 40 50 60 MLPDGPGSSL WGNPGLQTSD SPNAVHEVEK WLPRLHALVV GPGLGRDDAL LRNVQGILEV 70 80 90 100 110 120 SKARDIPVVI DADGLWLVAQ QPALIHGYRK AVLTPNHVEF SRLYDAVLRG PMDSDDSHGS 130 140 150 160 170 180 VLRLSQALGN VTVVQKGERD ILSNGQQVLV CSQEGSSRRC GGQGDLLSGS LGVLVHWALL 190 200 210 220 230 AGPQKTNGSS PLLVAAFGAC SLTRQCNHQA FQKHGRSTTT SDMIAEVGAA FSKLFET

References

[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00645172. IPI00873027. IPI00910136.
RefSeq	NP_001229810.1. NM_001242881.1. NP_001229811.1. NM_001242882.1. NP_001229812.1. NM_001242883.1. NP_060680.2. NM_018210.3.
UniGene	Hs.408324.
3D structure databases
ProteinModelPortal	Q8IW45.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000311984.
PTM databases
PhosphoSite	Q8IW45.
Polymorphism databases
DMDM	74728128.
Proteomic databases
PaxDb	Q8IW45.
PRIDE	Q8IW45.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000309957; ENSP00000311984; ENSG00000213995. ENST00000424185; ENSP00000413191; ENSG00000213995.
GeneID	55739.
KEGG	hsa:55739.
UCSC	uc001vrb.3. human. uc001vrc.3. human. uc021rmn.1. human.
Organism-specific databases
CTD	55739.
GeneCards	GC13P111267.
H-InvDB	HIX0011456. HIX0011457. HIX0171873.
HGNC	HGNC:25576. CARKD.
HPA	HPA010551.
neXtProt	NX_Q8IW45.
PharmGKB	PA164717652.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0063.
HOGENOM	HOG000163126.
HOVERGEN	HBG103700.
Gene expression databases
ArrayExpress	Q8IW45.
Bgee	Q8IW45.
CleanEx	HS_CARKD.
Genevestigator	Q8IW45.
Family and domain databases
HAMAP	MF_01965. NADHX_dehydratase.
InterPro	IPR026599. NnrD/CARKD. IPR000631. YjeF_C_carb_kinase-rel. [Graphical view]
Pfam	PF01256. Carb_kinase. 1 hit. [Graphical view]
TIGRFAMs	TIGR00196. yjeF_cterm. 1 hit.
PROSITE	PS01049. YJEF_C_1. False negative. PS01050. YJEF_C_2. False negative. PS51383. YJEF_C_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CARKD. human.
GenomeRNAi	55739.
NextBio	60690.

Entry information

Entry name

NNRD_HUMAN

Accession

Primary (citable) accession number: Q8IW45
Secondary accession number(s): B4DXT4 , Q5T9X3, Q9H7W1, Q9NVF5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	March 1, 2003
Last modified:	April 3, 2013
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.