Q14894 (CRYM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thiomorpholine-carboxylate dehydrogenase
EC=1.5.1.25

Alternative name(s):
Mu-crystallin homolog
NADP-regulated thyroid-hormone-binding protein
ketimine reductase

Gene names

Name:	CRYM
Synonyms:	THBP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	314 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Specifically catalyzes the reduction of imine bonds in brain substrates that may include cystathionine ketimine (CysK) and lanthionine ketimine (LK). Binds thyroid hormone which is a strong reversible inhibitor. Presumably involved in the regulation of the free intracellular concentration of triiodothyronine and access to its nuclear receptors. Ref.12
Catalytic activity	Thiomorpholine 3-carboxylate + NAD(P)+ = 3,4-dehydro-thiomorpholine-3-carboxylate + NAD(P)H. Ref.12
Cofactor	NAD or NADP. Ref.12
Subunit structure	Homodimer. Ref.13
Subcellular location	Cytoplasm.
Tissue specificity	Expressed in neural tissue, muscle and kidney.
Sequence similarities	Belongs to the ornithine cyclodeaminase family.
Biophysicochemical properties	pH dependence: Optimum pH is 4.5. Ref.12

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	NAD NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: UniProtKB sensory perception of sound Inferred from mutant phenotype. Source: UniProtKB thyroid hormone transport Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular function	NADP binding Inferred from direct assay Ref.13. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB thiomorpholine-carboxylate dehydrogenase activity Inferred from electronic annotation. Source: EC thyroid hormone binding Inferred from direct assay Ref.2. Source: UniProtKB transcription corepressor activity Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 314

314

Thiomorpholine-carboxylate dehydrogenase

PRO_0000200678

Regions

Nucleotide binding

143 – 148

6

NADP

Sites

Binding site

168

1

NADP

Binding site

169

1

NADP

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

314

Helix Strand Turn

Details...

Beta strand

6 – 8

3

Helix

10 – 16

7

Helix

20 – 23

4

Helix

24 – 35

12

Helix

53 – 55

3

Beta strand

62 – 66

5

Turn

67 – 70

4

Beta strand

71 – 79

9

Beta strand

89 – 99

11

Beta strand

106 – 110

5

Helix

114 – 131

18

Beta strand

138 – 142

5

Helix

147 – 158

12

Beta strand

162 – 166

5

Helix

171 – 180

10

Helix

191 – 195

5

Beta strand

200 – 203

4

Beta strand

222 – 225

4

Helix

238 – 243

6

Beta strand

244 – 249

6

Helix

251 – 257

7

Beta strand

288 – 291

4

Helix

296 – 310

15

Sequences

	Sequence		Length	Mass (Da)
	Q14894 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: A49D316B41CE6648	FASTA	314	33,776
	10 20 30 40 50 60 MSRVPAFLSA AEVEEHLRSS SLLIPPLETA LANFSSGPEG GVMQPVRTVV PVTKHRGYLG 70 80 90 100 110 120 VMPAYSAAED ALTTKLVTFY EDRGITSVVP SHQATVLLFE PSNGTLLAVM DGNVITAKRT 130 140 150 160 170 180 AAVSAIATKF LKPPSSEVLC ILGAGVQAYS HYEIFTEQFS FKEVRIWNRT KENAEKFADT 190 200 210 220 230 240 VQGEVRVCSS VQEAVAGADV IITVTLATEP ILFGEWVKPG AHINAVGASR PDWRELDDEL 250 260 270 280 290 300 MKEAVLYVDS QEAALKESGD VLLSGAEIFA ELGEVIKGVK PAHCEKTTVF KSLGMAVEDT 310 VAAKLIYDSW SSGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two roles for mu-crystallin: a lens structural protein in diurnal marsupials and a possible enzyme in mammalian retinas." Segovia L., Horwitz J., Gasser R., Wistow G. Mol. Vis. 3:9-9(1997) [PubMed: 9285773] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[2]	"Purification, molecular cloning, and functional expression of the human nicodinamide-adenine dinucleotide phosphate-regulated thyroid hormone-binding protein." Vie M.-P., Evrard C., Osty J., Breton-Gilet A., Blanchet P., Pomerance M., Rouget P., Francon J., Blondeau J.-P. Mol. Endocrinol. 11:1728-1736(1997) [PubMed: 9328354] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Human and mouse Mu-crystallin." Sperbeck S.J., Segovia L., Wistow G.J. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q." Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D. Genomics 60:295-308(1999) [PubMed: 10493829] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterine endothelium.
[7]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton 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].
[9]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[10]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 4-18; 57-83; 177-186; 243-277 AND 292-314, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[11]	"Mu-crystallin is a mammalian homologue of Agrobacterium ornithine cyclodeaminase and is expressed in human retina." Kim R.Y., Gasser R., Wistow G.J. Proc. Natl. Acad. Sci. U.S.A. 89:9292-9296(1992) [PubMed: 1384048] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 37-314. Tissue: Retina.
[12]	"Mammalian forebrain ketimine reductase identified as mu-crystallin; potential regulation by thyroid hormones." Hallen A., Cooper A.J., Jamie J.F., Haynes P.A., Willows R.D. J. Neurochem. 118:379-387(2011) [PubMed: 21332720] [Abstract] Cited for: FUNCTION AS A THIOMORPHOLINE-CARBOXYLATE DEHYDROGENASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR.
[13]	"Crystal structure of human micro-crystallin complexed with NADPH." Cheng Z., Sun L., He J., Gong W. Protein Sci. 16:329-335(2007) [PubMed: 17242435] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 2-313 IN COMPLEX WITH NADPH, SUBUNIT, NADP-BINDING SITES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L02950 mRNA. Translation: AAC16914.1.
U85772 mRNA. Translation: AAB81564.1.
AF039397 , AF039392, AF039393, AF039394, AF039395, AF039396 Genomic DNA. Translation: AAB94938.1.
AK290852 mRNA. Translation: BAF83541.1.
BX648477 mRNA. Translation: CAI46030.1.
AF001550 Genomic DNA. Translation: AAB67600.1.
CH471228 Genomic DNA. Translation: EAW66863.1.
BC018061 mRNA. Translation: AAH18061.1.

IPI

IPI00000949.

PIR

B46290.

RefSeq

NP_001014444.1. NM_001014444.2.
NP_001879.1. NM_001888.3.

UniGene

Hs.924.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I99	X-ray	2.60	A/B	2-313	[»]

ProteinModelPortal

Q14894.

SMR

Q14894. Positions 2-313.

ModBase

Search...

Protein-protein interaction databases

STRING

Q14894.

Polymorphism databases

DMDM

2498259.

Proteomic databases

PRIDE

Q14894.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000219599; ENSP00000219599; ENSG00000103316.
ENST00000396023; ENSP00000379341; ENSG00000103316.

GeneID

1428.

KEGG

hsa:1428.

UCSC

uc002dik.1. human.

Organism-specific databases

CTD

1428.

GeneCards

GC16M021177.

H-InvDB

HIX0012871.

HGNC

HGNC:2418. CRYM.

HPA

HPA019086.

MIM

123740. gene.

neXtProt

NX_Q14894.

Orphanet

90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.

PharmGKB

PA26924.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18602.

HOGENOM

HBG300196.

HOVERGEN

HBG005408.

InParanoid

Q14894.

OMA

LVTFYED.

OrthoDB

EOG454900.

PhylomeDB

Q14894.

Gene expression databases

ArrayExpress

Q14894.

Bgee

Q14894.

CleanEx

HS_CRYM.

Genevestigator

Q14894.

GermOnline

ENSG00000103316. Homo sapiens.

Family and domain databases

InterPro

IPR016040. NAD(P)-bd_dom.
IPR003462. ODC_Mu_crystall.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

Pfam

PF02423. OCD_Mu_crystall. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00451. Levothyroxine.

NextBio

5823.

SOURCE

Search...

Entry information

Entry name

CRYM_HUMAN

Accession

Primary (citable) accession number: Q14894
Secondary accession number(s): D5MNX0, Q5HYB7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 109 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.