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Q9H3L0 (MMAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methylmalonic aciduria and homocystinuria type D protein, mitochondrial
Gene names
Name:MMADHC
Synonyms:C2orf25, CL25022
ORF Names:HSPC161, My011
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length296 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in cobalamin metabolism. Ref.8

Subcellular location

Mitochondrion Potential.

Tissue specificity

Widely expressed at high levels. Ref.8

Involvement in disease

Methylmalonic aciduria and homocystinuria type cblD (MMAHCD) [MIM:277410]: A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include developmental delay, hyotonia, mental retardation, seizures, megaloblastic anemia. Some patients manifest combined methylmalonic aciduria and homocystinuria (referred to as cblD original), some have only isolated homocystinuria (cblD variant 1), and others have only methylmalonic aciduria (cblD variant 2).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence caution

The sequence AAG43124.1 differs from that shown. Reason: Frameshift at positions 171, 178, 185, 188 and 200.

Ontologies

Keywords
   Cellular componentMitochondrion
   DiseaseDisease mutation
   DomainTransit peptide
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcobalamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3838Mitochondrion Potential
Chain39 – 296258Methylmalonic aciduria and homocystinuria type D protein, mitochondrial
PRO_0000019534

Amino acid modifications

Modified residue2031N6-acetyllysine Ref.9

Natural variations

Natural variant1081S → SLAEPLS in MMAHCD; cblD variant 2.
VAR_043843
Natural variant1821T → N in MMAHCD; cblD variant 1. Ref.8
VAR_043844
Natural variant204 – 23229Missing in MMAHCD; cblD original.
VAR_043845
Natural variant2491Y → C in MMAHCD; cblD variant 1. Ref.8
VAR_043846
Natural variant2591L → P in MMAHCD; cblD variant 1. Ref.8
VAR_043847

Experimental info

Sequence conflict2041F → S in AAG43124. Ref.1
Sequence conflict2111I → N in AAG43124. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9H3L0 [UniParc].

Last modified July 5, 2005. Version 2.
Checksum: 749C2A91D7E6C95D

FASTA29632,940
        10         20         30         40         50         60 
MANVLCNRAR LVSYLPGFCS LVKRVVNPKA FSTAGSSGSD ESHVAAAPPD ICSRTVWPDE 

        70         80         90        100        110        120 
TMGPFGPQDQ RFQLPGNIGF DCHLNGTASQ KKSLVHKTLP DVLAEPLSSE RHEFVMAQYV 

       130        140        150        160        170        180 
NEFQGNDAPV EQEINSAETY FESARVECAI QTCPELLRKD FESLFPEVAN GKLMILTVTQ 

       190        200        210        220        230        240 
KTKNDMTVWS EEVEIEREVL LEKFINGAKE ICYALRAEGY WADFIDPSSG LAFFGPYTNN 

       250        260        270        280        290 
TLFETDERYR HLGFSVDDLG CCKVIRHSLW GTHVVVGSIF TNATPDSHIM KKLSGN 

« Hide

References

« Hide 'large scale' references
[1]Mao Y.M., Xie Y., Zheng Z.H., Gu S.H., Ying K., Lin Q., Dai J.L., Tang R., Dong H., Wu X.Z.
Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Fetal brain.
[2]Mei G., Yu W., Gibbs R.A.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. expand/collapse author list , Gu J., Chen S.-J., Chen Z.
Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Umbilical cord blood.
[4]"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. expand/collapse author list , 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].
Tissue: Skeletal muscle.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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. expand/collapse author list , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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].
Tissue: Brain, Kidney, Placenta and Skeletal muscle.
[8]"Gene identification for the cblD defect of vitamin B12 metabolism."
Coelho D., Suormala T., Stucki M., Lerner-Ellis J.P., Rosenblatt D.S., Newbold R.F., Baumgartner M.R., Fowler B.
N. Engl. J. Med. 358:1454-1464(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, VARIANTS MMAHCD LEU-ALA-GLU-PRO-LEU-SER-108 INS; ASN-182; 204-PHE--ALA-232 DEL; CYS-249 AND PRO-259.
[9]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-203, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF060224 mRNA. Translation: AAG43124.1. Frameshift.
AF131802 mRNA. Translation: AAD20048.1.
AF161510 mRNA. Translation: AAF29125.1.
AK313284 mRNA. Translation: BAG36092.1.
AC110782 Genomic DNA. Translation: AAY14891.1.
CH471058 Genomic DNA. Translation: EAX11533.1.
CH471058 Genomic DNA. Translation: EAX11534.1.
CH471058 Genomic DNA. Translation: EAX11535.1.
CH471058 Genomic DNA. Translation: EAX11537.1.
BC000932 mRNA. Translation: AAH00932.1.
BC010894 mRNA. Translation: AAH10894.1.
BC022859 mRNA. Translation: AAH22859.1.
BC023995 mRNA. Translation: AAH23995.1.
RefSeqNP_056517.1. NM_015702.2.
UniGeneHs.5324.

3D structure databases

ProteinModelPortalQ9H3L0.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118097. 2 interactions.
STRING9606.ENSP00000301920.

PTM databases

PhosphoSiteQ9H3L0.

Polymorphism databases

DMDM68565296.

Proteomic databases

PaxDbQ9H3L0.
PRIDEQ9H3L0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303319; ENSP00000301920; ENSG00000168288.
ENST00000428879; ENSP00000389060; ENSG00000168288.
GeneID27249.
KEGGhsa:27249.
UCSCuc002txc.3. human.

Organism-specific databases

CTD27249.
GeneCardsGC02M150426.
HGNCHGNC:25221. MMADHC.
HPAHPA037531.
MIM277410. phenotype.
611935. gene.
neXtProtNX_Q9H3L0.
Orphanet308380. Methylcobalamin deficiency type cblDv1.
79283. Methylmalonic acidemia with homocystinuria, type cblD.
308442. Vitamin B12-responsive methylmalonic acidemia, type cblDv2.
PharmGKBPA164723053.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG276245.
HOGENOMHOG000231797.
InParanoidQ9H3L0.
OrthoDBEOG7RBZ9D.
PhylomeDBQ9H3L0.
TreeFamTF314208.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressQ9H3L0.
BgeeQ9H3L0.
GenevestigatorQ9H3L0.

Family and domain databases

InterProIPR019362. MMADHC.
[Graphical view]
PANTHERPTHR13192. PTHR13192. 1 hit.
PfamPF10229. DUF2246. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMMADHC.
GenomeRNAi27249.
NextBio50175.
PROQ9H3L0.
SOURCESearch...

Entry information

Entry nameMMAD_HUMAN
AccessionPrimary (citable) accession number: Q9H3L0
Secondary accession number(s): B2R895, D3DP91, O95891
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: March 19, 2014
This is version 87 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

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 2

Human chromosome 2: entries, gene names and cross-references to MIM