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Protein

Methylmalonic aciduria and homocystinuria type D protein, mitochondrial

Gene

MMADHC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Involved in cobalamin metabolism.1 Publication

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.
R-HSA-3359473. Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD.

Names & Taxonomyi

Protein namesi
Recommended name:
Methylmalonic aciduria and homocystinuria type D protein, mitochondrial
Gene namesi
Name:MMADHC
Synonyms:C2orf25, CL25022
ORF Names:HSPC161, My011
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:25221. MMADHC.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Methylmalonic aciduria and homocystinuria type cblD (MMAHCD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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).
See also OMIM:277410
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti108 – 1081S → SLAEPLS in MMAHCD; cblD variant 2.
VAR_043843
Natural varianti182 – 1821T → N in MMAHCD; cblD variant 1. 1 Publication
Corresponds to variant rs118204045 [ dbSNP | Ensembl ].
VAR_043844
Natural varianti204 – 23229Missing in MMAHCD; cblD original. 1 Publication
VAR_043845Add
BLAST
Natural varianti249 – 2491Y → C in MMAHCD; cblD variant 1. 1 Publication
Corresponds to variant rs118204046 [ dbSNP | Ensembl ].
VAR_043846
Natural varianti259 – 2591L → P in MMAHCD; cblD variant 1. 1 Publication
Corresponds to variant rs118204044 [ dbSNP | Ensembl ].
VAR_043847

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiMMADHC.
MIMi277410. phenotype.
Orphaneti308380. Methylcobalamin deficiency type cblDv1.
79283. Methylmalonic acidemia with homocystinuria, type cblD.
308442. Vitamin B12-responsive methylmalonic acidemia, type cblDv2.
PharmGKBiPA164723053.

Polymorphism and mutation databases

BioMutaiMMADHC.
DMDMi68565296.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3838MitochondrionSequence analysisAdd
BLAST
Chaini39 – 296258Methylmalonic aciduria and homocystinuria type D protein, mitochondrialPRO_0000019534Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei203 – 2031N6-acetyllysineCombined sources

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9H3L0.
MaxQBiQ9H3L0.
PaxDbiQ9H3L0.
PeptideAtlasiQ9H3L0.
PRIDEiQ9H3L0.

PTM databases

iPTMnetiQ9H3L0.
PhosphoSiteiQ9H3L0.

Expressioni

Tissue specificityi

Widely expressed at high levels.1 Publication

Gene expression databases

BgeeiQ9H3L0.
ExpressionAtlasiQ9H3L0. baseline and differential.
GenevisibleiQ9H3L0. HS.

Organism-specific databases

HPAiHPA037531.
HPA037532.

Interactioni

Protein-protein interaction databases

BioGridi118097. 13 interactions.
IntActiQ9H3L0. 1 interaction.
STRINGi9606.ENSP00000301920.

Structurei

Secondary structure

1
296
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi137 – 1404Combined sources
Beta strandi146 – 1527Combined sources
Helixi155 – 1628Combined sources
Beta strandi174 – 1818Combined sources
Helixi191 – 21727Combined sources
Beta strandi222 – 2254Combined sources
Turni227 – 2293Combined sources
Beta strandi231 – 2355Combined sources
Helixi247 – 2515Combined sources
Beta strandi255 – 2584Combined sources
Beta strandi263 – 2675Combined sources
Turni268 – 2703Combined sources
Beta strandi273 – 2819Combined sources
Helixi288 – 2936Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5CUZX-ray2.31A108-296[»]
5CV0X-ray1.90A/B108-296[»]
ProteinModelPortaliQ9H3L0.
SMRiQ9H3L0. Positions 133-296.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG3994. Eukaryota.
ENOG410XRBP. LUCA.
GeneTreeiENSGT00390000015050.
HOGENOMiHOG000231797.
InParanoidiQ9H3L0.
OrthoDBiEOG7RBZ9D.
PhylomeDBiQ9H3L0.
TreeFamiTF314208.

Family and domain databases

InterProiIPR019362. MMADHC.
[Graphical view]
PANTHERiPTHR13192. PTHR13192. 1 hit.
PfamiPF10229. DUF2246. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9H3L0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANVLCNRAR LVSYLPGFCS LVKRVVNPKA FSTAGSSGSD ESHVAAAPPD
60 70 80 90 100
ICSRTVWPDE TMGPFGPQDQ RFQLPGNIGF DCHLNGTASQ KKSLVHKTLP
110 120 130 140 150
DVLAEPLSSE RHEFVMAQYV NEFQGNDAPV EQEINSAETY FESARVECAI
160 170 180 190 200
QTCPELLRKD FESLFPEVAN GKLMILTVTQ KTKNDMTVWS EEVEIEREVL
210 220 230 240 250
LEKFINGAKE ICYALRAEGY WADFIDPSSG LAFFGPYTNN TLFETDERYR
260 270 280 290
HLGFSVDDLG CCKVIRHSLW GTHVVVGSIF TNATPDSHIM KKLSGN
Length:296
Mass (Da):32,940
Last modified:July 5, 2005 - v2
Checksum:i749C2A91D7E6C95D
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti204 – 2041F → S in AAG43124 (Ref. 1) Curated
Sequence conflicti211 – 2111I → N in AAG43124 (Ref. 1) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti108 – 1081S → SLAEPLS in MMAHCD; cblD variant 2.
VAR_043843
Natural varianti182 – 1821T → N in MMAHCD; cblD variant 1. 1 Publication
Corresponds to variant rs118204045 [ dbSNP | Ensembl ].
VAR_043844
Natural varianti204 – 23229Missing in MMAHCD; cblD original. 1 Publication
VAR_043845Add
BLAST
Natural varianti249 – 2491Y → C in MMAHCD; cblD variant 1. 1 Publication
Corresponds to variant rs118204046 [ dbSNP | Ensembl ].
VAR_043846
Natural varianti259 – 2591L → P in MMAHCD; cblD variant 1. 1 Publication
Corresponds to variant rs118204044 [ dbSNP | Ensembl ].
VAR_043847

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2189.1.
RefSeqiNP_056517.1. NM_015702.2.
UniGeneiHs.5324.

Genome annotation databases

EnsembliENST00000303319; ENSP00000301920; ENSG00000168288.
ENST00000428879; ENSP00000389060; ENSG00000168288.
GeneIDi27249.
KEGGihsa:27249.
UCSCiuc002txc.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2189.1.
RefSeqiNP_056517.1. NM_015702.2.
UniGeneiHs.5324.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5CUZX-ray2.31A108-296[»]
5CV0X-ray1.90A/B108-296[»]
ProteinModelPortaliQ9H3L0.
SMRiQ9H3L0. Positions 133-296.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118097. 13 interactions.
IntActiQ9H3L0. 1 interaction.
STRINGi9606.ENSP00000301920.

PTM databases

iPTMnetiQ9H3L0.
PhosphoSiteiQ9H3L0.

Polymorphism and mutation databases

BioMutaiMMADHC.
DMDMi68565296.

Proteomic databases

EPDiQ9H3L0.
MaxQBiQ9H3L0.
PaxDbiQ9H3L0.
PeptideAtlasiQ9H3L0.
PRIDEiQ9H3L0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303319; ENSP00000301920; ENSG00000168288.
ENST00000428879; ENSP00000389060; ENSG00000168288.
GeneIDi27249.
KEGGihsa:27249.
UCSCiuc002txc.4. human.

Organism-specific databases

CTDi27249.
GeneCardsiMMADHC.
GeneReviewsiMMADHC.
HGNCiHGNC:25221. MMADHC.
HPAiHPA037531.
HPA037532.
MalaCardsiMMADHC.
MIMi277410. phenotype.
611935. gene.
neXtProtiNX_Q9H3L0.
Orphaneti308380. Methylcobalamin deficiency type cblDv1.
79283. Methylmalonic acidemia with homocystinuria, type cblD.
308442. Vitamin B12-responsive methylmalonic acidemia, type cblDv2.
PharmGKBiPA164723053.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3994. Eukaryota.
ENOG410XRBP. LUCA.
GeneTreeiENSGT00390000015050.
HOGENOMiHOG000231797.
InParanoidiQ9H3L0.
OrthoDBiEOG7RBZ9D.
PhylomeDBiQ9H3L0.
TreeFamiTF314208.

Enzyme and pathway databases

ReactomeiR-HSA-196741. Cobalamin (Cbl, vitamin B12) transport and metabolism.
R-HSA-3359473. Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD.

Miscellaneous databases

ChiTaRSiMMADHC. human.
GeneWikiiMMADHC.
GenomeRNAii27249.
PROiQ9H3L0.
SOURCEiSearch...

Gene expression databases

BgeeiQ9H3L0.
ExpressionAtlasiQ9H3L0. baseline and differential.
GenevisibleiQ9H3L0. HS.

Family and domain databases

InterProiIPR019362. MMADHC.
[Graphical view]
PANTHERiPTHR13192. PTHR13192. 1 hit.
PfamiPF10229. DUF2246. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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.
    , 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. 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. 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].
  10. "Subcellular location of MMACHC and MMADHC, two human proteins central to intracellular vitamin B(12) metabolism."
    Mah W., Deme J.C., Watkins D., Fung S., Janer A., Shoubridge E.A., Rosenblatt D.S., Coulton J.W.
    Mol. Genet. Metab. 108:112-118(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.

Entry informationi

Entry nameiMMAD_HUMAN
AccessioniPrimary (citable) accession number: Q9H3L0
Secondary accession number(s): B2R895, D3DP91, O95891
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: July 6, 2016
This is version 107 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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 one 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.