Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P14384 (CBPM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carboxypeptidase M

Short name=CPM
EC=3.4.17.12
Gene names
Name:CPM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length443 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins. It is believed to play important roles in the control of peptide hormone and growth factor activity at the cell surface, and in the membrane-localized degradation of extracellular proteins. Ref.7

Catalytic activity

Cleavage of C-terminal arginine or lysine residues from polypeptides.

Cofactor

Binds 1 zinc ion per subunit.

Enzyme regulation

Inhibited by O-phenanthroline and MGTA and activated by cobalt.

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor Ref.7.

Sequence similarities

Belongs to the peptidase M14 family.

Biophysicochemical properties

Kinetic parameters:

KM=59 µM for synthetic dansyl-Ala-Arg Ref.7

KM=57 µM for placental peptide hormones

pH dependence:

Optimum pH is 7.0.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Ref.1 Ref.7
Chain18 – 423406Carboxypeptidase M
PRO_0000004391
Propeptide424 – 44320Removed in mature form Probable
PRO_0000251910

Sites

Active site2811Nucleophile
Metal binding831Zinc
Metal binding861Zinc
Metal binding1901Zinc
Site2771Probable structural role

Amino acid modifications

Lipidation4231GPI-anchor amidated serine Ref.7 Ref.8 Ref.9
Glycosylation381N-linked (GlcNAc...) Ref.11
Glycosylation1151N-linked (GlcNAc...) Ref.10 Ref.11
Glycosylation1641N-linked (GlcNAc...) Ref.10
Glycosylation3631N-linked (GlcNAc...) Potential
Glycosylation3841N-linked (GlcNAc...) Potential
Disulfide bond138 ↔ 285 Ref.11
Disulfide bond242 ↔ 284 Ref.11
Disulfide bond341 ↔ 410 Ref.11

Natural variations

Natural variant241R → H.
Corresponds to variant rs7978197 [ dbSNP | Ensembl ].
VAR_048600
Natural variant1331V → I.
Corresponds to variant rs7309831 [ dbSNP | Ensembl ].
VAR_048601

Experimental info

Mutagenesis2771E → A: 5-fold decrease in substrate affinity. 22-fold decrease in specific affinity. 104-fold decrease in catalytic efficiency. Greatly reduced heat stability. Ref.7
Mutagenesis2771E → Q: 2-fold decrease in substrate affinity. Small increase in specific affinity. Reduced heat stability by 50%. Ref.7
Mutagenesis2811E → Q: Abolishes enzyme activity. Ref.7
Mutagenesis4231S → A or T: Expressed on cell membrane. Released from membrane by PI-PLC. Ref.7
Mutagenesis4231S → P: Little expression on cell membrane. Perinuclear localization. Not released from membrane by PI-PLC. Ref.7

Secondary structure

................................................................... 443
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P14384 [UniParc].

Last modified July 11, 2001. Version 2.
Checksum: 98EB0C94E201B901

FASTA44350,514
        10         20         30         40         50         60 
MDFPCLWLGL LLPLVAALDF NYHRQEGMEA FLKTVAQNYS SVTHLHSIGK SVKGRNLWVL 

        70         80         90        100        110        120 
VVGRFPKEHR IGIPEFKYVA NMHGDETVGR ELLLHLIDYL VTSDGKDPEI TNLINSTRIH 

       130        140        150        160        170        180 
IMPSMNPDGF EAVKKPDCYY SIGRENYNQY DLNRNFPDAF EYNNVSRQPE TVAVMKWLKT 

       190        200        210        220        230        240 
ETFVLSANLH GGALVASYPF DNGVQATGAL YSRSLTPDDD VFQYLAHTYA SRNPNMKKGD 

       250        260        270        280        290        300 
ECKNKMNFPN GVTNGYSWYP LQGGMQDYNY IWAQCFEITL ELSCCKYPRE EKLPSFWNNN 

       310        320        330        340        350        360 
KASLIEYIKQ VHLGVKGQVF DQNGNPLPNV IVEVQDRKHI CPYRTNKYGE YYLLLLPGSY 

       370        380        390        400        410        420 
IINVTVPGHD PHITKVIIPE KSQNFSALKK DILLPFQGQL DSIPVSNPSC PMIPLYRNLP 

       430        440 
DHSAATKPSL FLFLVSLLHI FFK 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and sequencing of the cDNA for human membrane-bound carboxypeptidase M. Comparison with carboxypeptidases A, B, H, and N."
Tan F., Chan S.J., Steiner D.F., Schilling J.W., Skidgel R.A.
J. Biol. Chem. 264:13165-13170(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 18-48.
Tissue: Placenta.
[2]Skidgel R.A.
Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Type 2 diabetes locus on 12q15: further mapping and mutation screening of two candidate genes."
Bektas A., Hughes J.N., Warram J.H., Krolewski A.S., Doria A.
Diabetes 50:204-208(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Molecular structure and alternative splicing of the human carboxypeptidase M gene."
Pessoa L.G., Guerreiro da S.I., Baptista H.A., Pesquero J.L., Paiva A.C.M., Bader M., Pesquero J.B.
Biol. Chem. 383:263-269(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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. 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: Lung.
[6]"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: Placenta.
[7]"Effect of mutation of two critical glutamic acid residues on the activity and stability of human carboxypeptidase M and characterization of its signal for glycosylphosphatidylinositol anchoring."
Tan F., Balsitis S., Black J.K., Bloechl A., Mao J.-F., Becker R.P., Schacht D., Skidgel R.A.
Biochem. J. 370:567-578(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-21, GPI-ANCHOR AT SER-423, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF GLU-277; GLU-281 AND SER-423.
[8]"Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins."
Elortza F., Nuehse T.S., Foster L.J., Stensballe A., Peck S.C., Jensen O.N.
Mol. Cell. Proteomics 2:1261-1270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment."
Elortza F., Mohammed S., Bunkenborg J., Foster L.J., Nuehse T.S., Brodbeck U., Peck S.C., Jensen O.N.
J. Proteome Res. 5:935-943(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"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-115 AND ASN-164.
Tissue: Liver.
[11]"Crystal structure of human carboxypeptidase M, a membrane-bound enzyme that regulates peptide hormone activity."
Reverter D., Maskos K., Tan F., Skidgel R.A., Bode W.
J. Mol. Biol. 338:257-269(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 18-443, DISULFIDE BONDS, GLYCOSYLATION AT ASN-38 AND ASN-115.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04970 mRNA. Translation: AAA35651.2.
AF262947 expand/collapse EMBL AC list , AF262940, AF262941, AF262942, AF262943, AF262944, AF262945, AF262946 Genomic DNA. Translation: AAG47641.1.
AF368463 mRNA. Translation: AAK69717.1.
AK313180 mRNA. Translation: BAG35997.1.
BC022276 mRNA. Translation: AAH22276.1.
CCDSCCDS8987.1.
PIRA32619.
RefSeqNP_001005502.1. NM_001005502.2.
NP_001865.1. NM_001874.4.
NP_938079.1. NM_198320.3.
UniGeneHs.654387.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UWYX-ray3.00A18-443[»]
ProteinModelPortalP14384.
SMRP14384. Positions 18-419.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107760. 2 interactions.
IntActP14384. 3 interactions.
STRING9606.ENSP00000339157.

Chemistry

BindingDBP14384.
ChEMBLCHEMBL3038.

Protein family/group databases

MEROPSM14.006.

PTM databases

PhosphoSiteP14384.

Polymorphism databases

DMDM14916957.

Proteomic databases

MaxQBP14384.
PaxDbP14384.
PRIDEP14384.

Protocols and materials databases

DNASU1368.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338356; ENSP00000339157; ENSG00000135678.
ENST00000546373; ENSP00000447255; ENSG00000135678.
ENST00000551568; ENSP00000448517; ENSG00000135678.
GeneID1368.
KEGGhsa:1368.
UCSCuc001sup.3. human.

Organism-specific databases

CTD1368.
GeneCardsGC12M069244.
HGNCHGNC:2311. CPM.
HPAHPA002657.
MIM114860. gene.
neXtProtNX_P14384.
PharmGKBPA26828.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2866.
HOGENOMHOG000232185.
HOVERGENHBG003410.
InParanoidP14384.
KOK01296.
OMAITNGYSW.
PhylomeDBP14384.
TreeFamTF315592.

Enzyme and pathway databases

SABIO-RKP14384.

Gene expression databases

ArrayExpressP14384.
BgeeP14384.
CleanExHS_CPM.
GenevestigatorP14384.

Family and domain databases

Gene3D2.60.40.1120. 1 hit.
InterProIPR008969. CarboxyPept-like_regulatory.
IPR014766. CarboxyPept_regulatory_dom.
IPR027062. CPM.
IPR000834. Peptidase_M14.
[Graphical view]
PANTHERPTHR11532:SF53. PTHR11532:SF53. 1 hit.
PfamPF00246. Peptidase_M14. 1 hit.
[Graphical view]
PRINTSPR00765. CRBOXYPTASEA.
SMARTSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMSSF49464. SSF49464. 1 hit.
PROSITEPS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCPM. human.
EvolutionaryTraceP14384.
GeneWikiCPM_(gene).
GenomeRNAi1368.
NextBio5541.
PROP14384.
SOURCESearch...

Entry information

Entry nameCBPM_HUMAN
AccessionPrimary (citable) accession number: P14384
Secondary accession number(s): B2R800, Q9H2K9
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: July 11, 2001
Last modified: July 9, 2014
This is version 148 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

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 12

Human chromosome 12: entries, gene names and cross-references to MIM