P14384 (CBPM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carboxypeptidase M
Short name=CPM
EC=3.4.17.12

Gene names

Name:

CPM

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	443 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	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-anchor › GPI-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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	anatomical structure morphogenesis Traceable author statement PubMed 7797563. Source: ProtInc proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	metallocarboxypeptidase activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Ref.1 Ref.7

Chain

18 – 423

406

Carboxypeptidase M

PRO_0000004391

Propeptide

424 – 443

20

Removed in mature form Probable

PRO_0000251910

Sites

Active site

281

1

Nucleophile

Metal binding

83

1

Zinc

Metal binding

86

1

Zinc

Metal binding

190

1

Zinc

Site

277

1

Probable structural role

Amino acid modifications

Lipidation

423

1

GPI-anchor amidated serine Ref.7 Ref.8 Ref.9

Glycosylation

38

1

N-linked (GlcNAc...) Ref.11

Glycosylation

115

1

N-linked (GlcNAc...) Ref.10 Ref.11

Glycosylation

164

1

N-linked (GlcNAc...) Ref.10

Glycosylation

363

1

N-linked (GlcNAc...) Potential

Glycosylation

384

1

N-linked (GlcNAc...) Potential

Disulfide bond

138 ↔ 285

Ref.11

Disulfide bond

242 ↔ 284

Ref.11

Disulfide bond

341 ↔ 410

Ref.11

Natural variations

Natural variant

24

1

R → H.
Corresponds to variant rs7978197 [ dbSNP | Ensembl ].

VAR_048600

Natural variant

133

1

V → I.
Corresponds to variant rs7309831 [ dbSNP | Ensembl ].

VAR_048601

Experimental info

Mutagenesis

277

1

E → 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

Mutagenesis

277

1

E → Q: 2-fold decrease in substrate affinity. Small increase in specific affinity. Reduced heat stability by 50%. Ref.7

Mutagenesis

281

1

E → Q: Abolishes enzyme activity. Ref.7

Mutagenesis

423

1

S → A or T: Expressed on cell membrane. Released from membrane by PI-PLC. Ref.7

Mutagenesis

423

1

S → P: Little expression on cell membrane. Perinuclear localization. Not released from membrane by PI-PLC. Ref.7

Secondary structure

1

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443

Helix Strand Turn

Details...

Helix

25 – 38

14

Turn

39 – 41

3

Beta strand

42 – 50

9

Beta strand

56 – 65

10

Beta strand

75 – 80

6

Helix

88 – 103

16

Turn

104 – 106

3

Helix

108 – 116

9

Beta strand

118 – 123

6

Helix

127 – 132

6

Beta strand

159 – 161

3

Helix

169 – 180

12

Beta strand

183 – 185

3

Beta strand

188 – 190

3

Beta strand

192 – 199

8

Helix

205 – 207

3

Helix

209 – 211

3

Helix

219 – 231

13

Turn

234 – 238

5

Beta strand

243 – 245

3

Beta strand

252 – 255

4

Turn

256 – 258

3

Helix

265 – 271

7

Beta strand

279 – 287

9

Helix

290 – 292

3

Helix

293 – 298

6

Helix

301 – 308

8

Helix

309 – 312

4

Beta strand

314 – 320

7

Beta strand

331 – 334

4

Beta strand

350 – 353

4

Beta strand

357 – 365

9

Beta strand

367 – 369

3

Beta strand

372 – 378

7

Beta strand

383 – 386

4

Turn

415 – 418

4

Sequences

	Sequence		Length	Mass (Da)
	P14384 [UniParc]. Last modified July 11, 2001. Version 2. Checksum: 98EB0C94E201B901	FASTA	443	50,514
	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

References

	« Hide 'large scale' referencesShow '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. , 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, 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], MASS SPECTROMETRY. 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], MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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 , 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.

IPI

IPI00026270.

PIR

A32619.

RefSeq

NP_001005502.1. NM_001005502.2.
NP_001865.1. NM_001874.4.
NP_938079.1. NM_198320.3.

UniGene

Hs.654387.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UWY	X-ray	3.00	A	18-443	[»]

ProteinModelPortal

P14384.

ModBase

Search...

Protein-protein interaction databases

IntAct

P14384. 3 interactions.

STRING

9606.ENSP00000339157.

Protein family/group databases

MEROPS

M14.006.

PTM databases

PhosphoSite

P14384.

Polymorphism databases

DMDM

14916957.

Proteomic databases

PaxDb

P14384.

PRIDE

P14384.

Protocols and materials databases

DNASU

1368.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338356; ENSP00000339157; ENSG00000135678.
ENST00000546373; ENSP00000447255; ENSG00000135678.
ENST00000547827; ENSP00000450338; ENSG00000135678.
ENST00000551568; ENSP00000448517; ENSG00000135678.

GeneID

1368.

KEGG

hsa:1368.

UCSC

uc001sup.3. human.

Organism-specific databases

CTD

1368.

GeneCards

GC12M069244.

HGNC

HGNC:2311. CPM.

HPA

HPA002657.

MIM

114860. gene.

neXtProt

NX_P14384.

PharmGKB

PA26828.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2866.

HOGENOM

HOG000232185.

HOVERGEN

HBG003410.

InParanoid

P14384.

KO

K01296.

OMA

QEGMEAF.

OrthoDB

EOG42RD77.

PhylomeDB

P14384.

Enzyme and pathway databases

SABIO-RK

P14384.

Gene expression databases

ArrayExpress

P14384.

Bgee

P14384.

CleanEx

HS_CPM.

Genevestigator

P14384.

GermOnline

ENSG00000135678. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.1120. 1 hit.

InterPro

IPR008969. CarboxyPept-like_regulatory.
IPR014766. CarboxyPept_regulatory_dom.
IPR027062. CPM.
IPR000834. Peptidase_M14.
[Graphical view]

PANTHER

PTHR11532:SF2. PTHR11532:SF2. 1 hit.

Pfam

PF00246. Peptidase_M14. 1 hit.
[Graphical view]

PRINTS

PR00765. CRBOXYPTASEA.

SMART

SM00631. Zn_pept. 1 hit.
[Graphical view]

SUPFAM

SSF49464. CarboxypepD_reg. 1 hit.

PROSITE

PS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P14384.

ChEMBL

CHEMBL3038.

ChiTaRS

CPM. human.

EvolutionaryTrace

P14384.

GenomeRNAi

1368.

NextBio

5541.

SOURCE

Search...

Entry information

Entry name

CBPM_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 137 of the entry and version 2 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.