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P26927 (HGFL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 147. 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:
Hepatocyte growth factor-like protein
Alternative name(s):
Macrophage stimulatory protein
Macrophage-stimulating protein
Short name=MSP
Gene names
Name:MST1
Synonyms:D3F15S2, DNF15S2, HGFL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length711 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Subunit structure

Dimer of an alpha chain and a beta chain linked by a disulfide bond. Interacts (via beta chain) with MST1R (via SEMA domain). Ref.5 Ref.6 Ref.12

Subcellular location

Secreted.

Post-translational modification

Cleaved after Arg-483, probably by HPN/Hepsin, to yield the active form consisting of two disulfide-linked chains.

Involvement in disease

MST1 variant Cys-686 may be associated with inflammatory bowel disease (IBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is unsure whether Cys-689 itself or a variation in linkage disequilibrium with Cys-689 is responsible for the association with IBD. Ref.8 Ref.10

Sequence similarities

Belongs to the peptidase S1 family. Plasminogen subfamily.

Contains 4 kringle domains.

Contains 1 PAN domain.

Contains 1 peptidase S1 domain.

Caution

Although related to peptidase S1 family, the active site residues characteristic of serine proteases appear to be absent from this protein, which may therefore lack protease activity.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainKringle
Repeat
Signal
   Molecular functionSerine protease homolog
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processproteolysis

Inferred from electronic annotation. Source: InterPro

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionserine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 711693Hepatocyte growth factor-like protein
PRO_0000028085
Chain19 – 483465Hepatocyte growth factor-like protein alpha chain Probable
PRO_0000028086
Chain484 – 711228Hepatocyte growth factor-like protein beta chain Probable
PRO_0000028087

Regions

Domain21 – 10585PAN
Domain110 – 18677Kringle 1
Domain191 – 26878Kringle 2
Domain283 – 36179Kringle 3
Domain370 – 44879Kringle 4
Domain484 – 709226Peptidase S1

Amino acid modifications

Glycosylation721N-linked (GlcNAc...) Potential
Glycosylation2961N-linked (GlcNAc...) Ref.7
Glycosylation6151N-linked (GlcNAc...) Ref.9
Disulfide bond56 ↔ 78 By similarity
Disulfide bond60 ↔ 66 By similarity
Disulfide bond110 ↔ 186 By similarity
Disulfide bond131 ↔ 169 By similarity
Disulfide bond157 ↔ 181 By similarity
Disulfide bond191 ↔ 268 By similarity
Disulfide bond194 ↔ 324 By similarity
Disulfide bond212 ↔ 251 By similarity
Disulfide bond240 ↔ 263 By similarity
Disulfide bond283 ↔ 361 By similarity
Disulfide bond304 ↔ 343 By similarity
Disulfide bond332 ↔ 355 By similarity
Disulfide bond370 ↔ 448 By similarity
Disulfide bond391 ↔ 431 By similarity
Disulfide bond419 ↔ 443 By similarity
Disulfide bond468 ↔ 588Interchain (between alpha and beta chains) Ref.13
Disulfide bond507 ↔ 523 By similarity
Disulfide bond602 ↔ 667 By similarity
Disulfide bond632 ↔ 646 By similarity
Disulfide bond657 ↔ 685 By similarity

Natural variations

Natural variant131C → Y. Ref.1
VAR_006631
Natural variant2121C → F.
VAR_006632
Natural variant5511S → G.
Corresponds to variant rs6791037 [ dbSNP | Ensembl ].
VAR_059787
Natural variant6761E → K.
Corresponds to variant rs7798 [ dbSNP | Ensembl ].
VAR_014569
Natural variant6891R → C Common polymorphism; may be associated with inflammatory bowel disease; results in reduced binding affinity to MST1R. Ref.8 Ref.10 Ref.12
Corresponds to variant rs3197999 [ dbSNP | Ensembl ].
VAR_070224

Experimental info

Sequence conflict2921R → G AA sequence Ref.5
Sequence conflict3041C → E AA sequence Ref.5
Sequence conflict3061R → E AA sequence Ref.5
Sequence conflict5501Missing AA sequence Ref.5
Sequence conflict5931W → E AA sequence Ref.5
Sequence conflict6231L → F in AAA59872. Ref.2

Secondary structure

...................................... 711
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P26927 [UniParc].

Last modified May 15, 2007. Version 2.
Checksum: 2E4B3C7D4AA9B566

FASTA71180,320
        10         20         30         40         50         60 
MGWLPLLLLL TQCLGVPGQR SPLNDFQVLR GTELQHLLHA VVPGPWQEDV ADAEECAGRC 

        70         80         90        100        110        120 
GPLMDCRAFH YNVSSHGCQL LPWTQHSPHT RLRRSGRCDL FQKKDYVRTC IMNNGVGYRG 

       130        140        150        160        170        180 
TMATTVGGLP CQAWSHKFPN DHKYTPTLRN GLEENFCRNP DGDPGGPWCY TTDPAVRFQS 

       190        200        210        220        230        240 
CGIKSCREAA CVWCNGEEYR GAVDRTESGR ECQRWDLQHP HQHPFEPGKF LDQGLDDNYC 

       250        260        270        280        290        300 
RNPDGSERPW CYTTDPQIER EFCDLPRCGS EAQPRQEATT VSCFRGKGEG YRGTANTTTA 

       310        320        330        340        350        360 
GVPCQRWDAQ IPHQHRFTPE KYACKDLREN FCRNPDGSEA PWCFTLRPGM RAAFCYQIRR 

       370        380        390        400        410        420 
CTDDVRPQDC YHGAGEQYRG TVSKTRKGVQ CQRWSAETPH KPQFTFTSEP HAQLEENFCR 

       430        440        450        460        470        480 
NPDGDSHGPW CYTMDPRTPF DYCALRRCAD DQPPSILDPP DQVQFEKCGK RVDRLDQRRS 

       490        500        510        520        530        540 
KLRVVGGHPG NSPWTVSLRN RQGQHFCGGS LVKEQWILTA RQCFSSCHMP LTGYEVWLGT 

       550        560        570        580        590        600 
LFQNPQHGEP SLQRVPVAKM VCGPSGSQLV LLKLERSVTL NQRVALICLP PEWYVVPPGT 

       610        620        630        640        650        660 
KCEIAGWGET KGTGNDTVLN VALLNVISNQ ECNIKHRGRV RESEMCTEGL LAPVGACEGD 

       670        680        690        700        710 
YGGPLACFTH NCWVLEGIII PNRVCARSRW PAVFTRVSVF VDWIHKVMRL G 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor."
Han S., Stuart L.A., Friezner Degen S.J.
Biochemistry 30:9768-9780(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYR-13.
Tissue: Liver.
[2]"Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3."
Yoshimura T., Yuhki N., Wang M.H., Skeel A., Leonard E.J.
J. Biol. Chem. 268:15461-15468(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
[5]"Macrophage stimulating protein: purification, partial amino acid sequence, and cellular activity."
Skeel A., Yoshimura T., Showalter S.D., Tanaka S., Appella E., Leonard E.J.
J. Exp. Med. 173:1227-1234(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 230-247; 288-310; 326-341; 484-501; 530-552; 574-596 AND 602-611, SUBUNIT.
Tissue: Plasma.
[6]"Macrophage stimulating protein (MSP) binds to its receptor via the MSP beta chain."
Wang M.H., Julian F.M., Breathnach R., Godowski P.J., Takehara T., Yoshikawa W., Hagiya M., Leonard E.J.
J. Biol. Chem. 272:16999-17004(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MST1R.
[7]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-296.
Tissue: Plasma.
[8]"Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis."
Goyette P., Lefebvre C., Ng A., Brant S.R., Cho J.H., Duerr R.H., Silverberg M.S., Taylor K.D., Latiano A., Aumais G., Deslandres C., Jobin G., Annese V., Daly M.J., Xavier R.J., Rioux J.D.
Mucosal Immunol. 1:131-138(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN INFLAMMATORY BOWEL DISEASE, VARIANT CYS-689.
[9]"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-615.
Tissue: Liver.
[10]"Genome-wide association identifies multiple ulcerative colitis susceptibility loci."
McGovern D.P., Gardet A., Torkvist L., Goyette P., Essers J., Taylor K.D., Neale B.M., Ong R.T., Lagace C., Li C., Green T., Stevens C.R., Beauchamp C., Fleshner P.R., Carlson M., D'Amato M., Halfvarson J., Hibberd M.L. expand/collapse author list , Lordal M., Padyukov L., Andriulli A., Colombo E., Latiano A., Palmieri O., Bernard E.J., Deslandres C., Hommes D.W., de Jong D.J., Stokkers P.C., Weersma R.K., Sharma Y., Silverberg M.S., Cho J.H., Wu J., Roeder K., Brant S.R., Schumm L.P., Duerr R.H., Dubinsky M.C., Glazer N.L., Haritunians T., Ippoliti A., Melmed G.Y., Siscovick D.S., Vasiliauskas E.A., Targan S.R., Annese V., Wijmenga C., Pettersson S., Rotter J.I., Xavier R.J., Daly M.J., Rioux J.D., Seielstad M.
Nat. Genet. 42:332-337(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN INFLAMMATORY BOWEL DISEASE, VARIANT CYS-689.
[11]"Proteolytic activation of pro-macrophage-stimulating protein by hepsin."
Ganesan R., Kolumam G.A., Lin S.J., Xie M.H., Santell L., Wu T.D., Lazarus R.A., Chaudhuri A., Kirchhofer D.
Mol. Cancer Res. 9:1175-1186(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC CLEAVAGE.
[12]"Protein characterization of a candidate mechanism SNP for Crohn's disease: the macrophage stimulating protein R689C substitution."
Gorlatova N., Chao K., Pal L.R., Araj R.H., Galkin A., Turko I., Moult J., Herzberg O.
PLoS ONE 6:E27269-E27269(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MST1R, CHARACTERIZATION OF VARIANT CYS-689.
[13]"Crystal structure of the beta-chain of human hepatocyte growth factor-like/macrophage stimulating protein."
Carafoli F., Chirgadze D.Y., Blundell T.L., Gherardi E.
FEBS J. 272:5799-5807(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 465-711, INTERCHAIN DISULFIDE BOND.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M74178 mRNA. Translation: AAA50165.1.
U37055 Genomic DNA. Translation: AAC50471.1.
L11924 mRNA. Translation: AAA59872.1.
AC099668 Genomic DNA. No translation available.
BC048330 mRNA. Translation: AAH48330.1.
PIRA47136. A40331.
RefSeqNP_066278.3. NM_020998.3.
UniGeneHs.349110.
Hs.512587.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ASUX-ray1.85A465-483[»]
B484-711[»]
ProteinModelPortalP26927.
SMRP26927. Positions 22-709.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110591. 4 interactions.
DIPDIP-6028N.
IntActP26927. 3 interactions.
MINTMINT-4787531.
STRING9606.ENSP00000308226.

Chemistry

ChEMBLCHEMBL6042.

Protein family/group databases

MEROPSS01.975.

PTM databases

PhosphoSiteP26927.

Polymorphism databases

DMDM147744563.

Proteomic databases

PaxDbP26927.
PRIDEP26927.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000383728; ENSP00000373234; ENSG00000173531.
GeneID4485.
KEGGhsa:4485.

Organism-specific databases

CTD4485.
GeneCardsGC03M049696.
H-InvDBHIX0024339.
HGNCHGNC:7380. MST1.
HPAHPA024036.
MIM142408. gene.
neXtProtNX_P26927.
Orphanet171. Primary sclerosing cholangitis.
PharmGKBPA31185.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000112892.
HOVERGENHBG004381.
InParanoidP26927.

Enzyme and pathway databases

SignaLinkP26927.

Gene expression databases

ArrayExpressP26927.
BgeeP26927.
CleanExHS_MST1.
GenevestigatorP26927.

Family and domain databases

Gene3D2.40.20.10. 4 hits.
InterProIPR024174. HGF_MST1.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR003014. PAN-1_domain.
IPR003609. Pan_app.
IPR001254. Peptidase_S1.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00051. Kringle. 4 hits.
PF00024. PAN_1. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF001152. HGF_MST1. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00130. KR. 4 hits.
SM00473. PAN_AP. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 4 hits.
PROSITEPS00021. KRINGLE_1. 4 hits.
PS50070. KRINGLE_2. 4 hits.
PS50948. PAN. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP26927.
GeneWikiMST1.
GenomeRNAi4485.
NextBio17351.
PMAP-CutDBP26927.
PROP26927.
SOURCESearch...

Entry information

Entry nameHGFL_HUMAN
AccessionPrimary (citable) accession number: P26927
Secondary accession number(s): A6NLA3 expand/collapse secondary AC list , A8MSX3, Q13350, Q14870, Q6GTN4
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: May 15, 2007
Last modified: March 19, 2014
This is version 147 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 3

Human chromosome 3: entries, gene names and cross-references to MIM