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Protein

Hepatocyte growth factor-like protein

Gene

MST1

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

Functioni

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.Curated

GO - Molecular functioni

  • receptor tyrosine kinase binding Source: UniProtKB
  • serine-type endopeptidase activity Source: InterPro

GO - Biological processi

  • hepatocyte growth factor receptor signaling pathway Source: Reactome
  • negative regulation of gluconeogenesis Source: UniProtKB
  • regulation of cAMP-dependent protein kinase activity Source: UniProtKB

Keywordsi

Molecular functionSerine protease homolog

Enzyme and pathway databases

ReactomeiR-HSA-8852405 Signaling by MST1
SignaLinkiP26927
SIGNORiP26927

Protein family/group databases

MEROPSiS01.975

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte growth factor-like protein
Alternative name(s):
Macrophage stimulatory protein
Macrophage-stimulating protein
Short name:
MSP
Cleaved into the following 2 chains:
Gene namesi
Name:MST1
Synonyms:D3F15S2, DNF15S2, HGFL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:7380 MST1
MIMi142408 gene
neXtProtiNX_P26927

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

MST1 variant Cys-689 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.2 Publications

Organism-specific databases

DisGeNETi4485
MalaCardsiMST1
Orphaneti171 Primary sclerosing cholangitis
PharmGKBiPA31185

Chemistry databases

ChEMBLiCHEMBL6042

Polymorphism and mutation databases

BioMutaiMST1
DMDMi147744563

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000002808519 – 711Hepatocyte growth factor-like proteinAdd BLAST693
ChainiPRO_000002808619 – 483Hepatocyte growth factor-like protein alpha chainCuratedAdd BLAST465
ChainiPRO_0000028087484 – 711Hepatocyte growth factor-like protein beta chainCuratedAdd BLAST228

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi56 ↔ 78By similarity
Disulfide bondi60 ↔ 66By similarity
Glycosylationi72N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi110 ↔ 186By similarity
Disulfide bondi131 ↔ 169By similarity
Disulfide bondi157 ↔ 181By similarity
Disulfide bondi191 ↔ 268By similarity
Disulfide bondi194 ↔ 324By similarity
Disulfide bondi212 ↔ 251By similarity
Disulfide bondi240 ↔ 263By similarity
Disulfide bondi283 ↔ 361By similarity
Glycosylationi296N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi304 ↔ 343By similarity
Disulfide bondi332 ↔ 355By similarity
Disulfide bondi370 ↔ 448By similarity
Disulfide bondi391 ↔ 431By similarity
Disulfide bondi419 ↔ 443By similarity
Disulfide bondi468 ↔ 588Interchain (between alpha and beta chains)
Disulfide bondi507 ↔ 523By similarity
Disulfide bondi602 ↔ 667By similarity
Glycosylationi615N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi632 ↔ 646By similarity
Disulfide bondi657 ↔ 685By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP26927
PaxDbiP26927
PeptideAtlasiP26927
PRIDEiP26927

PTM databases

iPTMnetiP26927
PhosphoSitePlusiP26927

Miscellaneous databases

PMAP-CutDBP26927

Expressioni

Gene expression databases

CleanExiHS_MST1

Organism-specific databases

HPAiHPA024036

Interactioni

Subunit structurei

Dimer of an alpha chain and a beta chain linked by a disulfide bond. Interacts (via beta chain) with MST1R (via SEMA domain).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • receptor tyrosine kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110591, 3 interactors
DIPiDIP-6028N
IntActiP26927, 9 interactors
MINTiP26927
STRINGi9606.ENSP00000414287

Structurei

Secondary structure

1711
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni475 – 479Combined sources5
Beta strandi495 – 499Combined sources5
Beta strandi505 – 513Combined sources9
Beta strandi516 – 520Combined sources5
Helixi521 – 523Combined sources3
Beta strandi535 – 539Combined sources5
Beta strandi541 – 544Combined sources4
Beta strandi553 – 562Combined sources10
Beta strandi569 – 576Combined sources8
Beta strandi581 – 584Combined sources4
Beta strandi601 – 608Combined sources8
Beta strandi620 – 627Combined sources8
Helixi629 – 635Combined sources7
Turni636 – 638Combined sources3
Beta strandi644 – 647Combined sources4
Beta strandi651 – 653Combined sources3
Beta strandi664 – 669Combined sources6
Beta strandi672 – 679Combined sources8
Beta strandi683 – 686Combined sources4
Beta strandi692 – 696Combined sources5
Helixi697 – 699Combined sources3
Helixi701 – 707Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ASUX-ray1.85A465-483[»]
B484-711[»]
4QT8X-ray3.00C/D465-711[»]
ProteinModelPortaliP26927
SMRiP26927
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26927

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 105PANPROSITE-ProRule annotationAdd BLAST85
Domaini110 – 186Kringle 1PROSITE-ProRule annotationAdd BLAST77
Domaini191 – 268Kringle 2PROSITE-ProRule annotationAdd BLAST78
Domaini283 – 361Kringle 3PROSITE-ProRule annotationAdd BLAST79
Domaini370 – 448Kringle 4PROSITE-ProRule annotationAdd BLAST79
Domaini484 – 709Peptidase S1PROSITE-ProRule annotationAdd BLAST226

Sequence similaritiesi

Belongs to the peptidase S1 family. Plasminogen subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IDXR Eukaryota
COG5640 LUCA
HOGENOMiHOG000112892
HOVERGENiHBG004381
InParanoidiP26927
PhylomeDBiP26927

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di2.40.20.10, 4 hits
InterProiView protein in InterPro
IPR024174 HGF-like
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR003609 Pan_app
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
PfamiView protein in Pfam
PF00051 Kringle, 4 hits
PF00024 PAN_1, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001152 HGF_MST1, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00130 KR, 4 hits
SM00473 PAN_AP, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57440 SSF57440, 4 hits
PROSITEiView protein in PROSITE
PS00021 KRINGLE_1, 4 hits
PS50070 KRINGLE_2, 4 hits
PS50948 PAN, 1 hit
PS50240 TRYPSIN_DOM, 1 hit

Sequencei

Sequence statusi: Complete.

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

P26927-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGWLPLLLLL TQCLGVPGQR SPLNDFQVLR GTELQHLLHA VVPGPWQEDV
60 70 80 90 100
ADAEECAGRC GPLMDCRAFH YNVSSHGCQL LPWTQHSPHT RLRRSGRCDL
110 120 130 140 150
FQKKDYVRTC IMNNGVGYRG TMATTVGGLP CQAWSHKFPN DHKYTPTLRN
160 170 180 190 200
GLEENFCRNP DGDPGGPWCY TTDPAVRFQS CGIKSCREAA CVWCNGEEYR
210 220 230 240 250
GAVDRTESGR ECQRWDLQHP HQHPFEPGKF LDQGLDDNYC RNPDGSERPW
260 270 280 290 300
CYTTDPQIER EFCDLPRCGS EAQPRQEATT VSCFRGKGEG YRGTANTTTA
310 320 330 340 350
GVPCQRWDAQ IPHQHRFTPE KYACKDLREN FCRNPDGSEA PWCFTLRPGM
360 370 380 390 400
RAAFCYQIRR CTDDVRPQDC YHGAGEQYRG TVSKTRKGVQ CQRWSAETPH
410 420 430 440 450
KPQFTFTSEP HAQLEENFCR NPDGDSHGPW CYTMDPRTPF DYCALRRCAD
460 470 480 490 500
DQPPSILDPP DQVQFEKCGK RVDRLDQRRS KLRVVGGHPG NSPWTVSLRN
510 520 530 540 550
RQGQHFCGGS LVKEQWILTA RQCFSSCHMP LTGYEVWLGT LFQNPQHGEP
560 570 580 590 600
SLQRVPVAKM VCGPSGSQLV LLKLERSVTL NQRVALICLP PEWYVVPPGT
610 620 630 640 650
KCEIAGWGET KGTGNDTVLN VALLNVISNQ ECNIKHRGRV RESEMCTEGL
660 670 680 690 700
LAPVGACEGD YGGPLACFTH NCWVLEGIII PNRVCARSRW PAVFTRVSVF
710
VDWIHKVMRL G
Length:711
Mass (Da):80,320
Last modified:May 15, 2007 - v2
Checksum:i2E4B3C7D4AA9B566
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti292R → G AA sequence (PubMed:1827141).Curated1
Sequence conflicti304C → E AA sequence (PubMed:1827141).Curated1
Sequence conflicti306R → E AA sequence (PubMed:1827141).Curated1
Sequence conflicti550Missing AA sequence (PubMed:1827141).Curated1
Sequence conflicti593W → E AA sequence (PubMed:1827141).Curated1
Sequence conflicti623L → F in AAA59872 (PubMed:8393443).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00663113C → Y1 Publication1
Natural variantiVAR_006632212C → F. 1
Natural variantiVAR_059787551S → G. Corresponds to variant dbSNP:rs6791037Ensembl.1
Natural variantiVAR_070224689R → C Common polymorphism; may be associated with inflammatory bowel disease; results in reduced binding affinity to MST1R. 3 PublicationsCorresponds to variant dbSNP:rs3197999Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
PIRiA40331 A47136
RefSeqiNP_066278.3, NM_020998.3
UniGeneiHs.349110
Hs.512587

Genome annotation databases

EnsembliENST00000383728; ENSP00000373234; ENSG00000173531
GeneIDi4485
KEGGihsa:4485

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHGFL_HUMAN
AccessioniPrimary (citable) accession number: P26927
Secondary accession number(s): A6NLA3
, A8MSX3, Q13350, Q14870, Q6GTN4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: May 15, 2007
Last modified: May 23, 2018
This is version 180 of the entry and version 2 of the sequence. See 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, Direct protein sequencing, Reference proteome

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