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Protein

Cell migration-inducing and hyaluronan-binding protein

Gene

CEMIP

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

Functioni

Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product, a process that may occur through rapid vesicle endocytosis and recycling without intracytoplasmic accumulation or digestion in lysosomes. Involved in hyaluronan catabolism in the dermis of the skin and arthritic synovium. Positively regulates epithelial-mesenchymal transition (EMT), and hence tumor cell growth, invasion and cancer dissemination. In collaboration with HSPA5/BIP, promotes cancer cell migration in a calcium and PKC-dependent manner. May be involved in hearing.3 Publications

Catalytic activityi

Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.2 Publications

Enzyme regulationi

Activity is up-regulated by histamine.1 Publication

GO - Molecular functioni

  • clathrin heavy chain binding Source: UniProtKB
  • ER retention sequence binding Source: UniProtKB
  • hyaluronic acid binding Source: UniProtKB
  • hyalurononglucosaminidase activity Source: UniProtKB

GO - Biological processi

  • hyaluronan biosynthetic process Source: Reactome
  • hyaluronan catabolic process Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
  • positive regulation of protein kinase C activity Source: UniProtKB
  • positive regulation of protein targeting to membrane Source: UniProtKB
  • positive regulation of release of sequestered calcium ion into cytosol Source: UniProtKB
  • sensory perception of sound Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Hyaluronic acid

Enzyme and pathway databases

ReactomeiR-HSA-2142850. Hyaluronan biosynthesis and export.

Names & Taxonomyi

Protein namesi
Recommended name:
Cell migration-inducing and hyaluronan-binding protein (EC:3.2.1.35)
Gene namesi
Name:CEMIP
Synonyms:KIAA1199
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:29213. CEMIP.

Subcellular locationi

  • Nucleus
  • Cytoplasm
  • Endoplasmic reticulum
  • Cell membrane
  • Membraneclathrin-coated pit
  • Secreted

  • Note: Retained in the endoplasmic reticulum (ER) in a HSPA5/BIP-dependent manner. Colocalized with clathrin heavy chain/CLTC in clathrin-coated vesicles. Strongly detected in the cytoplasm of breast carcinoma cells, whereas poorly detected in adjacent normal epithelial cells, stromal cells, or benign breast tissues. Localized in the nucleus and cytoplasm of colon adenocarcinomas.

GO - Cellular componenti

  • clathrin-coated pit Source: UniProtKB-SubCell
  • clathrin-coated vesicle membrane Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • extracellular region Source: Reactome
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi57214.
OpenTargetsiENSG00000103888.
PharmGKBiPA134967531.

Polymorphism and mutation databases

BioMutaiKIAA1199.
DMDMi46396475.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 301 PublicationAdd BLAST30
ChainiPRO_000002153831 – 1361Cell migration-inducing and hyaluronan-binding proteinAdd BLAST1331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi119N-linked (GlcNAc...)Sequence analysis1
Glycosylationi165N-linked (GlcNAc...)Sequence analysis1
Glycosylationi312N-linked (GlcNAc...)Sequence analysis1
Glycosylationi370N-linked (GlcNAc...)Sequence analysis1
Glycosylationi420N-linked (GlcNAc...)Sequence analysis1
Glycosylationi889N-linked (GlcNAc...)Sequence analysis1
Glycosylationi921N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated; glycosylation is not necessary for HA-binding.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8WUJ3.
PeptideAtlasiQ8WUJ3.
PRIDEiQ8WUJ3.

PTM databases

iPTMnetiQ8WUJ3.
PhosphoSitePlusiQ8WUJ3.

Expressioni

Tissue specificityi

Expressed in dermal and in synovial fibroblasts. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in both ductal carcinoma and invasive breast cancer cells compared with benign epithelial cells (at protein level). Strongly expressed in brain, placenta, prostate, breast, lung and testis. Expressed in fibroblasts, epithelial cells and cancer cells. In ear, it is specifically expressed in inner ear. Expressed in cochlea and vestibule tissues. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in colon adenocarcinomas compared with normal colonic mucosas. Strongly expressed in breast cancer as compared to normal breast tissue.8 Publications

Inductioni

Up-regulated by histamine. Up-regulated by the adapter protein complex 1 (AP-1) and NF-kappaB/RELA. Down-regulated by transforming growth factor TGFB1.2 Publications

Gene expression databases

BgeeiENSG00000103888.
CleanExiHS_KIAA1199.
ExpressionAtlasiQ8WUJ3. baseline and differential.
GenevisibleiQ8WUJ3. HS.

Organism-specific databases

HPAiHPA007090.
HPA044676.

Interactioni

Subunit structurei

Interacts with EPHA2 and ITPR3. Interacts with HSPA5/BIP; the interaction induces calcium leakage from the endoplasmic reticulum and cell migration. Interacts with clathrin heavy chain/CLTC.3 Publications

GO - Molecular functioni

  • clathrin heavy chain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121452. 2 interactors.
IntActiQ8WUJ3. 1 interactor.
STRINGi9606.ENSP00000220244.

Structurei

3D structure databases

ProteinModelPortaliQ8WUJ3.
SMRiQ8WUJ3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 166G8PROSITE-ProRule annotationAdd BLAST123
Repeati572 – 594PbH1 1Add BLAST23
Repeati595 – 617PbH1 2Add BLAST23
Repeati719 – 741PbH1 3Add BLAST23
Repeati798 – 819PbH1 4Add BLAST22

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni295 – 591Necessary for its endoplasmic reticulum (ER) retention and interaction with HSPA51 PublicationAdd BLAST297

Domaini

The signal sequence is essential in mediating its proper translocation, hyaluronic acid (HA) degradation activity and secretion.

Sequence similaritiesi

Belongs to the TMEM2 family.Curated
Contains 1 G8 domain.PROSITE-ProRule annotation
Contains 4 PbH1 repeats.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IFCM. Eukaryota.
ENOG410XQ01. LUCA.
GeneTreeiENSGT00780000121902.
HOGENOMiHOG000290723.
HOVERGENiHBG052198.
InParanoidiQ8WUJ3.
KOiK19031.
OMAiRHPWSFI.
OrthoDBiEOG091G00JT.
PhylomeDBiQ8WUJ3.
TreeFamiTF316575.

Family and domain databases

Gene3Di2.160.20.10. 2 hits.
InterProiIPR019316. G8_domain.
IPR012334. Pectin_lyas_fold.
IPR011050. Pectin_lyase_fold/virulence.
IPR025155. WxxW_domain.
[Graphical view]
PfamiPF10162. G8. 1 hit.
PF13330. Mucin2_WxxW. 1 hit.
[Graphical view]
SMARTiSM01225. G8. 1 hit.
[Graphical view]
SUPFAMiSSF51126. SSF51126. 5 hits.
PROSITEiPS51484. G8. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WUJ3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGAAGRQDFL FKAMLTISWL TLTCFPGATS TVAAGCPDQS PELQPWNPGH
60 70 80 90 100
DQDHHVHIGQ GKTLLLTSSA TVYSIHISEG GKLVIKDHDE PIVLRTRHIL
110 120 130 140 150
IDNGGELHAG SALCPFQGNF TIILYGRADE GIQPDPYYGL KYIGVGKGGA
160 170 180 190 200
LELHGQKKLS WTFLNKTLHP GGMAEGGYFF ERSWGHRGVI VHVIDPKSGT
210 220 230 240 250
VIHSDRFDTY RSKKESERLV QYLNAVPDGR ILSVAVNDEG SRNLDDMARK
260 270 280 290 300
AMTKLGSKHF LHLGFRHPWS FLTVKGNPSS SVEDHIEYHG HRGSAAARVF
310 320 330 340 350
KLFQTEHGEY FNVSLSSEWV QDVEWTEWFD HDKVSQTKGG EKISDLWKAH
360 370 380 390 400
PGKICNRPID IQATTMDGVN LSTEVVYKKG QDYRFACYDR GRACRSYRVR
410 420 430 440 450
FLCGKPVRPK LTVTIDTNVN STILNLEDNV QSWKPGDTLV IASTDYSMYQ
460 470 480 490 500
AEEFQVLPCR SCAPNQVKVA GKPMYLHIGE EIDGVDMRAE VGLLSRNIIV
510 520 530 540 550
MGEMEDKCYP YRNHICNFFD FDTFGGHIKF ALGFKAAHLE GTELKHMGQQ
560 570 580 590 600
LVGQYPIHFH LAGDVDERGG YDPPTYIRDL SIHHTFSRCV TVHGSNGLLI
610 620 630 640 650
KDVVGYNSLG HCFFTEDGPE ERNTFDHCLG LLVKSGTLLP SDRDSKMCKM
660 670 680 690 700
ITEDSYPGYI PKPRQDCNAV STFWMANPNN NLINCAAAGS EETGFWFIFH
710 720 730 740 750
HVPTGPSVGM YSPGYSEHIP LGKFYNNRAH SNYRAGMIID NGVKTTEASA
760 770 780 790 800
KDKRPFLSII SARYSPHQDA DPLKPREPAI IRHFIAYKNQ DHGAWLRGGD
810 820 830 840 850
VWLDSCRFAD NGIGLTLASG GTFPYDDGSK QEIKNSLFVG ESGNVGTEMM
860 870 880 890 900
DNRIWGPGGL DHSGRTLPIG QNFPIRGIQL YDGPINIQNC TFRKFVALEG
910 920 930 940 950
RHTSALAFRL NNAWQSCPHN NVTGIAFEDV PITSRVFFGE PGPWFNQLDM
960 970 980 990 1000
DGDKTSVFHD VDGSVSEYPG SYLTKNDNWL VRHPDCINVP DWRGAICSGC
1010 1020 1030 1040 1050
YAQMYIQAYK TSNLRMKIIK NDFPSHPLYL EGALTRSTHY QQYQPVVTLQ
1060 1070 1080 1090 1100
KGYTIHWDQT APAELAIWLI NFNKGDWIRV GLCYPRGTTF SILSDVHNRL
1110 1120 1130 1140 1150
LKQTSKTGVF VRTLQMDKVE QSYPGRSHYY WDEDSGLLFL KLKAQNEREK
1160 1170 1180 1190 1200
FAFCSMKGCE RIKIKALIPK NAGVSDCTAT AYPKFTERAV VDVPMPKKLF
1210 1220 1230 1240 1250
GSQLKTKDHF LEVKMESSKQ HFFHLWNDFA YIEVDGKKYP SSEDGIQVVV
1260 1270 1280 1290 1300
IDGNQGRVVS HTSFRNSILQ GIPWQLFNYV ATIPDNSIVL MASKGRYVSR
1310 1320 1330 1340 1350
GPWTRVLEKL GADRGLKLKE QMAFVGFKGS FRPIWVTLDT EDHKAKIFQV
1360
VPIPVVKKKK L
Length:1,361
Mass (Da):152,998
Last modified:April 13, 2004 - v2
Checksum:i40CDFFB84F99516C
GO
Isoform 2 (identifier: Q8WUJ3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     978-992: NWLVRHPDCINVPDW → KWHSLASKAASGPSG
     993-1361: Missing.

Note: No experimental confirmation available.
Show »
Length:992
Mass (Da):110,357
Checksum:iAF371C2A8633012D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti558 – 564HFHLAGD → TRPPTRP in CAB94391 (Ref. 6) Curated7
Sequence conflicti862H → T in AAG41059 (PubMed:11247670).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018165187R → C in a family with non-syndromic hearing loss; reduces hyaluronic acid degradation activity. 2 PublicationsCorresponds to variant rs368854657dbSNPEnsembl.1
Natural variantiVAR_018166187R → H in two unrelated families with non-syndromic hearing loss; reduces hyaluronic acid (HA) degradation activity. 2 PublicationsCorresponds to variant rs144446375dbSNPEnsembl.1
Natural variantiVAR_018167783H → R Does not inhibit hyaluronic acid degradation activity. 2 PublicationsCorresponds to variant rs12441101dbSNPEnsembl.1
Natural variantiVAR_018168783H → Y in a sporadic case of non-syndromic hearing loss. 1 Publication1
Natural variantiVAR_0181691109V → I Does not inhibit hyaluronic acid degradation activity. 2 PublicationsCorresponds to variant rs751807711dbSNPEnsembl.1
Natural variantiVAR_0181701169P → A Common polymorphism. 1 PublicationCorresponds to variant rs16972583dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009814978 – 992NWLVR…NVPDW → KWHSLASKAASGPSG in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_009815993 – 1361Missing in isoform 2. 1 PublicationAdd BLAST369

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB103330 mRNA. Translation: BAD02451.1.
CH471136 Genomic DNA. Translation: EAW99111.1.
BC020256 mRNA. Translation: AAH20256.1.
AB033025 mRNA. Translation: BAA86513.1.
AL359061 mRNA. Translation: CAB94391.1.
AY007811 mRNA. Translation: AAG41059.1.
CCDSiCCDS10315.1. [Q8WUJ3-1]
RefSeqiNP_001280227.1. NM_001293298.1. [Q8WUJ3-1]
NP_001280233.1. NM_001293304.1. [Q8WUJ3-1]
NP_061159.1. NM_018689.2. [Q8WUJ3-1]
UniGeneiHs.459088.

Genome annotation databases

EnsembliENST00000220244; ENSP00000220244; ENSG00000103888. [Q8WUJ3-1]
ENST00000356249; ENSP00000348583; ENSG00000103888. [Q8WUJ3-1]
ENST00000394685; ENSP00000378177; ENSG00000103888. [Q8WUJ3-1]
ENST00000611615; ENSP00000480324; ENSG00000103888. [Q8WUJ3-2]
GeneIDi57214.
KEGGihsa:57214.
UCSCiuc002bfw.2. human. [Q8WUJ3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB103330 mRNA. Translation: BAD02451.1.
CH471136 Genomic DNA. Translation: EAW99111.1.
BC020256 mRNA. Translation: AAH20256.1.
AB033025 mRNA. Translation: BAA86513.1.
AL359061 mRNA. Translation: CAB94391.1.
AY007811 mRNA. Translation: AAG41059.1.
CCDSiCCDS10315.1. [Q8WUJ3-1]
RefSeqiNP_001280227.1. NM_001293298.1. [Q8WUJ3-1]
NP_001280233.1. NM_001293304.1. [Q8WUJ3-1]
NP_061159.1. NM_018689.2. [Q8WUJ3-1]
UniGeneiHs.459088.

3D structure databases

ProteinModelPortaliQ8WUJ3.
SMRiQ8WUJ3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121452. 2 interactors.
IntActiQ8WUJ3. 1 interactor.
STRINGi9606.ENSP00000220244.

PTM databases

iPTMnetiQ8WUJ3.
PhosphoSitePlusiQ8WUJ3.

Polymorphism and mutation databases

BioMutaiKIAA1199.
DMDMi46396475.

Proteomic databases

PaxDbiQ8WUJ3.
PeptideAtlasiQ8WUJ3.
PRIDEiQ8WUJ3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220244; ENSP00000220244; ENSG00000103888. [Q8WUJ3-1]
ENST00000356249; ENSP00000348583; ENSG00000103888. [Q8WUJ3-1]
ENST00000394685; ENSP00000378177; ENSG00000103888. [Q8WUJ3-1]
ENST00000611615; ENSP00000480324; ENSG00000103888. [Q8WUJ3-2]
GeneIDi57214.
KEGGihsa:57214.
UCSCiuc002bfw.2. human. [Q8WUJ3-1]

Organism-specific databases

CTDi57214.
DisGeNETi57214.
GeneCardsiCEMIP.
HGNCiHGNC:29213. CEMIP.
HPAiHPA007090.
HPA044676.
MIMi608366. gene.
neXtProtiNX_Q8WUJ3.
OpenTargetsiENSG00000103888.
PharmGKBiPA134967531.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFCM. Eukaryota.
ENOG410XQ01. LUCA.
GeneTreeiENSGT00780000121902.
HOGENOMiHOG000290723.
HOVERGENiHBG052198.
InParanoidiQ8WUJ3.
KOiK19031.
OMAiRHPWSFI.
OrthoDBiEOG091G00JT.
PhylomeDBiQ8WUJ3.
TreeFamiTF316575.

Enzyme and pathway databases

ReactomeiR-HSA-2142850. Hyaluronan biosynthesis and export.

Miscellaneous databases

GeneWikiiKIAA1199.
GenomeRNAii57214.
PROiQ8WUJ3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103888.
CleanExiHS_KIAA1199.
ExpressionAtlasiQ8WUJ3. baseline and differential.
GenevisibleiQ8WUJ3. HS.

Family and domain databases

Gene3Di2.160.20.10. 2 hits.
InterProiIPR019316. G8_domain.
IPR012334. Pectin_lyas_fold.
IPR011050. Pectin_lyase_fold/virulence.
IPR025155. WxxW_domain.
[Graphical view]
PfamiPF10162. G8. 1 hit.
PF13330. Mucin2_WxxW. 1 hit.
[Graphical view]
SMARTiSM01225. G8. 1 hit.
[Graphical view]
SUPFAMiSSF51126. SSF51126. 5 hits.
PROSITEiPS51484. G8. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCEMIP_HUMAN
AccessioniPrimary (citable) accession number: Q8WUJ3
Secondary accession number(s): Q6L9J5
, Q9H1K5, Q9NPN9, Q9ULM1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: November 2, 2016
This is version 118 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

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

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.